22sep

Cardio Diabetes Medicine 2018 248

a health system”.   the arachidonic acid-prostacyclin pathway,

Function of platelets  the L-arginine nitric oxide pathway, and

In the year 1963, Born and Cross 1 published a  the endothelial ectoadenosine diphosphate
study on platelet aggregation in the Journal of (Ecto-ADPase) route2, 3.
Physiology. The study of platelet function in the
coagulation was started consistently.  Currently, Endothelial cells convert arachidonic acid into
this function is of great importance in the patho- prostacyclins by action of cyclooxygenase 1
physiology of coronary syndromes. (COX1), cyclooxygenase 2 (COX2) and prosta-
cyclin synthetase.  Prostacyclins inhibit platelet
Platelets adhere, activate and aggregate on a function, raising levels of intracellular cyclic ade-
rotating atherosclerotic plaque, or on the injured nosine monophosphate (AMP) 2, 3.
endothelium, contributing significantly to the for-
mation of thrombi within the coronary arteries, Nitric oxide, diffused within the platelets, stim-
which may totally or partially obstruct these ves- ulates the production of guanosine monophos-
sels. phate, causing a decrease in the flow of intracel-
lular calcium.  Such calcium reduction modifies
Initially, the platelets adhere to the extracellu- the glycoprotein IIb / IIIa conformation, allowing
lar matrix, being this adhesion mediated by the the formation of fibrinogen bridges and platelet
glycoproteins Ib, V, IX, with the von Willebrand aggregation 2, 3.
factor as the major ligand. It is important to note
that glycoproteins VI and Ia, important collagen Ecto-ADPase limits the plasma level of nucle-
receptors, also play a relevant role in platelet ad- otides.  The activity of this enzyme cancels the
hesion2. critical phase of recruitment of platelet reactivity,
as it removes the nucleotides from the fluid en-
Upon adhesion, ADP, thrombin, epinephrine and vironment 2.
thromboxane A2 (TXA2) amplify the mechanism
& recruit more circulating platelets, which con- Platelet aggregation
tribute to thrombus formation 2, 3.
Blockade of platelet aggregation is considered
At this time, platelets activate and secrete a an effective strategy in the prevention and treat-
number of substances, such as: ADP, serotonin, ment of cardiovascular events due to atheroscle-
fibrinogen, von Willebrand factor, fibronectin, rotic disease.
growth factors (platelet-derived growth factors,
alpha growth factor, and beta growth factor), pro- The search for therapeutic strategies capable of
coagulants (platelet factor 4 and factor V) and blocking platelet aggregation in patients with ath-
TXA23. erosclerotic disease, in order to reduce the oc-
currence of clinical events, has been the target
Another relevant event for thrombus formation is of several studies.
platelet aggregation, that is, the binding of one
platelet to another. The final pathway for platelet Aspirin, because of its inhibition of cyclooxygen-
aggregation is the glycoprotein IIb / IIIa receptor, ase 1, which prevents the formation of thrombox-
which is also the main receptor for adhesion. Fi- ane A2, is considered an excellent antiplatelet
brinogen, for stabilizing the platelet thrombus drug.
and serving as a bridge between platelets, also
plays an important role in this process2, 3. The effectiveness of aspirin in the prevention of
cardiovascular events was demonstrated by a
Vascular endothelium controls platelet reactivity meta-analysis that evaluated 287 studies with
through three main mechanisms: more than 200 thousand patients and revealed
a 22% reduction in deaths and ischemic vascu-

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lar events in the group of patients taking aspirin, Patients who are “resistant” to aspirin are at
when compared to those did not take this med- greater risk of clinically important adverse car-
ication. diovascular events, regardless of the assay
used to measure aspirin resistance. Patients
American, European and Brazilian guidelines who were classified as aspirin resistant were at
recommend the use of acetylsalicylic acid (ASA) about a fourfold increased risk of non-fatal and
in the treatment of patients with atherosclerotic fatal cardiovascular, cerebrovascular, or vascu-
disease and as a preventive measure of future lar events while taking aspirin than their aspirin
events. sensitive counterparts.

However, clinical studies have shown that pa- The concept of aspirin resistance has been debat-
tients taking aspirin regularly had cardiovascu- ed since the 1980s, but discussions in the recent
lar events. This finding led to a questioning: if, in literature have focused on reasons why aspirin
some patients, aspirin was not effective in block- resistance is probably a misnomer, and to which
ing platelet aggregation, these patients were de- little clinical relevance can be attached.  More
nominated nonresponsive or resistant to aspirin. recently, however, interest has been renewed in
aspirin resistance, which has focused primarily
Resistance to aspirin on identifying the platelet related assay that best
reflects the phenomenon. To date this issue has
The finding of the occurrence of cardiovascular not been resolved. Few studies have tackled the
events in patients taking aspirin represented the matter of aspirin resistance and its impact on
basis for the emergence of the concept of resis- clinical outcome.
tance to aspirin, a resistance that may be clinical
or laboratory 4, 5.

Although there is no consensus definition, There is no standard laboratory test that can be
used as an ideal test for the assessment of plate-
o clinical resistance to aspirin is consid- let antiaggregation determined by aspirin.

ered to be the occurrence of cardiovascular Laboratory tests used to assess the action of as-
events in patients under treatment with aspi- pirin on platelets evaluate the function ( in vivo )
rin, with a prevalence of 5% to 45% 4, while, and platelet aggregation ( ex vivo )  .

o laboratory resistance is defined as ab- The main tests to evaluate the action of aspirin
on platelet function are: urinary level of TXB2,
sence of aspirin’s effect to produce an antic- quantification of the expression of P selectin and
ipated effect on one or more tests of platelet P selectin soluble. 
function, such as
The main tests that evaluate the action of aspi-
• inhibiting the biosynthesis of thromboxane, rin in platelet aggregation are: optic platelet ag-
gregation test (AOAP), platelet function analyzer
• inhibiting platelet aggregation, and (AFP), aspirin rapid test of action (VRAA) and
thromboelastogram 5.
• causing a prolongation of the bleeding time,
Tests that evaluate the action of aspirin may
documented by laboratory test (in patients tak- or may not be specific for COX1. Specifics use
ing aspirin regularly), with a prevalence of 5% to arachidonic acid as a stimulator of platelet ag-
60% 5. gregation, or dosage the metabolites of TBX2
(P selectin) in the urine or blood. Non-specifics
This has been called biochemical aspirin resis-
tance, although the tests are not all truly bio-
chemical in nature.

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Cardio Diabetes Medicine 2018 250

use collagen, ADP or epinephrine as inducers of tylsalicylic acid and the recommendations that
platelet aggregation. doctors give to their patients, a considerable
number of them do not take this drug adequately
In the optical evaluation of platelet aggregation, and regularly or it is not adherent after some time
a sample of blood in citrate is centrifuged and of use(non-compliance).  
two plasmas are obtained: one, rich in plate-
lets(PRP), and another, poor. Then, the platelet Smoking, according to some authors, would in-
aggregation stimulants arachidonic acid, ADP crease platelet activation, accentuating platelet
and collagen are added. From the comparative thrombus formation.  However, the scientific in-
analysis of color change of platelet-rich plasma, formation does not consistently support this hy-
aggregation is assessed. pothesis.

Resistance is defined as a change of coloration> Regarding the pharmacodynamics of ASA, it is
20% with AA, or> 70% with ADP or collagen. believed that, in certain patients, the antiaggre-
gant effect is dose dependent;  that the longer
In the platelet function analyzer, whole blood duration of therapy reduces the antiaggregant
passes through an orifice that contains a thin potency;  and that non-hormonal anti-inflamma-
membrane coated with collagen and epineph- tory attenuate the long-term effect of aspirin on
rine. The occlusion time of the orifice, which oc- platelets.
curs by platelet aggregation, is used to evaluate
platelet aggregation. Some patients have COX2-induced TXA2 gen-
eration, or from new COX1 formation of macro-
In the rapid test of aspirin action, whole blood phages or endothelial cells.  Platelet activation
is placed in a tube, which contains a mem- may also occur through other pathways, such
brane coated with fibrinogen and arachidonic as: increased sensitivity to collagen, which also
acid. Platelet function is assessed by the platelet increases platelet adhesion, and failure to inhibit
binding to fibrinogen, and resistance to aspirin platelet activation mediated by catecholamine,
is considered to be the occurrence of more than or by mechanisms not mediated by TXA2.
550 reaction units.
Certain isoprostanes (similar to prostaglandins)
In the thromboelastogram, reptilase, factor VII, are produced from arachidonic acid or lipid per
heparin and arachidonic acid are added to the oxidation and possibly have properties similar to
whole blood.  In this examination, the throm- TXA2, which may stimulate platelet aggregation.
boelastogram of the intrinsic and extrinsic path-
ways is initially evaluated, and when the fibrin The increase in the expression of the platelet
thromboelastogram (altered clot formation time) membrane CD40 ligand possibly represents a
is altered; the fibrin thromboelastogram should new pathway of platelet aggregation and may be
be evaluated. The abnormality of thromboembo- associated with the activation of platelet aggre-
lagoglases indicates a quantitative or qualitative gation in situations of vascular inflammation.
change in platelets.
Genetic mutations or polymorphisms of COX1
Mechanisms of inadequate platelet an- genes and gene polymorphisms encoding glyco-
tiaggregation in patients taking aspirin proteins IIb / IIIa represent genetic mechanisms
of resistance to ASA.
The causes for inadequate platelet antiaggrega-
tion in patients taking aspirin are clinical, phar- Clinical impact of laboratory resis-
macodynamic, biological and genetic. tance to aspirin

It is known that, despite the prescription of ace- As we have already mentioned, although there is

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Cardio Diabetes Medicine 2018 251

no ideal, standard and single laboratory test for • Future studies, with standardization of the lab-
assessing the action of ASA on platelet aggrega- oratory tests used and the clinical outcomes
tion, several studies have evaluated the clinical and greater number of patients, will contribute
implications of laboratory resistance to ASA, ac- to a better knowledge of the phenomenon of
cording to the available laboratory tests . resistance to aspirin.

The prevalence of laboratory resistance to aspi- • Physicians should be aware of potential in-
rin was 27.4%. Patients resistant to ASA, when teractions with concurrently (self) prescribed
compared to nonresistant, had 4.37 times plus drugs that may limit the desired pharmacody-
ischemic clinical events;  2.43 plus reocclusion namic effect of aspirin.
of the treated artery; 3.11 plus myonecrosis; and
3.78 plus clinical events. • Given the multifactorial nature of atherothrom-
bosis, it is not surprising that vascular events
Krasopoulos et al. 6 recently published a meta- can occur while on aspirin therapy (in fact the
analysis that included 20 studies evaluating the opposite would be surprising) as they occur
action of ASA on platelet aggregation, according while on clopidogrel or on statin therapy.
to laboratory tests.
References
The prevalence of aspirin resistance was lower
in men when compared to women, and higher in 1 Born GVR, Cross MJ. The aggregation of
patients with chronic kidney disease. platelets. J Physiol. 1963; 168: 178-95. 

The various studies support the concept that, al- 2 David G, Patron C. Platelet activation and ath-
though there is no single standard method used erothrombosis. N Engl J Med. 2007; 357: 2482-
to diagnose laboratory resistance to aspirin, pa- 94. 
tients who have such resistance, according to
laboratory tests, are at a higher risk for cardio- 3 Konkle BA, Simon D, Schafer A. Hemostasis,
vascular ischemic events including death. thrombosis, fibrinolysis, and cardiovascular dis-
ease. In: Libby P, Bonow RO, Mann DL, Zipes
BULLET POINTS: DP (eds). Braunwald’s heart disease: a textbook
of cardiovascular medicine. (8th ed.). Philadel-
• It is an undeniable fact that certain patients phia: Saunders Elsevier; 2008. p. 2049-78. 
taking aspirin present a recurrence of cardio-
vascular events. 4. Akay OM, Canturk Z, Akin E, Bal C, Gulbas
Z. Aspirin-resistance frequency: a prospective
• These patients have been called resistant study in 280 healthy Turkish volunteers. Clin
or nonresponsive to aspirin, and the mecha- Appl Thromb Hesmost. 2009; 15 (1): 98-102
nisms responsible for this resistance are mul-
tifactorial. 5. Shenkman B, Matetsky S, Feper P, Hod H,
Einav Y, Lubestky A, et al. Variable responsive-
• There is no accepted laboratory test to evalu- ness to clopidogrel and aspirin among patients
ate the action of acetylsalicylic acid on plate- with acute coronary syndrome as assessed by
let aggregation. There was also no uniformity platelet functions tests. Thromb Res. 2008; 122:
in the tests used for the diagnosis of ASA re- 336-45. 
sistance in studies with clinical endpoints.
6. Krasopoulos G, Brister SJ, Beattie WS, Elliot
• However, patients who are resistant to ASA, RF, Buchanan MR. Aspirin resistance and risk of
according to laboratory tests available for use, cardiovascular morbidity: systematic review and
have a higher occurrence of cardiovascular mata-analysis. BMJ. 2008; 336: 195-8. 
events when compared to nonresistant ones.
 

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DIABETIC DYSRHYTHMIAS

Dr Ulhas Pandurangi

Chief: Dept of Cardiac Electrophysiology and Pacing
Arrhythmia-Heart Failure Academy
Madras Medical Mission

Abstract common in DM. The implanted devices are more
prone for infections.
Diabetes mellitus (DM) is the leading cause of
cardiovascular diseases. It is one of the stron- Introduction
gest and independent risk factors for cardiovas-
cular morbidity and mortality. The accelerated DM is recognized as a major cardiovascular risk
atherosclerosis in large arteries and typically in factor and its close relationship with cardiovas-
coronary arteries lead to ischemic heart disease cular morbidity and mortality is well established1.
(IHD) at an early age with more severe sequel. Although coronary artery disease and related
Metabolic abnormalities may lead to cardiomy- cardiac events are the most documented diabet-
opathy. The increased prevalence of IHD and ic cardiovascular complications, cardiac electri-
cardiomyopathy leads to increased incidence of cal system is also an important target for diabetic
cardiac arrhythmias especially atrial fibrillation damage. DM is established as an independent
(AF) and ventricular tachyarrhythmia (VA). Dia- risk factor for AF, VA, SCD and bradyarrhyth-
betic cardiac autonomic neuropathy (DCAN) is mias. There has been growing evidence about
increasingly recognised as the cause of more the relationship between hypoglycaemic epi-
frequent paroxysmal AF episodes and their con- sodes and ventricular rhythm disorders. The re-
version into persistent forms. The increased in- lationship between DM and arrhythmic disorders
cidence of sudden cardiac death (SCD) due to is not fully understood. This article is on overview
VA is attributed to a large extent to DCAN. The of etiopathogenesis and management diabetic
increased susceptibility to postural hypotension dysrhythmias.
and syncopal episodes are the result of DCAN.
The tolerance level of DCAN patients specifically Diabetes and AF
and DM patients in general towards the episodes
of more common regular supraventricular tachy- AF is the most common arrhythmia in clinical
cardias may be lower. Acute changes in meta- practice resulting in major cardiovascular mor-
bolic profile during ketoacidosis episodes might bidity and mortality6. Earlier The Framingham
trigger arrhythmias. Study and recently a study from Movahed et al7
clearly established that DM is a powerful and
In the absence of specific therapy for diabetic independent risk factor for the development of
dysrhythmias general measures including antiar- AF. Although there is no single and easy expla-
rhythmic drugs, radio frequency ablation (RFA) nation, the electrical and anatomical remodelling
and devices such as pacemakers and defibril- atria and increasing incidence of IHD and cardio-
lators are empirically used. Hypoglycaemia can myopathy in DM seem to be reasons for AF.
be a potential trigger for arrhythmias and sugar
control needs meticulous monitoring. Sinus node Fibrosis in the atrial tissue is the anatomical
dysfunction and degeneration of conduction sys- hallmark of AF with a role in both starting and
tem leading to symptomatic bradycardia is more perpetuation of the arrhythmia and as the fibro-
sis expands it is more likely that paroxysmal AF

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transforms into permanent or anti arrhythmic re- correlation between glucose levels, insulin lev-
sistant type. Kato et al showed that DM related els, HbA1c levels and AF onset in DM patients.
atrial fibrosis has a potential role in starting AF in Fatemi et al prospectively evaluated the affect of
diabetic rat models. Exaggerated systemic and intense glycemic control on incidence of AF in di-
tissue level oxidative stress seems to be the key abetic patients. Interestingly, they failed to pres-
element in atrial fibrosis related to DM. ent any association between incident AF and
intense therapy comparing to standard therapy
Non­enzymatic glycosylation of proteins and the group. However, their choice of periodic electro-
end products of this pathway (Advanced Glyca- cardiographic testing instead of event recorders
tion End products; AGEs) interact with their re- might alter the results in terms of missing the
ceptors (RAGE) and upregulate the connective paroxysmal AF episodes occurring any time be-
tissue growth factor (CGTF). This system (AG- sides the time of ECG taken in the clinic.
ERAGE) may start or contribute to atrial fibrosis Overall, DM seems to be acting a pivotal role in
in diabetic patients via stimulation of connective generation and maintenance of AF in diabetic
tissue growth factor in the atrial myocardium. patients. Specific structural, electrical and elec-
tromechanical alterations in diabetic heart might
Several clinical and electrophysiological studies create fertile substrate for the development of
have demonstrated DCAN to play significant role AF. On the other hand, acute hypo or hypergly-
in the genesis of AF. cemia changes in electrolyte levels or acid­base
status and autonomic system distortions may be
Atrial electrical structure is also affected in dia- trigger mechanisms for the arrhythmia (Figure
betic patients. Shortened atrial effective refracto- 1). It is clear that there are still knowledge gaps
ry period (AERP), increased dispersion of AERP, about the relationship between AF and DM that
inter and intra atrial conduction time, which are warrant further studies.
the key elements of atrial electrical remodelling
have been documented. Chao et al11 analyzed Figure 1 Potential pathophysiological
the detailed three­dimensional electro anatomic mechanisms of atrial fibrillation in DM
mapping of 228 patients who has DM or abnor-
mal glucose metabolism (AGM) and underwent
AF ablation for the first time. Results showed
that biatrial voltage measurements in DM and
AGM group were significantly lower than control
group. Furthermore these patients also had in-
creased recurrence rate of AF in the follow up
period. The relationship between the degree of
control of hyperglycaemia and the incidence of
AF is not clear. While fluctuations in the blood
glucose level rather than the long-term hypergly-
cemic environment has been implicated for the
increase in the incidence of AF in diabetic pa-
tients another clinical study failed to show any

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Cardio Diabetes Medicine 2018 254

Diabetes and ventricular arrhythmias

Figure 2: Mechanisms of ventricular arrhythmias in DM
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Cardio Diabetes Medicine 2018 255

Diabetes and complete heart blocks: factors. In a paper studying the prevalence of
diabetes in elderly patients requiring permanent
Bundle branch blocks (BBBs) are common con- cardiac pacemaker insertion, there were more
duction abnormalities in the population. By an- number of diabetic population (11.1%). DM con-
alysing 14,500 ECGs, Movahed et al. found a ferred an excessive risk of 1.34 (p<0.01) for per-
high prevalence of bifascicular block (37.5%) in manent pacemaker implantation in the elderly.
DM patients. Although the prevalence of LBBB In a study of the adult individuals with DM (2006
was not increased in DM patients, the presence patients), age-adjusted CKD prevalence was
of LBBB in DM signifies advance cardiovascu- 38.3% during 2007–2012. In patients with chron-
lar disease in this population. A higher mortality ic kidney disease with a pacemaker, higher mor-
rate in patients with BBB has been found in the tality rates were observed compared with end
Framingham study. Whether or not the presence stage renal disease patients without pacemaker.
of BBB in DM contributes to the increased risk of In 2778 patients who were on renal replacement
sudden death in this population requires further therapy (RRT), 110 had a pacemaker implant-
investigation. ed. Mortality was higher in the pacemaker group
The prevalence of high-degree atrioventricular averaging 24.3 deaths per 100 patient-years
(AV) block in DM patients appears to be signifi- versus 14.9 deaths per 100 patient-years in the
cantly higher than that of the normal population. RRT population without pacemaker.
Podlaha et al.studied 258 patients with pace-
makers retrospectively. Second- or third-degree Pacemaker therapy in DM
AV block was present in 126 (48.8%) of the 258
patients. DM was found in 127 (49.2%) patients. There are no published reports or recommenda-
AV block was significantly more prevalent in DM tions for the evaluation of conduction abnormal-
patients (53.9%) and was independent of DM-re- ities in DM patients. The occurrence of high-de-
lated risk factors for atherosclerosis. The largest gree AV block or severe bradycardia in the
cross-sectional study involving over 800,000 pa- asymptomatic population is unpredictable, and
tients was conducted by Movahed et al.DM was data for progression of BBB to high-degree AV
found to be independently associated with third block in DM patients are lacking. There are no
degree AV block in uni- and multivariant analysis indications for routine 24-h Holter monitoring of
with an odds ratio of 3.1 after adjusting for CAD, asymptomatic DM patient at this time. The pres-
CHF, smoking and hyperlipidaemia. However ence of autonomic neuropathy appears to be at
plausible explanations for the increased prev- least partially reversible with better glycaemic
alence of high-degree AV block in DM patients control, which, in theory, could decrease the risk
have been enunciated yet. of arrhythmias in this population.
In an analysis of 3,115 patients presenting with Treatment with permanent pacemaker insertion
STEMI who underwent primary PCI, High-grade for high-grade conduction abnormalities in DM
atrioventricular block (HAVB) (second-degree patients should follow the same guidelines as
Mobitz II or third-degree atrioventricular block) in a non-diabetic population. Reversible cause
was present at baseline in 46 patients (1.5%). Di- of BBB and high-degree AV block has been de-
abetes mellitus was one of the independent pre- scribed in case reports of DM patients secondary
dictors of HAVB. Mortality rate was significantly to electrolytes or metabolic abnormalities or isch-
higher in patients with versus without HAVB at aemia, which needs to be ruled out and treated
1-, and 3-year follow-ups. The greater risk of AV before considering permanent pacemaker in-
blocks in diabetics in setting of STEMI could be sertion. The most certain indications for perma-
due to dysautonomic disturbances of the dis- nent pacing include the following: Symptomatic
ease or the deleterious effects of hyperglycemia bradycardia due to sinus node dysfunction (sick
on the conduction system. sinus syndrome), Symptomatic chronotropic in-
Most of the elderly patients have many underly- competence, Second- or third-degree AV block
ing systemic diseases and multiple coronary risk in asymptomatic awake patients in sinus rhythm

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Cardio Diabetes Medicine 2018 256

resulting in periods of asystole longer than 3.0 The risk of infection of implanted devices is high.
seconds or ventricular rates less than 40 beats Risk factors for an arrhythmogenic substrate in
per minute, Second -or third-degree AV block in DM, such as heterogeneities in atrial and ven-
asymptomatic awake patients in atrial fibrillation tricular repolarization, the extend of myocardial
resulting in pauses of at least 5 seconds, Neu- damage, scar formation, autonomic system dis-
rocardiogenic syncope, in the setting of chronic tortion, glucose fluctuations as well as structural
bifascicular block for advanced second-degree and electrical alterations have been well identi-
AV block or intermittent third-degree AV block or fied. The causal pathophysiological and electro-
Type II second-degree AV block or alternating physiological mechanisms and effect of specific
bundle branch block. therapies however are warranted in further stud-
The implant of defibrillators and cardiac resyn- ies.
chronization devices should also follow the same
indications as for the normal population. Indica- References:
tions for implantable cardioverter-defibrillator
(ICD) implant can be divided into 2 broad cat- 1. Garcia MJ, McNamara PM, Gordon T, Kannel
egories: secondary prophylaxis against sudden WB. Morbidity and mortality in diabetics in the
cardiac death and primary prophylaxis. An ICD is Framingham population. Sixteen year follow-up
recommended as therapy in survivors of cardiac study. Diabetes 1974; 23: 105-111

arrest due to VF or hemodynamically unstable
VT. ICD implantation is appropriate for primary 2. Benjamin EJ, Levy D, Vaziri SM, D’Agostino
prophylaxis for LVEF <35% and NYHA class I RB, Belanger AJ, Wolf PA. Independent risk fac-
to III symptoms. The SCD Heft trial (23) showed tors for atrial fibrillation in a population-based co-
that in patients with NYHA class II or III CHF and hort. The Framingham Heart Study. JAMA 1994;
LVEF of ≤35 % amiodarone has no favorable ef- 271: 840-844
fect on survival, whereas single-lead, shock-on-
ly ICD therapy reduces overall mortality by 23 3. Huxley RR, Filion KB, Konety S, Alonso A. Me-
percent. As compared with placebo, amiodarone ta-analysis of cohort and case-control studies of
therapy was associated with a similar risk of type 2 diabetes mellitus and risk of atrial brilla-
death and ICD therapy was associated with tion. Am J Cardiol 2011; 108: 56-
a decreased risk of death (hazard ratio, 0.77;
97.5 percent confidence interval, 0.62 to 0.96; 4. Stahn A, Pistrosch F, Ganz X, Teige M, Koe-
P=0.007). DM was seen in 32% of the placebo hler C, Bornstein S, Hanefeld M. Relationship
and 31% of the ICD group. The observed ben- between hypoglycemic episodes and ventricular
efit of ICD therapy was similar in both DM and arrhythmias in patients with type 2 diabetes and
non-DM patients. Recent meta-analyses of CRT cardiovascular diseases: silent hypoglycemias
trials have suggested that the benefit of CRT is and silent arrhythmias. Diabetes Care 2014; 37:
dependent on QRS duration, with a significant 516-520
benefit associated with CRT in patients with QRS
≥150 ms, but not in patients with QRS <150 ms. 5. Pistrosch F, Ganz X, Bornstein SR, Birkenfeld
Clinical response to CRT is also dependent on AL, Henkel E, Hanefeld M. Risk of and risk factors
QRS morphology, with the greatest response for for hypoglycemia and associated arrhythmias in
patients with LBBB and QRS ≥150 ms. patients with type 2 diabetes and cardiovascular
disease: a cohort study under real-world condi-
CONCLUSION tions. Acta Diabetol 2015; 52: 889-895

AF and VA are most common form of arrhyth- 6. Ball J, Carrington MJ, McMurray JJ, Stewart S.
mias, which lead to cardiovascular complications Atrial brillation: pro le and burden of an evolving
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D7.i Maboevtaehsemd eMlliRtu,sHisasahesmtrozandge, hindMe,pJeanmdeanl tMriMsk.
for atrial fibrillation and flutter in addition to other
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ropace. 2013 Aug;15(8):1070-118

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EVIDENCE BASED NUTRITION PRIORITIES IN THE

MANAGEMENT OF NON-COMMUNICABLE DISEASES

Dr.Jagmeet Madan,
Professor and Principal, Department of Food and Nutrition ,
Sir Vithaldas Thackersey College of Home Science (Autonomous)

SNDT Women’s University, Mumbai, India,
Co-Author:Namrata Manyal

Abstract: NCD include rapid globalization, urbanization &
ageing population. These behavioural determi-
NCD’s are the pivotal cause of disease burden nants lead to four main metabolic risk factors
& mortality in the Asia Pacific region. Cardio- i.e. overweight & obesity, raised lipids, raised
vascular Diseases are the most frequent of blood sugars, high blood pressure.
NCD deaths. Number of deaths by NCD is ex-
pected to increase by 21 % in the next decade. Role of Nutrition in the development
There is a robust body of evidence based re- of Non-Communicable Diseases:
search in the space of Nutritional Management
of CVD. The role of Food and Gut Microbiota Globally diets are undergoing rapid nutrition
and its linkage to the predisposition of NCD is transition. From a diet rich in fibre, low-fat &
cited in the recent studies. Additionally the new- low- calorie there is a shift occurring towards
er insights of the use of Quality Carbs, Plant increased consumption of calorie-dense foods,
Protein and Good Quality Fats is of immense high intake of refined carbohydrates, poor qual-
significance in the dietary management of CVD. ity fats, red meats & low-fibre, along with intake
of lager number of meals outside home .
Introduction: Dietary habits have undergone drastic change
with a shift towards a Western- diet culture.
Non-communicable Diseases (NCD) are the Dietary habits play a major role in the develop-
chronic outcomes of interaction of genes, nutri- ment of NCD’s. Specific dietary habits, nutrient
tion transition and lifestyle factors over a period excess and nutrient inadequacy can lead to the
of time. NCD’s are the leading cause of mortali- development of NCD’s.
ty & morbidity worldwide, principally in low-and-
middle income countries. In the WHO SEAR, What are the Nutrition Priorities in
each year an estimated 7.9 million lives are lost NCD Management?
due to NCD, accounting for 55% of all deaths. Gut Health
Implications of NCD are not just restricted to
being a health burden, but it also affects the so- Chronic NCD’s are associated with underlying
cio-economic status of a country. The increase low-grade inflammation. While inflammation
in NCD is a major hurdle to global & national and the pathways to disease are multifactorial,
development the altered gut colonization patterns associat-
ed with declining microbial diversity is a central
The Big 4’s of NCD: theme, and increasingly implicated in the phys-
iological, immunological and metabolic dysreg-
The Big 4 of NCD includes majorly Cardiovas- ulation seen in many NCDs. The three main
cular Diseases, Diabetes, Cancer & Respira- predominating bacterial phyla in human gut
tory Diseases. The total number of disability are: (i) Gram-positive Firmicutes (ii) Gram-pos-
adjusted life years (DALYs) lost due to these itive Actinobacteria & (iii) Gram-negative Bac-
diseases is significantly higher compared to teroidetes. Dietary habits have a major impact
other NCDs. on diversity & variability of gut microbiota. A diet
The Four major modifiable determinants of NCD high in animal fat results in increased Bacte-
are unhealthy diets, physical inactivity, tobacco roidetes enterotype, whereas a diet high in fi-
use and abuse of alcohol. The driving forces bre & dense carbohydrates results in increased
that have led to an increase in determinants of Firmicutes enterotype. This in turn affects host

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physiological & metabolic pathways leading to toxins that results in a pro- inflammatory
the development of NCD’s. It has been noted cascade reaction. The ‘Leaky’ intestinal
that a shift from a High fat Low fibre diet to a mucosa provides a link between diet & the
Low fat High fibre diet causes beneficial chang- low-grade inflammation drives peripheral
es in the gut microbiota within 24 hours. These insulin resistance. The resulting endotox-
include: inemia triggers adipocyte inflammation &
(i) Production of beneficial metabolites (SCFA, thus obesity.
lactate, niacin)
(ii) Anti-inflammatory effects
(iii) Prevention of pathogen growth & establish-
ment
An energy rich diet favours the intestinal epi-
thelium to become more permeable to endo-

Figure 1 depicts molecular pathways that link gut microbiota to cardio-metabolic diseases.
Source: Tang et al . Gut Microbiota in Cardiovascular Health and Disease . Circ Res.

2017;120:1183-1196. DOI:10.1161/CIRCRESAHA.117.309715.

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A strong body of evidence suggest that im- mode of treatment & prevention of NCD
provements in microbiome diversity have a pos-
itive impact on markers of metabolic syndrome. Carbohydrates: Resistant Starch &
The food based approach to increase resistant Dietary Fiber
starch content of the diet showed a beneficial
effect on gut microflora and anthropometric pa- Resistant starch (RS) is a part of dietary fiber &
rameters in healthy adults. A recent study was refers to the portion of starch & starch products
done to examine the influence of increased Re- that enters the large bowel in humans, resisting
sistant Starch content of the diet on selected the process of digestion through the gastroin-
anthropometric measurements, fecal microflo- testinal tract. . In the large intestine, it under-
ra and biochemical parameters. Ten healthy goes fermentation & results in the production
adults in the age group 25-45 years participat- of short-chain fatty acids. Different types of RS
ed in the study. Habitual energy, macronutri- ranging from RS1 to RS 5 have been discussed
ents and RS intake was calculated using 7 day in literature. RS acts a prebiotic thereby pro-
food diary. Subjects were then provided with an moting the growth of beneficial microorganisms
experimental diet for an intervention period of such as Bifidobacteria, thus exerting beneficial
14 days. Experimental diet was designed using effects on human body. Regular consumption
Indian preparations with foods relatively rich of both RS & dietary fiber has many potential
in RS. Recording of anthropometric measure- health benefits such as improvements in bow-
ments, collection of fecal and blood samples el health, decreasing postprandial glycaemic
was done pre and post intervention. Bacteri- and insulinemic responses, lowering plasma
al count as log colony forming units (cfu) was cholesterol and triglyceride concentrations, in-
measured in fecal samples. Serum lipid pro- creasing satiety through a range of processes
file and fasting blood glucose was estimated. including a delayed emptying rate, a prolonged
The experimental diet provided approximately release of hormonal signals, a slowing of nu-
1g RS/100kcal which was approximately three trient absorption or altered fermentation in the
times higher than the amount consumed ha- large intestine and decreasing fat storage. In
bitually. Significant decrease was observed in the EPIC-InterAct Study,a 10.8 years follow-up
weight, body mass index, waist circumference study dietary fibre intake was associated with
and hip circumference post intervention. Fe- a lower risk of diabetes after adjustment for
cal samples showed a significant increase in lifestyle and dietary factors. RS4 is able to re-
Bifidobacteria, Lactobacilli, E Coli count and a duce cholesterols, fasting glucose, glycosylat-
significant decrease in Salmonella count post ed haemoglobin, and pro inflammatory markers
intervention. Fasting blood glucose decreased in the blood as well as waist circumference and
significantly post intervention. . Another study percentage of body fat. These properties of RS
on 93 centrally obese volunteers who were make it a novel dietary factor in the manage-
supplemented with whole grains, tradition- ment & prevention of many non-communicable
al Chinese medicinal foods & probiotics for diseases.
9-weeks, followed by a 14-week maintenance
phase observed that modulation of the gut mi-
crobiota via dietary intervention enhanced the
intestinal barrier integrity, reduce circulating
antigen load, and ultimately ameliorate the in-
flammation and metabolic phenotypes. . Spe-
cific strains of probiotics & prebiotics have also
been known to have positive improvements in
markers of metabolic syndrome, hypercholes-
terolemia, blood sugar control & obesity.
Thus, gut therapy may be used a complimentary

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Figure 2 depicts metabolic effects of RS:

Food Sample RS (g/100g)

Basmati Rice 20.22
Kolam Rice 27.67

Whole Wheat Flour 0.5
Refined Wheat Flour 0.65
Whole Moong 4.52
Kabuli Chana 1.93
Chana Flour 1.98

Freshly Cooked/ Processed Food RS (g/100g)
Sample

Pressure Cooked Basmati Rice 0.47

Pressure Cooked Kolam Rice 0.46

Pulao 0.55
Khichadi 0.78
Chapatti 0.49
Paratha 0.61
Puri 0.47
Bhatura 0.54

Germinated (sprouted) moong 0.79

Germinated (sprouted) moong usal 0.87

Soaked Kabuli Channa 0.73
Chhole 2.38
Pithale 0.09

Table 1
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Fat Evidence of quality of fat on development of NCD:

Year Effect Subjects Results & Conclusion

2013 All-cause 1853 In the 7-yr old follow up study, higher trans fat intake
Mortality was associated with increased risk of all-cause mor-
Kiage et al tality. Number of deaths in the lowest quintile of trans
AJCN fat were 238 and in highest quintile were 442
2013
Use of unhydrogenated oil and soft margarine re-
Noushin.M et al Serum Lipids 265 sulted in reduction of LDL. Apo-B was reduced with
the use of unhydrogenated oil. Total cholesterol and
Atherosclerosis TG reduced in all groups besides hydrogenated oil
group.

2013 Membrane 52 Intake of 15.5g/d of TFA for 12 weeks elevated lipid
Gozde.G et al Lipids post-mena- profile. Up-regualation of LDL levels and unsaturation
Plos one pausal . These specific changes in membrane lipid species
women may be related to the mechanisms of TFA-induced
disease

2012 CVD 5209 Higher intake of SFA associated with greater risk of
CVD Replacing 2% energy from meat SF to dairy SF
De oliveira otto reduces the risk of CVD by 25%
et al
AJCN T2DM- Gly- 93 obese Low carbohydrate group achieved greater reductions
2014 cemic control subjects in TG, Glycaemic variability HbA1 C medication re-
and CVD with T2DM quirements and increases in HDL in 24 weeks A low
Jeannee.T risk CHO diet with low SFA is an effective approach for
dietary management in T2DM
Diabetes Care

2012 Mortality 2222 High n6:n3 ratios were positively associated with
Jan.F et al deaths due to NCD.

Increased n6:n3 ratio, western type foods and decline in
prudent foods increases the risk of death due to NCD

The Open Nutra-
ceuticals Journal

2013 DHA and EPA were inversely associated with incident
Marcia.C et al CVD.

JAHA Incidence of 2837 No significant associations with CVD were observed
CVD for circulating n-3 alphalinolenic acid or n-6 PUFA (lin-
oleic acid, arachidonic acid)

Both dietary and circulating eicosapentaenoic acid
and docosahexaenoic acid were inversely associated
with CVD incidence.

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2011 3.4g/d of EPA+DHA lowered triglycerides by 27%
over 8 weeks in adults with moderate hyper-triglycer-
Triglycerides 26 idemia. Whereas, a lower dose (0.85g/d) had no
effect on lipids.
Skulas-ray et al
American journal An inverse association between DHA and Diastolic
of clinical Nutrition BP was seen in adults not on antihypertensive. In-
creased DHA consumption through diet modification
2011 may be a strategy for hypertension prevention

James C. High Blood 265 Supplementation of 4g/d n-3 PUFA for 12 weeks sig-
Pressure nificantly lowered TG with modest increases in LDL-C
in hypertriglyceridemic adults
American Journal

of Hypertension

2011

B.Oelrich

Triglycerides 42
and LDL-C
Nutrition, Metab-

olism and Cardio-

vascular Diseases

Recommendations on quality of fat: Protein in NCD

For optimal health across the life course High Protein Diet improves lipid profile, blood

the following recommendations, along with pressure, hepatic TAG accumulation. In a 12-week

food-based guidelines, are suggested: open-label, parallel-arm randomised controlled

trial, 122 overweight/obese Asian Indian men and

1. Fats should provide not more than 30% of women were administered either a High Protein
total energy/ day and SFAs should provide Meal Replacer or a control diet after 2 weeks of
no more than 10% of total energy/day. For diet and exercise run-in. Significant weight loss
individuals having low-density lipoprotein and improvement in obesity measures, metabol-
cholesterol of 100 mg/dL, SFAs should be ic, lipid and inflammatory parameters and hepatic
<7% of total energy/day. transaminases were observed in the intervention
2. Essential PUFAs (LA) should provide group. Partial substitution of carbohydrate with
5–8% of total energy/day. protein can lower blood pressure in pre hyperten-
3. ALA should be 1–2% of total energy/day. sive and hypertensive subjects and reduce esti-
4. The optimal ratio of LA/ALA should be mated CVD risk. Whey proteins contain certain
5–10. compounds that act as natural angiotensin con-
5. Long-chain n-3 PUFAs should be obtained verting- enzyme inhibitors, which could possibly
from fish, walnuts, flaxseeds, canola oil, etc. lead to lowering the blood pressure

6. Cis MUFAs should provide 10–15% of to- ↓ hyperinsulinaemia ↓ IR ↓ Metabolic Syndrome
tal energy/ day.

7. TFAs should be <1% of total energy/day. Abdominal obesity (high waist: hip ratio) increas-
8. Cholesterol intake should be limited to es the odds of developing myocardial infarction by
200–300 mg/ day. 2·44 (2·05–2·91) times in South Asians.

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A 1 cm increase in WC or a 0·01 unit increase abolic risk factors. Paleo diet is known to show
in the waist: hip ratio measurement is associat- improvements in waist circumference, blood
ed with a 2 and 5% increase in the risk for CVD, lipids, blood sugars, fasting & postpandrial in-
respectively High Protein Diet reduces WC (ab- sulin, inflammatory markers such as C-reactive
dominal obesity) protein. ( 20, 21). In a 4-week randomized tri-
al 39 healthy women were randomised either
Ketogenic Diet to a Paleolithic or Australian Guide to Healthy
Eating. Although, no differences in cardiovas-
Substantial evidence supports the use of ke- cular and metabolic markers were observed be-
togenic diets for weight loss therapy; however, tween groups, significantly higher weight loss
there are contrasting theories regarding the occurred in the Paleolithic group. Paleolithic
mechanisms through which they work. (18)
Figure 3 depicts mechanisms through which
Ketogenic Diets work in pathologies of certain
conditions

Figure 3

Source: A Paoli et al. Beyond weight loss: a review of the therapeutic uses of very-low-car-

bohydrate (ketogenic) diets. European Journal of Clinical Nutrition (2013) 67, 789–796

An Online Intervention Comparing a Very group had lower intakes of carbohydrates, sodi-
Low-Carbohydrate Ketogenic Diet and Lifestyle um, calcium & iodine and higher intakes of fat &
Recommendations Versus a Plate Method Diet beta-carotene. Larger studies are recommend-
in Overweight Individuals With Type 2 Diabetes, ed to assess the impact of the Paleolithic diets
revealed that individuals on very low-carbohy- on metabolic and cardiovascular risk factors
drate ketogenic diet and lifestyle online program in healthy populations. (21). Moderate quality
improved their glycaemic control and lost more evidence exists from randomized controlled in-
weight rather than a conventional, low-fat diabe- tervention studies that suggest Paleolithic diet
tes diet online program. can improve metabolic syndrome components
however more studies are required before Pa-

Paleo Diet leolithic nutrition can be recommended in future
guidelines.(20)
Paleo diet encourages consumption of fruits,

vegetables, lean meats, nuts and eggs. Short-du- Thus the final word still remains Emphasis on
ration uncontrolled studies show promising ef- Quality of Macronutrients in Restricted Defined
fects of Paleolithic Diet on cardiovascular & met- Quantities is the Key to Nutritional Manage-

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Cardio Diabetes Medicine 2018 266

ment of NCD. A blend of Specific Dietary Chang- diet rich in resistant starch on fecal microflora,
es customised to Indian ethnic variation and life anthropometric and biochemical parameters in
style modifications is the way forward. healthy adults. International Journal of Applied
Home Science Volume 5 (2), February (2018) :
References: 289-300
11. Nigudkar. Estimation of Resistant Starch
1. W.-Y. LOW et al. Non-communicable diseases Content of Selected Routinely Consumed Indian
in the asia-pacific region: prevalence, risk factors Food Preparations. Current Research in Nutri-
and community-based prevention. International tion and Food Science Vol. 2(2), 73-83 (2014)
Journal of Occupational Medicine and Environ- 12. Nigudkar & Madan. Resistant Starch Con-
mental Health 2015;28(1):20–26 tent of Traditional Indian Legume Preparations.
Current Research in Nutrition and Food Science.
2. World Health Organization 2013. Action plan Vol. 5, No. (3) 2017, Pg. 238-246
for the prevention and control of Noncommuni- 13. Yang et al.: Resistant Starch Regulates Gut
cable Diseases in South-East Asia, 2013–2020. Microbiota to Control Nutritional Events. Cell
3. World Health Organization Regional Office of Physiol Biochem 2017;42:306-318
South East Asia. Noncommunicable Diseases in
the South-East Asia Region. 2011. Situation and
Response

4.Misra et al. Obesity, the Metabolic Syndrome, 14. The InterAct Consortium. Dietary fibre and
and Type 2 Diabetes in Developing Countries: incidence of type 2 diabetes in eight European
Role of Dietary Fats and Oils. Journal of the countries: the EPIC-InterAct Study and a me-
American College of Nutrition, Vol. 29, No. 3, ta-analysis of prospective studies. Diabetologia
289S–301S (2010) 15. Misra et al. Consensus Dietary Guidelines
5. Naicker et al. Dietary quality and patterns and for Healthy Living and Prevention of Obesity,
non-communicable disease risk of an Indian the Metabolic Syndrome, Diabetes, and Related
community in KwaZulu-Natal, South AfricaJour- Disorders in Asian Indians. Diabetes Technology
nal of Health, Population and Nutrition (2015) & Therapeutics. Volume 13, Number 6, 2011
33:12 16. S. Gulati et al. Effect of high-protein meal re-
6. West et al. The gut microbiota and inflamma- placement on weight and cardiometabolic profile
tory noncommunicable diseases: Associations in overweight/obese Asian Indians in North India
and potentials for gut microbiota therapies. Jour- 2017 British Journal of Nutrition
nal of Allergy and Clinical Immunology · January 17. A Paoli et al. Beyond weight loss: a review
2015 of the therapeutic uses of very-low-carbohydrate
7. Manco et al. LPS and Cardiovascular Risk. (ketogenic) diets. European Journal of Clinical
Endocrine Reviews. December 2010, 31(6): Nutrition (2013) 67, 789–796
817-844 18. Saslow et al. An Online Intervention Com-
8. Clemente et al, Cell; 2012 paring a Very Low-Carbohydrate Ketogenic Diet
9. Tang et al . Gut Microbiota in Cardiovascular and Lifestyle Recommendations Versus a Plate
Health and Disease . Circ Res. 2017;120:1183- Method Diet in Overweight Individuals With Type
1196. DOI:10.1161/CIRCRESAHA.117.309715. 2 Diabetes: A Randomized Controlled Trial. J
Med Internet Res. 2017 Feb; 19(2): e36.

10. Madhuri Nigudkar, Jagmeet Madan, Effect of 19. Genoni et al. Cardiovascular, Metabolic Ef-

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fects and Dietary Composition of Ad-Libitum Pa-
leolithic vs. Australian Guide to Healthy Eating
Diets: A 4-Week Randomised Trial.
20. Manheimer et al. Paleolithic nutrition for met-
abolic syndrome: systematic review and me-
ta-analysis. American Journal of Clinical Nutri-
tion.2015;102:922–32.

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METFORMIN IN RENAL AND HEPATIC FAILURE-
TO BE CONTINUED?

Dr. Dhiraj Bhattad ,M. D. (Medicine)

Consultant in Internal Medicine,
Sir H N Reliance Foundation Hospital, Mumbai

Metformin in renal and hepatic failure- Metformin can be called the ‘king’ of all the di-
to be continued? abetes medicines. All guidelines recommend it
as the first pharmacological agent of choice af-
Abstract: ter lifestyle measures for management of T2DM;
other diabetes medicines come later on in the
Metformin has been traditionally contraindicated treatment algorithm. Clinicians have a rich clinical
in chronic kidney disease (CKD) due to perceived experience with it and are very comfortable using
risk of lactic acidosis; but this fear is disproportion- it in non-CKD diabetic patients.
ate as lactic acidosis (LA) is a rare complication
in type 2 diabetes mellitus (T2DM) with incidence Why to discuss role of metformin in
of 6/1,00,000 patient years (1). Metformin has CKD?
number of desirable effects in a diabetic patient.
It increases insulin sensitivity, reduces glucose Diabetes mellitus is the most common contribu-
absorption from the intestine, increases peripher- tor to CKD worldwide with estimated prevalence
al intake of glucose in cells and reduces hepatic of CKD among non-institutionalized adults with
gluconeogenesis in the liver. There are other pos- T2DM at 34.5–42.3%, with most CKD cases iden-
itive clinical effects (eg. slight weight loss, reduc- tified as early stage (stage 1 or 2). The gradual re-
tion in cardiovascular mortality) independent of duction in GFR challenges sustained use of met-
glucose reduction. On the contrary, hypoglycemia formin in the same dose as it is not metabolized
is a rare complication of metformin (2). Depriv- by liver but excreted completely through kidneys.
ing a CKD patient of all these beneficial effects Hence, obviously, level of metformin in the blood
of metformin which is a time tested molecule for will rise as CKD stage increases, warranting re-
an exaggerated fear of lactic acidosis is not right. duction in its dose. But at the same time, as the
Hence the recent guidelines have been relaxed fear of lactic acidosis with metformin in CKD is
to permit therapy with metformin if the glomerular exaggerated, we may deprive our CKD patients
filtration rate (GFR) is > 30 mL/min. Of course, of stage 3 or 4 of the beneficial effects of this time
you need to take more precautions when you use tested medicine by not using it in this subset of
this molecule in CKD as opposed to a non-CKD patients. Considering the number of people with
patient; like reduction of dose of metformin as CKD and T2DM, there are potentially millions of
per the CKD stage, close monitoring of creatinine people who are not currently taking metformin
(and more specifically creatinine clearance) and who might benefit from this medication. Hence
withholding the molecule temporarily when the the need to discuss the role of this molecule in
patient has acute serious medical conditions or if CKD to alleviate the fear of using it in CKD with
a contrast study is planned (1). due precautions.
For similar reasons, metformin needs to be con-
tinued even in liver dysfunction, albeit with close Positive effects of Metformin in
monitoring. This will be elucidated further in this Diabetes
write-up.
Metformin does not appear to have a single
Introduction

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Cardio Diabetes Medicine 2018 269

mechanistic target: rather it counters insulin re- failure and kidney disease, but it did not confer
sistance and impacts metabolic, vascular and a lower risk for major cardiovascular events in
other physiological functions through multiple those patients.
effects that are individually modest but collec-
tively substantial. It increases insulin sensitivity, Truth about lactic acidosis (LA) due to metformin
reduces glucose absorption from the intestine, In an exhaustive study published in the Journal
increases peripheral intake of glucose in cells of the American Medical Association, Inzucchi et
and reduces hepatic gluconeogenesis in the liv- al address the important issue of whether met-
er. It is weight neutral or helps with slight weight formin increases the risk of LA in people with
loss. Further advantages are a reduction in blood CKD (1). They reviewed published studies from
pressure, plasma lipids, plasminogen activator January 1950 through June 2014 to determine
inhibitor and an increase in fibrinolytic activity. All the risk of metformin-associated lactic acidosis
these are highly desirable effects in T2DM. (MALA) in patients with T2DM and CKD. The sig-
Metformin is the first molecule to demonstrate nificant strengths of this study in comparison to
cardiovascular benefit in T2DM. In 1998, the previous studies were that the authors reviewed
epic UKPDS study noted that in addition to glu- published articles that comprised the entire his-
cose-lowering effects, weight neutrality and low tory of metformin use, focused on studies specif-
hypoglycaemia risk, long-term metformin ther- ically directed at patients with decreased kidney
apy might reduce cardiovascular events and function, and reviewed an extensive number of
improve survival (2). Reduced cardiovascular relevant articles. Their analysis revealed that lac-
risk appeared to be largely independent of glu- tate level was often normal in patients taking met-
cose-lowering efficacy and attention is drawn formin with mild (creatinine clearance of 60-90
to a substantial literature noting potentially ad- mL/min) to moderate CKD (creatinine clearance
vantageous effects of metformin on the macro- of 30-60 mL/min). In studies in which metformin
and microvasculature (3). Interrogation of large use was associated with increased lactate level,
databases that captured long-term treatment of none increased to the level of overt LA (defined
type 2 diabetes consistently confirmed the re- as lactate level>5mmol/L and pH<7.35). In the
duced cardiovascular risk with metformin, and a reported cases of LA, there were other associat-
10-year follow-up of the UKPDS in 2008 showed ed causes such as infection, liver failure, acute
a continued cardiovascular benefit of early use kidney injury (AKI), or cardiovascular collapse.
of the drug (4). Metformin reduces risk of death Metformin use was concomitant but not clearly
and cardiovascular disease by 1/3rd in non-CKD causative. The rate of LA in patients taking met-
patients. formin was the same as the rate of LA in people
with T2DM who did not take metformin.
Crowley and colleagues (5) conducted a sys-
tematic review of metformin use and its effect on The potential benefits on death and myocardial
several relevant clinical outcomes, including all- infarction mentioned above far outweigh the risk
cause mortality and major cardiovascular events of LA. Therefore, depriving a CKD patient of all
in patients with kidney disease (eGFR <60 mL/ the benefits of metformin which is a time tested
min/1.73 m2), congestive heart failure, or chron- molecule for an exaggerated fear of lactic acido-
ic liver disease with hepatic impairment. They sis is not right. Hence the recent guidelines have
reviewed 17 studies comparing treatment regi- been relaxed to permit therapy with metformin if
mens that included metformin with those that did the estimated glomerular filtration rate (eGFR) is
not and found that metformin use was associat- > 30 mL/min.
ed with lower all-cause mortality among patients
with each of the 3 chronic conditions. In addition, Suggested doses of metformin by the authors as
metformin was associated with a lower risk for per the eGFR are as follows-
heart failure readmission in patients with heart For eGFR>60 mL/min/1.73 m2, use a maximal

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Cardio Diabetes Medicine 2018 270

daily dose of 2,550mg and glomerular filtration in the urine. As met-
formin is not metabolized via the hepatic CYP450
For eGFR of 45 to 59 mL/min/1.73 m2, use no system, its pharmacokinetic characteristics do
more than 2,000 mg per day not expose patients to drug–drug interactions.
Metformin is beneficial in patients with nonal-
For eGFR of 30 to 44 mL/min/1.73 m2, use no- coholic fatty liver disease. It is considered first
more than 1,000 mg per day. line treatment in patients with diabetes who are
known to have liver disease. However, it is pres-
The authors further suggest that metformin ther- ently not recommended for those with advanced
apy should not be initiated in patients with eG- hepatic disease again because of the perceived
FRs<45 mL/min/1.73 m2 and advise against risk of lactic acidosis. Literature evidence of liver
using metformin in patients with eGFRs<30 mL/ disease being associated with metformin-asso-
min/1.73 m2. ciated metabolic acidosis is largely represented
by case reports (6). Most such patients had cir-
Considering the efficacy of metformin, the low rhosis and were also actively using alcohol. The
risk of lactic acidosis, and the increasing num- risk of lactic acidosis associated with metformin
ber of people with T2DM and CKD, the recom- therapy appears to occur in patients with multi-
mendations by Inzucchi et al are reasonable. ple comorbidities, such as renal, liver, and cardi-
Prospective studies would be ideal but it is very ac diseases, particularly when there is an acute
unlikely that definitive prospective studies will deterioration. Metformin per se does not appear
ever be performed because event rates are so to cause or exacerbate liver injury. Infact, it has
low that the sample size for any study would a protective effect against liver cancer develop-
have to be very large, with participants followed ment in cirrhosis.
up over many years. But in light of the recently
relaxed contraindications for its use, bolstering In a large study done by Zhang X et al (7), the
the evidence base for metformin might be a wise authors investigated whether continuation of
investment. metformin after cirrhosis diagnosis improves
survival of patients with diabetes. No patients
What precautions should the clinician developed metformin-associated lactic acidosis
take while using metformin in T2DM during follow-up. Continuation of metformin after
with CKD? cirrhosis diagnosis reduced the risk of death by
57%. Metformin should therefore be continued
Estimated glomerular filtration rate (eGFR) in diabetic patients with cirrhosis if there is no
should be measured every 3 to 6 months de- specific contraindication. If a patient has stable
pending on baseline eGFR, stability of eGFR, CLD and few other comorbidities, metformin is
other medications used (ACE inhibitors, ARBs, likely to be reason­ably safe, but the dose should
diuretcis, etc) and chronic comorbid condi- be decreased to a maximum of 1500 mg daily,
tions and more frequently during acute medical and the drug should be withdrawn if liver or renal
events. Discontinue metformin in inpatients if function is deteriorating, or in the setting of acute
unstable, hypotensive, hypoxic, septic or if there illness or decompensation.
is AKI. Withhold metformin 2 to 3 days prior to
radiocontrast dye study and restart after 1 or 2 References
days (depending on the eGFR).

Metformin in liver dysfunction 1. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ,
McGuire DK. Metformin in patients with type 2 di-
Metformin does not undergo hepatic metabolism abetes and kidney disease: a systematic review.
and is excreted unchanged by tubular secretion JAMA. 2014;312(24):2668-2675.

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2. UK Prospective Diabetes Study (UKPDS)
Group (1998) Effect of intensive blood glucose
control with metformin on complications in over-
weight patients with type 2 diabetes (UKPDS
34). Lancet 352:854–865.
3. Bailey CJ (2008) Metformin: effects on micro
and macro vascular complications in type 2 dia-
betes. Cardiovasc Drug Ther 22:215–224.
4. Holman RR, Paul SK, Bethel MA, Matthews
DR, Neil HAW (2008) 10-year follow-up of inten-
sive glucose control in type 2 diabetes. N Engl J
Med 359:1577–1589.
5.  Crowley MJ, Diamantidis CJ, McDuffie JR,
Cameron CB, Stanifer JW, Mock CK, et al. Clin-
ical outcomes of metformin use in populations
with chronic kidney disease, congestive heart
failure, or chronic liver disease. A systematic re-
view. Ann Intern Med. 2016 doi: 10.7326/M16-
1901. 
6. Brackett CC. Clarifying metformin's role and
risks in liver dysfunction. J Am Pharm Assoc
(2003)2010;50:407–410 
7. Zhang X et al. Continuation of metformin use
after a diagnosis of cirrhosis significantly im-
proves survival of patients with diabetes. Hepa-
tology 2014 Dec;60(6):2008-16

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05.Prevention

1 Principles of Lifestyle Medicine-Dr.Amit Saraf

2 Prevention of DKD-Dr.Georgi Abraham

3 NCD awareness and prevention in Schools and colleges - a project by AACCI & DY Patil
Medical College-Dr.SwatiBhave&Dr.Amitava

4 Role of Lifestyle Modification : Yoga and the Body, to prevent-Dr. Vivek Chandra

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LIFE STYLE MEDICINE

Dr Amit Saraf

MD FRCP (London) FACP (USA) FCPS

Consultant Physician, Jupiter Hospital

Dr Viplav Deogaonkar

MBBC, Seth GS Medical College and KEM Hospital, Mumbai

Introduction: Pathophysiology towards to metabol-
ic syndrome:
Diabetes, Hypertension and Obesity are char-
acterized by a high incidence of cardiovascular Atherosclerosis (Greek “athero” for “gruel” and
disease (CVD). Poor control of lifestyle plays a “sclero” for “hard”-- hardening of the normally
significant role in its development and is a con- soluble “gruel” that flows through the vascular
tributing factor to the development of atheroscle- system): This caused due to too much food, too
rosis. little exercise. The food consumed overwhelms
Metabolic Syndrome: Metabolic syndrome is the body’s normal metabolic needs and the fat
characterized by a group of metabolic risk accumulates throughout the cardiovascular
factors, including: system. Poor sedentary lifestyle and the Thrifty
genotype, especially in Asians, contribute to this
• High LDL cholesterol
• High triglycerides process.
• Low HDL cholesterol
• Elevated blood pressure Specific components of metabolic
• Abdominal obesity syndrome:
• Insulin resistance or glucose intolerance Coronary Heart Diseases CHD

Risk factor reduction has been the long-stand- The major underlying cause is atherosclerosis.
ing cornerstone in the prevention and treatment Atherosclerosis is a slow, progressive disease
of cardiovascular disease (CVD). Implement- which begins in childhood and takes decades
ing healthy lifestyle behaviors including diet is to advance. Plaque (the build-up of lipid/choles-
a foundation for reducing CVD risk. Lifestyle terol) in the artery wall forms as a response to
related risk factors play an important role in the injury to the endothelium in the artery wall.
development of metabolic syndrome. Some of
these risk factors like dietary choices, smoking, Risk Factors for CHD: Can be classified as
and alcohol consumption, overweight and sed- fixed and modifiable
entary lifestyle are modifiable.
Fixed
Lifestyle factors that cause the above diseases
• Smoking • Family History
• Unhealthy diet
• Overweight • Female > 55
• Excess alcohol
• No Exercise Modifiable
• Stress
• Inactivity
• Obesity
• High LDL Cholesterol (>100 with CHD,

>130 without CHD)
• Low HDL Cholesterol (<40)
• Diabetes
• Hypertension (>140/90)
• Smoking

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Lifestyle modification for CHD includes • Consume fish, especially oily fish, at least twice
a week.
• Balanced diet • Limit your intake of saturated fat to 7% of ener-
gy, trans fat to 1% of energy and cholesterol to
• Regular aerobic exercise for 30-60  minutes 300 mg per day by
three to five times each week. — choosing lean meats and vegetable alterna-
tives;
• Moderating alcohol. — selecting fat-free (skim), 1%-fat, and low-fat
dairy products; and
• Restriction of dietary sodium salt to<6 g / day. — minimizing intake of partially hydrogenated
fats.
• Weight reduction • Minimize your intake of beverages and foods
with added sugars.
• Restricting coffee consumption (and other • Choose and prepare foods with little or no salt.
caffeine-rich drinks) to fewer than five cups
per day. • If you consume alcohol, do so in moderation.

Dietary recommendations for CHD: Practical tips to Implement Diet and
Lifestyle Recommendations.
Reduce starchy foods, eat more fruit and veg- Lifestyle
etables, reduce animal or saturated fat, cut down
on sugar and reduce salt ● Know your caloric needs to achieve and main-
tain a healthy weight.
Aim for a Normal Blood Glucose Level: ● Know the calorie content of the foods and bev-
erages you consume.
A normal fasting glucose level is 100 mg/dL, ● Track your weight, physical activity, and calorie
whereas diabetes is defined by a fasting glu- intake.
cose level 126 mg/dL. Hyperglycemia and the ● Prepare and eat smaller portions.
often-associated insulin resistance are related to ● Track and, when possible, decrease screen
numerous cardiovascular complications, includ- time (eg, watching television, surfing the Web,
ing CHD, stroke, peripheral vascular disease, playing computer games).
cardiomyopathy, and heart failure. Reducing ● Incorporate physical movement into habitual
caloric intake and increasing physical activity activities.
to achieve even a modest weight loss can de- ● Do not smoke or use tobacco products.
crease insulin resistance and improve glucose ● If you consume alcohol, do so in moderation
control and the concomitant metabolic abnor- (equivalent of no more than 1 drink in women
malities. In nondiabetic individuals, weight loss
and increased physical activity can delay the on- or 2 drinks in men per day).
set of and possibly prevent diabetes.
Lifestyle Medicine:
Obesity
Diet:
Weight loss is recommended for patients with a Food choices and preparation
BMI of 25 to 29.9 kg/m² who have two or more
risk factors, as it is for persons with a BMI 30 Use the nutrition facts panel and ingredients list
kgm/2, regardless of their risk of health compli- when choosing foods to buy. Eat fresh, frozen, and
cations3,7. Three major components of lifestyle canned vegetables and fruits without high-calo-
modification for obesity: (1) diet (2) exercise and rie sauces and added salt and sugars1,3. Replace
(3) behavior therapy. high-calorie foods with fruits and vegetables. In-
crease fiber intake by eating beans (legumes),
Balance calorie intake and physical activity to whole-grain products, fruits, and vegetables.
achieve or maintain a healthy body weight, which
include.
• Consume a diet rich in vegetables and fruits.
• Choose whole-grain, high-fiber foods.

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Cardio Diabetes Medicine 2018 275

Use liquid vegetable oils in place of solid fats. food while cooking.
Limit beverages and foods high in added sugars.
Common forms of added sugars are sucrose, Choose the right sort of fat:
glucose, fructose, maltose, dextrose, corn syr- Saturated
ups, concentrated fruit juice, and honey. Choose
foods made with whole grains. Common forms • Full fat dairy produce (eg cheese, butter,
of whole grains are whole wheat, oats/oatmeal, full cream milk)
rye, barley, corn, popcorn, brown rice, wild rice,
buckwheat, triticale, bulgur (cracked wheat), mil- • Pies
let, quinoa, and sorghum. Cut back on pastries • Biscuits
and high-calorie bakery products (eg, muffins, • Savoury snacks
doughnuts). Select milk and dairy products that • Lard
are either fat free or low fat. Reduce salt intake • Hard vegetable fat
by comparing the sodium content of similar prod-
ucts (eg, different brands of tomato sauce) and Mono-Unsaturated
choosing products with less salt; choosing ver-
sions of processed foods, including cereals and • Olive oil
baked goods, that are reduced in salt and lim- • Rapeseed oil
iting condiments (eg, soy sauce, ketchup). Use • Groundnut oil
lean cuts of meat and remove skin from poultry
before eating. Limit processed meats that are Poly-Saturated
high in saturated fat and sodium. Grill, bake, or
broil fish, meat, and poultry. Incorporate vegeta- • Sunflower oil (products)
ble-based meat substitutes into favorite recipes. • Oily fish
Encourage the consumption of whole vegetables
Lower daily fat intake:
and fruits in place of juices.
Fat has 9 calories/ gram (vs. 4 in CHO’s and pro-
Carbohydrates tein) and thus contributes to obesity. LDL- cho-
lesterol can decrease as much as 30% with diet
Keep your carbohydrates (starch/sugar) and cal- alone (very strict regimen), representing a 60%
orie intake constant. Ask for a referral to a reg- decrease in CHD risk. Strategy is to lower intake
istered dietitian (RD) or a certified diabetes ed- of saturated and trans fatty acids (found in red
ucator (CDE) for the correct individualized diet. meat, poultry skin, butter, margarine, pastries,
Choose foods that contain carbohydrates (sugar cakes, cookies, whole-fat dairy, candy bars) to
and starch) in amounts that help keep your blood improve cholesterol. Lower total fat intake to
sugar normal. Carbohydrate needs may change control weight.
with your daily activity. Eat starchy foods regu-
larly, eg. Bread, Potatoes, Cereals etc. To help Omega-3 Fatty Acids
maintain blood glucose levels and cholesterol
levels, choose more high fibre foods, eg. Fruit, Help to thin blood and prevent blood platelets
Vegetables etc. To help to maintain a healthy from clotting and sticking to artery walls. Food
gut, regularly consume, wholegrain cereals, Sources: fatty fish, such as salmon, sardines,
trout, swordfish, herring, albacore tuna, macker-
wholemeal bread, brown rice. el and soy, canola and flaxseed oil. Consumption
of 2 servings (~8ounces) per week of fish high in
Fats α-linolenic acid is healthy.

Reduce animal or saturated fat intake, use low Reduce salt intake
fat milk, use low fat spread instead of butter and
use oil high in unsaturated fat, eg olive oil, rape- Cut down on added salt. Use alternative season-
seed oil. Preferably use less fat in cooking and ings in place of salt. Look out for reduced/low
rather grill, dry-roast, microwave and or steam sodium foods and avoid salt substitutes.

Weight Control

On average ~ 1/2 to 1mm decrease in blood

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pressure is seen for each pound weight loss in 6.Healthy lifestyle behaviors and control of hy-
obese hypertensives (up to ~20# loss). Weight pertension among adult hypertensive patients,
reduction can raise HDL-cholesterol. Obesity is Samaneh Akbarpour, Scientific Reports vol-
ume 8, Article number: 8508 2018.
the major risk for NIDDM. 7.Treatment of the metabolic syndrome: The im-
pact of lifestyle modification, Allison M. Pritch-
Behavioral Changes ett, John P. Foreyt, Douglas L. Mann, Current
Atherosclerosis Reports March 2005, Volume
Changing your behaviors or habits related to 7, Issue 2, pp 95–102.
food and physical activity is important for los- 8.Metabolic syndrome and lifestyle modifica-
ing weight. The first step is to understand which tions, Takahara M, Reviews in Endocrine and
habits lead you to overeat or have an inactive Metabolic disorders, 01 Dec 2014, 15(4);317-
lifestyle. 327.
9.Impact of lifestyle modification on glycemic
Physical Activity control in patients with type 2 diabetes mellitus,
Nandita B Sanghani, Indian Journal of Endocri-
Reduces the risk of developing non-insulin-de- nology and Metabolism, Year : 2013, Volume :
pendent diabetes mellitus by 6% for each 17, Issue : 6, 1030-1039.
500-kcal/week expended. Exercise reduces
mortality in people with NIDDM and reduces
blood pressure up to 10/8 mm Hg in hyperten-
sive patients (moderate activity >30 minutes
most days. It also helps prevent obesity and re-
quired for long term weight control. Daily physical
activity raises HDL and lowers LDL cholesterol,
also results in lower morbidity and mortality in
overweight individuals even if they remain over-

weight.

References:
1.Lifestyle modification in the management of

the metabolic syndrome: achievements and
challenges, Riccardo Dalle Grave, Diabetes Me-
tab Syndr Obes. 2010; 3: 373–385.

2.Effects of lifestyle modification on metabolic
syndrome: a systematic review and meta-analy-
sis, Kazue Yamaoka, Toshiro Tango, BMC Med-
icine201210:138.

3.Lifestyle changes and prevention of metabolic
syndrome in the Heart of New Ulm Project, Jef-
frey J.VanWormer, Preventive Medicine Reports
Volume 6, June 2017, Pages 242-245.
4.Benefits of lifestyle modification on the meta-
bolic syndrome, Luiza Armani Valmorbida, Fisiot-
er.mov. vol.26 no.4 Curitiba Sept./Dec. 2013
5.Exercise benefits in cardiovascular disease:
beyond attenuation of traditional risk factors,
Carmen Fiuza-Luces, Nature Reviews Cardiol-
ogy, Aug 18.

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DIABETIC KIDNEY DISEASE- CHALLENGES IN INDIA

Georgi Abraham MD FRCP

Professor of Medicine/Nephrology
Madras Medical Mission Hospital and PIMS,Chennai

Co-Author:Sneha Haridas Anupama MBBS,
Sri Ramachandra Medical College and RI

Abstract disease(CKD) in the general population is less
than 10%. Diabetics have nearly 2-fold higher
A high percentage of Asians with Type 2 DM have odds of CKD than those without Diabetes Mel-
Diabetic Kidney Disease (DKD) . Hence there is litus. Type II DM is more common with an inci-
an urgent need to identify type 2 DM patients at dence of 87-91% among whom 50% eventually
high risk for developing DKD. This calls for early develop DKD. The incidence of type I diabetes is
intervention to retard progression of DKD. This 7-12% and 33% of them develop DKD. The odd
may be achieved by strict glycemic and blood thing is that 25-41% have non-proteinuric DKD
pressure control. There is a critical need to char- eluding the diagnosis. The diagnosis of DKD is
acterise the underlying mechanisms of DKD in made only in 12% of the population by the pri-
India. Different tools can be applied to facilitate mary care practitioners while more than 50% of
the discovery of new biomarkers for DKD. Fo- DM 2 has DKD which are not diagnosed in US.
cus should be on Transcriptomics, Genomics, The lowest values are in low-socioeconomic and
Proteomics, and Metobolomics. Identification of lower educational status individuals.
new therapies to target the mechanisms of DKD

is key to progress in this field. Kidney biopsies The heterogeneity of diabetes diagnosis and
must be performed in those most likely to have care in India is attributed to dietary pattern, lack
DKD diagnosed with application of new tools. It of exercise, poverty and genetic factors. It is es-
is critical that the existing knowledge gap with re- timated that the cost per individual for diabetic
gards to diabetic care amongst patients and their care in India is Rs. 25000/year. The GDP per
families should be addressed for proper follow capita income currently is Rs. 121720. If the
up at defined intervals. Quantification of eGFR, patient has to receive newer molecules includ-
albumin-creatinine ratio, HbA1c and home blood ing oral hypoglycemic agents(OHA) and insulin
pressure monitoring are basic requirements for analogues, the cost would skyrocket causing
management of DKD. an economic burden to the families. However,

India being the second most populous country metformin along with sulfonylureas are cheap
has enormous burden of predominantly type II compared to the gliptins, SGLT-2 inhibitors and
diabetes mellitus. It is estimated that the preva- insulin analogues. The lack of early diagnosis
lence of pre-diabetes is more than 70 million and of diabetes mellitus and poor follow up makes
diabetes over 62 million. One in three adults with people vulnerable to the microvascular and mac-
diabetes mellitus are estimated to have CKD and rovascular complications of DM 2 in India as re-
most are not aware of having DKD. Definition ported in the DEDICOM india survey. (1) A study
of diabetic kidney disease as per KDOQI (Kid- showed that 41% of the DM 2 patients do not
ney disease outcome quality initiative): elevat- follow up within a year of the diagnosis of diabe-
ed urine albumin excretion, progressive decline tes mellitus in India. This highlights the fact that
in GFR, increased systolic BP and high risk of there is a knowledge gap with is a critical issue
kidney failure. The awareness of Chronic kidney in the management of type 2 DM.(2) The Indi-
an CKD Registry reported diabetic nephropathy

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Cardio Diabetes Medicine 2018 278

among 30.9 % of the CKD patients in India. (3) The initiation factors for DKD are hyperglycemia
IDF-WPR study showed CKD prevalence in 39% and acute kidney injury in diabetics. The pro-
of the study population. Blood pressure control is gression factors for DKD are hypertension, diet
not achieved in a large percentage of the DM 2 and obesity( 4).
population especially in those with DKD. There are various risk factors contributing to de-
There are a variety of causes for kidney disease velopment of DKD. They can be broadly classi-
fied as:
in diabetes mellitus as shown in Figure 1
1.Non- modifiable: Genetic factors, male

sex, Age at onset of diabetes between 5 and
15yrs, long duration of diabetes, increasing age,
family history of diabetic kidney disease, type 2
diabetes, hypertension, and insulin resistance.

2.Modifiable: Poor glycemic control, hyper-

tension, lipid abnormalities, smoking, metabolic

syndrome, Insulin resistance, low grade inflam-

mation, endotoxins, advanced glycation end

products, low intensity of physical activity and

increased salt intake.

Figure 2

Different pathways and networks involved in the initiation and progression of diabetic kidney disease.
The DKD risk factors are susceptibility factors
such as age, gender, race and family history.

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Cardio Diabetes Medicine 2018 279

Recent studies have shown pre-diabetes
as a precursor to DKD as shown in Fig-
ure 1.

hyperfilteration and albuminuria in hperglycemic state

With the onset of DM, kidney size and weight in- Application of transciptomics, genomic, proteom-
crease by an average of 15%, and this size in- ics and metabolomics are being used for the ear-
crease persists even after progressive reductions ly detection and elucidating the mechanism of
in kidney function occur. Proteinuria appears 11 DKD. However, as technology progresses, and
to 23 years after the T1DM diagnosis, serum becomes cost effective, these tools can be wide-
creatinine concentration begins to increase af- ly used for the management of DKD.
ter 13to 25 years, and end-stage kidney disease
develops after 18to 30 years. With the subse- The annual transition rate through stages of al-
quent development of more sensitive assays to buminuria in DM 2 is 2% to microalbuminuria,
detect urinary albumin excretion, small amounts 2.8% macroalbuminuria and 2.3% to decreased
of albumin in the urine (microalbuminuria;30-300 GFR. However, the annual death rate increas-
mg/g creatinine) were noted to precede the de- es steeply from 1.4% without nephropathy to
velopment of overt proteinuria (macroalbumin- 3% with microalbuminuria, 4.6% with macroal-
uria;>300 mg/g creatinine) in most patients, oc- buminuria and 19.2% with advanced CKD(5).
curring 5 to 10years after the diagnosis of DM. Recent advances in the understanding of the
The timing of onset of diabetic kidney disease in pathophysiology of DKD unmasked different
patients with T2DM is difficult to predict. There- pathways such as hemodynamic, metabolic,
fore, a patient may present with proteinuria and
on kidney biopsy may have diabetic nephropathy
even before T2DM is diagnosed.

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inflammatory and, fibrotic involved in the initiation and progression of DKD as shown in Flow chart 1.
Flow chart 1

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The algorithm given by KDIGO is used in pro- There are intricacies in the interpretation of al-
filing each DKD patient during follow up visits buminuria. DKD may not be present if :Absence
in looking at the regression or progression of of diabetic retinopathy
kidney disease.
CKD-EPI formula can be applied using serum a. Rapid decline in eGFR (>1ml/min per month)
creatinine for measuring eGFR as shown below.
b. Sudden onset of Nephrotic syndrome
(6)
c. Refractory hypertension

d. Active urinary sediments (hematuria)

e. Signs or symptoms of systemic disease

f. >30% reduction in eGFR after starting an
ACEi or ARB

Table 1 We cite below a recent example of a patient
whose diagnosis was not diabetic kidney dis-
ease. The kidney biopsy helped in arriving at a
definite diagnosis and management.

CAasSeESScCenEaNriAoRIO 15 years, hyperten-sion for 3 years, HIV-positive for 10 years on

55 years male, T2DM for
sTieonnoffoorv3ir y3e0a0rsm, gH,ILVa-pmoisviutidvienefo3r0100myega, rEsfaovnirenz 600m. Insulin for 10 years,
TOeHnAofsovainrd30A0RmBsg,foLra1m5ivyuedainres,300 mg, Efa-
virenz 600m. Insulin for 10 years,
OCHDA4=s3a9n0dcAeRllsB.s for 15 years, 1+, =4-5hpf, casts,
Diabetic retinopathy treated with laser..
DCHSieDbarAb4u1e=mct3ic59c.0r7e%CatitnE,inoBLipnLPaeS-t1h:.2y06.t8/r7em4agtme/ddml wHigth, Urine albumin RBC WBC= 3-4hpf, Granular ,
laser..
HmbinA11c+,5R.7B%C, BP-126/74 mmHg, Urine albu-
=4-5hpf, WBC= 3-4hpf, Granular
casts, , Serum creatinine : 0.8mg/dl

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Figure. 3 Hypoglycemic use as per eGFR

Figure 4. Ideal HbA1c for T2DM
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Table 2 Dosage of SGLT-2 inhibitors

Management of DKD found to associated with worse renal outcomes.
Better renal outcomes were observed with BP
1. Glycemic control as primary prevention 130/80 mmHg.
for DKD (Fig.3 & 4).
4.Multiple clinical studies have shown dia-
2. SGLT-2 inhibitors dosage and benefits betes mellitus is an independent risk factor
are given in Table 2. for the development of acute kidney injury.
Sustained or uncontrolled hyperglycaemia
3. Treatment of DKD with hypertension produces proximal tubule and podocyte
control and Renin angiotensin system damage via a host of metabolic stressors.
inhibition. The onset of albuminuria signifies a critical
level of podocyte loss and disruption of the
A. Hypertension is highly prevalent glomerular filtration barrier. Although many
in patients with DKD. Treatment of treatments have been targeted at improv-
hypertension in patients with DKD ing renal outcomes in clinical trials, only the
helps with reduction of cardiovas- blockade of the renin-angiotensin-aldoste-
cular risk and slows progression of rone system has proven utility.
renal disease.

B. Inhibition of RAAS remains a corner- 5.Intensive glycemic control has shown
stone of therapy for managing DKD. evidence to reduce microvascular compica-
tions.(Table 3) .
C. Significant residual risk remains in
these patients in spite of maximal 6.Novel treatment for DKD
RAAS inhibition and ongoing explo-
ration for alternative risk reduction
strategies is imperative.

❖ Mean systolic blood pressure >140
mmHg and mean diastolic blood pressure ≥ 80
mmHg in patients with type 2 diabetes were

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Trial Population n Intervention Achieved Findings in Comment
DCCT target Intensive
T1DM 1441 Care Group
Intensive
therapy HbA1c 7.3% Decreased
tageting vs 9.1%
fasting and
postprandial
blood
glucose vs
conventional
therapy

EDIC T1DM 1375 Observational HbA1c 7.8% Reduction
UKPDS patients follow-up of vs 7.9% in
Newly that DCCT with
diagnosed all getting
T2DM 3867 intensive
therapy

Intensive HbA1c 7% vs Reduction Reduction
therapy 7.9% in any not seen
targeting a
fasting blood diabetes- in kidney-
glucose vs
conventional related end specific
therapy
point in events

aggregate

ACCORD T2DM and 10251 HbA1c <6.0% HbA1c 6.4% Increased No benefit
CV events 11140 vs 7-7.9% vs 7.5% CV and totalon kidney
history or
risk mortality end points

ADVANCE T2DM and HbA1c <6.5% HbA1c 6.3% No benefit Albuminuria
CV events vs routine care vs 7.0% on CV reduced by
history or
risk outcomes; 21%

reduction in

VADT T2DM and 1791 Reduction in HbA1c 6.9% No benefit No benefit
poor BP HbA1c of 1.5% vs 8.4% on kidney
control vs routine care end points

Table 3 Summary of key glycemic control trials

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Several trials are undergoing using
molecules as a novel treatment fro
diabetic kidney disease. (Table 4)

Drugs Tested intervention Outcomes

PKC inhibitor Ruboxistaurin Decreased albuminuria,
stabilised kidney function

Anti-AGE treatment PYR-311 Halted
Pentoxyphylline
Anti-Inflammatory, eGFR decline 4.3ml/min 1.73
antifibrotic action Baricitinib m2 less than control group;
Atrasentan mean difference in albuminuria
JAK 1/2 inhibitor Allopurinol of 21%
Finerenone
ETA Albuminuria reduction by 40%
Xanthine Oxidase Liraglutide and semaglutide in the highest treatment group;
Steroid mineralocorticoid no effect on eGFR
receptor antagonist
35% reduction of albuminuria
GLP-1 analogues
ongoing

No difference in eGFR, 17%-
40% albuminuria reduction
dose dependant

Reduction of albuminuria and
better control of HbA1c

SGLT-2 inhibitors Empagliflozin, Canagiflozin Improvement in GFR, decrease
in albuminuria

Table 4. Novel treatment of DKD

7.Ketone 3-beta-hydroxybutyric acid (3-OHB) 8.Lipoxins (LXs ) are lipid mediators that
reduces molecular response to glucose. Ex- promote rate resolution of inflammation.
perimental studies demonstrate that diabetic The potential of LXA4 and a synthetic LX
nephropathy can be reversed by a relatively analogue (Benzo-LXA4) as therapeutics in a
simple dietary intervention. Whether reduced murine model of DKD (streptozocin ‘diabet-
glucose metabolism mediates the protective ic ApoE-/- mouse) was investigated. Using
effect of the ketogenic diet remains to be deter- human renal epithelial cells, LXs attenuate
Egr-1 activation was demonstrated. These
mined. data demonstrate for the first time that LXs
can reverse established diabetic complica-
tions and support a therapeutic paradigm to

promote the resolution of inflammation.

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Highlights

• One in three adults with diabetes mellitus
are estimated to have CKD and most are not
aware of having DKD.

• Type II DM is more common with an incidence
of 87-91% among whom 50% eventually de-
velop DKD. The incidence of type I diabetes
is 7-12% and 33% of them develop DKD.

• 25-41% have non-proteinuric DKD eluding
the diagnosis.

• Kidney biopsy will help in arriving at a definite
diagnosis and management when diabetics
present with atypical features.

• Glycemic control and blood pressure control
with RAAS blockade are the current thera-
peutic choices in the treatment of DKD.

References

1. Sahay r et al., Diabetes research and
Clinical Practice- volume 106, supplement-1.
PO162
2. Nagpal J et al., Diabetes Care.
2006:29:2341-2348
3 1. Rajapurkar M, John G, Kirpalani A, Abra-
ham G, Agarwal S, Almeida A et al. What
do we know about chronic kidney disease in
India: first report of the Indian CKD registry.
BMC Nephrology. 2012;13(1).
4. Clin J Am Soc Nephrol 12: 2032–2045,
2017.
5. Adler A et. al, Kidney Int. 2003
Jan;63(1):225-32.
6. Levey AS, Stevens LA, et al. A New
Equation to Estimate Glomerular Filtration
Rate. Ann Intern Med. 2009; 150:604-612.
7. Alicic R, Johnson E, Tuttle K. SGLT2 Inhi-
bition for the Prevention and Treatment of Di-
abetic Kidney Disease: A Review. American
Journal of Kidney Diseases. 2018;72(2):267-
277.

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AACCI – Dr D.Y.Patil Project on NCD awareness and Preven-
tion in School and Colleges

Dr Swati Y Bhave
Executive Director AACCI – Association of Adolescent and Child Care in India &
Adjunct Professor of Adolescent Medicine ,Dr. D.Y .Patil Medical College, Pimpri, Pune and D.r

D.Y. Patil Vidyapeeth ,Pune

Dr Amitav Banerjee
Professor & HOD Dept of Community Medicine. Dr D.Y. Patil Medical College, Pimpri, Pune and

Dr D.Y. Patil Vidyapeeth ,Pune

Abstract

Most NCD screening and prevention programs cular diseases 2) Cancers 3) Chronic respirato-
in India are focused on people above the age of ry diseases 4) Diabetes? These four NCDs kill
30 years .However it has been well documented 41 million people annually, contributing to 71%
that over half of NCD-related deaths each year of all deaths globally. Cardiovascular diseas-
are associated with behaviors beginning in ad- es account for 17.9 million deaths, followed by
olescence. WHO has identified four behavioral cancers (9.0 million), respiratory diseases (3.9
risk factors – 1) Physical inactivity 2) Unhealthy million) and diabetes (1.6 million). These four
diet 3) Tobacco use 4) harmful use of alcohol groups of diseases account for 80% of all prema-
Thus it is very important to begin awareness,
education and screening for NCD from the pedi- ture NCD deaths. . Most NCD screening and pre-
atric and adolescent age group .We need to in-
crease awareness in the community and do ca- vention programs in India are focused on people
pacity building of the stake holders for the same. above the age of 30 years .However it has been
This age group requires different approach than well documented that over half of NCD-related
adults. School and college programs are the deaths each year are associated with behaviors
best way to increase awareness in young stu- beginning in adolescence. WHO has identified
dents. AACCI -Association of Adolescent and four behavioral risk factors – 1) Physical inactivi-
Child Care in India www.aacci.in was established ty 2) Unhealthy diet 3) Tobacco use and harmful
in 2007, for prevention of Life Style diseases us- use of and alcohol?
ing a Life Skill approach for behavioral change. There are approximately 1.8 billion adolescents
We have created an AACCI module for a 3 -6 and young people across the globe; about 243
hours workshop for schools and colleges which million of them live in India. What happens
consists of Lectures and work stations. Over the during this period have profound impact on adult
last ten years we have conducted programs for life and on national development. There may be
many schools in many cities in India. We have millions of children and adolescents living with
also covered college students from many cities NCDs who may be unrecorded.
and various streams: Medical, Engineering, Arts,
Science, Commerce and Vocational. We have Importance of NCD prevention in Chil-
an active AACCI youth wing for our peer edu- dren and Adolescents
cator program. Our experience has been shared
in many National and International forums- con- Childhood and adolescence represent an “age
ferences and meetings including research pa- of opportunity” for prevention and control, early
pers presented on physical and mental status of detection, treatment, and care of NCDs’. .A life-
these students and also won award course approach, addressing the early origins of
disease and adoption of risky behaviors in ado-
Introduction: lescence, is needed.
1.Since the nidus of high risk of NCD begins
WHO has identified four top NCDs: 1) Cardiovas from LBW in a malnourished mother specially in

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a teen pregnancy (Barkers hypothesis- FOAD addressed
Fetal Origin of Adult Disease) the prevention
should begin from adolescent girls in the precon- AACCI has been working for last 10
ception period. This includes ensuring good nu- yrs to educate young people, parents
trition and prevention of teen pregnancies and teachers in schools, colleges and
in the community
2 . Exclusive breast feeding in the first six months
of life should be encouraged and importance of Background of AACCI
healthy weaning food and avoidance of junk food
right from the toddler age is very important. En- AACCI – Association of Adolescents and Child
suring physical activity as a life style should also Care in India (www.aacci.in) established in 2007
be encouraged from the toddler age which will in Mumbai functions as a civil society.
track into adolescence and adulthood. This im-
portant, as we are now awareabout the concept Our mission is promoting Healthy Life
of DOHaD – Developmental Origins of Health & style to prevent Life style associated
disease. diseases.

3.In adolescence, it is important to make them Our core faculty consists of Doctors from all spe-
aware and educate to prevent the four high risk cialties, mental health professionals, Teachers,
behavioral factors by promoting Physical activity; and Parents from various professions. We have
Increase consumption of healthy food and pre- no sustained grants or full time staff. Our core
vent consumption of Tobacco and Alcohol. faculty works on an voluntary Basis in addition
Thus it is very important to begin awareness, ed- to their full time profession. We sustain on dona-
ucation and screening for NCD from the pediatric tions from well wishers and income from work-
and adolescent age group .We need to increase
awareness in the community about this and also shops

do capacity building of the stake holders for the

same If we have to do early interventions in Our Vision is spreading awareness

childhood & Adolescence to prevent Adult NCD’s and helping teachers and parents to
- then school and college programs are the best
way to increase awareness in young students promote Holistic Wellbeing.

This age group requires different approach to the Most NGOS working on adolescence address
prevention and treatment of NCDs than adults the poorer and marginalized section .We partic-

•Access to youth-friendly services and involving ularly focus on issues of urban children and ado-
young people in prevention interventions are lescents that come from high, upper middle and
crucial. middle socio-economic status, whose issues are
very much neglected.. In families that stay in

•Nearly 3 out of 4 obese adolescents remain metro and big cities in India, there is a rising inci-
obese as adults, increasing their risk of heart dis- dence of a variety of issues in children and ado-
ease, type 2 diabetes, stroke and cancers lescents like: sedentary life style and l junk food,
leading to obesity and NCDS’s; consumption of

•A large percentage (19.0%) of adolescents tobacco, alcohol and substance abuse; behav-
specially boys are current tobacco users , the ioral issues: high risk behavior like drinking and
prevalence is also increasing in girls (8.3%). driving, Internet and Social media addictions;
extreme academic stress due to intense com-

•External factors such as policy and structur- petition, peer pressure depression and suicide.
al measures, availability (i.e., access to sug- We conduct awareness and training programs
ar-sweetened beverages), and media (i.e., to- to deal with these issues for school and college
bacco use by popular movie stars) must also be students with involvement of both teachers and

parents for a longer lasting impact.

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Cardio Diabetes Medicine 2018 289

• In addition we also do charity programs ects over the years in collaboration with AACCI
faculty in Pune, Mumbai, Delhi and other cities
for schools in slums and those that cater to poor 1)Screening for metabolic syndrome and PCOS
section of society. in schools and colleges.
• Multicentric research is ongoing to under- Teaching them to track their own BMI and also
stand youth behavior to plan effective interven- make them aware of the limitations of doing BMI
only for fat deposition and teach them to take
tions. their abdominal girth and W/Hip ratio.
Where ever possible we do a complete physical
AACCI Project for NCD awareness and examination, BP measurement, anthropometric
prevention in Schools and colleges measuremenst. We also take a Family history of
risk factors for NCD
Only education and creating awareness about Those children who show high risk factors or
NCD will not bring about a behavioral change, it suggestion of metabolic syndrome are referred
is important to impart them skills to do this .WHO for further investigations and management to the
Life skill education LSE is a program designed various AACCI core faculties who are clinicians
for adolescents 13-17 years for dealing with all 2)Screening for Life style of school and college
adolescent issues .Global research has shown students
that the teens that have undergone LSE training We have designed an AACCI life style ques-
have reduced high risk behavior and better suc- tionnaire which surveys the eating habits: daily
cess rate in life. AACCI has modified LSE to be breakfast, type of Food consumed-; Exercise
useful for even young people and adults .We use habits and type of exercise; sleep hours daily;
the LSE approach for to bringing about a change Use of Internet and social media; Consumption
in unhealthy life style in students , parents and of tobacco and alcohol etc.
teachers. 3)Screening for Mental health and well being
From 2008 to date we have done multiple pro- We use standardized questionnaires to asses
grams in schools in the states of Maharashtra: self esteem, self motivation, self regulation, self
Mumbai, Pune,Nagpur, Haryana – Gurgaon, Ut- efficacy, GHQ 28, Peer pressure, Anger and ag-
tar Pradesh – Noida , Rajasthan – Jaipur , Mad- gression, Emotional Intelligence, etc
hya Pradesh – Indore , old Andhra Pradesh – 4)Use of Peer educators for awareness of NCD
Hyderabad and Delhi state prevention – doing workshops in schools to teach
We also have done programs in colleges Mumbai children – about the 1) importance of Healthy
–Medical, Arts Commerce Science and Arts. We diet 2) learning to read food labels on packaged
have worked for nursing and medical students in foods and understand the nutrient value of what-
Mumbai, Delhi and Pune. We have also worked ever food they eat .This helps them to avoid or at
in slum schools in Nagpur, Delhi and poor SE least limit High density/High salt/ High sugar or
schools in Pune so called junk food. .3) Education for reduction of
sedentary habits and increasing physical activity.
In the year 2009 we started working in collab- 4) Avoid temptation of tobacco and alcohol.
oration with the Dept of Pediatrics at Dr D.Y In the last 10 yrs we have presented papers in
Patil Medical College, Pimpri Pune for work many International and National conferences
on Life skill education and Healthy life style and won awards.
of first year Medical students.

From -2018 we have started collaboration International Presentation of AACCI
with the Community Medicine Dept to do a projects
five year project for NCD awareness and pre-
vention in the Medical students. We have 1.In 2010 at the APPA( Asia Pacific Pediatric As-
trained medical students as peer educators
for NCD awareness programs in Schools. sociations ) at Shanghai,China Dr Swati Bhave

AACCI has done the following activities and proj- gave a plenary lecture on Life skill education im-

pact in adolescents where she also shared AAC-

CI experience the use of LSE to make a behav-

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Cardio Diabetes Medicine 2018 290

ioral changes in adolescents for healthy life style -100 students. Each topic is taught in 10-15 min-

2.Dr Swati Y Bhave was on the Governing coun- utes

cil ( 2015-17 ) of a global Body -NCD child ( b)Then they are divided into smaller groups of 20

www.ncdchild.org ) .She was faculty for a Pre to 35 each and rotate in all 3 workstations

conf training workshop for Pediatricians as NCD

champions at the APPA( Asia Pacific Pediatric The 3 lecture topics and workstations cover

Societies) ) and Annual Pedicon 2016 at Hyder- the following

abad conducted by NCD child and AAP – Amer- 1)What is meant by healthy life style: importance

ican Academy of Pediatrics along with AAPA of healthy diet, physical activity and adequate

and IAP ( Indian Academy of Pediatrics) for 30 sleep .Obesity is the precursor of NCD’s and we

nominated pediatricians from various countries teach them self monitoring with tracking of their

of Asia- Pacific region BMI and e importance of taking abdominal girth

3.AACCI did a school project with NCD child and waist hip circumference ratio and tracking

in 2015 on “Awareness for NCD in School chil- them.

dren”in n a school from Dwarka, Delhi. It showed We also explain in detail the various types of ex-

that a even a short 6 week project was very effec- ercises and physical activities to keep healthy

tive in making a behavioral change in both staff and the ill effects of sedentary life style on mind

and students who started bringing healthy home and body.

lunch and there was a reduction in the junk food 2)The nutrient values of various food items in-

consumption and increased willingness to take cluding packaged food. Explain concept of trans

part in sports. This was presented as a model in fat and the suga-r salt craving which is addict-

the above workshop ing .They are also taught about risk obesity, dia-

betes and hypertension due to high sugar, high

AACCI Module ( 6 hours) for promot- transfat and high salt consumption. Learning to
read food labels to eat the right kind of food and
ing healthy life style through Life skill eating consciously i.e. understanding the nutri-
approach and awareness of NCD risk ent value of whatever they are eating.
factors 3) We teach how adolescents are vulnerable
to addictions due to the hypothalamus and lim-
We conduct programs according to the time giv- bic preponderance of the developing brain at this
age. Consumption of tobacco and alcohol at this
en by the school authorities. We require 3 to 4 age has a very high chance of lifelong addiction.

faculties per session which includes AACCI Core

Faculty and Peer Educators

Part a Contents (Three hours) Instead of just saying DON’T smoke , use to-
Format – lectures, group discussions, case bacco products or drink we explain scientifically
scenarios, debates etc the short term and long term damage (changes
1)Core ten WHO Life skills are taught and in the brain and damage to body ) due to these
products and empower them to use Life Skills to
through interactive group discussions and case prevent succumbing to negative peer pressure
and experimentation.
scenarios. We empower them to use these skills

to make behavioral changes for inculcating a

healthy life style and prevent high risk behavior. High lights
2)Understanding elements of healthy life style 1.NCD prevention is a life course issue. Pre-
:healthy diet, regular exercise, adequate sleep vention has to start from preconception period –
and positive mental health by dealing with stress good nutrition of adolescent girls and prevention
and negative emotions of teen pregnancy. Intervention from infancy and

Part B Contents (Three hours) pediatric age group –Exclusive breast feeding ,
Format: Three Lectures and three worksta- healthy weaning , promotion of physical activity,
tions avoidance of junk food ,healthy diet and ade-
a)We start with interactive power-point lectures quate sleep .
2.In adolescent age group, in addition, preven-
with attractive graphics for the whole group 60 tion of various addictions tobacco, alcohol and

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Cardio Diabetes Medicine 2018 291

prevention of sedentary life style by addiction to Focus on Epigenetic Mechanisms. Semin Re-
electronic gadgets . prod Med 2009; 27: 5: 358 – 368.
3.School and college programs are the best way 6.Global Youth Tobacco Survey (GYTS) India
to increase awareness in young students. (Ages 13 – 15) Fact Sheet. Available at: http://
4.AACCI Association of Adolescent and Child www.who.int/fctc/reporting/Annexoneindia.pdf
Care in India www.aacci.in was established in (accessed 27 July 2018)
2007 for prevention of Life Style diseases us- 7.Swati Bhave- Innovative Methods of Life skill
ing a Life Skill approach for behavioral change. Training Program .Indian Journal of Life Skills
We have created an AACCI module for a 3 -6 Education Volume 1 Number 1 July 2009 P: 1-12
hours workshop for schools and colleges which
consists of Lectures Interactive case scenarios,
group discussions and work stations.
5.Over the last ten years we have conducted
programs for many schools in many cities in
India. We have covered college students from
various streams: Medical, Engineering, Arts,
Science, Commerce and Vocational. We have
active AACCI youth wing for our peer educator
program. We also conduct master trainer pro-
grams for our modules .You can contact us at
[email protected]
6.Our experience has been shared in many Na-
tional and International forums- conferences and
meetings. Our data on surveys for physical and
mental status of these students presented in
conferences and also won awards.

References

1.UNICEF. Adolescence – An Age of Opportuni-
ty. United Nations Children’s Fund. India Coun-
try Office, UNICEF House, 73, Lodi Estate, New
Delhi 110003 2011. http://unicef.in/Uploads/Pub-
lications/Resources/pub_doc118.pdf (cited 26
July 2018)
2.Nair H, Bypass P. Mortality in older children
and adolescents: the forgotten ones. The Lancet
2018: 2: 306 – 307.
3.World Health Organization, Global Status Re-
port on No communicable Diseases (Geneva:
WHO, 2011), accessed at www.who.int/nmh/
publications/ncd_report2010/en/index.html (cit-
ed 27 July 2018)
4.Calkins K, Devaskar S U. Fetal Origins of Adult
Disease. Curr Probl Pediatr Adolesc Health Care
2011; 41: 6: 158 – 176.
5.Wadhwa P D, Buss C, Entringer S, Swanson
J M. Developmental Origins of Health and Dis-
ease: Brief History of the Approach and Current

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ROLE OF LIFESTYLE MODIFICATION : YOGA AND THE BODY,
TO PREVENT NON -COMMUNICABLE DISEASES IN HIGH RISK

POPULATION – A MULTI DIMENSIONAL APPROACH

Dr. Vivek Chandra MD

Consultant Physician, Gurakhpur

Abstract: A community-empowerment approach can en-
courage community participation which in turn
Non communicable Diseases are on the rise and may improve the citizen’s knowledge of the dan-
pose a significant threat to us. This has increased ger /impact of CVD and be a feasible way to
out of proportion more so for the mid and low prevent and control CVD. Studies incorporating
income populations globally. There is thus an Lifestyle interventions resulted in a significant
increased need for awareness, screening and decrease in the incidence of Type 2 diabetes and
diagnosis of NCDs at the earliest. Alongside in- better control of NCD risk factors in population
terventions to check the rise of cardiovascular based setting
diseases, respiratory diseases and metabolic The need for long-term community-based pro-
diseases like Hypertension and Diabetes, is it grammes which aims to evaluate lifestyle mod-
now time we give a patient hearing to our needs ification interventions to prevent or postpone the
of the mind and body. Will Yoga help us turn in development of NCDs has led to large studies
sync with nature and rectify our body and will cor- like The Tehran Lipid and Glucose Study (TLGS)
recting the dietary habits make the much needed which promise to throw light on future of manag-
impact to serve the call of the hour.

Content ing NCDs.On the other hand the recently pub-
lished PURE study suggests that High carbo-

hydrate intake is associated with higher risk of
Non communicable diseases (NCDs) are diseas- total mortality, whereas total fat and types of fat
es like Cardio vascular diseases (e.g. Heart at- are not associated with cardiovascular disease,
tack and stroke) malignancies, Diabetes, Chron- myocardial infarction, or cardiovascular disease
ic respiratory diseases which affect people of all mortality, whereas saturated fat had an inverse
age groups across the globe. Their prevalence is association with stroke.With so much of infor-
on the rise in the modern era. Lifestyle patterns mation available on the outside, ancient Indian
are mainly responsible for NCDs more so for techniques like yoga –aasanas(postures), pra-
the people in low- and middle-income countries nayama(breathing techniques) and meditation
where more than three quarters of global NCD certainly offer a way to combat the situation...so
deaths – 32million – occur. Physical inactivity, al- to say that the way out may be traversing the
cohol, tobacco, poor dietary habits, stress and path within.The human body is at its best when
ignorance all pre dispose to NCDs. This leads allowed to function in complete sync with nature
to approx.41 million deaths each year i.e. 71% and fuelled by balanced nutrition and rest.
deaths globally.

Cardiovascular diseases cause most number of References:
deaths followed by cancers, respiratory diseases
and Diabetes. Tobacco, alcohol and dietary hab- (1)WHO data on NCD India
its are modifiable behavioural risk factors. (2)Tetra Dewi FS, Stenlund H et al, A community
Metabolic risk factors such as Obesity, hyper- intervention for behaviour modification: an expe-
glycemia, hyperlipidemia and hypertension rience to control cardiovascular diseases in Yog-
are some more predisposing factors for NCDs. yakarta, BMC Public Health2013 Nov 4;13:1043.
Raised Blood pressure levels alone attribute to doi: 10.1186/1471-2458-13-1043.

19% of global NCD deaths data. Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 293

(3)Harati H, Hadaegh F et al, American Journal
of Preventive Medicine 2010
(4)Azizi F, Ghanbarian A, et al Prevention of
non-communicable disease in a population in
nutrition transition: Tehran Lipid and Glucose
Study phase II. Trials 2009 Jan 25;10:5. doi:
10.1186/1745-6215-10-5.
(5)Dr Mahshid Dehghan, PhD, Andrew Mente,
PhD et al, Associations of fats and carbohydrate
intake with cardiovascular disease and mortali-
ty in 18 countries from five continents (PURE):
a prospective cohort study, The Lancet, volume
390, issue 10107, P2050-2062, november 04,
2017

Highlights:

•Non communicable Diseases are on the rise
and pose a significant threat.

•There is an increased need for awareness,
screening and diagnosis of NCDs at the earliest.

•Cardiovascular diseases cause most number of
deaths followed by cancers, respiratory diseases
and Diabetes

•Lifestyle modification: Yoga may help us turn in
sync with nature and care for needs of the mind
and body.

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Cardio Diabetes Medicine 2018 294

06. Future

1 Legal Challenges in Medical Practice-Dr.RaviWankhedkar

2 Digital intervention in CardioDiabetes Medicine-Dr.S.Arulrhaj

3 Communication in Healthcare-Dr.Alex Thomas

4 Predictors of ISR in the Contemporary DES ERA-
Dr.RamasamiNandhakumar

5 Tips, Tricks, Traps of making an impactful presentation-Dr.Kulkarni

6 Artificial Intelligence & IOT in Medicine-Dr.Kulkarni

7 Undergraduate Medical Education for the Future-Prof.Sam Lingam

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Cardio Diabetes Medicine 2018 295

LEGAL ASPECTS OF MEDICAL PRACTICE

Dr. Ravi Wankhedkar

National President,
Indian Medical Association
Consulting Surgeon & Coloproctologist
Hon Prof Of Surgery, Sbh Govt Medical College,Dhule

SCENARIO ENTITLEMENT OF MEDICAL

TOO MANY LAWS GOVERNING THE HEALTH PRACTICE
SECTOR
After medical education comes regulation of

entitlement of medical practice.
HEALTH CARE PROVIDERS FEEL THAT THE This is by defining medical degrees, in the case
SECTOR IS OVER REGULATED
of modern medicine by Medical degrees act

1916 and MCI Act 1956.
LAW MAKERS AND ADMINISTRATORS FEEL Trainings and certificates also come under the
THAT THE SECTOR IS UNREGULATED
purview but are poorly defined.

Entitlement for speciality & super speciality prac-
Areas covered under laws and regulations in re- tice is also ill defined.
lations to medical practice can be categorised Encroachment & quackery: Lacunaes in regula-
under three headings
tion and implementation lead to encroachment,
(i) Medical Education: This topic again encom- quackery and mixopathy
passes a number of issues right from recognition

of qualifications, recognition of educational insti- CONTROL OF MEDICAL PRACTICE
tutions, the courses of study, right of admission
and various other aspects concerning rights of Control of medical practice is by Medical coun-
medical students, etc. cils & ethical regulations, Government control
(ii) Entitlement to medical practice and the lim- through various laws and regulations,
itations of the same: What does a given degree Protocols and guidelines also control practice.
entitle you to practise? Can an allopathic doctor These are published by the government, scien-
prescribe Homeopathic medicines, etc. tific bodies or by institutions.
(iii) Control over medical practice: Machinery Standard practice is defined by the common
which will ensure the enforcement of the laws practice adopted by majority of practioners in
referred to above. the particular country. Deviation from standard
practice is allowed if there is specific justifiable

MEDICAL EDUCATION reason.

Advancements in the medical field also govern

Medical education is covered by practice indirectly.

1. MCI ACT, Trial & experiments are part & parcel of medical

2.UNIVERSITIES ACT, and sector and are now governed by amended pro-

3.OTHER COUNCILS visions in the drugs & cosmetics act with regula-

tions of clinical trials & human experimentation

Recognition of educational institutions, the cours- published in 2012.

es of study, right of admission, various other as-

pects concerning rights of medical students, etc. MEDICAL ETHICS
come under laws governing medical education. Ethical regulations of MCI 2002 with its subse-
As you already know Medical council act 1956 quent amendments regulate ethical practice. Vi-
is of paramount importance regarding medical olation of regulation can be punished with fine,
education.
censuring and penal erasure from the medical
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Cardio Diabetes Medicine 2018 296

register CEA enacted by various states and Clinical es-
tablishment act, national.
The dilemma with the current ethical regulations
are whether medicine is a trade or profession. CONSUMER DISPUTE REDRESSAL
Self regulatory concept of the profession is being
threatened by frequent government interferenc- CPA act Passed in 1986. Medical profession
es. included in 1995 following supreme court verdict
Demarcation between ethics and law is vague in in V.P.shantha Vs IMA case
medical profession In Jacob Mathew case, Supreme court enacted
While individuals well regulated, institutions are regulations limiting arrest of doctors in alleged
poorly regulated regarding ethics. negligence. In Martin D’Souza case this was ex-
tende to civil & consumer cases by the supreme
MEDICAL MALPRACTICE LAWS court. But in Nikhil superspeciality case another
two judge bench reversed the order.
a) Consumer Dispute Redressal Agencies,
with its district fora, state commission and JUDGEMENTS AWARDING HIGH
national commission established under CPA COMPENSATION

b) Medical Council of India and Den- Nizam institute case 1.2crore
tal Council of India: Receive com- Kunal Saha case 11 crore
plaints regarding violation of ethics W&C Hospital, Tamilnadu 1.8 crore
 
c) Civil Courts also receive and tri- The reasons for such a high compensation
al medical negligence cases. awards was (i) Scientific facts were not properly
  presented before court (ii)Courts deviated from
d) MRTP (Monopolies and Restrictive Trade usual norms
Practices Commission) is now redundant
  IMA STAND
e) Public Interest Litigation can be filed
in high courts by the aggrieved party No practitioner should be booked under the pro-
  visions of IPC except under extraordinary cir-
f) Sections of Indian Penal Code, 1860 (Crim- cumstances. The provisions has to be clearly
inal courts): Criminal compalint against doc- defined
tors are taken up sections of IPC.
MCI ACT
g)Other Agencies like (i)Human Rights Com-
mission (ii)Vanitha Commission (iii) Lok Although MCI is called the regulatory body, it has
Adalat (iv) permanent Lok Adalat, (v) minori- limited regulatory role
ties commission, (vi)child commission etc NOC for medical colleges decided by the state
also take up medical negligence and related govt.
cases. Syllabi modified by respective universities
No financial and administrative autonomy
DRUG DISPENSATION & DRUG LAWS Overlap of portfolios with other councils and
agencies
Magic remedies act: 1954 Act to control advertis- Representation from states erratic and not ac-
ing of drugs in India. cording to the number of registered practitioners
Drugs and cosmetics act 1940 regulate, import
manufacture and distribution of drugs in India NMC

CONTROL OVER HOSPITALS Predominantly nominated body without repre-
sentational nature, control over powers of states,
Nursing homes registration act of various states, impractical reforms in medical education like exit
exams, provision for bridge course & mixopathy

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Cardio Diabetes Medicine 2018 297

Success saga of IMA, due to our historical strug- Bio-Medical Waste (Management and Han-
gle, many provisions amended and the amended dling) Rules, 1998
bill was not brought before Loksabha The Pharmacy Act, 1948
The Transplantation of Human Organs Act
CLINICAL ESTABLISHMENT ACT and Rules
Environmental Acts and Rules
For Registration and regulation of clinical estab- Consumer Protection Act and Medical Pro-
lishments. fession
State council Mental Health Act, 1987
District authority of registration Food Safety and Standards Regulations
Provisional and Permanent registration The Protection of Women From Domestic Vi-
Cancellation of registration olence Act, 2005
Penalties The Marriage Laws (Amendment) Bill, 2010
The Prohibition Of Sexual Harassment Of
OUR DEMANDS Women At Workplace Bill, 2010
Food Safety and Standards (Prohibition and
Registration of clinical establishments and main- Restrictions on Sales) Regulations, 2011
tenance of appropriate standards are necessary. Food Safety and Standards (Contaminants,
Govt regulation through licensing process is not Toxins and Residues) Regulations, 2011
required.
The state council should have a representative List of Licenses and Statutory Obliga-
character of stake holders. tions
The institution may conform to the prescribed All of them might not be applicable to
standards through independent accreditation all the Hospitals:
agencies and this should be adequate for regis-
tration without inspection by Govt agencies. 1.Building Permit (From the Municipality).
State level council is adequate. District authority
is not necessary. 2.No objection certificate from the Chief Fire of-
A minimum of 5 yr period should be given to the ficer.
institutions to achieve the standards.
This state authority should provide a single win- 3.Bio- medical Management and handling Rules,
dow for all legislations and regulations. 1998.
The stabilization clause is unrealistic and should
be deleted.  4.No objection certificate under Pollution Control
The act should include provision for promotion Act.
of clinical establishments.
The penalty clauses and complaint cell should 5.Radiation Protection Certificate in respect of all
be deleted. X-ray, Cath lab and CT Scanners from BARC.

SOME LAWS DIRECTLY RELATED TO HEALTH 6.Atomic energy regulatory body approvals.
The Medical Termination of Pregnancy Act
and Rules 7.Excise permit to store Spirit.
The Pre-Natal Diagnostic Techniques (PNDT)
Act and Rules 8.Income tax PAN.
Acts in Disability
Insecticides Act and Rules 9.Permit to operate lifts under the Lifts and Es-
Maternity Benefit Act and Rules calators Act.
Narcotic Drugs and Psychotropic Substanc-
es Act and Rules 10.Narcotics and Psychotropic substances Act
The Prevention of Food Adulteration Act, and License.
1954
Drugs and Cosmetics Act, 1940 11.Sales Tax Registration certificate.

12.Vehicle registration certificates for Ambulanc-
es.

13.Retail and Bulk drug license (Pharmacy).

14.Wireless operation certificate from Indian
post and telegraphs, (if applicable)

15.Air (prevention and control of pollution) Act,
1981 and License

Cardio Diabetes Medicine