Cardio Diabetes_2017 book

178 Cardio Diabetes Medicine 2017

put directly. Instead, arterial blood is drawn from a tion.
peripheral artery and recirculated through the aorta
via an extracorporeal pump that then returns blood Major concerns with early therapy include:Patients
through a second arterial access site. Increased aor- with ADHF may develop hypotension and/or wors-
tic flow is postulated to stimulate favorable hemody- ening renal function during initial therapy. Early initi-
namic changes, primarily through cardiac unloading ation of oral ACE inhibitor may be deletirious in pa-
and peripheral vasodilation. tients at high risk for hypotension (eg, low baseline
blood pressure or hyponatremia).Aggressive diuretic
In the MOMENTUM trial, 168 patients hospitalized therapy typically given for acute pulmonary edema
with HF with reduced LVEF were randomly assigned may increase sensitivity to ACE inhibition or angio-
to CAFA plus medical therapy or medical therapy tensin blockade, including risks of hypotension and
alone . The primary composite efficacy end point renal dysfunction.
included PCWP and days alive out of hospital off
mechanical support over 35 days and was similar in Ivabradine — Ivabradine reduces the risk of hospital-
the two treatment groups. CAFA improved cardiac in- ization in patients with chronic HFrEF esp with betbut
dex, cardiac performance and PCWP;however major has no proven role in acute HF.
bleeds occurred in 16.5 percent in the device group
and 5.1 percent in the control group. Mineralocorticoid receptor antagonist(MRA) —MRA
therapy (spironolactone or eplerenone) reduces mor-
CONTINUATION OR INITIATION OF LONG- tality when included in long-term management of se-
TERM THERAPY lected patients with systolic HF who can be carefully
monitored for serum potassium and renal function.
The approach to managing long-term therapy during In patients already taking an MRA, such therapy
hospitalization for acute heart failure (HF) differs for can generally be continued during an episode of
HF with reduced ejection fraction (HFrEF) and HF acute decompensation, with appropriate monitoring
with preserved ejection fraction (HFpEF). of blood pressure, renal function, and electrolytes.
For patients not taking a mineralocorticoid receptor
Approach to long-term therapy for heart failure with antagonist who have an indication for therapy, initia-
preserved ejection fraction tion is advised few days prior to discharge to monitor
serum potassium levels. In patients in whom an ACE
The general principles for treatment of HFpEF are inhibitor or ARB was started or uptitrated shortly prior
control of systolic and diastolic hypertension, control to discharge, it is recommended that mineralocorti-
of heart rate (particularly in patients with atrial fibrilla- coid receptor antagonist initiation be delayed until
tion), control of pulmonary congestion and peripheral the first outpatient visit and evaluation of potassium.
edema with diuresis (with care to avoid hypotension
and/or left ventricular outflow obstruction), and coro- Newer vistas for AHF treatment in CAD( ACS) setting
nary revascularization in patients with coronary heart -IABP ECMO , LVAD
disease with ischemia judged to impair diastolic func-
tion. Patients with small LV cavities and/or LVH are Cardiogenic shock is an acute emergency, which is
volume-sensitive and at risk for developing hypoten- classically managed by medical support with inotro-
sion with diuresis. pes or vasopressors and frequently requires invasive
ventilation. Mechanical circulatory support is increas-
Approach to long-term therapy for heart failure with ingly being considered to allow for recovery or to
reduced ejection fraction bridge until making a decision or definite treatment.
Several modes and devices of mechanical support
Evidence-based therapy to reduce morbidity and are currently available , of which each has its own
mortality for patients with chronic HFrEF includes an features and advantages.Intuitively the most logical
angiotensin converting enzyme (ACE) inhibitor, sin- treatment in acute coronary syndrome(ACS)- related
gle-agent angiotensin receptor blocker (ARB), or an- AHF would be expeditious coronary revascularisa-
giotensin receptor-neprilysin inhibitor (ARNI); a beta tion, generally with PCI.The use of adjunct support
blocker; and a mineralocorticoid antagonist . Once devices used in the Cath lab in AHF in ACS patients
the patient has stabilized from AHF, evidence-based is by itself a voluminous subject of intense research
therapies are carefully initiated, re-initiated, or titrat- and discussion and details are beyond the scope of
ed with arrangements for appropriate outpatient fol- this article.
low-up. Long-acting drugs, such as ACE inhibitors,
ARBs, or ARNI should be administered with caution Briefly,the intra-aortic balloon pump (IABP) consists
or avoided during the first few hours of hospitaliza- of a catheter-mounted balloon that inflates during di-

GCDC 2017

Clinical Presentation and Management 179
of Acute Heart Failure

Pic 1: Strategies of Mechanical Circulatory support

astole and deflates during systole in the descending provide cardiopulmonary support. ECMO does not
thoracic aorta ,thereby afterload is decreased during provide treatment of the underlying disease. The indi-
systole when the left ventricle (LV) ejects. Notwith- cations for ECMO support have expanded from acute
standing the attractive pathophysiological principle,- respiratory failure to acute cardiac failure refractory
several well -conducted studies have demonstrated to conventional treatments from wide patient subsets
that IABP support is equivocal in infarct-related car- involving neonates to adults. Desaturated blood is
diogenic shock, yet it still continues to be the most drained via a venous cannula. CO2 is removed, O2
commonly available adjunct in PCI -related cardio- added through an “extracorporeal” device. The blood
genic shock. is then returned to systemic circulation via another
vein (VV ECMO) or artery (VA ECMO).
The TandemHeart® consists of a pump and two can-
nulas, of which one is inserted via venous access and The upcoming next generation is a shift from the
transseptal approach into the left atrium (LA), and the conventional methodology and are directed toward:
other one via arterial access into the femoral artery. 1) paracorporeal approaches (wearable devices that
By this, the TandemHeart® introduces a right-to-left will be attached directly to patients); 2) intravascular
shunt, reduces LV preload by LA drainage, but in- approaches (respiratory catheters placed within the
creases afterload by retrograde flow support toward vena cava through a peripheral vein); and 3) intra-
the aorta. The TandemHeart requires experienced thoracic-intra-abdominal approaches. Few of the no-
transseptal cannula placement, which is assumed to table developments are: iVOX™, that was developed
harbor considerable risk in the acute situation. by Mortensen and colleagues at Cardio Pulmonics,
Inc. (Salt Lake City, UT), as the only intravascular ar-
Transaortic microaxial pumps (Impella®2.5 or 5.0, tificial lung that has undergone human clinical trials;
Heartmate PHP®) are introduced via arterial access another design requiring placement through the right
through the aorta across the aortic valve into the LV. ventricle into the PA was developed at Penn State
This elegant approach, which follows the physiolog- University as PENSIL, for Penn State Intravascular
ical blood flow direction, uses devices that directly Lung, and other in development include ITAL ,Bio
unload the LV, transport the drained volume inside Lung and the CORx system.
of the pump toward the aorta and eject into the aor-
tic root. However, microaxial pumps do not offer gas SUMMARY AND RECOMMENDATIONS
exchange or temperature control.
APPROACH TO MANAGEMENT OF ACUTE
Probably, the most often used form of mechanical HEART FAILURE
circulatory support today is ECMO. Extracorporeal
membrane oxygenation (ECMO) is an adaptation of • Initial therapy includes supplemental oxygen and
conventional cardiopulmonary bypass techniques to assisted ventilation if necessary and a loop diuretic

Cardio Diabetes Medicine

180 Cardio Diabetes Medicine 2017

for volume overload . • For selected patients with severe HFrEF with acute,
severe hemodynamic compromise, non-durable
• For patients with acute decompensated heart fail- mechanical support is an option.
ure (ADHF) with respiratory distress, respiratory
acidosis, and/or hypoxia with oxygen therapy.a • Patients with HF with preserved ejection fraction
trial of noninvasive ventilation (NIV) is allowed if (HFpEF) presenting with hypotension should not
emergent intubation is not indicated , no contra- receive inotropes and may require a vasopressor in
indications to NIV exist, and personnel with expe- addition to diuretic therapy. Patients who develop
rience in NIV are available. hypotension with dynamic left ventricular outflow
obstruction are treated with beta blocker therapy
• Patients with respiratory failure due to ADHF who and gentle hydration if pulmonary edema is not
fail to improve with NIV (within one-half to two present.
hours), do not tolerate NIV, or have contraindica-
tions to NIV require endotracheal intubation for • Ultrafiltration is an option for patients with HFrEF
conventional mechanical ventilation. or HFpEF with refractory volume overload not re-
sponding to appropriate diuretic strategies.
• In patients with ADHF and fluid overload, initial
therapy should include a loop diuretic (adminis- • Longer term continuation of treatment requires
tered intravenously) .Dosing is individualized, de- careful inititation and maintenance of oral thera-
termined largely by the patient’s renal function and pies after switching from the parenteral ones.
prior diuretic exposure.
In toto, the management of ADHF relies on the FOUR
• Vasodilators may be required to correct elevated PRONGED approach of :
filling pressures and/or LV afterload in patients
with ADHF. Indications for vasodilator therapy with • determining the “ hemodynamic subset” to
close hemodynamic monitoring in the setting of which the index patient belongs
ADHF include the following
• instituting acute relief of volume overload un-
•For patients with urgent need for afterload reduc- der monitored intensive care setting
tion (eg, severe hypertension) or as a temporizing
measure in patients with acute aortic regurgitation • treatment of precipitant factors of ADHF and
or acute mitral regurgitation, suggest balanced va- expiditing revascularisation if need be and
sodilator therapy (eg, nitroprusside).
• monitored switching of parenteral to oral drugs
•Vasodilator therapy (eg, nitroglycerin) is started as for continuation therapy to prevent AHF recur-
an adjunct to diuretic therapy for patients without ad- rences.
equate response to diuretics , and as a component
of therapy for patients with refractory HF and low
cardiac output .

• For most patients hospitalized with ADHF, nesir-
itide is not recommended . In carefully selected
patients with appropriate hemodynamics (includ-
ing absence of hypotension or cardiogenic shock)
who remain symptomatic despite routine therapy,
a trial of nesiritide may be helpful as an alternative
to other vasodilator therapy (nitroglycerin or nitro-
prusside). Nesiritide has a longer effective half-life
than nitroglycerin or nitroprusside, so side effects
such as hypotension may persist longer.

• Treatment of refractory HF and hypotension in
patients with HF with reduced ejection fraction
(HFrEF) is guided by hemodynamics, which is
most commonly imputed from the physical exam-
ination with more direct assessment by selective
right heart catheterization with intravenous inotro-
pic support as a temporizing measure.

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Cardio Diabetes Medicine 2017 181

Non-Infarct Related Artery Intervention in
St-Elevation Myocardial Infarction With Multivessel Disease:

MultiVessel PCI in STEMI - Timing of Intervention?

Dr. Shirish Hiremath, MD. DM(Card). MNAMS. FISE

Director, Cath Lab Ruby Hall, President CSI 2016-2017
Managing Trustee & Chairman AIMS, Pune

Approach to Multivessel disease in STEMI: Perfect Is The Enemy of Good!

For patients presenting with ST-elevation myocardial infarction (STEMI), primary angioplasty (pPCI) of the cul-
prit vessel, is the treatment of choice [1, 2]. Recent advances in PCI techniques, hardware and antithrombotic
therapy alongwith reduced transportation time have led to significantly reduced mortality in pPCI. But 40-

60% patients with STEMI have multivessel disease (MVD) at the time of presentation. In STEMI, presence of
multivessel disease is associated with poor outcome compared to single vessel disease, including a need for
repeat revascularisation and repeat admissions with MI (fig.1). This increase in risk may be caused by function
of a noninfarct zone, extent of atherosclerotic burden, combination of stunned and hibernating myocardium,
or slow flow in a nonculprit vessel.

Fig 1: Mortality in STEMI depending on angiographic findings [3].

Optimum management of multivessel disease in STEMI is till subject of debate. In hemodynamically unstable
patients, multivessel PCI at the time of index procedure is the preferred approach, though not supported by
suffient data[1,2]. Different “non-culprit lesion” strategies in stable patients with STEMI and MVD undergo-
ing p-PCI have been compared in randomised studies and non-randomised observational registries, yielding
conflicting results. In this review article, we will discuss why guideline recommendations regarding multivessel
PCI in STEMI changed over last 5-7years and how to integrate it into daily clinical decision making.

Evidence- Pre2011:

Various small randomised and observational trials have suggested the benefit of multivessel PCI over culprit
only PCI in MVD-STEMI. Meta-analysis by Banglore et at have showed that for early outcomes, there was no
difference between groups for outcomes of mortality, MI, stroke, and target vessel revascularization, with a
44% decrease in repeat PCI and a 32% decrease in MACEs with multivessel revascularization. Similarly, for
long-term outcomes, there was no difference for outcomes of MI, target vessel revascularization, and stent
thrombosis, with a 33% decrease in mortality, a 43% decrease in repeat PCI, a 53% decrease in coronary artery

Cardio Diabetes Medicine

Non-Infarct Related Artery Intervention in St-Elevation Myocardial Infarc-
182 tion With Multivessel Disease: MultiVessel PCI in STEMI:

Timing of Intervention?

bypass grafting, and a 40% decrease in MACEs with multivessel revascularization compared to culprit only
revascularisation [4]. But the timing multivessel PCI is variable from during index PCI to upto 60 days after
discharge. Another mata-analysis by Vlaar PJ et al[5] have defined 3 approaches for non-culprit intervention
in MVD-STEMI patients; aggressive approach (multivessel PCI at the time of index procedure), intermediate
approach (staged PCI during index hospital stay or within 30days of index procedure) or conservative ap-
proach (non-culprit intervention only in case of refractory symptoms or objective evidence of ischaemia). This
large meta-analysis which included more than 40,000 patients have suggested that non-culprit multivessel
PCI during the index p-PCI should be discouraged, and suitable significant non-culprit lesions treated only
during the staged procedure, this being associated with lower short- and long-term mortality as compared to
index non-culprit multivessel PCI (fig. ). This meta-analysis and a substudy of HORIZON-AMI[6] showed that
aggressive approach has the worst outcome. The main disadvantage of aggressive approach is increased
radiation dose, increased contrast use, increased procedural complications, and a theoretical increase in risk
of stent thrombosis because of a prothrombotic proinflammatory state with subsequent increase in in-hospi-
tal outcomes and length of stay. Few single centre trials and observational studies had shown benefit in the
aggressive approach. So 2011 AHA guidelines for percutaneous coronary interventions and 2012 European
society of cardiology STEMI guidelines have recommended PCI in non-infarct related artery in hemodynam-
ically STEMI patient as class III (level of evidence-B) intervention and limit the non-culprit PCI during the
index p-PCI only in the setting of cardiogenic shock (class of recommendation-IIa, level of evidence-B)[7,8].

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Cardio Diabetes Medicine 2017 183

Fig.2: Meta-analysis concerning the optimal management of multivessel disease in STEMI patients and long-term mor-
tality. Comparison between multivessel PCI, staged PCI, and culprit-only PCI[5].

Cardio Diabetes Medicine

Non-Infarct Related Artery Intervention in St-Elevation Myocardial Infarc-
184 tion With Multivessel Disease: MultiVessel PCI in STEMI:

Timing of Intervention?

Fig.3: Various strategies for PCI in MVD-STEMI

Evidence - Post 2011:

Proponents of aggressive approach argue that in STEMI heightened inflammation is not limited to the culprit
plaque, there is a Pan-inflammation leading to multiple plaque disruptions[9]. So multivessel PCI would afford
protection against plaque rupture of these lesions and prevent recurrent MI/ischemia and death. Also critical
stenosis in non-culprit vessel causes ‘ischeamia at distance’ which hampers the compensatory contractility of
remote myocardial segments, so multivessel PCI leads to faster improvement in LV function[10]. Also the evo-
lution of PCI with high penetration of latest-generation drug-eluting stents, better hardware and optimisation
of antithrombotic and Antiplatelet strategy, outcomes of PCI have improved significantly in the last decade.
PRAMI (Preventive Angioplasty in Acute Myocardial Infarction) study, patients with STEMI and MVD were
randomised to an aggressive approach designated as “preventive angioplasty” with non-culprit PCI imme-
diately following p-PCI, and a conservative approach with staged non-culprit PCI only in case of refractory
symptoms[11]. This was a open-label, single-blind study with small sample size and slow recruitment (465
patients enrolled over 5years from 5 high volume centres in UK, each performing >300 pPCI per year). Ran-
domisation in this trial was done after pPCI and there was high selection bias (2428 patients screened and
465 patients were enrolled). The “preventive angioplasty” strategy was proved to be superior with a significant
65% relative reduction in the combined primary endpoint of cardiovascular death, non-fatal MI and refractory
angina. Results were driven by a 65% reduction in refractory angina and a 68% reduction in non-fatal MI,
although a trend towards a reduction in mortality (p=0.07) was also documented. In this trial obstructive CAD
was defined only by angiographic criteria which led to overestimation of the non-culprit lesion and overtreat-
ment in “preventive angioplasty” arm. Moreover no information was provided about non-culprit lesions such
as QCA, TIMI flow or lesion characteristics. Because of highly selected patients, it is difficult to extrapolate
a concept of “preventive angioplasty” to an all-comer STEMI population. Very few interventionalist follow
the PRAMI trial as the real clinical questions about non-culprit lesions- “should we do it?” and “when to do
it?” remain partially unanswered after the PRAMI study. The PRAMI study probably suggests that non-culprit
lesions could be treated in specific cases according to both patient and anatomy, but does not address the
optimal timing for these patients.
CvLPRIT (Complete Versus Lesion-Only Primary PCI trial)[12] was multicentre, open randomised trial compar-
ing culprit lesion only with complete intervention in patients presenting with STEMI and evidence of multives-
sel disease. Complete revascularization was performed either at the time of P-PCI (two thirds of complete
revascularisation group) or before hospital discharge. As with PRAMI, this was also a small study with slow
recruitment (850 patients were screened over 48 months and 296 were enrolled from 7 centres in UK); but
randomisation was done prior to pPCI. The primary endpoint (composite of all-cause death, recurrent myocar-

GCDC 2017

Cardio Diabetes Medicine 2017 185

dial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months) occurred in 10.0% of
the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45;
95% confidence interval: 0.24 to 0.84; p=0.009), though statistically not signficant. A trend toward benefit
was seen early after complete revascularization (p=0.055 at 30 days). There was no reduction in ischemic
burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced
nephropathy, or stroke between the groups.

Both these trials were not in line with the current practice of physiological (FFR) or histopathological (IVUS/
OCT) assessment of coronary stenosis and angiographic assessment was used as criteria for non-culprit
PCI. uncertainty remains about whether PCI of noninfarct- related vessels should be done during primary
PCI (as was done in the PRAMI trial) or as a staged procedure, either during the index admission or within
2 months of primary PCI, which most large registries indicate.

Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarc-
tion The PRImary PCI in MULTIvessel Disease (DANAMI3-PRIMULTI) trial compared a strategy of fractional
flow reserve (FFR)-guided complete revascularisation 2 days after initial PCI of the infarct-related artery with
one of no further invasive treatment after PCI[13]. Events comprising the primary endpoint were recorded in
68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete
revascularisation (hazard ratio 0∙56, 95% CI 0∙38–0∙83; p=0∙004), this was driven by need for repeat revascu-
larisation. The use of FFR guidance changed the initial management plan substantially because, in almost a
third of patients allocated to complete revascularisation, FFR showed that the nonculprit-related lesions that
had appeared significant on angiography were non-significant led to fewer interventions. FFR was done 2
days after in index event to avoid the risk of invalid FFR measurements inferred from any acute changes in
macrovascular tone or microvascular flow obstruction.

In the PRAGUE-13 trial[14], 214 STEMI patients with double or triple vessel disease were randomly assigned to
culprit-lesion-only PCI or complete revascularization (non-culprit vessel PCI as a staged procedure within 3–40
days after the index event). Patients with stable angina for more than 1 month prior to the vent were excluded
from the trial. But the result indicate no significant difference between the two groups in hospitalization for
all-cause death, nonfatal MI and stroke, which occurred in 16% of patients in the multivessel PCI group vs.
13.9% in the conservative therapy group (HR = 1.35; 95% CI, 0.66-2.74) and unstable angina (P =0.193) or hos-
pitalization for HF (P =0.672), CV mortality (P =0.699) and revascularization for a noninfarct artery (P =0.089).
This study did not include ischaemia-driven revascularisation as part of the endpoint and was underpowered
to detect differences in hard endpoints. It is generally regarded as a trial of less significant non-IRA lesions.

Fig.4: Major randomized controlled trials comparing complete vs. culprit lesion only revascularization in pa-
tients presenting with ST-segment elevation myocardial infarction and multi-vessel coronary artery disease

These trials have led drastic changes in PCI recommendations by American and European societies[15,16],
modified the recommendation for non-culprit vessel PCI in case of hemodynamically stable MVD-STEMI
from class III (harmful) to Class IIb (might be considered), either at the time of primary PCI or as a planned,
staged procedure. The writing committee emphasizes that this change should not be interpreted as endors-
ing the routine performance of multivessel PCI in all patients with STEMI and multivessel disease. Rather,
when considering the indications for and timing of multivessel PCI, physicians should integrate clinical data,
lesion severity/complexity, and risk of contrast nephropathy to determine the optimal strategy. Guidelines

Cardio Diabetes Medicine

Non-Infarct Related Artery Intervention in St-Elevation Myocardial Infarc-
186 tion With Multivessel Disease: MultiVessel PCI in STEMI:

Timing of Intervention?

observed that, there is no sufficient data to recommend the optimal timing of nonculprit vessel PCI and the
optimal method of evaluating nonculprit lesions (eg, percent diameter stenosis , fractional flow reserve)[15].

Fig.5: Change Class of Recommendation by AHA in accordance with the recent trials

Ongoing trials:

The largest trial addressing this very issue is the currently recruiting COMPLETE trial (NCT01740479), which will
randomize 3900 STEMI patients with multi-vessel disease in North America and Europe to culprit-lesion-only
or staged complete revascularization.
The COMPARE-ACUTE trial (NCT01399736) is based on FFR measurements in the non-culprit vessels, but
aims at single procedure multi-vessel revascularization.
Finally, the CROSS-AMI trial (NCT01179126) was designed to compare stress echo-guided revascularization
vs. an angiography-based strategy.
Clinical perspective:
MVD-STEMI is a very heterogeneous population , so no common strategy will be applicable to this subset
and any revascularisation strategy should be individualised. Interventionalist should focus first on the best
possible p-PCI result on the culprit lesion which brought the patient to the cathlab i.e to achieve TIMI III flow
with good ST-resolution achieved. A complicated p-PCI with long procedural time, significant contrast load
and a suboptimal result, including “slow or no-reflow” and/ or distal embolisation, would definitively argue
against additional non-culprit PCI in a stable patient during the index procedure. Anatomical complexity of the
non-culprit disease, assessed by SYNTAX score, and left ventricular/valve function, a complete risk profile,
including age and comorbidities, has to be integrated into the decision-making process to select the best
revascularisation strategy which is best decided by ‘Heart Team approach’. Complete revascularisation can
be considered hemodynamically
stable patients with persisting chest pain or significant residual ST-segment elevation. As most of patients
with STEMI were asymptomatic prior to the event, nonculprit lesion should be considered as stable CAD and
unless this is evidence of ischeamia (FFR), such lesion should not be intervened. In a patient with complex
multivessel disease, impaired left ventricular function and diabetes, surgical revascularisation could be con-
sidered despite STEMI as the index event.
Complete revascularization should not be routinely performed ad-hoc, but based on individual and careful
patient and lesion assessments. The best timing of the staged PCI (during the index admission or within
weeks) and the question of stratification for evidence of ischaemia remain to be answered in upcoming trials.

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Cardio Diabetes Medicine 2017 187

Fig. Proposed management algorithm for patients with ST-segment elevation myocardial infarction and multi-vessel
coronary artery disease. Recommendation classes are based on current European Society of Cardiology guidelines [1].

References:

1. Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Ju¨ni P, Kappetein AP, et al. 2014 ESC/EACTS Guidelines on
myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association
for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions
(EAPCI). Eur Heart J 2014(35):2541–2619.

2. O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, et al. 2013 ACCF/AHA guideline for the manage-
ment of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice
Guidelines. J Am Coll Cardiol 2013;61:e78 –140.

3. Sorajja P, Gersh BJ, Cox BA, et al. Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous
coronary intervention for acute myocardial infarction. Eur Heart J. 2007;28:1709–16.

4. Bangalore S, Kumar S, Poddar KL, Ramasamy S, Rha S-W, Faxon DP. Meta-analysis of multivessel coronary artery revascularization versus culprit-only
revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease. Am J Cardiol. 2011;107:1300–10

5. Vlaar PJ, Mahmoud KD, Holmes DR Jr, van Valkenhoef G, Hillege HL, van der Horst IC, Zijlstra F, de Smet BJ. Culprit vessel only versus multivessel and
staged percutaneous coronary intervention for multivessel disease in patients presenting with ST-segment elevation myocardial infarction: a pairwise and
network meta-analysis. J Am Coll Cardiol. 2011;58:692-703.

6. Kornowski R, Mehran R, Dangas G, Nikolsky E, Assali A, Claessen BE, Gersh BJ, Wong SC, Witzenbichler B, Guagliumi G, Dudek D, Fahy M, Lansky AJ,
Stone GW; HORIZONS-AMI Trial Investigators. Prognostic impact of staged versus “one-time” multivessel percutaneous intervention in acute myocardial
infarction: analysis from the HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trial. J Am Coll
Cardiol. 2011;58:704-11.

7. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L,
Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the
American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography
and Interventions. Circulation. 2011;124:e574–e651

8. Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez- Aviles F, Gershlick AH, Gi-
annuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van ‘t Hof A, Widimsky P, Zahger D. ESC Guidelines
for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33:2569-619.

9. Goldstein JA, Demetriou D, Grines CL, Pica M, Shoukfeh M, O’Neill WW. Multiple complex coronary plaques in patients with acute myocardial infarction.
N Engl J Med 2000;343:915–922.

10. Ochala A, Smolka GA, Wojakowski W, Dudek D, Dziewierz A, Krolikowski Z, Gasior Z, Tendera M. The function of the left ventricle after complete
multivessel one-stage percutaneous coronary intervention in patients with acute myocardial infarction. J Invasive Cardiol 2004;16:699 –702

11. Wald DS, Morris JK, Wald NJ, Chase AJ, Edwards RJ, Hughes LO, Berry C, Oldroyd KG; PRAMI Investigators. Randomized trial of preventive angioplasty
in myocardial infarction. N Engl J Med. 2013;369:1115-23

12. Gershlick AH, Khan JN, Kelly DJ, et al. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous
coronary intervention for STEMI and multivessel disease: the CvLPRIT trial. J Am Coll Cardiol. 2015;65(10):963–72.

13. EngstrømT, KelbækH, HelqvistSE et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myo-
cardial infarction and multivessel disease (DANAMI-3—PRIMULTI): doi.org/10.1016/S0140-6736(15)60856-X

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188 Cardio Diabetes Medicine 2017

Obstructive Sleep Apnoea (OSA):
Cardiodiabetic issues

Professor Ram Dhillon (UK),

London North West Healthcare NHS Trust,
Plymouth University, UK, Medical Director, Rila Institute, London

Abstract parameters during a formal sleep study, either by tra-
ditional polysomnography, which is also a research
There is increasing evidence that there is an associ- tool8 or now, more commonly, by way of a home
ation between obstructive sleep apnoea (OSA) and sleep study providing a Tier 3 level study, which for
diabetes (Type 2). Furthermore, the association ex- clinical purposes is sufficient. An AHI of 5 or less is
tends to cardiovascular disease, particularly hyper- normal, 5-15 episodes are a mild grade OSA, 15-30
tension and most recently a link between OSA and episodes a moderate grade OSA and an AHI score
an increase in the progression of dementia. above 30 is severe OSA.

Keywords: The Cardiometabolic consequences of OSA

Obstructive sleep apnoea (OSA); Type 2 diabetes; The presence of OSA is an independent risk factor
cardiovascular disease; dementia for Cardiovascular Diseases (CVD)9. A wide range of
CVDs are associated with OSA, including hyperten-
Introduction sion and heart failure10-11. There is evidence that OSA
plays a role in the progression of atherosclerosis as
It is estimated that up to 4% of the UK population it has been associated with an increase in the mark-
suffer OSA with ~ 2% having severe OSA (1.3 million). ers of thrombotic risk, such as platelet activation and
Most importantly research suggests an occurrence increased fibrinogen12. A linear relationship has been
of 40% of individuals with OSA having type 2 Diabe- identified between the severity of OSA and preva-
tes1-2. It is predicted that the global burden of type 2 lence of hypertension13.
diabetes is expected to rise form the present level of
250 million to 380 million by 20253. The major cause The metabolic syndrome is a group of biochemical
of death amongst diabetics is cardiovascular disease and physiological defects that are associated with
and this is compounded by the presence of OSA4-5. the development of CVD and type 2 diabetes14. These
Other studies have shown a link with the severity of defects include central obesity and two additional
OSA and weight gain6, the latter being, in its own abnormalities from raised triglycerides, raised HDL
right, a risk factor for developing type 2 diabetes6-7. cholesterol, raised BP and a raised fasting plasma
glucose15. In patients with type 2 diabetes these mul-
Obstructive Sleep Apnoea tiple factors coalesce as the Metabolic Syndrome and
have a synergistic additional risk of CVD compared
An apnoea is absence or cessation of breathing, for to the sum of the individual risk factors16.
a minimum of 10 seconds, which can be due to a
central issue (a neurological condition) affecting the There is evidence that also reveal a link between
respiratory centre, or by far the commonest disorder OSA and cerebrovascular diseases, stroke in partic-
due to a total obstruction, effectively a strangulation, ular17. This may be due to the association of OSA with
of the pharyngeal airway. A hypopnoea is a reduced hypertension, increased progression of atherosclero-
airflow due to a partial obstruction. Obstructive ap- sis and atrial fibrillation. A previous study reported a
noea is graded according to the total hourly episodes 20% reduction in cerebral blood flow during an ob-
of apnoea and hypopnoea per hour, the AHI index. structive apnoea18.
These can be determined by measuring a variety of

GCDC 2017

Obstructive Sleep Apnoea (OSA): Cardiodiabetic issues 189

Treatment 2009:136:1668-77

The most effective treatment for OSA is weight re- 16. Loeppky JA, Voyles WF et al Sleep apnea and autonomic cerebrovascular
duction, with a loss of 10.7kg resulting in a 40% drop dysfunction. Sleep 1987:10:25-34
in the AHI/strangulation score19, in the mild severity.
Lifestyle changes in those with moderate and severe 17. Tuomilehto HP, Seppa J et al Lifestyle intervention with weight reduction:
OSA is much more difficult as they patients are gen- first line treatment in mild obstructive sleep apnoea
erally very fatigued and are unable to comply with
physical activity regimes. 18. Pepperell J, Ramdassingh-Dow S et al Ambulatory blood pressure after
therapeutic and sub-therapeutic nasal continuous positive airway pressure
CPAP (continuous positive airway pressure) is, for for obstructive sleep apnea: a randomized parallel trial. Lancet 2002:
most patients, the treatment of choice due both to its 359:204-10
effectiveness in reducing the subjective symptoms
e.g. fatigue and tiredness but also the complications 19. Babu AR, Herdegen J et al Type 2 diabetes, glycaemic control and con-
of the diseases as discussed. Improved blood pres- tinuous positive airway pressure in obstructive sleep apnoea. Arch Intern
sure, better control and reduction of HBA1c21 and Med 165(4):447-453: 2005
heart failure22.

References

1. Meslier N; Gagnadoux F et al Impaired glucose-insulin metabolism in
males with obstructive sleep apnoea. EurRespir J2003 22(1):156-160,

2. Emasry A, Lindberg E et al Sleep disordered breathing and glucose me-
tabolism in hypertensive men; a population based study. J Intern Med
2001 ,249(2):153-161,

3. Diabetes Atlas, 3rd Edition, International Diabetes Federation, 2006

4. Peppard PE; Young T et al Prospective study of the association between
sleep disordered breathing and hypertension NEJM 2000, 342(19):1378-
1384,

5. http://www.sciencedaily.com/releases/2007/05/070520183533.htm re-
trieved 010817

6. The report of the American Academy of Sleep Medicine Task Force.
Sleep related breathing disorders in adults:recommendations for syn-
drome definition and measurement techniques in clinical research. Sleep:
1999:22:667-89

7. Marin JM; Carrizo SJ et al Long term cardiovascular outcomes in men with
obstructive apnoea-hypopnoea with or without treatment with continuous
positive airway pressure, an observational study. Lancet: 2005:365:1046-
53

8. Bottini P, Dottorini ML et al Sleep disordered breathing in non- obese di-
abetic subjects with autonomic neuropathy. EurRespir J 22:654-660, 2003

9. Dincer HE & O’Neill W; Deleterious effects of sleep disordered breathing
on the heart and vascular system. Respiration 73(1):124-130, 2006

10. Von Kanel R, Loredo JS et al; Association between polysomnographic
measures of disrupted sleep and pro-thrombotic factors; Chest: 2007:
131:733-9

11. Nieto FJ, Young TB et al: Association of sleep disordered breathing, sleep
apnea and hypertension in a large community based study: Sleep Heart
ealth Study: JAMA 2000:282:1829-36

12. Gruber A, Horwood F et al Obstructive Sleep apnoea is independently
associated with metabolic syndrome but not insulin resistance. Cardiovasc
Diabetol 5:22: 2006

13. The IDF consensus worldwide definition of metabolic syndrome 2006

14. Golden SH; Folsom AR et al Risk factor grouping related to insulin re-
sistance and their synergistic effects on subclinical atherosclerosis: the
atherosclerosis risk in communities study: Diabetes: 2002: 52: 3069-76

15. Dyken ME &Im KB; Obstructive sleep apnoea and stroke. Chest

Cardio Diabetes Medicine

190 Cardio Diabetes Medicine 2017

Diabetes And Systemic Complications in
Immune Deficiency Syndrome

Prof. Kutikuppala Surya Rao

MD., MNAMS., DFM., FHM(CMC Vellore)., PhD., FRCP(London)
Chief Consultant Family Physician & HIV Medicine Specialist, Sri Surya Clinic,Visakhapatnam-08

Honorary Professor, Dept of Human Genetics,A ndhra University, waltair

Introduction: 100 to 300 cell/cumm.

A diverse HIV/AIDS patients are increasingly de- Conclusions: This original study first of its kind in the
veloping Diabetes and its complications; hence the world has a significant discovery of 37% were with
morbidity and mortality due to this metabolic disor- high levels of Hb A1c , a clear indication of high
der have been causing more threat than HIV dis- diabetes among HIV infected,20.5% positive for tTG
ease itself. Therefore an original study was conduct- so that the HIV positives prone to developing celiac
ed for the Comprehensive Autoimmune Diabetes disease. 13.75% patients had elevated levels of TPO
and Complications profile measuring such as Insu- antibodies suggestive of autoimmune inflammation
lin Antibody (IAA), Glutamate decarboxylase (GAD- of the thyroid gland and prone for high risk of devel-
65) antibody. Insulinoma Associates 2 antibodies oping thyroid diseases. It is recommended to have an
(IA-2antibody),Thyroglobulin antibody, Thyroid Per- annual TSH test to monitor for thyroid disease. The
oxidase antibody, (TPO)Tissue Transglutaminase an- C-Peptide is suggestive of insulin production and to
tibody (tTG) ,Total Serum IgA,Estimated average glu- help determine the cause of low blood sugar (Hypo-
cose(eAG),C-Peptide and Hemoglobin A1c levels in a glycemia) and pancreatic autoimmunity. Mandatory
scientifically diagnosed HIV/AIDS cohort of positive autoimmune diabetes and complications profile test-
non diabetic patients. ing amongst HIV/AIDS patients would help to predict
the onset of said diseases much earlier than classical
Material: One Hundred (100) non Diabetic HIV Pos- presentation per.se.
itive naive patients were enrolled in the study by
following ethical guidelines for comprehensive Au- Background: Diabetes is not a single disease enti-
toimmune Diabetes and Complication Profile study ty. In 1997, it announced the etiological division of
at Sri Surya Clinic, Visakhapatnam South India. The diabetes, which distinguishes two main forms: type
DiabetOmics, Hillsboro USA, a global medical diag- 1 and type 2. In the pathogenesis of both forms ge-
nostics company extended scientific support of test- netic and environmental factors play the role. Type 2
ing the samples for the research from January 2014 to is the more common form, representing about 90%
March 2016. The analysis of the experimental study of all cases of the disease in the developed regions
was done in an institutional setting. of the world civilization. It is characterized by the
coexistence of insulin deficiency and the peripheral
Observation: In the subject studied 71% Male and 29% effects of the hormone . Immunological markers do
Female. Among Males 42% are 41years and above not appear, and the genetic basis has no connection
, 28% are 21 to 40 years and 1% is below 20 years. with the HLA system. In addition, there is rising inci-
Among women 15% are 41 and above years 14% are dence of type 2 diabetes in children and adolescents
21 to 40 years. The study revealed that 41% positive . In the end, the last two decades have produced im-
for C-Peptide, 37% positive for Hb A1c, 20.5% were portant findings about monogenic forms of diabetes,
Positive for tTG, 13.75% patients had elevated levels revealing mainly in the developmental age and young
of TPO antibodies. Regarding the viremia 37% had adults . These findings have proved that diabetes has
Undetected HIV Viral Load 40% had below 1 Lakhs much more diverse etiology, than recently thought.
copies/ml, 23% had more than 1 Lakhs copies/ml vi- In the last few years, it has been shown that auto-
ral load in plasma while 59% had CD4 counts from

GCDC 2017

Diabetes And Systemic Complications in 191
Immune Deficiency Syndrome

immune diabetes in adults occurs much more often extra-intestinal sites, including endocrine manifesta-
than it was previously thought . Chronic autoimmune tions. Of these, two endocrine disorders are partic-
process leading to the destruction of the B cells of ularly prominent, thyroiditis, especially, but not ex-
pancreatic islets is a cellular response and observed clusively, in adults, and insulin-dependent diabetes,
in type 1 diabetes antibodies associated with humoral particularly, but also not exclusively, in children.
response is a marker of ongoing autoimmune de-
struction process. The presence of antibodies can de- T2DM in patients with HIV
fine a person at risk of developing type 1 diabetes as
early as during the pre-clinical stage of disease . The Findings from the Multicentre AIDS Cohort Study
prevalence of anti-GAD antibodies in type 1 diabetes (MACS) showed a T2DM incidence of 47 in HIV-in-
was found in 80-90% patients with newly diagnosed fected white males who were on cART versus 17 in
diabetes and 70 -80% in patients with the preclinical those who were cART naïve; however, this study
diabetes is present preceded by several years of be- used only a single increased fasting plasma glucose
fore clinical manifestation of the disease1 as their diagnostic criteria. Nigatu et al, in 2013 con-
ducted a systematic review looking at incidence of
Celiac disease (CD) various comorbidities, including T2DM, with HIV in-
fection, and found a combined T2DM incidence rate
Celiac disease (CD) is an immune-mediated small of 6 (with a range of 4.2–36) in a sample of 44 484
intestinal disorder that occurs in genetically suscep- individuals. In the studies included in their system-
tible people and is characterized by an intolerance to atic review, ART exposure increased incidence rates
gluten-containing proteins found in wheat, rye and when compared with ART-naïve patients. Therefore,
barley grains. Often, symptomatic persons present although incidence does not seem to be higher in
with diarrhea, nutrient malabsorption and weight loss patients with HIV infection in Africa compared with a
associated with a mucosal inflammatory process in normal ageing population in Africa; T2DM incidence
the proximal small intestine. Mucosal architecture in HIV-infected people in Africa does appear to be
may be severely altered in the duodenum and, with higher than rates reported internationally for patients
increasing severity, may extend for variable distanc- with HIV infection, and those reported for a healthy
es into more distal jejunum and ileum. It may be that American population3
the severity of the individual inflammatory response,
the timing of its appearance as well as the extent Incidence rates of DM as high as 5–14 cases per
and localization within the small intestine are genet- 1000 person years of follow up have been report-
ically-programmed ed in HIV/AIDS patients after initiation of HAART .
These alarming rates draw particular attention be-
In recent years, the disorder has become increasing- cause multiple high-risk conditions and cardiovas-
ly appreciated even without significant gastrointes- cular disease have been found to have worsened
tinal symptoms, being documented in up to 2% of clinical outcomes in HIV/AIDS patients having DM as
the serologically-studied populations, and perhaps, co-morbidity . Hence early identification of patients
higher in referred patients using endoscopic screen- at risk of DM is of utmost importance. Even though
ing biopsies2. The disorder is not only common, but we found no study that quantified and compared the
has been increasingly recognized as a phenotypically risk of having diabetes in these patients using the
heterogeneous disorder. Increased clinician aware- DRS, a Norwegian study had results similar to ours
ness as well as widespread use of serological testing using the Framingham risk score. This study found a
for case-finding have been important factors in the higher Framingham risk score and mean estimated
emergence of this disorder in the scientific commu- risk of cardiovascular heart disease in patients on
nity.. HAART than in HAART-naïve patients, even though
the Framingham risk score has been reported to be
As a result, clinical features attributed to celiac dis- a less accurate predictor of DM than the metabolic
ease or its complications have been noted in other syndrome4 .

However, in Italy, investigators reported a higher
prevalence of 4.1% among ART-experienced patients
, and in China 10.5% of ART-naive patients had T2DM.
Patients in Italy were older (46 vs 37 years) and had
significantly higher CD4+ counts than patients in our
study (538 vs 206 cells/µL), while the prevalence of
diabetes in a Chinese population was higher than

Cardio Diabetes Medicine

192 Cardio Diabetes Medicine 2017

in Nigeria, suggesting that prevalence of T2DM may major European LADA studies to date . Moreover,
vary with the overall T2DM prevalence in the general the former consistently have higher HbA1c levels
population, HIV disease progression, and the disease than the latter (OR 1.8 in Sweden) . Clearly, we do
stage when patients access ART5. not manage these patients as well as those with non-
insulin requiring non-autoimmune diabetes (i.e. type
Immune reactivity influences clinical progression 2 diabetes). Finally, autoimmune diabetic patients,
irrespective of age, have a substantially increased
Islet autoimmunity in early childhood, especially for risk of thyroid and parietal cell autoimmunity . The
multiple DAA or for insulinoma-associated antigen-2 presence of DAA should encourage regular review of
autoantibodies, is strongly linked to rapid disease comorbidities and the quality of glycaemic control6.
progression . In diabetic children, those with DAA had
greater C-peptide decline (48%/year) than those with- Non-autoimmune patients require variable
out DAA-negative children (∼8%/year). Importantly, management
this decline was independent of demographics, HLA
risk, BMI and insulin resistance; while in children with As the loss of beta cell function is strongly age-de-
non-autoimmune diabetes, there was marked het- pendent and young patients predominantly have
erogeneity, suggesting a mixed group, with a mean autoimmune diabetes, therapeutic decisions are
rate of decline in C-peptide comparable to adult type usually made without recourse to testing for DAA
2 diabetes (∼8%/year).For any given individual with or C-peptide. This approach courts error, notably
diabetes, there is substantial variability in the nature in children, in whom the prevalence of obesity and
of their disease, risk of complications and response both type 1 and type 2 diabetes have increased
to any given drug. Based on studies carried out in dramatically. By measuring DAA initially and C-pep-
2004 on a group of people of the population of North tide subsequently, it is possible to identify, as ap-
America and Europe, it is known that anti-GAD are propriate, patients with MODY, type 2 diabetes in
present in 4.2% of people with newly diagnosed type children, non-insulin-requiring autoimmune diabetes
2 diabetes previously treated with oral ant diabetic and non-autoimmune diabetes without the metabol-
agents. ic syndrome—potentially some 20–30% of all diabetes
patients diagnosed under 40 years of age . Such
Autoimmunity impacts management a definition also has utility for setting targets and
strategy therapy because cardiovascular complications differ
between the major types of diabetes, e.g. guidelines
Identifying (DAA) Diabetes-associated auto antibod- offer statins to type 2 diabetes cases at an earlier
ies is a valuable test for disease management as they age.
are characteristic of a form of autoimmune diabetes,
especially in adults, which is often inappropriately Summary
treated and that requires more frequent review and
a different perspective. Patients with autoimmune This original study first of its kind in the world has a
non-insulin-requiring diabetes, including (LADA) La- significant discovery of 37% were with high levels of
tent autoimmune diabetes in adults should be started Hb A1c , a clear indication of high diabetes among
on insulin or an incretin-based therapy or, potential- HIV infected,20.5% positive for tTG so that the HIV
ly, a combination of the two. Sulfonylurea treatment positives prone to developing celiac disease. 13.75%
should likely be avoided, as patients on this class
of drugs have a faster loss of insulin secretory ca-
pacity than when treated with insulin . Autoimmunity
does not equate with insulin therapy, as indicated by
a Phase 2 study of adult patients with autoimmune
diabetes; the combination of gliptin plus insulin was
superior at sustaining C-peptide than insulin alone .
Although patients with typical type 1 diabetes at all
ages presenting with ketoacidosis require immediate
insulin therapy, not everyone with adult-onset auto-
immune diabetes such as LADA, need progress to
insulin therapy; in one study, 44% were still not on
insulin after 12 years of disease . However, disease
progression to insulin treatment is more rapid in
LADA than with type 2 diabetes, as reported by all

GCDC 2017

Diabetes And Systemic Complications in 193
Immune Deficiency Syndrome

, that our finding is very significant in comparison of 5. Samson E. Isa Agbaji O. Oche Arthur R. Kang’ombe Joseph A. Okopi John
global studies. Our patients had elevated levels of A. IdokoLuis E. Cuevas Geoffrey V. Gill ‘ Human Immunodeficiency Virus
TPO antibodies suggestive of autoimmune inflam- and Risk of Type 2 Diabetes in a Large Adult Cohort in Jos, Nigeria’ 
mation of the thyroid gland and prone for high risk Clin Infect Dis (2016) 63 (6): 830-835.
of developing thyroid diseases. It is recommended
to have an annual TSH test to monitor for thyroid 6.  Leslie RD, Palmer J, Schloot NC, Lernmark A Diabetes at the crossroads:
disease. The C-Peptide is suggestive of insulin pro- relevance of disease classification to pathophysiology and treatment, Dia-
duction and to help determine the cause of low blood betologia (2015) 59: 13-20.
sugar (Hypoglycemia) and pancreatic autoimmunity.
Mandatory autoimmune diabetes and complications 7. Piatkiewicz P1*, Hajduk JL1, Chow KL1, Kowrach M1 and Kuszyk JC2 Au-
profile testing amongst HIV/AIDS patients would toimmunity Markers in Patients with Type 2 Diabetes RESEARCh.Diabetes
help to predict the onset of said diseases much ear- Manag (2016) 6(3), 055–061
lier than classical presentation per.se so that suitable
strategy can be evolved to bring down morbidly and
mortality.

In newly diagnosed diabetes, showing the presence
of anti-GAD), lower levels of fasting insulin, increased
insulin sensitivity, lower (HOMA) Homeostatic Model
Assessment  are found .Recent data have shed light
on the link between pancreatic damage and subse-
quent impairments in glucose homeostasis7. Further-
more, epidemiological studies provided insights into
the relationship between diabetes and the risk of
pancreatic carcinoma or pancreatitis.

Highlights

20.5% positive for tTG so that the HIV positives prone
to developing celiac disease.

Autoimmune inflammation of the thyroid gland and
prone for high risk of developing thyroid diseases
and pancreatic autoimmunity.

Mandatory autoimmune diabetes and complications
profile testing amongst HIV/AIDS patients would
help to predict the onset of said diseases much ear-
lier than classical presentation per.se

13.75% patients had elevated levels of TPO antibodies

37% positive for HB1Ac suggestive of AIDS patients
highly prone for Diabetes.

References :

1. Ipadeola A, Adeleye JO, Akinlade KS ‘Latent autoimmune diabetes amongst
adults with type 2 diabetes in a Nigerian tertiary hospital’ Prim Care
Diabetes(2015) 9: 231-236.

2. Hugh James Freeman Endocrine manifestations in celiac disease World
J Gastroenterol. 2016 Oct 14; 22(38): 8472–8479

3. Prioreschi A, Munthali RJ, Soepnel L, et al. Incidence and prevalence of
type 2 diabetes mellitus with HIV infection in Africa: a systematic review
and metaanalysis. BMJ Open 2017;7: e013953. doi:10.1136.

4. Dimala CA, Atashili J, Mbuagbaw JC, Wilfred A, Monekosso GL A Com-
parison of the Diabetes Risk Score in HIV/AIDS Patients on Highly Active
Antiretroviral Therapy (HAART) and HAART-Naïve Patients at the Limbe
Regional Hospital, Cameroon. PLoS ONE(2016) 11(5): e01555602.

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194 Cardio Diabetes Medicine 2017

Low Body Weight T2DM and
Macro Vascular Disease

Prof. Dr. Sidhartha Das,

MD, FRCP(Glasg), FRCP(Edin), FRCP(London)

Senior Consultant in Medicine & Diabetes, Dean and Principal
S. C. B. Medical College and Hospital, Cuttack, Odisha-753007

Abstract : Studies from the United Kingdom Prospective Dia-
betes Study (UKPDS) had revealed that patients with
Low Body Weight Type 2 DM is a distinct clinical en- Type2DM have a two to three fold increase in dis-
tity which is neither related clinically nor pathophys- eases related to atheroma. Besides, those diabetic
iologically to LADA nor former fruste of Type 1DM subjects who develop atheroma related disease in
. They have absence of markers for autoimmune the age range of 40 to 50 years of age have a two-
destruction of β-cells along with good insulin and fold higher rate of mortality.
C-peptide reserve for a prolonged period of life. The
clinical presentation and profile of associated com- Type 2 Diabetes Mellitus: (DM) is the most prevalent
plications in Low Body weight Type 2 DM are visi- form of DM seen in India and constitutes more than
bly different from those described for subjects with 95% of the diabetic population.
classical Type 2 DM. The Low Body weight Type 2
DM patients have a marked lower incidence of hy- Epidemiological data has revealed that the clinical
pertension, CAD, nephropathy vis-a-vis marginally and phenotypic profile of patients with Type 2 DM
higher prevalence of retinopathy and a markedly are different in India and certain developing coun-
higher incidence of peripheral neuropathy and in- tries of Asia and Africa when compared to the West.
fections. A lipid profile which is non-conducive for (R2). The profile , presentation and complications in
atherogenesis, lower levels of non-lipid risk factors subjects with Non-Insulin Dependent Diabetes Mel-
like homocysteine and lower levels of inflammatory litus (NIDDM) seen in India was much different from
markers like hsCRP with lesser expression of NF-κB those NIDDM of the West. This was recorded, for
in mononuclear cells are probable explanations to the first time, as a consensus statement adopted
the lesser prevalence of macrovascular disese (MVD) at the “ International Workshop on Types of Dia-
in Low Body Weight Type2 DM. betes Peculiar to the Tropics”, held at Cuttack, India.
The consensus statement published in Diabetes
Introduction: Care (1996) read as, “This group supports the WHO
classification of NIDDM into Obese & Non-obese sub-
The post insulin era experienced the visible decline classes. In some developing countries, non-obese
in prevalence of acute complications and infections patients constitute the more common category,
in patients with diabetes mellitus (DM). However, and a proportion of them have BMI<18.5. There are
macrovascular disease (MVD) emerged as the most many factors that are not well understood in these
threatening complication in diabetics of the west. Al- subjects with NIDDM and Low body weight ; further
most 2/3rd of deaths in diabetics was attributed to research is required in this group.(R3)
coronary artery disease (CAD), cerebrovascular dis-
ease (CVD) or peripheral vascular disease (PVD). The Burden of MVD in Diabetics with special
problem although more marked with Type-2 diabet- reference to Indians:
ics (earlier nomenclature as NIDDM) is also a major
cause of morbidity and mortality in Type-1 diabetics. Atherosclerosis (AS) is more prevalent in subjects
Therefore, the American Heart Association (AHA) with DM. Involvement of vascular channels is more
has designated DM as a major risk factor for car- wide spread in diabetic subjects as compared to non
diovascular disease. diabetics. The duration of chronic hyperglycemias is

GCDC 2017

Low Body Weight T2DM and Macro Vascular Disease 195

supposed to be the common determinant for devel- However, MVD is one of the most established com-
oping excess of MVD. Prospective study and retro- plications in diabetics in India and further there is
spective analysis in families with Type 2 diabetes had steady rise in the incidence of CAD amongst the
revealed that MVD foreruns the overt development of urban population as well as amongst diabetics. The
chronic hyperglycaemia by decades. Further suggest- prevalence of PVD is much less amongst Indians as
ing a likelihood of AS and DM sharing a “common compared to diabetics from the West.(R5) The preva-
soil” for growth and development in the individual. lence of CVD varies from 3.4 to 9.2% amongst diabet-
(R4) ics in India. However the prevalence of DM amongst
patient with CVD is much higher as compared to
Studies from USA and other western countries had CAD or PVD. Further DM is more common (22.1%) a
shown that CAD, both chronic stable angina and cause for cerebral infarction then cerebral haemor-
acute coronary syndrome (ASC), congestive heart rhage (6.35%) as shown by studies from India. (R6)
failure and PVD are the commonest morbidities as-
sociated with DM. The situation in Indians is different Profile of Complications in Low bodyweight
as compared to the West because the four major risk TYPE 2 DM
factors for CAD viz hypercholesterolemia, hyperten-
sion, DM and cigarette smoking are not very prom- Anthropometry is not the only criterion that distin-
inent among Indians with CAD as compared to the guishes Low Bodyweight subjects with Type 2 DM as
Framingham cohorts. ICMR had conducted a study a distinct entity. Studies on newly diagnosed patients
on complications in NIDDM (Type 2 DM) between with Type 2 DM had revealed that peripheral neurop-
1985-1990. The data collected were pooled from nine athy (PN) was the commonest presenting feature in
centres across India, as part of a multicentre study the Low Bodyweight Type 2 DM, while hypertension
on “Morbidity events in NIDDM (Type 2 DM)”. Centres (HTN) and coronary artery disease (CAD) were more
involved were AIIMS, New Delhi, Government medi- common in the obese while microangiopathy in the
cal colleges at Udaipur, Lucknow, Calcutta, Cuttack, non-obese-standard weight (BMI > 19 and < 25) Type
Jabalpur, Poona, Madras (Chennai) and Trivendrum 2 DM respectively. (R7).
. The pooled data was published by the coordinat-
ing centre (R 5). The prevalence of hypertension was
26.4%, CAD (diagnosed by ECG using Minnesota
Code) 24.7%, Nephropathy 17 and Retinopathy 36 %
respectively.

Table- 2 : Blood glucose, HbA1c, lipid profiles in patients with Type 2 diabetics Low body Weight, Standard
Body Weight and Obese and healthy controls

Cardio Diabetes Medicine

196 Cardio Diabetes Medicine 2017

Hypertension Lean Type 2 DM Madras our recent studies assessing the clinical, biochemical
CAD Cuttack Jaipur Male Female profile as well as autoimmune status and state of
PVD insulin resistance has also revealed that Low Body
Peripheral 8.8 14.5 -- Weight Type 2 diabetics had lower cholesterol visa
neuropathy 8.8 9.1 18.9 21.0 vis raised Tg and normal HDLc levels as depicted in
Nephropathy 5.5 7.5 5.2 7.0 Table 2. On the whole, Low Body weight Type 2 DM
Retinopathy 49.5 23.3 44.6 38.6 have a favourable lipid profile that could be a conse-
Tuberculosis quence of hepatic handling of HDL and CHO metab-
Other infections 6.6 9.1 4.7 4.4 olism and lack of hyperinsulinemia-insulin resistance
33.3 in the peripheral bed.(R 7,8)
19.8 16.9 37.3
- Plasma levels of homocysteine is an acknowledged
7.7 9.6 - - independent marker/risk factor of macrovascular
disease. On evaluation of plasma levels of homo-
28.6 - - cysteine in subjects with Typ2 DM, it was found that
levels were significantly lower (p < 0.05) in the Low
Table- 1: Prevalence of Complications in Low Body Body Weight Type 2 DM as compared to healthy con-
weight Type 2 DM at Different places versus pooled trols and definitely lower than both standard weight
and obese Type 2 DM. (R9)
data on Type 2 DM of all types (in percent)
Inflammation and macrovascular Disease in
The profile of associated complications in Low Body- Diabetics. (R 10,11)
weight Type 2 DM are different from those described
for classical Type 2 diabetics in textbooks. The data Data from the Atherosclerosis Risk in Communi-
from three centres, Cuttack in the East, Jaipur in the ties (ARIC) study, had demonstrated that a variety
West and Chennai in the South are presented in Ta- of in-flammatory markers, including white blood
ble 1. The Type 2 DM-Lean patients had a marked cell count α-1 acid glycoprotein, fibrinogen and si-
lower incidence of hypertension, CAD, nephropathy alic acid predict the development of type 2 DM in
vis-a-vis a marginally higher prevalence of retinop- a middle-aged population. Recent evidences show
athy and a markedly higher incidence of peripheral that diabetic atherosclerosis is not only a disease of
neuropathy and infections. hyperlipidemia but also has an inflammatory com-
ponent involving multiple media-tors viz. CRP, cyto-
Peculiarities in prevalence of established Risk Fac- kines like Tumor necrosis factor alpha (TNF-α) and
tors for Atheroscelosis :Both clinical presentation and IL6. . Increased levels of hsCRP, TLR2, TLR4 and
mortality profile indicate that neither CAD nor other PAI-1 , soluble cell adhesion molecules, sCD40 and
macrovascular complications are common in Low pro-inflammatory cytokines IL-1β, IL-6 and TNF-α are
Body weight Type 2 DM. Analyses of the biochemi- observed in patients with atherosclerosis. Gene pro-
cal milieu followed up in two consecutive years, in a filing has determined that high glucose treatment of
prospective study, revealed that those patients with monocytes leads to increased expression of multi-
Type 2 DM did not have hyperlipidemia which would ple inflammatory cytokines , chemokines and related
have been conducive to the development of athero- factors, many of which are regulated by the pro-in-
sclerosis and CAD. (R7,8) (Table 2) flammatory transcription factor, Nuclear factor kap-
pa-B (NF-κB ). The above statements suggest a close
The high density lipoprotein cholesterol (HDLc) lev- association of hyperglycemia with pro-inflammatory
els were never low even with mean glycosylated Hb state . Cross-sectional studies on newly diagnosed
values above 10%. In our first publication in 1984 we or estab-lished patients with type 2 diabetes have
showed that Indian Type 2 DM, particularly under- revealed that acute-phase markers such as C reac-
weight diabetics (Low Body weight Type 2 DM) do tive protein (CRP) and IL-6 levels were elevated when
not have low HDLc .(R9) This could be owing to the compared to non-diabetic subjects . Literature on in-
fact that hepatic lipase activity is primed by insulin flammatory markers in relation to the vascular com-
during its first pass and is in excess plications of Type 2 DM is sparse from India. We had
evaluated the prevalence of inflammatory markers in
in lean patients with Type 2 DM. Its activity is directly subjects with Type 2 DM with and without macrovas-
related to HDLc metabolism. Higher levels of Tg in cular complications ( Table 3).
these diabetics were a fact established by us which
was duly acknowledged by the international commu-
nity. Type-IV dyslipidemia is by far the commonest
form of dyslipidemia seen in these diabetics, and
that too in a glycemic uncontrolled state. In one of

GCDC 2017

Low Body Weight T2DM and Macro Vascular Disease 197

Table- 3 : Values of Inflammatory Markers in plasma of Type 2 Highly Sensitive C-Reactive proptein
Diabetics with and Without Macro Vascular Disease (MVD) (hsCRP) :

The levels of hsCRP were higher in diabetics, more The study revealed that, the level of hsCRP in all
three group of diabetic subjects was significantly
in those having MVD, as compared to healthy con- more than in the healthy controls but, patients with
Low bodyweight Type 2 DM had significantly lower
trols. Similarly the levels of adiponectin was lower in levels of serum hsCRP compared to obese patients
with Type 2 DM (Table 5). Raised levels of hsCRP in
diabetics as compared to controls. The expression of diabetics is well documented in literature. Low body-
weight, standard weight and obese diabetics had
NF-κB was higher in diabetics with MVD.(R10). In another lower values of serum adiponectin as compared
to healthy controls. Reduced adiponectin levels in
study, the diabetic subjects were divided into three patients with Type2 DM is well recognized in world
literature. However, in the present study, statistical
groups as per BMI as Low Body Weight, Normal Body significance of difference in the values of adiponec-
tin was seen between Low bodyweight and standard
Weight and Obese. All the three groups of diabetics bodyweight diabetics (both groups are non-obese
Type2 diabetics) when compared with healthy con-
were comparable with respect to age and duration trols.

of diabetes. Patients with Low bodyweight Type 2 In Low bodyweight Type 2 diabetics, values of serum
hsCRP were found to have significant positive cor-
DM (group A) had significantly higher values of FBG, relation with age , negative with serum total cho-
lesterol, serum HDL-C and serum LDL-C respectively.
2hPPBG and HbA1c than standard body- The above correlation of hsCRP with age and HDL
cholesterol levels is well recognised. The negative
weight (Group B) and obese (Group C) diabetics. correlation of hsCRP with serum total cholesterol
and serum LDL cholesterol , and the positive cor-
Levels of total cholesterol were comparable in all relation of serum adiponectin levels with waist-hip
ratio and HbA1c levels encountered in this group of
the three groups of diabetics, though higher than diabetics is likely to be an inherent characteristic of
Low bodyweight Type 2 DM. Lean habitus is most-
healthy controls ( Group D) (Table 4 ). Serum LDL-C was ly due to lack of fat depot and central adiposity
rather than nutritional deficiency. The above obser-
significantly higher in Group C as compared to group vation is an expected aberration in subjects with
Low Bodyweight Type2 DM and compatible with our
A (p = 0.005), and this was significantly higher in earlier observations of low Homocysteine, high Glu-
cokinase and brisk hepatic metabolic state in Low
all diabetics compared to healthy controls (Table 4). Bodyweight type2 diabetics.

Value of serum triglycerides was significantly higher Expression of Nuclear Factor Kappa-B (NF-
κB) :
in Group C compared to Group B (p =0.01), and was
The levels of expression of NF-κB in peripheral blood
of a higher value compared to healthy controls. mononuclear cells were found to be higher in di-
abetic subjects as compared to healthy controls.
Adiponectin : Significant positive correlation between NF-κB ex-
pression in peripheral blood mononuclear cells and
Adiponectin is an adipocyte derived protein, the plas- HbA1c levels has been reported previously, wherein
ma concentration of which correlates inversely with exposure to hyperglycemia induced activation of
severity of insulin resistance. the transcription factor NF-kappaB in ex vivo-isolated
peripheral blood mononuclear cells. NF-κB belongs
Adiponectin is anti-inflammatory in nature, and has to a family of transcription factors, originally identi-
potential inhibitory activity on atherogenic cellular fied by B cells. These transcription factors of NF-κB
phenomena . Adiponectin was shown to inhibit the group are pro -inflammatory markers. NF-κB released
TNF-alpha-induced NF-kappa B activation through
the inhibition of IkB phosphorylation, which might
be a major molecular mechanism for the inhibition
of monocyte adhesion to endothelial cells and thus
the inflammation .

Subjects with type 2 DM have been found to have
lower adiponectin levels than healthy nondiabetic in-
dividuals .

It has been found that diabetic patients have lower
Adiponectin levels than control subjects . Diabetic pa-
tients with macroangiopathy also have lower levels
of Adiponectin than those without macroangiopathy
(Table 5).

Cardio Diabetes Medicine

198 Cardio Diabetes Medicine 2017

by the stimuli of cytokines/ TNFalpha/ Interleukin-1/ The level of hsCRP in all three group of subjects with
Viral products/ Bacterial component/ yeast products diabetes was significantly more than in the healthy
can activate more than 160 specific inflammatory. controls but, patients with Low bodyweight Type 2
and immune target genes by specific binding with DM had significantly lower levels of serum hsCRP
NF-κB decameric consensus sequences in DNA . A compared to obese patients with Type 2 DM. In Low
recent gene profiling study showed that high glucose bodyweight Type 2 diabetics, values of serum hsCRP
treatment of monocytes leads to increased expres- were found to have significant positive correlation
sion of multiple inflammatory cytokines, chemokines with age and waist hip ratio.
and related factors many of which are regulated by
pro-inflammatory transcription factor, nuclear fac- Low bodyweight, standard weight and obese subjects
tor Kappa B (NF-Κb) synthesis. Significant positive with diabetes had lower values of serum adiponectin
correlation between NF-κB expression in peripheral as compared to healthy controls. Reduced adiponec-
blood mononuclear cells and HbA1c levels has been tin levels in patients with Type2 DM is well recognized
reported previously, wherein exposure to hy- in world literature. Statistical significant difference in
perglycemia induced activation of the transcription the values of adiponectin between Obese Type2DM
factor NF-kappaB in ex vivo-isolated peripheral blood and Low Bodyweight Type2DM subjects ( p = 0.01)
mononuclear cells . suggest a lesser proinflammatory load in the latter..

The levels of expression of NF-κB in peripheral blood Lean habitus is mostly due to lack of fat depot and
mononuclear cells were found to be higher in diabet- central adiposity rather than nutritional deficiency.
ic subjects as compared to healthy controls. Interest- The above observation is an expected aberration in
ingly, statistical significance of difference was seen subjects with Low Bodyweight Type2 DM and com-
only between standard bodyweight diabetics and patible with our earlier observations of low Homocys-
healthy controls , but not between Low bodyweight teine, high Glucokinase and brisk hepatic metabolic
diabetics and healthy controls . The most revealing ob- state in Low Bodyweight Type2 diabetics (7,8).
seravation was that the expression of NF-κB was lowest
in Low Bodyweight Type2 diabetics as compared to The expression of NF-κB was lowest in Low Body-
both Group B and C while the value of optical density weight Type2 diabetics as compared to both standard
observed in them was near similar to that observed weight and obese. This also indicates that, the lower
in healthy controls (Table 4). level of inflammatory stress experienced by subjects
with Low Body weight type 2 DM as compared to the
standard weight and obese diabetics.

Table- 4 : Values of inflammatory markers in plasma of Type Conclusion :
2 diabetics Low body Weight, Standard Body Weight and
Obese and healthy controls Observation of lower hsCRP, relatively lower levels
of adiponectin (probably due to sparse fat pool) and
Low Body Weight Type2 DM and reasons for lower expression of NF-κB which is similar to that ob-
lesser MVD served in healthy controls, supplement to the already
observed lipid profile which is not conducive for ath-
On the whole, subjects with Low Body Weight Type2 erogenesis, and low plasma levels of homocysteine
DM have a lipid profile which is not atherogenic. The in explaining the lesser prevalence of MVD in Low
HDL Cholesterol levels were never low even in states Body Weight Type 2 DM.
with poor glycemic control where the mean HbA1c
values were above 10%. Type IV hyperlipoproteinemia References
is by far the commonest form of dyslipidemia seen
in these subjects and that too in a glycemic uncon- 1. Das S and Behera M. Coronary Artery Disease in Diabetes. In. World
trolled state. Clinics Diabetology Complications of Diabetes.Eds. V.Mohan and Ranjit
Unnikrishnan. Jaypee Brothers Medical Publishers Private Limited New
Delhi. 2016 Vol.2,Number 1; Pgs.172 - 190.

2. Powers Alvin C. Diabetes Mellitus : Diagnosis, Classification, and Patho-
physiology. In Harrison’s Principles of Internal Medicine. 19th Edition, vol-
ume 2, 2015.Pgs2399 – 2407.

3. Tripathy B B and Rao H. Malnutrition and Diabetes in theTtropics.
Report of the International Workshop on Types of Diabetes Peculiar to
the Tropics.Diabetes Care, 1996;19 : 1014—07.

4. Das S. Macrovascular Diseases in Diabetes: Determinants and Risk
Factors. In. RSSDI Text Book of Diabetes Mellitus, ,3rd Edition,

GCDC 2017

Low Body Weight T2DM and Macro Vascular Disease 199

Chapter 57, Jaypee The Health Science Publications (P) Ltd.New Del-
hi,London,2014;846-854.
5. Rao PV, Ahuja MMS : In Endocrine metabolism and Diabetes, Ed. N.Ku-
chupilai, Mac Millan Publication, 1994 : 33-38.
6. Das S, Cerebrovascular complications in NIDDM. J Assn Phys Ind
1993;41 (Suppl. 1) :57-65.
7. Das S and Fonseca V. Low Bodyweight type 2 diabetics in India: Clini-
cal characteristics and pathophysiology. Diabetes & Metabolic Syn-
drome: Clinical Research and Reviews.2009; 3(1): 60 -66.
8. Das S. Type 2 diabetes in the Lean. In RSSDI Text Book of Diabetes
Mellitus, 2nd Edition, Vol.1, Jaypee Brothers Medical Publication (P)
Ltd.,2012;381-390.
9. Das S,Tripathy,BB, Samal KC and panda NC, Plasma lipids and lipoprotein
cholesterol in undernourished diabetic subjects and adults with protein
energy malnutrition. Diabetes Care 1984;7:579-86.
10. Mishra D.P.,Das S and Sahu P.K. Prevalence of inflammatory markers
(hsCRP,NF-κB, adiponectin) in indian patients with Type 2 Diabetes Melli-
tus with and without macrovascular complications.Metabolic Syndrome
and Related Disorders. 2012,10 (3): 209- 213.
11. Das S, Misra D.P. and Sahu P.K. Study of hsCRP, adiponectin, NF-κB in
low bodyweight, standard bodyweight and obese subjects with type 2
diabetes mellitus in India. Journal of Diabetes Mellitus. 2012, Vol.2,
No.4, 386-392 .

Cardio Diabetes Medicine

200 Cardio Diabetes Medicine 2017

Alcohol Heart, Diabetes and Lipids

Dr. Meenakshi Sundaram, MD

Asst.Prof. Medicine, TKMCH, Tuticorin

Abstract Moderate Women Men
No more than two
Longterm alcohol consumption in well nourished Heavy No more than drinks per day
diabetics can result in excessive blood sugar level. Binge one drink per
Long term alcohol ingestion in diabetics who are day More than two drink
not adequately nourished can lead to dangerously per day
low blood sugar. Alcohol consumption can worsen More than one >5 drinks on single
diabetes related medical complications, such as dis- drink per day occasion
turbances in fat metabolism, nerve damage and eye
disease. Consuming moderate amount of alcohol re- >4 drinks on
duce the incidence of diabetes .Moderate intake of single occa-
alcohol has been shown to reduce the risk of CAD sion
(Coronary Artery Disease) by 40 to 70% compared
with non-drinkers and heavy drinkers in several pro- Excessive drink means either binge ,heavy or both
spective cohort studies. Several factors such as an- in both gender.
tioxidant, antithrombotic, enhanced insulin sensitivity
and increase in HDL(High Density Lipoprotein) have According to the centres for Disease control and
been hypothesized for this benefit. However binge Diabetes (CDC), one standard drink is equal to 14
drinking and heavy drinking have shown to be as- gms (0.6 ounces) of pure alcohol. drinks such as
sociated with metabolic syndrome through eleva- beer and wine can have content of anywhere from
tion of blood pressure and Triglycerides in patients 2-20 %.spirits and liquor can contain 40-50 percent
with Diabetes. Accordingly more studies are needed or even more alcohol. below is the alcohol content in
to determine whether the beneficial effects of daily common alcoholic drinks according to CDC. each is
moderate alcohol consumption outweigh the delete- equal to one drink.
rious effects .Diabetics should avoid heavy drinking
because it can cause hypoglycaemia and ketoaci- • 12 ounces of beer -5% alcohol content
dosis and ultimately increase diabetics risk of death
from non cardiovascular causes. • 8 ounces of malt liquor-7 %alcohol content

Alcohol and Heart • 5 ounces of wine -12 %alcohol content.

Alcohol percentages by volume (ABV) of some com- Association between heart disease and alcohol con-
mon type of drinks are as follows sumption has been described as a U or J shaped
curve with increasing alcohol consumption plotted
1. Beer : 3-10% on the X axis and increasing incidence of heart dis-
ease plotted on the Y axis. the curve shows that
2. Wine : 8-14% abstinence from alcohol consumption is associated
with more heart disease than is low to moderate al-
3. Fortified wines : 16-22% cohol consumption(2 drinks/day).Increasing alcohol
consumption beyond moderation is associated with
4. Spirit : 20-70% increasing heart disease.

GCDC 2017

Alcohol Heart, Diabetes and Lipids 201

Cardioprotective effects of low to moderate Negative effects of increased alcohol
alcohol consumption consumption

↑ HDL Hypertension and transient increase in BP
↑ A-I,A-II apolipoprotein
↓ Level of oxidised LDL Endothelial dysfunction &oxidative stress
↓ CRP, Fibrinogen level
↓ Platelet reactivity, aggregability ↑ Plasminogen Activator Inhibitor
↑ Insulin sensitivity
↓ Fibrinolysis

↑ thrombus formation

Alcoholic cardiomyopathy

Alcohol and its metabolite acetaldehyde are cardio-
toxins. Myocardial depression is initially reversible
but, if sustained ,can lead to irreversible vacuoliza-
tion, mitochondrial abnormalities and fibrosis. The
amount of alcohol necessary to produce symptom-
atic cardiomyopathy in susceptible individuals is not
known but has been estimated to be six drinks(~4 oz
of pure ethanol)a day for 5 to 10yrs.Frequent binging
without heavy daily consumption may also be suffi-
cient to produce cardiac disease. Abstinence leads
to improvement in atleast 50% of patients with se-
vere symptoms, some of whom normalize their left
ventricular ejection fraction. In addition to its role in
Dilated Cardiomyopathy (DCM) heavy alcohol use is
associated with hypertension which can aggravate
DCM and may be refractory to treatment.

Alcohol and hypertension

The alcohol intake elevates the arterial pressure in
a dose dependent response. The rennin angiotensin
system might be involved in the mechanism that al-
cohol to induce hypertension. The increased plasma
rennin is caused by dehydration due to ethanol di-
uresis or to the inhibiting action of ethanol in the
aldosterone secretion. A reduction in the ingestion
of alcohol between heavy consumers significantly
reduces the systolic and diastolic arterial pressure.
Therefore the reduction of alcohol consumption must
be recommended as a lifestyle modification in heavy
drinkers.

Alcohol and Diabetes

Regularly drinking a moderate amount of alcohol
could reduce the chances of developing diabetes
.Consuming alcohol three or four days a week is as-
sociated with a reduced risk of developing diabetes
a 27%reduction in men and a 32%reduction in women
compared with abstaining .Wine is considered par-
ticularly beneficial ,probably because it has chemi-
cal compounds that improve blood sugar balance.
Gin have the opposite effect along with other spirits
.Chances of getting hypoglycaemia are higher in di-

Cardio Diabetes Medicine

202 Cardio Diabetes Medicine 2017

abetics who are taking insulin or oral hypoglycemic alcohol.
agents when they consume alcohol in excess level.
• Patients who abuse alcohol are at high risk of liver
Occasional episodes of alcohol consumption gen- damage and must not take metformin and trogl-
erally do not worsen blood sugar control in people itazone
with diabetes and may even have beneficial effects
.Regular consumption of 2 to 4 drinks per day clearly Wine is considered particularly beneficial, probably
interferes with diabetic blood sugar control and in- because it has chemical compounds that improve
creases the risk of peripheral neuropathy, retinopa- blood sugar balance. Gin have the opposite effect
thy and impotence. along with other spirits. Chances of getting hypogly-
caemia are higher in diabetics who are taking insulin
Effects of alcohol consumption in fed state or oral hypoglycemic agents when they consume al-
cohol in excess level.
• Chronic alcohol consumption increases the blood
sugar level in the fed state. The American Diabetes Association (ADA) recom-
mends the following for people diabetes when they
Effects of alcohol consumption in fasting drink.
state
• Women should not have more than one drink per
• Profound reduction in blood sugar level(Reduced day
reserve of glycogen and impaired gluconeogenisis)
• Men should not have more than two drinks per day
• Unawareness,of hypoglycaemia and delayed re-
coveryfrom hypoglycaemia. • Do not drink on an empty stomach or when blood
sugar levels are low
Effects of alcohol on DKA
• Do not replace food with alcohol in a meal plan-do
Poor food intake and impaired gluconeogensis lead not account alcohol in a food plan as a carbohy-
to lower blood sugar level and as a result insulin se- drate choice
cretion is reduced. Because insulin restrains gucagon
secretion, lower insulin secretion allows increased • Sips drinks slowly to make them last
glucagon secretion, setting stage for development
of ketoacidosis. Dehydration and reduced blood vol- Keep hydrated with zero-calorie drinks like water or
ume increases the levels of stress hormones which diet soda.
further decrease the insulin production and increase
glucagon production. Accordingly Physicians who Alcohol and Lipid
treat diabetics known to consume large amount of
alcohol must be aware of risk of alcoholic ketoaci- Alcoholic hyperlipidemia results primarily from in-
dosis in those patients. creased hepatic secretion of very low density pro-
tein(VLDL) and secondarily from impairment in the
Effects of alcohol on nerves removal of triacylglycerol rich lipoprotein from the
plasma. It is estimated that the cardioprotector effect
Diabetics and alcohol consumption are the two most of alcohol may be attributed to 50% of HDL (High
common underlying causes of peripheral neuropathy. Density Lipoprotein) cholesterol increase . Moderate
Symptomatic peripheral neuropathy is more common consumption of Alcohol(30gm Ethanol per day) re-
in men who consumes a tleast 3 to 4 alcohol con- sults in increasing the concentration of HDL choles-
taining beverages almost every night compared with terol in approximately 4mg/dl, apoA1 in 8.82mg/dl,
men who drinks less alcohol and diabetics can en- with a reduction to the risk of cardiac disease esti-
hance each others effects in terms of causing nerve mated at 24.7%. In the postprandial period the alco-
damage. hol is responsible for an increase in the triglycerides,
with the inhibition of the oxidation of Free Fatty Acid
Alcohol reduces blood levels of testosterone. Heavy (FFA). The hypertriglyceridemia or the increase of FFA
drinkers are at high risk to develop impotence if they are associated to a reduction of the endothelial va-
are diabetic too. sodilatation in normal individuals and those who are
insulin resistant.
Effects of alcohol on OHA
Conclusion
• People treated with chlorpropamide experience an
unpleasant disulfiram like reaction after drinking Alcohol is a drug of complex physiological effects
that vary according to gender, age, race, bodyweight

GCDC 2017

Alcohol Heart, Diabetes and Lipids 203

and consumption pattern. Regularly drinking a mod-
erate amount of alcohol could reduce the chances
of developing diabetes. Consuming alcohol three or
four days a week is associated with a reduced risk
of developing diabetes a 27%reduction in men and
a 32%reduction in women compared with abstain-
ing. Recommending a moderate use of alcohol with
a purpose of taking advantage of its health benefits
must not be done. The additional consumption of
ethanol will promote metabolic changes, weight gain
and increasing the risk of cardiovascular diseases,
altering the lipid profile and promoting hypertension
in both gender.

Accordingly more studies are needed to determine
whether the beneficial effects of daily moderate al-
cohol consumption outweigh the deleterious effects
.Diabetics should avoid heavy drinking because it can
cause hypoglycaemia and ketoacidosis and ultimate-
ly increase diabetics risk of death from non cardio-
vascular causes.

References

1. Rodney H.Falk and Ray E.Hershberger, Alcoholic and Diabetic cardio-
myopathies, Braunwalds Heart Disease A textbook of cardiovascular
Medicine, 10th Edition, volume–II, page 1557.

2. CharlotteHolst, Ulrik Becker, Marit E Jorgensen, Morton Gronbaek, Al-
cohol drinking pattern and risk of diabetes, Diabetologia, Article 27,
July 2017.

3. Ronksley PE, Brien SE, Turner BS, Mukammal KJ, Ghaliwa, Association
alcohol consumption with selected cardio vascular disease outcomes – A
systemic review and meta analysis. BMJ, 2011; 342; d671.doi:10.1136/
Bmj.d671 pmid;2134 3207.

4. Mayla Cardoso Fernandes, Toffolo Aline Silvade Aguiar Nemer vilma Apa-
recidaSilva Fonseca doi:http://dx.doi.org/10.4021/jem128e – Journal of
Endocrinology & Metabolism, Volume 2, Number 6, December 2012,
pages 205-211.

5. Khanh N, Vu. christe M, Ballantyne, Ron.c Hoogeveen, Vijay Nambi,
Kelly A,Volcik, Eric Boerwinkle, Alanna c Morrison, Casual role of Alcohol
Consumption in an improved lipid profile – The Atherosclerosis risk in
community (ARIC) study PLoSONE 11(2);e0148765.doi10.1371/journal.
pone.0148765.-Journals.plos.org February 5 ,2016

Cardio Diabetes Medicine

204 Cardio Diabetes Medicine 2017

Anxiety And Diabetes

Dr. Avinash De Sousa

Founder Trustee and Consultant Psychiatrist
Desousa Foundation, Mumbai
&

Ms Pragya Lodha, Research Assistan

Diabetes mellitus is a chronic disorder which arises • having trouble relaxing » being so restless that it’s
as a result of problems in the body’s production and/ hard to sit still
or uptake of insulin. Diabetes mellitus is diagnosed
by the presence of abnormally high blood glucose • becoming easily annoyed or irritable
levels, which is also known as hyperglycemia. Dia-
betes, as known, may be Type 1 (juvenile onset and • feeling afraid that something awful might happen.
occurs in less than 5-10% of the population suffer-
ing from diabetes); Type 2 (adult onset diabetes that Diabetes is associated with an increased risk of both
makes up for 90-95% of the cases of diabetes) or physical and psychological complications, both of
gestational diabetes, a form of high blood sugar af- which impact the quality of life and overall mortality.
fecting pregnant women. Irrespective of the type, the Psychological symptomatology is a common occur-
pathophysiology of diabetes shows comorbidty with rence in the pathophysiology of diabetes. It is one
several psychiatric disorders. The focus of this article of the rapidly growing illnesses with every third per-
explores the associative links between diabetes and son being diagnosed with diabetes. Depression and
anxiety issues. anxiety are highly prevalent psychological disorders
in the population already suffering from diabetes.
Not officially, but India is referred to as the diabe- Though depression is the most investigated psycho-
tes capital, housing approximately 69 million people logical disorder associated with diabetes, there has
suffering from diabetes which places the nation on been little research conducted on the association be-
the second rank after China. Epidemiological studies tween diabetes with anxiety. The lack of research is
show an increasing trend for diabetes on a global due to an ambiguity seen in the structural nature of
level and inevitably in India as well. In support, the symptoms of depression and anxiety, for two reason-
WHO also projects that the morbidity due to diabetes (i) there is lack of research on association of symp-
will only double between 2016 and 2030. Data from toms and (i) it is difficult to differentiate specific and
the World Health Organization adds an estimate that non specific symptoms of depression and anxiety in
80 per cent of diabetes deaths occur in low and mid- patients of diabetes.
dle-income countries which places India in a crisis.
However, anxiety has been shown to have links with
Anxiety is when a person experiences an excessive poor outcomes in people with diabetes and the re-
amount of fear in anticipation of something bad hap- search that has been conducted to study this do-
pening. Usually, this is a healthy response to a real main, shows positive and significant correlational
threat. For example, certain situations, such as public links between diabetes and elevated symptoms of
speaking or having a hypo, can trigger anxious feel- anxiety.
ings. Symptoms of anxiety include:
Complications arise in diagnosing and delineating
• feeling nervous or on edge upon the comorbidity of anxiety in patients who
suffer from diabetes. This is attributable to the over-
• being unable to stop worrying or control worrying lapping symptoms of diabetes and anxiety that in-
thoughts clude- feelings of fatigue, concentration difficulties,
restlessness, change in appetite, irritability and au-
• worrying too much about things tonomic arousal. This difficulty in understanding the

GCDC 2017

Anxiety And Diabetes 205

co-prevalence of symptoms leads to under-diagnosis who don’t. Stress, at a neurochemical level, increas-
and thence, under-treatment of anxiety issues in di- es levels of cortisol in the body, which can make lev-
abetes. What is clear is that anxiety can affect the els of blood sugar rise. Cortisol, in action with other
way people manage their diabetes and, in turn, their hormones, releases a surge of energy in the form of
physical health, like: glucose (sugar), which the body can use to fight or
flee. Thus, management of diabetes becomes a further
-- checking blood glucose levels continuously due to problem due to the presence of stress.
intense fears of hypos or developing complications
Anxiety is also seen to rise due to lack of sleep which
-- avoiding injecting in public, or not injecting at all, is a commonly reported distress in people suffering
due to worry about what others might think. Among from diabetes. Disturbed sleep patterns add to the
people with diabetes, some have anxiety before burden of anxiety by elevating the abnormal sugar
a diagnosis of diabetes, while for others, anxiety levels in diabetic conditions. The affective states that
may be triggered by specific fears associated an individual experiences as a result of developing and
with managing diabetes (e.g., fear of developing suffering from diabetes include worry, frustration and
complications). Anxiety may be a symptom in pa- feelings of being out of control that may add on to
tients with diabetes and the distress developed the anxiety. Another factor that may load on the anxi-
due to the diabetic condition can aggravate anxi- ety of diabetic individuals is their thought patterns and
ety. Thus, there is a two way connection between thinking styles. Research has shown anxious thinking,
the co-prevalence. fuzzy thoughts and the worry of symptoms of diabetes
may enhance the overall anxiety levels in the patients.
• Common symptoms seen in anxiety and diabe- Thinking styles among diabetics can further be ex-
tes- plored to outline that their worrisome thoughts about
the ‘right’ food to eat, the fear of development of other
• Panic, fear, and uneasiness physiological or medical conditions and their glucose
levels can elevate symptoms of anxiety.
• Sleep problems
What is important to differentiate is the condition of
• Frequent urges to urinate anxiety in diabetes and diabetic distress. With an under-
standing of anxiety and diabetes, one must remember
• Heart palpitations that diabetes distress is a commonly prevalent but
hard to nail down condition as it overlaps with several
• Dry Mouth related conditions, including depression, anxiety, and
stress. They are diabetes-specific emotional state ex-
• Nausea ists. A finding reports that people who were experienc-
ing unique emotional issues directly related to the
• Tense muscles burdens and worries of living with a chronic disease
were said to have diabetes distress. The condition is
Research literature reveals the prevalence of Gen- characterized by “worry, frustration, concern, and
eralized Anxiety Disorder (GAD) and panic attacks maybe a bit of burnout.
among patients with diabetes. Individuals who suffer
from panic attacks, for example, are hyper-alert to The prevalence of anxiety disorders in patients with
signs of impending danger. It is estimated that 14% diabetes is found to be higher in female population
of people with diabetes have generalized anxiety as a result of the neurobiological underpinnings as-
disorder. As many as 40% of people with diabetes sociated with the two health conditions.
have at least some of the anxiety symptoms and the
fear of hypoglycemia is also commonly seen in them. Diabetes mellitus is a chronic condition with progres-
Anxiety disorders in people with diabetes may be as- sively increasing trends over the years. Prevalence
sociated with poor blood sugar control. This can be of anxiety tends to be higher among this population
aggravated by the diet followed by an individual and group. This adds to the cost, morbidity, and mortali-
the stress that an individual faces on a day to day ty of the prevalent health conditions. Association of
basis. Sleep patterns, thinking styles and affective anxiety with diabetes could be detrimental to the care
states are also implicated. of either of these conditions and could worsen the
prognosis. Monitoring of biochemical parameters like
Diet, which is full of sugar and fat, does not neces- HbA1c and postprandial blood glucose levels and BMI
sarily cause anxiety but it does appear to be respon- could be a guide to development of anxiety in these
sible in worsening anxiety symptoms and impair the
body’s ability to cope with stress. A study showed
that people with diabetes who have panic disor-
der have higher HbA1c levels (a measure of blood
glucose control over time) in comparison to people

Cardio Diabetes Medicine

206 Cardio Diabetes Medicine 2017

patients. Also, physical exercise and yoga seem to
have a protective effect on anxiety in those with
diabetes mellitus. Additionally, keep fixed sleeping
times during the night, eating a nutritional diet and
regular follow up with the medical professionals can
help manage anxiety and diabetes

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Cardio Diabetes Medicine 2017 207

Diabetes Mellitus and
Tuberculosis - Double Jeopardy

Dr. Prof. Preetam Arthur, MD, FRCP

Professor and Head of General Medicine, Sri Ramachandra Medical University
&

Dr. Harshavardhan TS, MD.,

Senior Resident, General Medicine, Sri Ramachandra Medical University

Abstract hand we have reduced, by many folds, very many
infectious diseases that once were the scourge of
This chapter attempts to throw light on the sinister mankind, but the resilient Mycobacterium tubercu-
association between Diabetes mellitus and tubercu- losis continues to plague us constantly in everyday
losis and how they influence each other. Diabetes medical practice. In fact many prior articles on this
is a recognised risk factor to develop tuberculosis, concurrence of diseases have called it the ‘double
and this correlates with poor glycemic control. This epidemic’ – signifying the paralleled rise in the diag-
has been attributed to a weakened immune response nosis of both of these diseases in recent times. We
to Mycobacterium tuberculosis among diabetics and are deeming it ‘Double Jeopardy’. A national level,
genetic factors have also been implicated. Clinical multi-centric study from the India Diabetes-TB study
presentation of tuberculosis in diabetics has been group, in which our institute was a part, studied the
described to be different from that in non-diabetics, prevalence of diabetes in patients with a diagnosis
though various studies have differed in their find- of tuberculosis. Of the patients who were diagnosed
ings. Multifocal, lower lobe predominant and cavi- to have tuberculosis, 20% of south Indian patients
tatory disease has been described in some studies and 10% of patients from North India had diabetes
as more common in diabetics. Tuberculosis is also mellitus. This chapter attempts to throw light on the
considered to influence diabetes. During acute dis- sinister association between these two very common
ease, glycemic control is worsened in diabetics and diseases and how they influence each other. A phy-
can cause glucose intolerance in people with no pri- sician must be aware of how the occurrence of both
or diabetes. Concurrent diabetes and tuberculosis tuberculosis and diabetes affects the clinical presen-
in a patient poses management issues that are im- tation and outcome of either disease process. We
portant for the treating physician. Drug interactions have also highlighted how the concurrence of both
between Rifampicin and oral glycemic agents are of these diseases affects practical management.(1) (2)
significant. Rifampicin levels have also been shown
to be reduced in diabetics probably due to reduced 2. Diabetes as a risk for latent tuberculosis :
absorption. Combined toxicities of drug therapy and
disease must also be considered in the treatment of Tuberculosis, as we know, is a two step process -
such a patient. It is therefore prudent to screen every infection and disease. The association between both
patient with tuberculosis for diabetes and engage in these entities and diabetes has been the subject of
strict glycemic control with heightened awareness on multiple observational studies. A recent meta-anal-
drug interactions and overlapping toxicities. Thus the ysis looking at the association between the occur-
double jeopardy of diabetes and tuberculosis is an rence of latent tuberculosis infection (LTBI) and dia-
entity that we have highlighted in this chapter. betes mellitus concludes that diabetes is associated
with a small but statistically significant risk for latent
1. Introduction: TB infection. However this risk is small and has not
prompted the World Health Organisation and other
Diabetes Mellitus is a ubiquitous disease that has international societies to recommend routine LTBI
taken centre stage in the realm of modern medicine, screening in all diabetics, unlike in HIV positive pa-
a disease that affects nearly every fifth patient that tients. Though the association with LTBI risk is not
walks into a physician’s office in India. On the other

Cardio Diabetes Medicine

208 Diabetes Mellitus and Tuberculosis - Double Jeopardy

very strong, other studies have shown higher rates strated reduced interferon gamma and Interleukin-12
of reactivation of tuberculosis in diabetics. (3) expression in diabetic murine models with tuberculo-
sis. Innate immunity consisting of macrophages, that
3. Diabetes as a risk for active tuberculosis form the first line of defence against tuberculosis is
less effective in diabetics. This is due to the metabol-
The association of diabetes with tubercular disease ic effects of hyperglycemia and advanced glycation
however is more worrisome. Several case control end products. The oxidative stress that results from
studies have pegged the relative odds of develop- hyperglycemia weakens the phagocytic and killing
ing tubercular disease in diabetic patients as ranging function of macrophages. Most adaptive immune
from 2.44 to 8.3 compared with non diabetics, mean- response studies suggest that diabetes patients
ing the chances of a diabetic acquiring tubercular with TB have a hyper-reactive, but poorly effective
disease is significantly higher than the non diabet- cell-mediated response to mycobacterial antigens.
ic population.(4) Long term follow up cohort studies This provides indirect evidence of dysfunctional im-
from Korea and South America have shown a high mune regulation of tuberculosis in diabetic patients.
incidence of tuberculosis amongst diabetics com- This leads to inadequate clearing of the tubercular
pared to non diabetics, confirming this association.(5) pathogen and in addition, also enhances the immune
(6) . Our Institute was part of a national level, multiple mediated injury in the human host. A genetic basis
centre study where we screened patients attending to this dysfunction has also been demonstrated.
diabetic clinics for active tuberculosis. Nearly 1.8 % of Reduced expressions of genes that regulate macro-
that population had already identified active tuber- phage activity (Hexokinase 2, CD28) have been not-
culosis or were newly diagnosed with tuberculosis. ed among diabetics, though the clinical significance
Nearly 50% of these patients had sputum positive of the same is not entirely clear. (8) (9)
pulmonary tuberculosis, meaning they were potential
sources of infection to the community. This is a sig- 5. The influence of tuberculosis on diabetes mellitus
nificant number considering the diabetes burden in
our country. This study also describes protocols that Does tuberculosis affect diabetes mellitus? This is
can be followed to carry out a similar screening pro- a question that is worth answering, considering that
gramme in diabetic clinics. Such a screening program 10-30% of cases of tuberculosis have concurrent dia-
will serve both as a public health measure in iden- betes. Infections, including tuberculosis are known to
tifying sputum positive tuberculosis to limit spread worsen glycemic control. Some studies suggest that
and also achieve early diagnosis and treatment of tuberculosis can cause diabetes in patients without
patients with tuberculosis.(7) results and challenges of prior evidence of the disease, by mechanisms that
screening patients with diabetes mellitus (DM are currently unclear. Others have demonstrated that
tuberculosis causes transient rise in blood glucose
Poor glycemic control among diabetics has been levels which revert to normal within 3 months of ini-
shown to have a higher association with the occur- tiation of therapy and continue to be normal atleast
rence of tuberculosis in a recent study of 4690 until 12 months after treatment. Long term follow up
elderly patients from Hong Kong . A Hba1c (glyco- studies are lacking. Many other workers have used
sylated haemoglobin) greater than 7% was found to oral glucose tolerance testing to show that tubercu-
represent a three times increased hazard for active losis patients have higher rates of glucose intoler-
tuberculosis compared to hba1c of less than 7%. (Haz- ance than do community controls. Whether the TB
ard ratio 3.11; 95% CI 1.63-5.92). This highlights that truly preceded the onset of diabetes or is this just
poor glycemic control rather than diabetes per se is better detection of pre existing diabetes is unclear.
a risk factor for tuberculosis. The clinical implication What therefore arises is the need to screen all pa-
of these findings suggest that every clinician must tients with a diagnosis of tuberculosis for glucose
consider diabetes mellitus as an important risk factor intolerance and to reiterate that TB infection per se
for active tuberculosis and therefore must invest in a may worsen glycemic control, thus needing initiation
diabetic screening. Glycemic control in diabetics with or titration of diabetic medications and suitable diet
tuberculosis should be an important goal of therapy. until tuberculosis is adequately treated.

(2) 6. Clinical presentation of Tuberculosis in
Diabetes:
4. Biological plausibility for diabetes as a risk
for tuberculosis It is evident that diabetes mellitus affects the im-
mune response to mycobacterial infections. Thus
Biologically the above risk has been explained on it is expected that the clinical presentation, extent
multiple fronts. Animal model studies have demon-

GCDC 2017

Cardio Diabetes Medicine 2017 209

of disease and outcomes of tuberculosis may vary diabetes had delayed sputum conversion and trend-
between diabetics and non diabetics. Some stud- ed towards poorer outcomes including death at the
ies have shown that diabetics with TB tend to be end of treatment in the diabetic subset. Retrospective
of older age. Such co-existent disease occurs at cohort studies from Maryland, USA and in separate
a higher frequency among men. Others have also work published by Wang and colleagues, showed
demonstrated increased symptoms at presentation, that there was an increased risk of death among
such as higher levels of hemoptysis and weight loss diabetics with tuberculosis than patients with tuber-
being reported among diabetics compared to non culosis alone. These studies suggest that treatment
diabetic controls. Diabetes has been shown to be failure and death are more frequent in diabetics.
associated with lower lobe predominant, more cavita- However it is not clear whether aggressive glycemic
tory and multi-focal tubercular disease in some stud- control would improve treatment response. Further-
ies. However extra-pulmonary TB is considered to be more most of these studies do not report cause of
of lower occurrence in patients with diabetes, than death, thus we do not know if the excess mortality
those without. However more recent studies have not is explained by increased severity of tuberculosis
shown many of these differences to be significant. in diabetics or the presence of other vascular and
Stark variations in presentation of disease between non vascular complications of diabetes per se. What
diabetics and non diabetics is possibly overstated. it tells us is that, diabetes and tuberculosis present
This variation amongst studies is probably due to the a lethal combination that poses a double jeopardy
fact that levels of glycemic control were not adjusted to the patient. The clinician must have heightened
for and the screening test for the diagnosis of diabe- awareness that this combination has been associat-
tes has also varied amongst studies. (10)and with the ed with poorer outcomes, including death and thus
increasing prevalence of type 2 DM in less developed engage in efforts to an early diagnosis and effective
regions, many patients with TB will have concomitant therapy for both diseases.
DM. Presently, little is known about the effect of DM
on the clinical presentation and treatment outcome 8. Issues in the co-management of TB and
of TB.\nMETHODS: In an urban setting in Indonesia, diabetes:
737 patients with pulmonary TB were screened for
DM and were followed up prospectively during TB In the scenario of coexistence of TB and Diabetes in
treatment. Clinical characteristics and outcome were a patient, the physician is expected to manage both
compared between patients with TB who had DM diseases with a fine balance, not allowing the treat-
and patients with TB who did not have DM.\nRE- ment of one to adversely affect the other. There are
SULTS: DM was diagnosed in 14.8% of patients with many practical points to note in the clinical manage-
TB and was associated with older age and a great- ment of such a patient.
er body weight. On presentation, diabetic patients
with TB had more symptoms but had no evidence A. Influence of tuberculosis on diabetic medica-
of more-severe TB. After 2 months, results of sputum tions:
microscopic examination was more often positive in
diabetic patients (18.1% vs. 10.0% (11) Infections like tuberculosis cause poorer glycemic
control and therefore need careful monitoring of
7. Microbiology of Tuberculosis in diabetes blood sugars during the acute phase of illness to
and overall outcomes: titrate anti diabetic medications to effective dos-
ages. Drug interaction is an important factor to
It was hypothesised and demonstrated in one study consider with Rifampicin being the usual suspect.
that rates of sputum positivity are lower in diabetics Rifampicin is a powerful enzyme inducer of cyto-
but other studies have shown no such significant chrome P450. The iso-enzyme 2C9 metabolises
difference. Some small retrospective studies have Glibenclamide and Glipizide. The serum concen-
shown that the initial bacterial burden among diabetic trations of both these oral sulfonylureas have
tuberculosis patients is higher. However this does not been shown to be reduced by 39% and 22 % re-
seem to have any impact on the final sputum con- spectively in the case of rifampicin co-treatment.
version beyond 3 months, though the median time to Rifampicin can also reduce the effective levels of
culture negativity was significantly longer in diabet- thiazolidenediones and meglitinides, causing hy-
ic patients than in controls (42 vs 37 days; p=0·03). perglycemia in diabetics who were earlier having
This difference of a few days probably does not as- blood sugars within acceptable limits. Moreover,
sume clinical significance. In a study from India that Rifampicin has also been demonstrated to cause
looked at 316 patients with tuberculosis, those with early phase hyperglycaemic and hyper-insulin-
emia even in non diabetic patients. (10)and with

Cardio Diabetes Medicine

210 Diabetes Mellitus and Tuberculosis - Double Jeopardy

the increasing prevalence of type 2 DM in less tend to have higher rates of compliance with ATT
developed regions, many patients with TB will medications than do non diabetics. This is per-
have concomitant DM. Presently, little is known haps attributed to the fact that they are tuned to
about the effect of DM on the clinical presenta- a regular medication regimen than non diabetics.
tion and treatment outcome of TB.\nMETHODS: Thus the physician must be aware that the phar-
In an urban setting in Indonesia, 737 patients macology of ATT and diabetes is prone to im-
with pulmonary TB were screened for DM and portant interactions and practical considerations
were followed up prospectively during TB treat- including dose readjustment, toxicity monitoring
ment. Clinical characteristics and outcome were and higher chance of treatment failure. Future
compared between patients with TB who had DM research is required to establish whether thera-
and patients with TB who did not have DM.\nRE- peutic drug monitoring is required routinely and
SULTS: DM was diagnosed in 14.8% of patients feasible in such patients.
with TB and was associated with older age and
a greater body weight. On presentation, diabet- 9. Conclusion:
ic patients with TB had more symptoms but had
no evidence of more-severe TB. After 2 months, Diabetes Mellitus and Tuberculosis are common dis-
results of sputum microscopic examination was eases that physicians will encounter in their lifetime
more often positive in diabetic patients (18.1% vs. of practice. But the deleterious relationship that they
10.0% share to jeopardize the human host is often under
recognised. It is rational to screen every patient with
B. Influence of diabetes on anti tubercular drugs: tuberculosis for diabetes and if detected, engage in
strict glycemic control. Atypical presentations of tu-
Diabetes can cause altered pharmacokinetics berculosis in diabetics must be borne in mind despite
of anti-tubercular drugs especially Rifampicin. conflicting evidence on such an association. Therapy
Rifampicin levels were demonstrated to be 53% for TB and diabetes must consider drug interactions,
lower in diabetics than non-diabetics in one study. combined toxicities of the diseases and medications
This could be perhaps explained by altered gut and adequate precautions taken. Future research
absorption, protein binding in serum and altered must be encouraged in elucidating the patho-biolo-
metabolism of the drug in diabetics. This is of crit- gy behind the immune dysfunction in the diabetics’
icality because low levels of the backbone drug of response to TB infection.
ATT (Rifampicin) raises concerns of development
of drug resistance and treatment failure. Drug 10. Highlights:
toxicity is also of significance in diabetics with
nephropathy and impaired drug clearance in pa- Diabetes and Tuberculosis are common diseases
tients with fatty liver. Diabetics with nephropathy that can occur concurrently with mutual influence
will need dose re-adjustment of Ethambutol and and doubly jeopardise patients.
Pyrazinamide in the setting of a low glomerular
filtration rate. In fact, studies from India and else- Diabetes blunts the immune response to Mycobac-
where have shown a higher incidence of adverse terium tuberculosis infections and results in a higher
drug reactions in diabetic patient with tuberculosis incidence of disease in diabetics with varying clinical
than with patients with TB alone. presentations and poorer outcomes.

C. Enhanced toxicity of drugs and disease: The patho-biology of this association has been de-
scribed in limited studies and needs more research
Overlapping toxicities are also important to keep for better understanding.
in mind. Peripheral neuropathy of diabetes can
be worsened by the one caused by Isoniazid and It is prudent to screen all patients with tuberculosis
requires prophylactic pyridoxine therapy. Macular for diabetes and engage in strict glycemic control, if
toxicity caused by Ethambutol may develop in a identified.
pre existing diabetic retinopathy and worsen vi-
sion in a patient. Considering that a diabetic is Screening of diabetics for tuberculosis can be of
usually on several medications, an add on diag- public health significance and lead to earlier identifi-
nosis of tuberculosis is bound to increase the pill cation and treatment.
burden for the patient. This raises concerns on
compliance and adherence to medications. How- In patients with co-existence of both diseases, poten-
ever studies from India have shown that diabetics tial drug interactions and overlapping toxicities must
be taken into consideration by the treating physician.

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Cardio Diabetes Medicine 2017 211

11. References:

1. Bharati DR, Pal R, Kar S, Rekha R, Yamuna TV, Basu M. Prevalence and
determinants of diabetes mellitus in Puducherry, South India. J Pharm
Bioallied Sci. 2011;3(4):513–8.

2. India Tuberculosis-Diabetes Study Group. Screening of patients with tu-
berculosis for diabetes mellitus in India. Trop Med Int Health TM IH.
2013 May;18(5):636–45.

3. Lee M-R, Huang Y-P, Kuo Y-T, Luo C-H, Shih Y-J, Shu C-C, et al. Di-
abetes Mellitus and Latent Tuberculosis Infection: A Systemic Review
and Metaanalysis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2017 Mar
15;64(6):719–27.

4. Coker R, McKee M, Atun R, Dimitrova B, Dodonova E, Kuznetsov S, et
al. Risk factors for pulmonary tuberculosis in Russia: case-control study.
BMJ. 2006 Jan 14;332(7533):85–7.

5. Kim SJ, Hong YP, Lew WJ, Yang SC, Lee EG. Incidence of pulmonary tu-
berculosis among diabetics. Tuber Lung Dis Off J Int Union Tuberc Lung
Dis. 1995 Dec;76(6):529–33.

6. Olmos P, Donoso J, Rojas N, Landeros P, Schurmann R, Retamal G, et al.
[Tuberculosis and diabetes mellitus: a longitudinal-retrospective study in a
teaching hospital]. Rev Med Chil. 1989 Sep;117(9):979–83.

7. India Diabetes Mellitus--Tuberculosis Study Group. Screening of patients
with diabetes mellitus for tuberculosis in India. Trop Med Int Health TM
IH. 2013 May;18(5):646–54.

8. Martinez N, Kornfeld H. Diabetes and immunity to tuberculosis. Eur J
Immunol. 2014 Mar;44(3):617–26.

9. Restrepo BI, Schlesinger LS. Host-pathogen interactions in tubercu-
losis patients with type 2 diabetes mellitus. Tuberc Edinb Scotl. 2013
Dec;93(0):S10–4.

10. Alisjahbana B, Sahiratmadja E, Nelwan EJ, Purwa AM, Ahmad Y, Ottenhoff
THM, et al. The effect of type 2 diabetes mellitus on the presentation
and treatment response of pulmonary tuberculosis. Clin Infect Dis Off Publ
Infect Dis Soc Am. 2007 Aug 15;45(4):428–35.

11. Dooley KE, Chaisson RE. Tuberculosis and diabetes mellitus: convergence
of two epidemics. Lancet Infect Dis. 2009 Dec;9(12):737–46.

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212 Cardio Diabetes Medicine 2017

Eating Disorders in Diabetes Mellitus

Dr. Davis Prabhakar, M.D (General Medicine)

Assistant Professor, Dept of General Medicine, Thoothukudi Govt.
Medical College and Hospital,

Consultant Physician, Ebenezer Hospital, Tuticorin

Abstract Why do people with diabetes get eating
disorders?
A verse from the bible says” A man is not defiled by
what  enters  his mouth, but by what  comes  out It has been established that eating disorders includ-
of  it.”(matthew15:11), yes!! In today’s modern era of ing anorexia, bulimia and EDNOS (eating disorder
medicine, the field of diabetology has taken the po- not otherwise specified) arise twice as often in ado-
sition of the fore runner among all the co-morbidities lescent females with diabetes as in the normal ado-
that causes mortality regardless of age and gender. lescent population. There are a number of probable
The emphasis on the ‘Golden triad’ of nutritious Diet, reasons for this phenomenon. First, when a child or
regular exercise and prescribed medication has al- adolescent is diagnosed with diabetes, they have
ways been repeatedly echoed in every diabetologists usually lost a significant amount of weight. This is
consulting chamber. because, in uncontrolled diabetes. When treatment
with insulin commences, there is normally a weight
There is concrete evidence that exercise and medica- gain. If a young person is vulnerable to an eating
tion when properly practiced do have a very import- disorder,they may find this body change difficult to
ant role in controlling the glycemic status, in turn re- deal with and may develop unhealthy strategies to
warding the practicing diabetologist with laurels and lose weight.
honours about his skill in treatment ,however when
the expected glycemic control is not attained despite Secondly, there is a unique method of controlling
religiously following the golden triad, the blame is weight available to the diabetic young person. By
ridiculously blamed on Diet. This write up throws light “under-dosing” with insulin, or failing to take insulin
on this scenario and also the associated eating pat- at all, a state of high blood glucose – equivalent to
terns and disorders with diabetes. having uncontrolled diabetes – is induced, leading to
weight loss.  Within the context of an eating disorder,
TEXT:- Diabetes mellitus is characterized by chronic this can be considered to be a form of “purging”. 
hyperglycaemia and its incidence is rising rapidly in
parallel with the obesity epidemic. Disordered eating, Thirdly, young people with diabetes are obliged to
especially sub-threshold eating disorders, is a com- engage with a self-care strategy which includes a
mon psychological problem in both type 1 and type 2 restrictive meal plan.  Those with a predisposition to
diabetes, and Is associated with poor diabetes con- become obsessive about calorie counting may be at
trol, complications, and an increased mortality rate. greater risk of developing an eating disorder as a
Eating problems tend to co-exist with other psycho- diabetic. Furthermore, many diabetic clinics counsel
logical difficulties, especially depression and anxiety strongly against weight gain – advice which may be
disorders. taken to the extreme by some vulnerable teenagers. 
Finally, the effects of being diagnosed with a chronic
In statically reviewed analysis eating disorders as- illness on a young person cannot be underestimated:
sociated with diabetes has been on a rising trend it may be enough to push those already predisposed
globally and reports suggests that the prevalence is to developing any mental illness over the clinical
high as 41.8% in Mexico, 22.1% in Brazil, 22.0% in threshold.
India, and 19.3% in Argentina.

GCDC 2017

Eating Disorders in Diabetes Mellitus 213

The rising incidence of eating disorders among dia- whole milk, was associated with a higher risk of type
betics is on an alarming rate, the cause for this can 2 diabetes. This study clearly contradicts the state-
be ascertained into two components, one being the ment that “vegetarian food is good for diabetics!!”
onset of eating disorders perse such as bulimia and Women with type 1 diabetes twice as likely to develop
anorexia nervosa which leads to early onset of dia- an eating disorder. A new type of Eating disorder
betes mellitus the other component is lack of proper seen more frequently in type 1 diabetes known as
counseling and advice regarding the eating patterns “diabulimia,”. Here the patients who are on a regular
among diabetics, one more unrecognized eating pat- dose of insulin, and have been advised to take it for
tern that is off late seen among diabetics are ‘binge their life time, deliberately give themselves less insu-
eating’ and ‘sugar craving’. lin or no insulin than what they need, for the purpose
of weight loss.
Binge eating along with skipping of meals has shown This condition also has a neuro-psychiatric compo-
a dramatic rise in blood sugar values .A study done nent associated with it and has to be addressed with
by jukka et all shows The prevalence of skipping a multidisciplinary approach of psycho-behavioural
breakfast has progressively increased over the past and psycho- social counselling.
decades in children, adolescents, and adults and
there is increasing evidence that skipping breakfast The tell-tale signs to recognize eating
is associated with excess weight gain and other ad- disorders in diabetes are:
verse health outcomes. In addition, eating frequency
or snacking may also impact body weight and risk • Unexplained elevations in A1C values
of metabolic diseases. • Repeated problems with diabetic ketoacidosis

Some recent reports and case studies done among (DKA)
health professionals in an urban setting, saw a trend • Extreme concerns about weight and body shape
of snacking frequently in between meals, the com- • Change in eating patterns
ponent of food being (junky oil foods).The studies • Unusual patterns of intense exercise (with fre-
showed that there was a marked rise in BMI as well a
direct increase in sugar values, the study prospective- quent hypoglycimia)
ly examined in Health Professionals whether break- • Amenorrhea
fast consumption, eating frequency, and snacking
were associated with T2D risk and whether these So what can be done about it!!
associations were mediated through BMI (in kg/m2).
The treatment as mentioned before is a multidisci-
And the results showed breakfast consumption has plinary approach, where the patient should be under
been shown to improve lipid metabolism by reduc- constant surveillance and monitoring.
ing fasting and total LDL cholesterol and the serum When designed to treat a patient with both type 1
triglyceride concentration. It also reduces risk of lip-
id-associated chronic diseases such as obesity, car-
diovascular disease, and diabetes mellitus because
of favourable changes in glycaemia and insulinemia.

The type of food, quantity, quality and frequency ,
plays a significant role in controlling sugar values ,
pure vegetarians who are more favoured to take diet
very rich in carbohydrates (potato, carrots, radish)
have a significant chance of becoming diabetics, a
study done where two type of food pattern was in-
troduced to two group of people, one had a pattern
characterized by higher intake of fruits and vegeta-
bles (prudent pattern) and the other a pattern charac-
terized by higher intake of foods typical of Western
diets (Western pattern).

The prudent dietary pattern, which was rich in fruits
and vegetables, was associated with a reduced risk
of type 2 diabetes. In contrast, the conservative pat-
tern, which was rich in butter, potatoes, red meat, and

Cardio Diabetes Medicine

214 Cardio Diabetes Medicine 2017

diabetes and an eating disorder, such a team should Reference
include a diabetologist, a diabetes educator, a nutri-
tionist with training in the treatment of eating disor- 1. Eating disorders and diabetes Volume, April 2008, Pages 179-182
ders and diabetes patients, a psychiatrist for psycho-
pharmacologic evaluation and treatment, and a men- 2. Eating disorders in adolescent girls and young adult women with Type
tal health professional to provide individual therapy. 1 Diabetes. Diabetes Spectrum 2002;15(2):83-105 Daneman, D et al

Because of the medical complexity caused by these 3. Diabetes and Eating DisordersJ Diabetes Sci Technol. 2008 May; 2(3):
two conditions, patients with diabetes and eating dis- 530–532. Published online 2008 May. 
orders require more medical monitoring than patients
with diabetes alone. Medical and psychiatric inpatient 4. Eating patterns and type 2 diabetes risk in men: breakfast omission,
treatment may be needed until patients are medi- eating frequency, and snacking.2012 May; 95(5): 1182–1189.Published
cally stable enough to engage in weekly outpatient online 2012 Mar 28. 
treatment. Monthly appointments with the diabetol-
ogist or dietitian may be necessary. Laboratory tests 5. Dietary Patterns and the Incidence of Type 2 Diabetes ,Jukka Mon-
(especially HbA1c.sugar values and electrolytes) and tonen Paul Knekt Tommi Härkänen Ritva Järvinen Markku HeliövaaraArpo
weight checks should occur at all medical appoint- Aromaa Antti Reunanen American Journal of Epidemiology, Volume 161,
ments and be shared with the treating mental health Issue 3, 1 February 2005,
professionals.

Many patients may be unable to access appropriate
treatment because it is difficult to find mental health
practitioners with both diabetes and eating disorder
treatment experience, hence diabetologist should be
well versed in both diabetes and diabetology related
psychiatry.

Take home message!!

• Diet does play a very important role in the inci-
dence and prevalence of diabetes mellitus among
the affluent population rather than the poorer sec-
tions.

• Apart from the existing known eating disorders
such as anorexia nervosa and bulimia. Which have
a direct role in the development of type 1 DM, a
new entity ‘diabulimia’ is the newest player among
the associations with DM.

• There are a lot of misconceptions about the type
of foods that can be advocated among diabetics,
foods with low glycemic index should be made
aware of and the strict implementation of this diet
should be looked into, Vegetarian food has its own
risks for the patient to develop Diabetes.

• There are certain food eating patterns that are on a
rise among established diabetics, patterns such as
‘binge eating’ and ‘sugar craving’ are being noted,
and proper dietician advice should be sought to
address this issue.

• Type 1 diabetics who suffer from associated eat-
ing disorders should be evaluated and offered
psycho-social multidisciplinary with a team of spe-
cialists from fields of diabetolgy, psychiatry and
nutrition.

GCDC 2017

Cardio Diabetes Medicine 2017 215

Obstructive Sleep Apnoea Syndrome and
Cardio Metabolic Risk

Dr. Solaiman Juman, FRCS

Lecturer in Otolaryngology,
University of the West Indies

Abstract ruptive to sleep and there are no apnoeas (cessation
of airflow for greater than 10 seconds or more).
In Obstructive sleep Apnoea Syndrome (OSAS) the
upper airway is obstructed many times during sleep Some authors believe that as the obstructive process
leading to a cascade of neurological, hormonal and worsens, Upper Airway Resistance Syndrome (UARS)
haematological changes that affect the cardio-met- occurs which is thought to be due to further narrow-
abolic status which in turn result in significant mor- ing of the airway but with no closures [1] . Because
bidity and mortality. of the work of breathing, the patient may have symp-
toms similar to Obstructive Sleep Apnoea Syndrome
There is an increasing prevalence of OSAS interna- (OSAS), fatigue, daytime sleepiness, unrefreshing
tionally and the phenotypes of patients can differ sleep- but there are no or minimal apnoeic episodes.
greatly, so medical personnel must be aware of the
different types of presentations and treatment mo- As the obstruction progresses, OSAS (Apnoea – Hy-
dalities to provide optimal care. popnea Index (AHI) of greater than 5 on polysom-
nography) is precipitated.. Apart from obesity, there
Advances in concepts and approaches dealing with are many other factors that cause obstruction in the
all aspects of OSAS will be discussed in this chapter. airway, such as old age, neuromuscular disorders,
structural abnormalities and adenotonsillar hypertro-
Introduction phy.

Obstructive Sleep Apnoea Syndrome (OSAS) is char- Incidence
acterized by disrupted fragmented sleep associated
with airflow obstruction which can lead to serious OSAS occurs in about 4% of middle-aged men and
life threatening consequences if not managed ad- 2% of women [2] and over the past two decades there
equately. has been an increase in prevalence of OSAS [3] and
a subsequent explosion in research about the ep-
Along with the related international epidemic of obe- idemiology, aetiology, diagnosis, management and
sity, prognosis of patients with OSAS.

OSAS has become increasingly relevant to the health Despite the increasing incidence of OSAS, Sia et.al.
and well being of adults and children worldwide. has shown that awareness and knowledge of OSA
among the general population in Singapore is poor
Benign Snoring, Upper Airway Resistance Syndrome [4]. Therefore ongoing health education should have
(UARS) and Obstructive Sleep Apnoea Syndrome OSAS issues included in the campaigns.
(OSAS)
There is a paucity of Indian studies in OSAS preva-
Definition lence, but Singh et al [5] looked at 1512 subjects in
Lucknow and found and that 6.2% were found to be
Noisy breathing due to obstruction of the upper air- high risk of OSAS and 12.2% were obese.
way develops in a progressive stepwise manner. As
the obstruction starts to develop (e.g. due to deposi- Screening
tion of fat in the pharynx) the individual may manifest
benign primary snoring which is noisy but is not dis-

Cardio Diabetes Medicine

216 Obstructive Sleep Apnoea Syndrome
and Cardio Metabolic Risk

Because of the consequences of OSAS, the issue predictor for OSAS.
of screening for OSAS in asymptomatic patients has
been assessed by Shafazand [6] and he concluded The role of ICT
that there is insufficient evidence for this to be rou-
tinely done. New developments in technology have been incor-
porated in the diagnosis and management of OSAS.
Diagnostic tools
Koo et.al [14] have investigated the usefulness of re-
In symptomatic patients, the Epworth sleepiness cording snoring sounds with the smartphone which
score has been traditionally used. are then analysed acoustically to determine the site
of obstruction in OSAS. It was found that retropala-
The STOP-Bang questionnaire [7] tool can also be tal level of obstruction tended to produce sharp and
applied as a reliable, concise and easy-to-use tool. regular peaks while retrolingual obstruction tended to
Snoring, Tiredness, Observed apnoea, high BP, BMI, show peaks with a gradual onset and decay. Acous-
Age, Neck circumference and male Gender are the tic analysis is non-invasive and can be applied at a
parameters assessed. relatively low cost.

Prudon et.al. used a novel postal –based approach to Coma-del-Coral et al [15] have assessed the reliabili-
diagnose OSAS in a high-risk patients. [8]. Patients ty of telemedicine in the diagnosis and treatment of
who interested in participating in the study were sent OSAS. Forty patients were studied from a population
a four-channel device (Apnea Link [AL}, ResMed, UK) 80km away using respiratory polygraphy transmitted
via the post with pictorial and written instructions. in real time. The level of compliance with the resultant
Following a single night study the AL device was re- CPAP treatment in a conventional clinic was 85% and
turned via a freepost service. 75% of the studies could 75% in those seen by teleconsultation suggesting
be analyzed, suggesting that this approach may be that is a useful application.
useful in clinic practice, avoiding clinic attendance.
CPAP is the most commonly used option for OSAS,
Full PSG testing can sometimes be economically and however it is not always clear how compliant is the
logistically difficult and Chai-Coetzer & McEvoy have patient. There was evaluation of the add-on NOWAPI
concluded that simplified cardiorespiratory sleep medical device for remote monitoring of compliance
tests are a reliable, cost-saving option for diagnos- to CPAP and treatment efficacy in OSA [16].
ing OSAS. [9]
The findings suggest that the NOWAPI estimate of
Biomarkers in OSAS CPAP treatment was clinically accurate and in agree-
ment with polygraphy.
Kheerandish-Gazal & Gozal [10] have given a succinct
overview of morbidity biomarkers that have been Phenotyping of OSAS
identified in Paediatric OSAS which would circum-
vent labour-intensive and onerous steps in diagnos- OSAS is a complex disease and Zinchuk et al [17]
ing OSAS and its morbidities. have made a case for enhanced phenotyping. The
OSA phenotype can be defined as “ A category of
Erdim et.al [11] found that the Mean platelet volume patients with OSA distinguished from others by a sin-
(MPV), neutrophil-to-lymphocyte (NLR) and plate- gle or combination of disease features, in relation to
let-to-lymphocyte ratio (PLR) were significantly high- clinically meaningful attributes (symptoms, response
er in children whose AHI was >5 than in children in to therapy, health outcomes, quality of life)”. Better
other groups. phenotyping improve can many aspects of diagnosis,
understanding of the pathophysiology and personal-
Li et al [12] have done a meta-analysis on CRP lev- ization of treatment for OSAS patients.
els and found that the level in the OSAS group was
1.98mmol/l higher than in the control group. This find- The use of Network science and applying it to respi-
ing is consistent with the inflammatory component of ratory medicine can lead to improved OSAS pheno-
OSAS and supports the role of CRP as a biomarker typing and severity prediction according to Mihaicuta
in this disease. et al [18]

Atan et al [13] looked at 336 patients and the Mono- Pathophysiology & Complications of OSAS
cyte to HDL Ratio (MHR) was assessed and com-
pared between the OSAS subjects and controls. It OSAS has a deleterious effect on almost all aspects
was found that MHR was significantly higher in pa- of life, including cardio-metabolic complications
tients with OSAS and can possibly be a new, useful which can be life threatening.

GCDC 2017

Cardio Diabetes Medicine 2017 217

The pathogenesis of OSAS-related consequences in patients with OSAS.
is assumed to be chronic intermittent hypoxia (IH)
inducing alterations at the molecular level, oxidative Pusuroglu et al [26] have shown that Galectin-3 is
stress, persistent systemic inflammation, oxygen associated with coronary plaque burden & OSAS se-
sensor activation and increase sympathetic activity verity. Galectin-3 is a chemical that plays an import-
[19]. ant role in the regulation of inflammation, develop-
ment of cardiac fibrosis and remodeling. The mean
New research is coming to fore about the mecha- Galectin-3 level was significantly higher with OSAS
nisms and effects of OSAS: patients compared to controls.

Pathophysiology There has been a meta-analysis of OSAS on cardio-
vascular events after percutaneous coronary inter-
May et al [20] looked at the mechanistic insights at vention [27], which revealed that OSAS could inde-
the production of cardiac arrhythmogenesis in OSAS. pendently increase the risk of cardiovascular events.
Abnormal sympathetic and parasympathetic fluctu-
ations, intermittent hypoxia and hypercapnia and There have been many other studies on OSAS and its
structural changes such as ventricular hypertrophy association with the cardiovascular system:
and fibrosis all play a part in the generation of car-
diac arrhythmia. -- OSAS was common in peripheral arterial disease
(PAD ) and the OSAS severity correlated with PAD
An et al [21] has strong evidence that microR- severity [28]
NA-130a (miR-130A) may be involved in the progres-
sion of OSAS-associated pulmonary hypertension by -- OSAS is associated with increased readmission
down-regulating the GAX gene. in heart failure [29]. Sommerfield et al looked at
344 patient encounters and found that heart fail-
Chen et al [22] concluded that the Oestrogen/ERR-al- ure patients with OSAS have an elevated rate of
phaa signaling axis is associated with fiber-type readmission compare to the general heart failure
conversion of upper airway muscles in patients with population.
OSAS. This finding may represent an interesting ther-
apeutic target , especially in postmenopausal women. -- Effects of OSAS on the response to hypertension
therapy [30] . Because of the sympathetic over-
According to Chen et.al [23] there is an apparent activity in OSAS, Beta1 blocker therapy may be
correlation between systemic inflammation and cere- required in these patients with resistant hyperten-
bral perfusion in OSAS because of haemodynamic sion.
alterations. [23]
-- Stroke and other cardiovascular events are more
Cardio Metabolic Complications common in patients with OSAS [31]. In this study,
1100 individuals were studied and it was found
Epidemiological studies have documented the host that cardiovascular events were significantly high-
of cardiometabolic effects of OSAS including arterial er with increasing OSAS severity and untreated
and/or pulmonary hypertension, arrhythmias, isch- OSAS patients had more cardiac events
aemic heart disease, diabetes mellitus and metabolic
syndrome. Over the past few years there have been -- Occurrence of OSAS in patients with TIA [32].
many new findings about the effects of OSAS on the It was found that there was a significant higher
cardiometabolic system. occurrence of OSAS in TIA patients compared to
patients without a vascular diagnosis.
Ruchala et al [24] suggests that bony and endo-
crine abnormalities that occur in OSAS lead to seri- -- The Pulmonary Artery Stiffness in patients with
ous consequences. The sex hormones, aldosterone, OSAS was evaluated in 52 patients. [33] . It was
insulin, prolactin and corticosteroids, are all affected found that the elastic properties of the pulmonary
in OSAS. artery deteriorate with severity of OSAS and may
be responsible for right ventricular dysfunction in
There is also some evidence of haematological mark- OSAS.
ers as predictors of cardiovascular disease in OSAS,
according to Saygin et al [25] . In a study containing -- Sommer field et al [34] showed that heart failure
142 patients, it was found that red cell distribution patients with OSAS have an elevated rate of read-
width (RDW), could be used with other markers, espe- mission particularly within the first 90 days after
cially other markers platelet count and platelet distri- discharge.
bution width, in prediction of cardiovascular disease

Cardio Diabetes Medicine

218 Obstructive Sleep Apnoea Syndrome
and Cardio Metabolic Risk

Management -- The continuum of Benign snoring, UARS and
OSAS need to be clarified .
Conservative
-- Early diagnosis and intervention is important in the
The fundamentals of weight loss are still applicable management of OSAS.
and CPAP is still the most widely used treatment for
OSAS. -- OSAS has significant effects on the Cardio-Meta-
bolic system which can be life threatening.
Hibbert & Yaggi [35] have advocated patient centred
care in OSAS. OSAS patients are diverse and may -- Bariatric surgery is emerging to be an important
have different needs, preferences and values that modality of management for OSAS.
may impact on optimal treatment.
References
There is some evidence that bed elevation [36] and
oropharyngeal exercises [37] can have a beneficial 1. Pépin JL, Guillot M, Tamisier R, Lévy P. The upper airway resistance syn-
effect on OSAS. drome. Respiration. 2012;83(6):559-66.

A systematic review & meta-analysis on the useful- 2. Hukins CA. Obstructive sleep apnea - management update. Neuropsychi-
ness of tongue-retaining devices for OSA [38] was atr Dis Treat. 2006 Sep;2(3):309-26.
conducted and it was found that these devices re-
duce apnoea-hypopnoea index by 53%, decrease ox- 3. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. In-
ygen desaturation index by 56% and decrease the
Epworth sleepiness scale by 2.8 points. creased prevalence of sleep-disordered breathing in adults. Am J

Surgical Epidemiology 2013 May 1;177(9):1006-14.

Surgical modeling of the bony and soft tissues of 4. Sia CH , Hong Y, Tan LWL, van Dam RM , Lee CH , Tan A. Awareness
the upper airway is still widely done for OSAS in ap- and knowledge of obstructive sleep apnea among the general population.
propriate patients. Sleep Med. 2017 Aug;36:10-17.

However, it is clear that bariatric surgery has an im- 5. Singh A, Prasad R, Garg R, Kant S, Hosmane GB, Dubey A, Agarwal A, Ver-
portant role to play in OSAS . Over 500,000 cases of ma RK. A study to estimate prevalence and risk factors of Obstructive
bariatric surgery were described by de Raff et al [39] Sleep Apnoea Syndrome in a semi-urban Indian population. Monaldi Arch
with OSAS being present in 35%-94% of cases. Del Chest Dis. 2017 May 18;87(1):773.
Genio et al [40] clearly showed that sleeve gastrec-
tomy improves OSAS in appropriate patients. 6. Shafazand S. Guideline: Insufficient evidence exists on screening for  ob-
structive sleep apnea in asymptomatic adults. Ann Intern Med. 2017
Effects of treatment of OSA on Cardiovascular risk May 16;166(10):JC50.

It is clear that the management of OSAS has a very 7. Chung F, Abdullah HR, Liao P. STOP-Bang Questionnaire: A Practical Approach
beneficial effect on individual’s lives, there is still a to Screen for Obstructive Sleep Apnea. Chest 2016 Mar;149(3):631-8.
need for clear documentation if it reduces cardiovas-
cular risk. 8. Prudon B, Hughes J, West S. A novel postal-based approach to diagnos-
ing obstructive sleep apnoea in a high-risk population. Sleep Med. 2017
Gottlieb [41] (AD 8) suggests that it is too early to May;33:1-5.
say if cardiovascular risk is reduced by the treatment
of OSAS. However Schipper et al (AD 15) did a very 9. Chai –Coetzer CL, McEvoy RD. The Debate Should Now Be Over. Simpli-
interesting analysis and concluded that patients with fied Cardiorespiratory Sleep Tests are a Reliable, Cost-saving Option for Di-
OSAS who received CPAP had less cardiovascular agnosing Obstructive Sleep Apnea. Am J Respir Crit Care Med 2017 Jun 29.
events than those who are not treated.
10. Kheirandish-Gozal L, Gozal D. Pediatric OSA Syndrome Morbidity Biomark-
Conclusion ers: The Hunt Is Finally On! Chest 2017 Feb;151(2):500-506.

Obstructive sleep apnoea syndrome is common and 11. Erdim I, Erdur O, Oghan F, Mete F, Celik M. Blood count values and ratios
can have serious effects on the cardi-metabolic sys- for predicting sleep apnea in obese children. Int J Pediatr Otorhinolaryn-
tem of patients leading to significant morbity and gol. 2017 Jul;98:85-90.
mortality.
12. (12) Li K, Wei P, Qin Y, Wei Y. Is C-reactive protein a marker of ob-
BULLET POINTS: structive sleep apnea?: A meta-analysis. Medicine (Baltimore 2017
May;96(19):e6850.
-- OSAS is very common, but there is still little aware-
ness of it by the public. 13. Atan D, Kundi FCS, Özcan KM, Dere H. A New Predictor for Obstructive
Sleep Apnea Syndrome: Monocyte to HDL Ratio. Indian L Otolaryngol
Head Neck Surg 2017 Jun;69(2):142-146.

14. Koo SK, Kwon SB, Kim YJ, Moon JIS, Kim YJ, Jung SH. Acoustic analysis of
snoring sounds recorded with a smartphone according to obstruction site
in OSAS patients.Eur Arch Otorhinolaryngol. 2017 Mar;274(3):1735-1740.

15. Coma-Del-Corral MJ, Alonso-Álvarez ML, Allende M, Cordero J, Ordax
E, Masa F, Terán-Santos J. Reliability of telemedicine in the diagnosis
and treatment of sleep apnea syndrome. Telemed J E Health. 2013
Jan;19(1):7-12

16. Leger D, Elbaz M, Piednoir B, Carron A, Texereau J. Evaluation of the

GCDC 2017

Cardio Diabetes Medicine 2017 219

add-on NOWAPI® medical device for remote monitoring of compliance to
Continuous Positive Airway Pressure and treatment efficacy in obstructive
sleep apnea. Biomed Eng Online. 2016 Feb 27;15:26.
17. Zinchuk AV, Gentry MJ, Concato J, Yaggi HK. Phenotypes in obstructive
sleep apnea: A definition, examples and evolution of approaches
18. Sleep Med Rev. 2016 Oct 12. pii: S1087-0792(16)30103-4.
19. Mihaicuta S, Udrescu M, Topirceanu A, Udrescu L. Network science meets
respiratory medicine for OSAS phenotyping and severity prediction. eerJ.
2017 May 9;5:e3289.

Cardio Diabetes Medicine

220 Cardio Diabetes Medicine 2017

Pre Diabetes as Risk Factor for Coronary Artery
Disease & Peripheral Vascular Disease.

Dr. Arulprakash,

MD., MRCP(UK)., FRCP(Lon).,
Indra diabetes Centre, Tuticorin

Prevalence of Pre diabetes: with normal FPG.The relationship between 2hPG and
mortality was linear (Figure1).
Prevalence of diabetes, impaired fasting glucose
and insulin resistance syndrome in an urban Indian Figure 1. Hazard ratios and 95% confidence intervals (verti-
population (CUPS- Chennai Urban population study) cal bars) for CVD mortality for FPG (hatched bars) and 2hPG
showed higher incidences. The main findings of this (dotted bars) intervals using previously diagnosed DM (dark
study are: (1) incidence of diabetes in this urban bar) as the common reference category. Data are adjusted
south Indian population was 20.2 per 1,000 person for age, sex, cohort, body mass index, systolic blood pres-
years, (2) incidence of pre-diabetes was 13.1 per 1,000 sure, total cholesterol, and smoking.
person years, (3) incidence of diabetes among sub- Several studies showed that increasing HbA1c is
jects with IGT at baseline was higher compared to associated with increasing CVD risk. Studies that
those with NGT. Subjects with diabetes as well as IRS compared all three glycaemic parameters (FPG, 2hPG,
have greater prevalence of obesity, central obesity, and HbA1c) for mortality and CVD risk revealed that
hypertension, hypertriglyceridemia and low HDL as the association is strongest for 2hPG and that the
compared with normal subjects. The burden of dia- risk observed with FPG and HbA1c is not significant
betes and impaired glucose tolerance in India using after controlling for the effect of 2hPG.
the WHO 1999 criteria: prevalence of diabetes in In- Although impaired glucose tolerance patients with
dia study (PODIS) revealed standardized prevalence a PCI-treated coronary stenosis showed preserved
rate for DM in the total Indian, urban and rural pop- response to CPT(cold pressor test), the %increase
ulations was 4.3, 5.9 and 2.7%, respectively. The cor- negatively correlated with risk factors in the non-PCI
responding IGT rates in the three populations was segments. Therefore, coronary risk factors may af-
5.2, 6.3 and 3.7%, respectively. The urban prevalence fect CAD lesions in PCI-treated patients.The coronary
of DM and IGT was significantly greater than in the plaques in CAD patients are more vulnerable when
rural population (P < 0.001 in both instances). The having IGT compared to those with NGT, and similar
prevalence of DM was significantly, more than that to those with DM. This finding may explain the high
of IGT (P < 0.001) within both the rural and urban risk of cardiovascular events in CAD patients with
populations. IGT.

Pre-diabetes and cardiovascular disease: The most
convincing evidence that disorders of glucose me-
tabolism are risk factors for CVD was provided by
the European DECODE study. Increased mortality
was observed in DM and IGT but not in impaired
fasting glucose (IFG). A high 2hPG predicted all-cause
and CVD mortality after adjustment for other major
cardiovascular risk factors, while a high FPG alone
was not predictive, once 2hPG was taken into account.
The highest excess CVD mortality in the population
was observed in people with IGT, especially those

GCDC 2017

Pre Diabetes as Risk Factor for Coronary Artery Disease & 221
Peripheral Vascular Disease

Response to interventions References:

A 12-year follow-up of men with IGT who participat- 1. DeFronzo RA, Abdul-Ghani M. Assessment and treatment of cardiovascular
ed in the Malmö Feasibility Study revealed that all- risk in prediabetes: impaired glucose tolerance and impaired fasting glu-
cause mortality among men in the lifestyle interven- cose. Am J Cardiol2011;108(Suppl):3B-24B. 
tion group was lower (and similar to that in men with
normal glucose tolerance) than that among men who 2. Rydén L, Grant PJ, Anker SD, et al. Authors/Task Force Members ESC
had received ‘routine care’ (6.5 vs. 6.4 per 1000 per- Committee for Practice Guidelines (CPG) Document Reviewers. ESC
son-years at risk; P = 0.009). In the Chinese Da Qing Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed
study, participants with IGT in the 6-year lifestyle in collaboration with the EASD: the Task Force on diabetes, pre-diabetes,
intervention group had, 20 years later, a persistent and cardiovascular diseases of the European Society of Cardiology (ESC)
reduction in the incidence of T2DM and a non-sig- and developed in collaboration with the European Association for the Study
nificant 17% reduction in CVD death while the adjust- of Diabetes (EASD). Eur Heart J2013;34:3035-87.
ed incidence of severe retinopathy was 47% lower in
the intervention group. In the 10-year follow-up of the 3. Prevalence and risk factors of peripheral vascular disease in a selected
Finnish Diabetes Prevent on Study (DPS), total mor- South Indian population: the Chennai Urban Population Study.Diabetes
tality and CVD incidence were no different between Care. 2000 Sep;23(9):1295-300
the intervention and control groups, but the DPS
participants, who had IGT at baseline, had lower all- 4. Tapp RJ, Balkau B, Shaw JE, Valensi P, Cailleau M, Eschwege E. Asso-
cause mortality and CVD incidence compared with a ciation of glucose metabolism, smoking and cardiovascular risk factors
Finnish population-based cohort of people with IGT. with incident peripheral arterial disease: the DESIR study. Atherosclero-
sis. 2007;190(1):84–89.
Pre diabetes and Peripheral vascular disease:
5. Vonbank A, Saely CH, Rein P, Drexel H. Insulin resistance is significantly
Impaired fasting glucose and diabetes are common associated with the metabolic syndrome, but not with sonographically
in patients with PAD. PAD patients with non-medi- proven peripheral arterial disease. CardiovascDiabetol. 2013;12:106.
cated diabetes showed higher rates of mortality and
peripheral artery intervention compared to patients .
with normal fasting glucose. The exact reasons for
this remain unclear but, may reflect poor glycaemic
control compared to patients receiving oral hypogly-
caemics. Previous data suggest that poor diabetes
control, evidenced by high HbA1c concentrations, is
positively associated with major adverse events in
patients with established cardiovascular disease.  It
is relevant to note that PAD patients with impaired
fasting glucose had similar mortality and requirement
for peripheral artery intervention as patients with
normal fasting glucose in this study.

The prevalence of PVD in this urban South Indian
population is considerably lower than that reported in
European and U.S. studies and is in marked contrast
to the high prevalence rate of CAD reported in this
population. Although incidence of IGT is high in our
population it is not associated with increased prev-
alence of atherosclerotic peripheral arterial disease.

Prevalence of Pre diabetes in PAD

High prevalence of glucose intolerance in Japanese
patients with high cardiovascular risk found also high
PAD. The US PARTNERS program, designed to study
the prevalence of PAD and other cardiovascular dis-
eases, found a prevalence of PAD of 29% in individ-
uals aged > 70 or > 50 with comorbidities (diabetes,
IGT and smoking).

Cardio Diabetes Medicine

222 Cardio Diabetes Medicine 2017

Bradyarrhythmias

Dr. Kader Sahib

Consultant. Cardiologist, Trichy.

Definition:

It is important to know what defines a normal sinus
rhythm before we discuss bradyarrhythmia.

Criteria for normal sinus rhythm: Figure 1: sinus arrhythmia

1. P wave upright in Lead 1 Bradyarrhythmias can be classified into

2. P wave inverted in avR 1. Disorders of impulse formation
- Sinus bradycardia
3. Constant P-P cycles : that is the next P wave - Sinus arrest
should come in the next expected time
2. Disorders of impulse conduction
4. Constant P-R intervals - Sino atrial (SA) block
- Atrioventricular (AV) block
5. Constant R-R intervals
When the sinus node doesn’t produce impulses ad-
6. Rate between 60 – 100 /min equately, it is a sign of impaired impulse formation.
When the sinus node produces the impulse correct-
7. Any rhythm with a heart rate of < 60 / min is ly but the impulses get blocked in the specialized
called bradyarrhythmia. conduction system, it is a sign of impaired impulse
conduction.
Sinus arrhythmia: it is a physiological phenomenon
seen in young healthy persons. Heart rate quickens For practical purposes, let us discuss sinus brady-
for few beats and then slows (Fig 1). These fast and cardia (disorder of impulse formation) and atrioven-
slow cycles goes on. Heart rate is faster during in- tricular block (disorder of impulse conduction) in this
spiration due to decreased vagal tone. It is the com- chapter.
monest arrhythmia in children and doesn’t require
treatment.

Sinus arrhythmia is normal in children; when absent,
suspect atrial septal defect.

Sinus arrhythmia is abnormal in adults. When seen in
adults, we should suspect one of sick sinus syndrome
or digoxin toxicity or right coronary artery disease.

Disorder of impulse formation:

Sinus bradycardia: it is the commonest disorder of
impulse formation and the commonest cause for it
in clinical practice is secondary to drugs

GCDC 2017

Bradyarrhythmias 223

Figure 2: sinus bradycardia in the setting of acute Fig 4: sinus pause demonstrating no P wave inside
IWMI the pause
Causes of sinus bradycardia: AV node disease: If a P wave is seen inside the pause
• Sportsman, good physique and it is not followed by a QRS complex, it is due to
• Ageing, sleep an AV block. (fig 5 ). This implies that the sinus node
• Right coronary artery disease has produced its impulse, and the impulse has depo-
• Hypothyroidism larized the atrium (seen as P wave), but the impulse
• Electrolyte disturbances – hyperkalemia is not going to the ventricles and is getting blocked
• Drugs: digoxin, beta blockers, calcium channel in the conduction pathway. The commonest cause
for disordered impulse conduction is disease of the
blockers AV node.
• Increased intracranial tension
Fig 5: pause due to AV block in which there are P
Fig 3: rhythm strip demonstrating a pause in which waves inside the pause
there is no QRS complex Classification of AV blocks
First degree AV block: all P waves are conducted but
Disorder of impulse conduction: with delay
Second degree AV block: some of the P waves are
Atrioventricular block: atrioventricular block is sus- conducted, some are not conducted. So there is in-
pected whenever we have a pause. Pause is an area termittent interruption of conduction.
where there is no QRS. Absence of a QRS complex Third degree AV block: none of the P waves are con-
in the next expected time is called pause ducted. There is total AV dissociation. Atrial rate is
Pause can be due to a) sinus node disease or due faster than ventricular rate.
to 2) AV node disease. Special types:
Sinus node disease: there are no P waves inside the 2: 1 AV block
pause, implying that the sinus node itself is diseased High grade AV block
and hence has not produced the P wave (figure 4). Normal atrioventricular conduction timings:
Any sinus pause of > 2 seconds warrants treatment.

Cardio Diabetes Medicine

224 Cardio Diabetes Medicine 2017

Figure 6: normal atrioventricular conduction timing Etiology:

Time taken for the sinus impulse to reach the AV • AV node disease
node: 30 msec
• Enhanced vagal tone
Delay in the AV node: 130 msec
• Acute inferior wall MI
Time taken for the impulse to travel from the AV
node to ventricle: 30 msec. • Electrolyte disturbances

So, the total time taken for the sinus impulse to reach Drugs: ß blockers, Calcium channel blockers, cardiac
the ventricle, which roughly corresponds to the PR glycosides
interval is < 200 msec. (120-200 msec)
Risk stratification: every atrial impulse is conducted
The PR interval prolongation can be due to a) intra to the ventricles but with a delay. The delay is usually
atrial delay b) AV node delay or c) delay in the distal due to disease of the AV node. If the QRS width is
conduction system. However, a prolonged PR inter- narrow, the prognosis is generally good.(fig 8)
val is most often due to disease of the AV node. (AV
blocks) If the QRS width is wide, the patient has a potential
to develop advanced AV blocks and should be care-
Let us discuss AV blocks in detail. fully monitored.

First degree AV block Fig 8: first degree AV block accompanied by narrow
QRS complex
Diagnosis: all P waves are followed by QRS but with
delay. PR interval is prolonged (> 200 milliseconds)
and fixed.

Fig 7: ECG showing a prolonged PR interval Fig 9: first degree AV block accompanied by wide QRS
complex

GCDC 2017

Bradyarrhythmias 225

Second degree AV block: Risk stratification
Diagnosis:
Mobitz type 1: progressive lengthening of the PR in- Type 1:
terval until one P wave is totally blocked and produc-
es no QRS (fig 10).The associated QRS is typically • Disease is at the AV node
of normal duration. This is usually due to AV node
fatigue. After a pause during which the AV node re- • Usually benign and self-limiting
covers, this cycle is repeated. This is called Wencke-
bach’s phenomenon. • Unlikely to progress to complete heart block

Fig 10: progressive lengthening of PR interval followed • Usually associated with inferior wall MI
by a blocked P wave
Mobitz type 2: PR interval in the conducted beats is Type 2:
fixed but there is a sudden non conduction of a P
wave in the presence of constant and consecutive • Block occurs at the distal conducting system
conduction
• Indicates severe disease

• Progresses to complete heart block; patient may
have Stoke – Adams attacks because escape
rhythm is from the ventricle

• Requires active treatment including pacemaker

2: 1 AV block

When every other P wave is not conducted to the
ventricles, it is 2: 1 AV block. The block can be in
the AV node or in the HIS Purkinje system. Clue to
the site of block can be obtained by looking at the
width of the QRS complex. (if the block is in the HIS
Purkinje syst em, QRS is wide)

Fig 11: Mobitz type 2 AV block where there is a sudden Figure 12: 2:1 AV block demonstrating non conduction
non conduction of P wave of every 2nd P wave
High grade AV block:
Etiology The term high grade AV block is applied to a pattern
where ≥ 2 sinus P waves are blocked consecutively in
• Type 1 the context of periodic AV conduction (fig 13).

• Athletes Figure 13: high grade AV block showing non conduc-
tion of > 2 consecutive P waves
• Acute inferior wall MI Third degree AV block
Diagnosis
• Drugs like beta blockers, digoxin, calcium chan- • None of the P waves are conducted
nel blockers, amiodarone

• Myocarditis

• Post mitral valve surgery, TOF repair

Type 2

• Acute anterior wall MI

• Idiopathic fibrosis of the conducting system

• Inflammatory conditions (rheumatic fever, myo-
carditis)

• Autoimmune diseases

• Drugs like beta blockers, calcium channel block-
ers, digoxin

Cardio Diabetes Medicine

226 Cardio Diabetes Medicine 2017

• There is total AV dissociation Supra HIS Infra HIS

• Junctional or ventricular escape rhythm maintains Block at AV node Block at bundle branch-
life. es, fascicles

• P wave rate more than QRS rate Narrow QRS Wide QRS

Etiology Escape rate faster; 40 – Escape rate slow; < 40/

1. Acute coronary syndrome 60 /minute minute

2. Idiopathic degeneration of the conducting sys- Stable rhythm Unstable rhythm
tem
SA attacks uncommon SA attacks common
3. AV node blocking drugs (beta blockers, calcium
channel blockers, etc) Type I AV block pre- Type II AV block pre-

4. Congenital cedes it cedes it

Risk stratification Associated with IWMI Associated with AWMI

Patients with complete heart block are at risk of ven- Conservative approach Needs pacemaker defi-
tricular standstill and syncope or cardiac arrest.If the nitely
block is supra HIS, the escape rhythm is of narrow
QRS and has relatively better prognosis. Most of the Good prognosis Prognosis not so good
congenital complete heart blocks are of this type. In-
tervention is warranted if the patient is symptomatic Summary of AV blocks

Fig 14: third degree AV block with narrow QRS escape Indications for permanent pacemaker
rhythm -- Symptomatic sinus bradycardia
If the block is infra HIS, the escape rhythm is of wide -- Any sinus pause > 2 seconds with symptoms
QRS and has bad prognosis warranting early inter- -- Identification of distal blocks (infra HIS) which are
vention (fig 15)
likely to produce to for Stoke’s Adam attack
Fig 15: third degree AV block with wide QRS escape -- First degree AV block with bundle branch block
rhythm -- Mobitz type 2 second degree AV block
-- 2:1 AV block
-- High grade AV block
-- Infra His complete heart block
Suggested reading:-

1. ECG Course - an interactive multimedia tutorial” by Dr.M.Chenniappan;
CD released by ECG and ECHO club of Trichy

2. Leo Schamroth ; an introduction to electrocardiography, 8th edition
3. Marriott’s practical electrocardiography; 12th edition

GCDC 2017

Cardio Diabetes Medicine 2017 227

Congestive Heart Failure in Diabetic...!
How it is Different?

Dr. Dhanushkodi, MD.,

TUTICORIN

ABSTRACT increased the risk for the other.(4) Patients with ad-
vanced CHF show marked insulin resistance a condi-
The prevalence of congestive heart failure in diabe- tion associated with an increased risk of developing
tes mellitus is growing exponentially compared to Type 2 DM compared to normal individual or patients
those patients without diabetes mellitus, patients of with coronary artery disease (CAD)
congestive heart failure with diabetes mellitus shows
specific metabolic, neurohumeral and structural heart EPIDEMIOLOGY
abnormalities
The prevalence of patients with both CHF and DM
Subgroup analysis of recent trials suggested that pa- in the general population is estimated at 0-5% in
tients of congestive heart failure with diabetes mel- men and 0.4% in women. CHF afflicts 1-2% of the
litus may respond difficulty to standard therapy and general population rising to >5-10% in subjects aged
data are emerging on the possible increase in the risk >65years whereas the prevalence of DM worldwide
visit of hospitalizations., when treated with specific is estimated at 5-6% (5) and it is predicted to increase
class of antidiabetic agents pointing to the need of to >8% of the adult population by 2030 (6)
developing specific medications to be tested in the
near future studies. The prevalence of both diseases is increasing world-
wide with the aging of the general population 1.5 to
INTRODUCTION 2% of individuals over the age of 65 have both CHF
and DM and the prevalence is expected to grow ex-
CHF is one of the most common reasons for hospital ponentially in the next decates.(7)
admission in those aged 65 and over with conse-
quent high costs for the health care system. (8) In addition these prevalence figures tend to under-
estimate the true impact as they do not adequately
“Despite improvements in the treatment of patients account for undiagnosed, CHF in patients with pre-
with chronic HF with reduced EF, the survival of the served ejection fraction (EF) or impaired fasting glu-
patients hospitalized form CHF remains poor, with cose (4)
one year mortality of 30% and 5-year mortality up to
50%. Approximately 40% of patients hospitalized with There are now emerging data that congestive heart
CHD and reduced ejection fraction (EF) have DM.”(1) failure with preserved ejection fracture (HFpEF) also
DM is one of the non cardiac co-morbidities associ- presents with multiple phenotypes including meta-
ated with notably higher risks for both all causes and bolic abnormalities and coronary microvascular in-
HT related preventable hospitalizations(9) and re-hos- flammation likewise HFpEF similar to heart failure
pitalization(10) with reduced ejection fraction is strongly associat-
ed with diabetes mellitus Compared to non-diabetic
In patients with DM the prevalence of CHF is be- HFpEF patients, diabetic HFpEF patients tend to be
tween 9-22% which is 4 times higher than the gen- younger, more obese, more likely hypertensive, have
eral population (11) and DM is a risk factor for CHF more renal function impairment and more vascular
development specially in women (5-fold) compared disease. HFpEF patients with diabetes have more
to, men (2-4fold)(12). The relationship between DM and left ventricular hypertrophy, a trend towards higher
CHF is bidirectional with each disease independently

Cardio Diabetes Medicine