The words you are searching are inside this book. To get more targeted content, please make full-text search by clicking here.
Discover the best professional documents and content resources in AnyFlip Document Base.
Search
Published by , 2018-09-22 10:39:45

22sep

22sep

Cardio Diabetes Medicine 2018

Cardio Diabetes Medicine 2018 2

Cardio Diabetes
Medicine- 2018

Theme: Liberate Heart Monitor Diabetes

“Importantly, a multidisciplinary team approach is required
to addresscardiovascular disease, including coronary heart
disease, stroke and heart failure,in patients with diabetes.
Collaboration within the team is essential, thus no onespe-
cialty should claim ownership ” - Nathan D. Wong

Editor in Chief

Prof. Dr. S. Arulrhaj, MD., FRCP (Glasg)

Chairman, Commonwealth Medical Association Trust,UK
Chief Physician and Intensivist
GCDC 2018, Mumbai, India

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 1

No part of this publications may be reproduces, stored in a retrival system or transmitted,
in any form or by means electronic, mechanical, photocopying, recording or otherwise with-
out pror permission of the copyright owner

This publications contains view or opinons of expert in field of cardio Diabatology Pub-
lished by Prof. Dr.S Arulrhaj,MD, FRCP(G) on behalf of Indo Global Cardio Diabetes Acad-
emy, Mumbai.

Date of Publishing: September 2018

Editor Chief

Prof. Dr.S Arulrhaj,MD, FRCP(Glasg)

Chairman Commonwealth Medical Association Trust, UK
Chief Physician Intensivist

Editorial Board : Dr. Aarathy Kannan
Dr. D. Selvaraj
Dr. E. Prabhu
Dr. Shahid Merchant



Editorial Assistants : Dr. Gurunadharao
Dr. Princy John
Dr.Ashwin Paul
Dr.Ankitha

Designed By:
Login Technique
Briyant Nagar
Tuticorin - 628008

DISCLAIMER
The editor have checked the information provided in the publications to the best of their knowl-
edge.However in view of possiblity of human errors and change in medical science nei-
ther the author nor the publisher or any other persons who has/have been involved in the
preparation of works warrents and the information contained herein is in every respect ac-
curate or complete and therfore disclaim all the responsibility for any errors or omissions or
for the results that may be obtained in the use of information contained in this publications.

Copyright belongs to IGCDA

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 1

DIGITAL INTERVENTION
IN CARDIODIABETES
MEDICINE

Prof.Dr.S.Arulrhaj.M.D,FRCP(G)

Cheif Physician & Intensivist, Tuticorin
Past President,Commonwealth Medical Association,UK

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 2

DIGITAL INTERVENTIONS IN CVD & DIABETES

Prof.Dr.S.Arulrhaj.M.D,FRCP(G)

Chairman,Commonwealth Medical Association Trust,UK &Commonwealth Medical eVarsity
Founder & Past Chairman,Commonwealth Health Professions Alliance,UK
Past President,Commonwealth Medical Association,UK
Past National President,IMA,NewDelhi
Chief Patron,IMACGP INDIA&IMA eVarsity
Vice President, Association of Physicans of India
Formerly Adjunct Professor f Medicine, Dr.MGR Medical University, Chennai

Co-Author:

Dr.Aarathy Kannan,MD,Dip.Diab

Consultant Physician &Diabetologist ,Sundaram Arulrhaj Hospitals,Tuticorin

Dr.Bhuvaneshwar,Dr.Kiran Palsania,Dr.Gurunadharao

Postgraduate Students,Sundaram Arulrhaj Hospitals,Tuticorin

E-HEALTH : According to who E-HEALTH is

defined as the use in the health sector of digital

data-transmitted, stored and retrieved electroni-

cally- in support of health care, both at the local

site and at a distance (WHO – 2003)

TERMINOLOGIES :
E-Health

m-Health

i-Health

TeleHealth

Digital Health

Connecting Care Provider & User WHAT IS DIGITAL HEALTH?
Personal Visit
Virtual Visit Digital health is the convergence of the digital,
and genomic revolutions with health, healthcare,
Ø I –Health living, and society.
Digital health is empowering people to better
Ø EHealth track, manage, and improve their own and their
family’s health, live better, more productive lives,
Ø Telehealth and improve society.

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 3

Digital health is not just mobile workers, and patients themselves. Ultimately
apps. an enabler, digital health helps governments
and other providers offer accessible, affordable
Mobile phones are an important – but not health services to their populations, empower-
singular – part of digital health. Digital health ing individuals and their families to make better
includes the use of any electronic or mo- choices to improve their quality of life. Digital
bile technologies that support better collec- health includes open source technologies (like
tion and use of data, improved quality and DHIS2 and LMIS) and health information sys-
reach of health service delivery, and better tems infrastructure that allows data to be shared
decision-making by health service providers, across provinces, regions, and countries.

TELEHEALTH :

The use of telecommunications and information
technologies to provide and support health care
when distance separates the participants.

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 4

WHY TELEHEALTH? E-prescribing: prescription options, printed pre-
• Current physician shortage scriptions and sometimes electronic transmis-
• Affordable Care sion of prescriptions from doctors to pharmacists
• consumers at the center • Telemedicine: physical and psychological
• Accessible treatments provided over networks, including
• Convenient telemonitoring of patients’ functions
• Accountability E-prescribing: prescription options, printed pre-
• Compliance scriptions and sometimes electronic transmis-
It is not possible for every one to own acomputer sion of prescriptions from doctors to pharmacists
or to use a computer for health, but smart phones • Telemedicine: physical and psychological
comes in handy, and so, forsure , all aspects of treatments provided over networks, including
healthcare will finally converge to mHealth” telemonitoring of patients’ functions
• Consumer health informatics: Use of elec-
WHY DIGITAL HEALTH? tronic medical resources by healthy individuals
or patients
• Connecting Care Givers and Patients • Consumer health informatics: Use of elec-
• Round the clock monitoring tronic medical resources by healthy individuals
• Reduces Travel & Waiting or patients
• Reduces cost • Health knowledge management: E.g. provid-
• Shortfall of HWF compensated ing an overview of latest medical journals, best
• Quality Health care practice guidelines or epidemiological tracking
• Uniform Health System (for example, physician resources such as Med-
scape and MDLinx)
TYPES OF DIGITAL HEALTH • M-health: Includes the use of mobile devices
in collecting aggregate and patient-level health
Types of E-Health has diverse applications in- data; providing health care information to prac-
cluding: titioners, researchers and patients; real-time
• Electronic health records: Patient data stored monitoring of patient vitals; and direct provision
on computers enabling the communication of pa-
tient data between different health care profes- of care via mobile telemedicine.
sionals (GPs, specialists, etc.)

LEADING CAUSES OF DEATH (ILLNESS)

CDC- 2015 total death in USA WHO INDIA data

• Heart disease: 611,105 1. Ischaemic heart disease 12%

• Cancer: 584,881 2. Chronic obstructive pulmonary dis-
• Chronic lower respiratory dis- ease 11%

eases: 149,205 3. Stroke 9%
• Accidents (unintentional inju- 4. Diarrheal disease 6%
5. Lower respiratory infections 5%
ries): 130,557 6. Preterm birth complications 4%
• Stroke (cerebrovascular diseas- 7. Tuberculosis 3%
8. Self-inflicted injuries 3%
es): 128,978 9. Falls 3%
• Alzheimer’s disease: 84,767 10. Road injury 2%
• Diabetes: 75,578
• Influenza and Pneumonia:

56,979

• Nephritis, nephrosis: 47,112

• Intentional self-harm (suicide):

41,149

• CDC 2015 total deaths in Uni-

ted states

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 5

• Medical research using grids: powerful com- POC IS THE NEW STANDARD FOR
puting and data management capabilities for DIAGNOSTICS
handling large amounts of heterogeneous data
• Health care information systems: software • Biometric Screening of SpO2 , Blood
solutions for appointment scheduling, patient
data management, work schedule management Pressure , Blood Sugar, Spirometry ,Total Cho-
and other administrative tasks surrounding
health lesterol ,ECG, Triglyceride , Body Composition.

DIGITAL CARDIAC HEALTH TELE ECG: NO LONGER NEWS
All Solutions that exist currently are portable ECG
recorders and Holter monitors but none provide Earlier it was over phone lines, or scan and
real-time, beat-by-beat event information .
Remote Monitoring email but No wireless, to smart phone which
India being the cardiac disease capital of the
worldand CVD’s being leading cause of deaths Makes the cardiologist more accessible
in the country makes Remote Monitoring Key .
The platform consists of wearable wireless health
sensors that provide continuous monitoring out-
side clinical settings with acceptable accuracy.
The sensors and electrodes are designed keep-
ing the patients comfort. Advanced data analyt-
ics to provide real time diagnosis on the smart
phone based on the sensed data and patient’s
digital health record

CARDIOVASCULAR DISEASE DIGITAL
INTERVENTIONS

Diagnostic
ECG – arrhythmias
PA Pressure – Pre LHF
Lung fluid level – LHF
Pulse Oxymeter – Hypoxia
BP – Low or High BP
Diet
Walking
Sleep
PFT
Drugs – Remainder & Adherence

Why?
• Detect Dysarrhythmia
• HTN
• Hypotension
• Early Cardiac Failure

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 6

Real time teleecho - Clinical teleradiol-
ogy

It is the use of telecommunications to deliver re-
al-time radiology services from one location to
another for interpretation, consultation, and col-

AMICOMED: A Digital Platform for blood pres- PATIENT WHO MONITORS HER
sure management combining innovative algo- HEALTH AT HOME :
rithms for remote monitoring, data interpretation
and personalized lifestyle change programs.
Presently available only in US &UK.

•TRACK Blood pressure tracking and instant per- • We have to taught how to use her new
sonalized feedback home monitoring devices
•Coach & program, 3 month personalised life- • Each day she will takes her vital signs
style program and answers a few questions about how she
•Insights on your blood pressure trend in different feels.
time bands and progress in the program • She can also view educational videos at
•Direct coonectivity with your physician her convenience.
• The data will be sent to a call center or
DIGITAL HEALTH AND TERTIARY physician’s office if medications are missed or if
CARE patient

Doctors mobility restored by using mHealth.Inpa- DIGITAL HEALTH - THERAPEUTICS
tient Data is transmitted through Mobile
• Defibrillator
• Emergency Reach
• HF

OMNIPOD
• Besides monitoring and notification,
wearable medical devices also have the poten-
tial to provide automated or remote treatment.
The OmniPod is an example of a wearable insu-
lin pump that coordinates with a glucose moni-
tor to automatically administer correct dosage.

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 7

ZOLL’s LifeVest The ‘Uberization’ of Healthcare
It is a wearable defibrillator worn by patients at
risk of a heart attack. It monitors heart rhythms In the information technology world, a recent
and in the event of a heart attack, releases
conductive gel from its electrodes and admin- innovation has been the software as a service
isters a life-saving electrical shock to restore (SaaS) model, where software access can be
normal heart rhythms. leased and operated and updated over the In-
Monitoring Arrhythimias Notably AF ternet
Common devices used for HF patients’ TLM are
the pulse oximeter, the scale, the BP/HR moni- This will be used as a business template for
tor, the ECG (one or more leads), the detector of greater electronic access to healthcare. Integrat-
motion and fall, and the personal alarm services. ing use of smartphones, patients will soon be
Environmental sensors including temperature, able to access physicians, or locate the closest
smoke, humidity, water, and gas detectors. healthcare kiosk, clinic or hospital using mobile
Implantable Devices apps. This will lead to an “Uberization” of health-
Cardiac implantable device (ID) may benefit from care, similar to customers who use the Uber app
monitoring, since all modern IDs can transmit- to quickly locate and electronically hail the clos-
technical and diagnostic data remotely, allowing est available cabs.
an integrated clinical management involving HF An insurance company launches wearable sen-
centres’ professionals and knowledgable gener- sor package
al practitioners (GPs) 2017 will be the year when the behemoth system
•High tech & High touch perspectives to be bal- of health insurance will start to change with data
anced provided by patients. The hipster insurance com-
HF - AF pany, Oscar Health made the first steps already.
HF patient management is the monitoring of ar- It has built upon the idea that without quantifying
rhythmias notably of atrial fibrillation health, insurance is the riskiest business of all.
•Use of remote monitoring devices as Class 1A With the help of Oscar Health, insured people
recommendation, both to reduce inappropriate can submit their Fitbit data; and if they reach
shocks, and for early detection of atrial fibrilla- their fitness goals, they get $1 every day. It helps
tion. keep people healthy and motivated with a simple
but quantifiable reward.
Cardiovascular Advances to Watch in I believe that in the future, smoking, drinking
the Next Decade heavily, eating trashy food and not doing any
sports might not only cost people a lot in terms
of their expenses and their health on the long
run, but it might also heavily burden their health
insurance with extra fees.

Defibrillator-equipped drones could be 1st on
scene in cardiac arrest.
A drone could get to a patient faster than emer-
gency services and could increase survival rates
Dispatching drones outfitted with defibrillators
could cut response times and increase survival
rates during cardiac arrest. Currently, only 10 per
cent of people survive a cardiac arrest that oc-
curs outside a hospital. (Ashley Burke/CBC)
Drones could fly 100 km/h directly to an emer-
gency.While drones can be piloted remotely,
An example of flexible electronics made by they can also fly themselves. Self-flying drones
MC10. These types of wearable devices may are guided by dependable GPS systems and
soon be used to remotely monitor patients could respond quickly to nearby aircraft, Schoe-
llig said.

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 8

In cognitive computing, a system or device is
trained by machine learning or deep learning al-
gorithms.

The goal of cognitive computing is to create
automated computerised models that can
solve problems without human assistance (Krit-
tanawong, 2017).

IBM Watson, a well-known example of cognitive

AI in cardiology computing, continuously learns from datasets
AI techniques such as machine learning, deep (eg EHR, social media, stock market) and can
learning, and cognitive computing, may play predict outcomes using multiple algorithms more
a critical role in the evolution of cardiovascular accurately than humans.

medicine to facilitate precision cardiovascular One example of this use in cardiology is the
medicine. In order to deal with cardiovascular research made by Dr. Partho Sengupta (2016)
big data, we will certainly need these techniques. where he developed an associative memory

classifier, a cognitive computing machine learn-
In cardiovascular biomedicine, there are four bio- ing algorithmic approach, to classify constrictive

medical big data sources which are important: pericarditis from restrictive cardiomyopathy, and
1. Functional phenotypes such as demograph- demonstrated its feasibility for automated inter-
ics, echocardiograms, haemodynamics ,electro- pretation of speckle-tracking echocardiography
cardiography, and imaging data data.
2. Molecular profiles derived from large-scale Artificial Intelligence in the field of cardiac
omics data that may be acquired in large trials imaging
or the clinical setting AI will have a role to aid reproducibility in car-
3. Medical records, including patient electronic diac imaging, for example Siemens Healthcare
medical records containing laboratory test re- was the first to introduce elements as algorithms
into its cardiac echo systems several years ago

sults, physician’s notes and other information on to speed automation.

disease, treatment, and epidemiology that may Philips Healthcare also has introduced elements
be mined for association studies and predictive of AI on its EPIQ ultrasound system some years
modelling on prognosis and drug responses ago. Here, they take a 3D echo dataset acquisi-
4. Literature knowledge: it is estimated that in tion which automatically analyses the image to
cardiovascular medicine there is a new publica- identify the heart’s anatomy, labels it and then
tion released approximately every three minutes. slices the optimal standard views for presen-
This amount of data overwhelms human intelli- tation. This tool eliminates issues with interop-
gence, but may be mined and structured by deep erated variability, because the software will al-

learning algorithms. ways choose the best views based on machine

Despite its fast and wide penetration of learning, which uses thousands of prior studies
medicine in general, as Kahneman (2016) points representing the spectrum of patient anatomical
out, “Most cardiologists today are more likely to variations. This would take years for a human
associate the term ‘artificial intelligence’ with a operator to accumulate the same information.

futuristic extraterrestrial phenomenon rather than Other vendors have also introduced elements of
with a tool that is just about to conquer medicine, deep learning algorithms to help analyse echo-
including cardiovascular medicine.” cardiograms or perform auto quantifications.
Cognitive computing
Cognitive computing involves self-learning sys- Next generation echo systems will incorporate
tems using machine learning, pattern recogni-
tion, and natural language processing to mim- more AI features to further improve workflow by
ic the operation of human thought processes.
auto-completing time- consuming tasks so they

can become more efficient and consistently be

more accurate.

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 9

All of the major imaging system vendors are ei-
ther developing their own AI or partnering with AI
vendors with big announcements during 2017.
Siemens Healthineers announced a partnership
with IBM Watson, GE Healthcare announced it
will be working with Partners HealthCare, which
will be executed through the newly formed Mas-
sachusetts General hospital and Brigham and
Women’s Hospital Center for Clinical Data Sci-
ence. In addition to its EPIQ echo software,
Philips also developed its own AI software to en-
hance its Intellispace Enterprise medical imag-
ing informatics platform, which is smart enough
to pull all of the patient’s relevant prior exams for
the same anatomy and open the images in the
exact same format and view as the current exam

Icaring: cognitive impairment and arrhythmia to provide automatic assessment of an import-
assist iwatch application with instant caring fea- ant number of respiratory and cardiac conditions
tures including Sleep Apnea, COPD, Atrial Fibrillation
and Asthma
Artificial Intelligence Detects AFib Us-
ing Apple Watch Heart Rate Sensor DIABETES MELLITUS DIGITAL
INTERVENTIONS

Benefits : Blood glucose control over 24 hrs,
CBGM , we can detect hypo & hyperglycemic
episodes, also able to detect cardiac and neuro-
logical complications.
Various technologies used in DIABETES

For Monitoring Blood Glucose, BP ,Diet,
Physical Activities ,Drugs – Remainder & Adher-
ence ,Walking, Drug Administration ,Sleep.
They are also used in treatment like Artificial
Pancreas , Hypoglycemia , Cardiac Arrhythmias

• Heart Rhythm 2017 late-breaking trial MOBILE DIABETES MONITORING
results shows opportunity for wearable devices
to effectively monitor atrial fibrillation in general
public
Researchers are using the Apple Watch heart
rate monitor app to track patient arrhythmias us-
ing an artificial intelligence-based algorithm

AcuPebble

The AcuPebble is a wearable breathing and
cardiac monitoring device that uses very inno-
vative and sophisticated engineering techniques

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 10

A tooth implant would dispense the right dose
of medicine at the right time, so patients never
have to remember to take their meds.A small pill
can deliver targeted doses of medicine to spe-
cific locations in the body.

A brain implant can be used to detect seizures
early on and mitigate them.

DIGITAL DIABETIC HEALTH
• Google patented a digital contact lens that

can measure blood glucose levels from tears as
Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 11

an added benefit.
• Over 10,000 health and wellness and
medical apps available across the Apple and
Google app stores
• Roche’s Accu-Check Connect diabetes
management app
• SMBGs
• A new era in diabetes care
• In 2016, the US Food and Drug Adminis-
tration approved the world’s first artificial pancre-
as. The device monitors blood sugar and sup-
plies insulin automatically.

WEARABLE HEALTHCARE
• Smart glucose monitors like the Dexcom

G5 can be placed on the body and link wire-
lessly with smartphones to provide continuous
blood-sugar monitoring. An app can alert users
to low or high blood-sugar events, and can share
data with loved ones or caregivers. Which pro-
vides a Personalised DM Care

LIFESTYLE MEDICINE - A NEW FIELD

Lifestyle Medicine recognizes the link between
lifestyle medicine and health outcomes. It
Uses science behind health behavior change. It
Emphasizes value of lifestyle medicine prescri-
tions by physicians. It will also emphasizes value
of support of those prescriptions by other health
professionals: dietitian, social worker, psycholo-
gist, health coach, exercise physiologist, etc.

TELEWELLNESS:

WEARABLE HEALTH DEVICES
Wearables like Clothing and Accessories In-
corporating Computer and Advanced Electronic
Technologies. These Wearable health devices
and mobile applications increase patient en-
gagement.

These Devices/Apps help patients to track-
Physical Activity, Diet, Weight , Sleep ,Blood
Pressure, Blood Glucose , Heart Rate, Pulse Ox

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 12

Prescription

“Take two wearables & let us prevent your Dis-
ease”

HOME CARE /SOLO CARE

It Provides wireless eHealth services for seniors
living with chronic conditions at home. Remote
access to Care Technology (Re-ACT©). It Pro-
vides remote monitoring of vital signs. The Cli-
ents identified and family physician provides a
target range for clients’ vital signs. The vital sign
measured are Blood Pressure , Pulse , Blood
Glucose ,Weight ,Pulse Oxygen.
eHealth RN monitors results daily as High risk,
Moderate risk or Normal

SAH MOBILE APP-HELLO DOCTOR

SAH mobile App for Android users
• It consists of two android/ iOS soft-
wares- one for doctor and another for patient.
All doctors of SAH will have android app in their
mobiles, The Patient app will have facilities
like videoconferencing with doctor, patient can
check his BP or blood sugar with Digital Appa-
ratus and can upload it online.
• All new patients will have mobile number
as registration ID and their data will be saved in
Cloud
• Those patients who are already in regu-
lar follow up, On demand their data can be up-
loaded to cloud and information can be retrived
in minutes by patient and doctor both,

DIGITAL CARD-HEALTH SMART CARD

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 13

FUTURE of Digital Health :

• Pharmacogenomics
• Nutrigenomics
• Doctors Inside
• Artificial Intelligence

PHARMACOGENOMICS AND PER-
SONALISED MEDICINE

• Personalized medicine is an emerging
concept for treating diseases, which involves
determining specific information of a particular
patient and then prescribing specific treatment.
Pharmacogenetics holds the promise of bring-
ing personalized medicine to drug dosing deci-
sions, to reduce morbidity and mortality, and to
improve life quality for T2DM patients.

NUTRIGENOMICS

• Nutrigenomics is a brand-new cross-
field combining genetics and nutrition science.
• After having your DNA sequenced (per-
haps already at home), a smart app could let
you know which food you should eat and what
you should avoid at all cost.

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 14

NANOTECHNOLOGY ed via rate of respiration, hypertension and sys-

• Sotiris Pratsinis, a professor at the Swiss tolic & diastolic blood pressure.

Federal Institute of Technology, Zurich, has de- Digital Healthcare is the intersection between

veloped a breath sensor able to detect very two giant sectors – Life Sciences and Technol-
high acetone levels, an indicator of diabetes. ogy
3 (Diabetics typically have twice the level of ace- “For the developed world, mHealth is an ad-

tone as non-diabetics). ditional option , but for the developing world,

• The sensor is also able to diagnose ke- mHealth is the only option” - Dr Rajendra

toacidosis, a dangerous insulin deficiency indi- Pratap Gupta, President, Disease Manage-

cated by especially high levels of acetone in the ment Association of India

breath.

• “Ideally, we want to create sensors that “An Apple a day keeps a doctor away

behave a lot like natural cells in the body,” Prof. An App a day keeps a doctor away “

Webster explained to MNT(Medical News To-

day) References:

• Constructing a sensor using nanotechnol- 1. medicalfuturist.com/vocal-biomark-
ogy to mimic human immune cells that circulate ers-new-opportunities-prevention

around the body, indicating when something is
wrong and responding positively to any prob- 2. https://lifevest.zoll.com/

lems that surface may be possible one day in 3. Clark RA, Inglis SC, McAlister FA, Cle-

the future
• So far, the team has trialed their nano sen- land JG, Stewart S. Telemonitoring or structured
sors by growing them on titanium hip implants telephone support programmes for patients with
chronic heart failure: systematic review and me-
and catheters.
• People who receive indwelling catheters ta-analysis. BMJ 2007;334:942..

are susceptible to infection, meaning that nano
sensors monitoring levels of bacteria could have 4. Chaudhry SI, Phillips CO, Stewart SS.,
Riegel B, Mattera JA, Jerant AF, Krumholz
a significant impact on their care.
Wired, The doctor inside: embedded nanosen- HM. Telemonitoring for patients with chronic
sors will start to monitor and treat our health - heart failure: a systematic review. J Card Fail
without the need for surgery, accessed 17 Sep- 2007;13:56–62

tember 2015 via Webster Nanomedicine Lab. 5. Chaudhry SI, Phillips CO, Stewart SS.,

ARTIFICIAL INTELLIGENCE Riegel B, Mattera JA, Jerant AF, Krumholz
HM. Telemonitoring for patients with chronic
• Artificial intelligence (AI), sometimes heart failure: a systematic review. J Card Fail
called machine intelligence, is intelligence 2007;13:56–62

demonstrated by machines, in contrast to the
natural intelligence displayed by humans and 6. https://www.dicardiology.com/article/car-
diovascular-advances-watch-next-decade
other animals.

• Microsoft India and Corporate Hospitals
announced the launch of the first ever Al-pow- 7. https://www.dicardiology.com/article/car-
ered Cardiovascular Disease Risk Score API diovascular-advances-watchnext-decade

(application program interface), designed specif-
ically to predict the risk of Cardiovascular Dis- 8. http://medicalfuturist.com/the-most-excit-
ing-medical-technologies-of-2017/
ease (CVD) in the Indian population.

• The scoring considers risk contributors in- 9. By Blair Bigham, CBC News Posted: Nov
cluding lifestyle attributes such as diet, tobacco 15, 2016 5:00 AM ET Last Updated: Nov 15,
& smoking preferences and physical activity as 2016 6:31 AM ET
well as psychological stress & anxiety as reflect-

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 15

10. PwC Health Research Institute and Con-
sumer Intelligence Series. (2014) “Health wear-
ables: Early days”.
11. http://www.acupebble.com/#what
12. h t t p : / / m e d i c a l f u t u r i s t . c o m / l i v -
ing-with-an-artificial-pancreas
13. http://fortune.com/2017/04/20/digi -
tal-health-revolution
14. http://www.healthline.com/diabetesmine/
diabnext-artificial-intelligence-diabetes#7
15. Kurt George Matthew Mayer Alberti and
PZ ft Zimmet, ‘Definition, diagnosis and classifi-
cation of diabetes mellitus and its complications.
part 1: diagnosis and classification of diabetes
mellitus. provisional report of a who consulta-
tion’, Diabetic medicine, 15(7), 539–553, (1998)
16. Personalized medicine for diabetes.
Klonoff DC,J Diabetes Sci Technol. 2008 May;
2(3):335-41
17. Medico Dialogues, 19th August 2018
18. Prioritizing integrated mHealth strategies
for universal health coverage Garrett Mehl1 *
and Alain Labrique2
19. HealthManagement, Volume 18 - Issue 1,
2018, Utility of artificial intelligence in cardiology
20. C Krittanawong (New York,US), A Tunha-
siriwet (bangkok,TH), M Aydar (Ohio,US), HU
Hassan Virk (Philadelphia,US), E Herzog (New
York,US),Icaring: cognitive impairment and ar-
rhythmia assist iwatch application with instant
caring feature

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 16

1. Epidemiology

1 Pancreatitis & high Triglycerides- Dr.ArulPrakash

2 Maternal Health – Link to NCD epidemics & the role of Insulin- Prof. Dr.V.Seshiah

3 Diabetic Cardiac Autonamic Neuropathy (DCAN)- Dr.UlhasPandhurangi

4 Symptomatic IHD – Angina in T2DM – Mangement- Dr.PravinKahale

5 The 'Obesity Paradox' in Silent Coronary Artery Disease and Diabetes-
Dr.AvijitLahiri

6 Cardio Metabolic Disease – Real Culprit- Dr.DinaNagodra

7 Metabolic Syndrome in PCOS – South Asia Profile- Prof. Chandrika

8 New Guidelines for AMI – 2018- Dr.Nihar Mehta

9 Newer Guidelines for HTN - Dr.AN Rai

10 DM- Cardiomyopathjy- Dr.Nitin Burkule

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 17
PANCREATITIS- AND HIGH TRIGLYCERIDES

Dr.Arulprakash. MD.,MRCP,SCE-Endo(UK),FRCP(UK)

Abstract (RAP). A recognition of HTG as a cause or con-
tributing factor for AP is often delayed or com-
Hypertriglyceridemia (HTG) is a well established pletely missed. Patients with HTG-induced pan-
but underestimated cause of acute (AP) and creatitis (HTG pancreatitis) often have recurrent
recurrent AP (RAP). The clinical presentation of attacks which may require repeated hospitaliza-
HTG-induced pancreatitis (HTG pancreatitis) is tions. Optimum control of serum triglyceride (TG)
similar to other causes. Pancreatitis secondary levels can prevent recurrences of pancreatitis.
to HTG is typically seen in the presence of one or In a review on this topic about ten years ago,
more secondary factors (uncontrolled diabetes, we discussed issues that clinicians face in the
alcoholism, medications, pregnancy) in a patient diagnosis and management of patients with HTG
with an underlying common genetic abnormali- pancreatitis. Since then, new data has emerged
ty of lipoprotein metabolism (Familial combined on distribution of HTG and other pancreatitis risk
hyperlipidemia or Familial HTG). Less com- factors in the general population, and prevalence
monly, a patient with rare genetic abnormality of pancreatitis in patients with severe HTG. Fur-
(Familial chylomicronemic syndrome) with thermore, clinical and experimental studies have
or without an additional secondary factor is evaluated the role of HTG in the severity of AP
encountered. The risk of AP in patients with se- and the mechanisms by which free fatty acids
rum triglycerides >1000 mg/dl and >2000 mg/dl is (FFA) may cause pancreatic injury.
5% and 10-20% respectively. It is not clear wheth- Using NHANES data from 2001-2006, Chris-
er HTG pancreatitis is more severe than when tian et al8 found serum TG levels to be 150-200
it is due to other causes. Clinical management mg/dl, 200-500 mg/dl and 500-2000 mg/dl in
of HTG pancreatitis is similar to that of other 14.2%,16.3% and 1.7% US adults respectively.
causes. Insulin infusion in diabetic patients with Unfortunately, the latter group (500-2000 mg/dl)
HTG can rapidly reduce triglyceride levels. Use was not subdivided to determine the prevalence
of apheresis is still experimental and better de- of TG >1000 mg/dl. Very severe HTG (i.e.
signed studies are needed to clarify its role in >2000 mg/dl) was seen in only 3/5680 (0.0005%).
management of HTG pancreatitis. Diet, lifestyle Subjects with TG over 500 mg/dl were more like-
changes, control of secondary factors are key to ly to be men, of middle age and have a higher
the treatment and medications are useful adjuncts prevalence of diabetes, chronic renal disease
to long term management of triglyceride levels. and concurrent
Control of triglyceride levels to well below 500 abnormalities in other serum lipids (high non-
mg/dl can effectively prevent recurrences of HDL and low HDL).
pancreatitis.

Introduction: Hypertriglyceridemia and risk of pan-

An association between lipid metab- creatitis:

olism and pancreas was noted many Three recent retrospective studies used preva-
years ago. The appearance of lactescent lence of pancreatitis as a surrogate for lifetime
serum during an attack of acute pancreatitis (AP) risk in patients with severe/very severe HTG10-
was first recognized by Speck in 1846 Hypertri- 12. Among 95 patients with TG levels of >1771
glyceridemia (HTG) is a well established cause mg/dl (mean TG 3376 mg/dl) evaluated at a ter-
of acute (AP) and recurrent acute pancreatitis tiary care outpatient lipid clinic over a 12 year

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 18

period12, Sandhu et al noted a history of pancre- activity (e.g. LPL deficiency, defects in apoC-II,

atitis in 15.8%. The lowest TG during episodes defective association of LPL with vascular wall

of pancreatitis was 1815 mg/dl. In an additional [antibodies to heparin]) reduced clearance of

cohort of 91 patients who had TG levels between VLDL and chylomicron remnants by the liver (e.g.

886-1771 mg/dl, a history of pancreatitis was mutations in apoC-III, apoE, apoA-V, angiopoie-

present in only 3.3%, tin like protein 4) or from a combination of these.

and in each of these patients, TG at the time of Diabetes is the most common secondary factor

pancreatitis was >1771 mg/dl. Linares et al11s- physicians would encounter in patients with

tudied 129 consecutive patients referred for an HTG pancreatitis.TG levels are higher in pa-

inpatient endocrinology consultation for severe tients with poorly controlled diabetes and in the

HTG (TG level >1000mg/ml) over a 6 year peri- setting of diabetic ketoacidosis, thereby in-

od. The vast majority of these patients had Fred- creasing the risk of pancreatitis. The prevalence

erickson type IV hyperlipidemia (92%), while of diabetes in HTG pancreatitis is much higher

the remainder had type V hyperlipidemia (8%). than the general population and patients with

A history of AP was present in 20.2% patients HTG but no pancreatitis. In the NHANES

after exclusion of other etiologies. The mean study, the prevalence of diabetes in US adults

maximum TG level was significantly higher in with normal TG level was 5.2% and in those

patients with AP when compared with patients with TG levels between 500-2000 mg/dl was

without AP (4470 vs. 2450 mg/ml, p<0.0001). 14.6%8. In contrast, the prevalence of diabetes

Furthermore, over 85% of patients who had AP was 42.3% and 72% in two series of patients

had maximal TG levels >3000 mg/ml and 65% with HTG pancreatitis. The mechanism of

had levels >5000 mg/ml. When compared with HTG in diabetes is linked to insulin resistance

patients without AP, those with AP were signifi- which leads to excess FFA return to the liv-

cantly younger at the time of admission (43.1 vs. er, increased VLDL production and decreased

48 years) and at diagnosis of HTG (32.4 vs. 40.2 apoB synthesis; and to hyperinsulinemia

years). which promotes de novo TG synthesis.

These data tend to support the commonly held While the effect of moderate alcohol con-

notion that the risk of pancreatitis is increased sumption on TG level does not appear to be

only with severe HTG (>1000 mg/dl)(1). While clinically significant, chronic heavy alcohol

more studies are needed to better define the consumption can result in significant HTG.

risk of pancreatitis with TG elevations of less Alcohol increases TG levels from an increase

than 1000 mg/dl, the following conclusions can in synthesis of large VLDL particles in the

be drawn from available data – when compared liver, increase in splanchnic extraction of

with the lifetime risk of pancreatitis in the gener- TG from VLDL remnants and chylomicrons,

al population (about 0.5-1%), the risk in patients decreased LPL activity, and decreased lipogen-

with severe HTG (TG levels >1000 mg/dl) is sim- esis and glucose oxidation in adipose tissue (9).

ilar to or slightly higher (5%) than among heavy Estrogens increase TG levels due to stim-

drinkers13. In individuals with very severe HTG ulation of VLDL production in the liver.

(TG >2000 ,g/dl), the risk is much greater (10- Presence of more than one secondary fac-

20%). tor further increases the risk of HTG.

Risk factors for HTG pancreatitis: Bessembinders et al reviewed records of 300

patients seen either as an out- or in-patient at

their institution and had at least one document-

HTG can occur from a primary (genetic) ab- ed serum TG measurement of >1000 mg/dl.

normality of lipid metabolism or presence of The prevalence of diabetes, overweight (BMI

secondary factor(s),due to an overproduction >25 kg/m2 or obesity diagnosis) or alcoholism

of TG (VLDL) (e.g. insulinresistance, visceral (>21 drinks/week men; >14 drinks/week wom-

obesity, alcohol use, pregnancy, oral estrogens) en) in this cohort was 49%, 80% and 28%

reduced clearance of TG due to defective LPL respectively. Mean TG levels were significant-
Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 19

ly higher in patients with alcohol abuse but of these lipases using the lipase inhibitor or-

did not differ based on the presence of diabe- listat in vitro prevents the injury to acinar cells

tes or overweight. The prevalence of alcoholism induced by this co-incubation. Orlistat also

and pancreatitis increased with the levels of prevents the lipolytic generation of free fat-

TG – 41% patients in the highest quartile had ty acids induced by these cells. Strong evi-

alcohol abuse when compared with 14% in dence, including electron microscopy showing

the lowest quartile; over two-third of patients mitochondrial damage in hypertriglyceri-

with pancreatitis were in the highest TG quar- demic mink exocrine pancreas, and recent

tile (>2411 mg/dl) and about one-fourth were findings demonstrating a decrease in ac-

in the third quartile (1415 - 2411 mg/dl). Alcohol, inar ATP levels, necrosis via inhibition of

overweight and diabetes were seen in mitochondrial complexes I and V by fatty ac-

some combination in close to 90% of all patients. ids45 support the role of fatty acid induced

The combination of any two risk factors mitochondrial toxicity in the adverse out-

resulted in higher TG levels than when present comes. The roles of protein kinase C in

alone; and patients with all three risk factors hypertriglyceridemic pancreatitis remains to be

had the highest TG levels. explored.

Presence of pancreatitis in a small fraction of pa-

tients with HTG has led to a search of genetic Clinical approach:

susceptibility factors. Chang et al evaluated the In a patient presenting with AP, HTG as the
frequency of mutations in cationic trypsinogen potential etiology should be suspected in the
(PRSS1), serine protease inhibitor Kazal type following scenarios with decreasing frequen-
1 (SPINK1), cystic fibrosis transmembrane con- cy: poorly controlled diabetes (established or
ductance regulator (CFTR), and tumor necrosis new diagnosis) in the absence of other risk
factor superfamily member 2 (TNF2) genes in factors like gallstones, significant alcohol
128 Taiwanese patients - 80 with HTG and 46 consumption or medications an alcoholic pa-
with HTG pancreatitis. The prevalence of poly- tient who has very high TG levels; the use of
morphisms in CFTR (M470V) and TNF (863A) medications known to cause HTG; and,
genes was significantly higher when compared during the third trimester of pregnancy. The
with patients with HTG alone.More studies are common theme in these scenarios is that pres-
needed to better understand the role of genet- ence of secondary factor(s) in a patient with an
ic factors that increase the risk of pancreatitis in underlying common genetic abnormality of li-
patients with severe/very severe HTG. poprotein metabolism (Familial combined

Mechanism of HTG induced AP: hyperlipidemia [FCHL] or Familial HTG) can

result in elevations of serum TG to levels that

The exact mechanism by which HTG can cause pancreatitis. Less commonly, a

causes AP has not been fully elucidated. patient with a genetic abnormality (Familial

Studies to determine how HTG may result chylomicronemic syndrome) will present with

in the outcomes include those focusing on HTG pancreatitis spontaneously or in the

the lipolytic generation of FFA from the presence of a secondary factor. Detec-

TG present in chylomicrons. The exocrine tion of lactascent or lipemic serum, physical

pancreas is rich in lipases which are secret- examination findings such as eruptive xan-

ed into the extracellular environment when thomas or lipemia retinalis, or features of

acinar cells harvested from rodents are stim- metabolic syndrome (e.g. abdominal obe-

ulated by hormones such as cholecystokinin. sity, premature coronary artery disease,

Co-incubation of acinar cells with chylomicrons nonalcoholic fatty liver disease, etc.)

and cholecystokinin results in an increase should raise suspicion for underlying HTG.

in FFA in the medium with a correspond- Clinical studies assessing the impact of HTG

ing decrease in TG. Pharmacologic inhibition on the severity of AP have had conflicting

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 20

results. Balachandra et al prospectively en- most patients, TG levels decrease by
rolled 43 consecutive patients with AP of all 65% and 85% after one or two sessions
etiologies to assess the relationship of ad- respectively. However, a clear benefit of apher-
mission TG level and severity. TG levels were esis in reducing the severity and improving
elevated in 33% of patients (mean 265 mg/ml). outcomes in AP has not been conclusively shown.
No difference detected in severity, based on Chen et al retrospectively analyzed clinical
APACHE II scores or complications in pa- outcomes in HTG pancreatitis patients before
tients with and without HTG. This small study (n=34) and after (n=60) the availability of apher-
suggests that mild elevations in serum TG esis at their institution. These groups had
level in AP do not appear to hold prognostic statistically similar background and clinical
value. characteristics; ultimately 20 patients in the
Based on available data from clinical studies, latter group opted for apheresis with a me-
it is safe to assume that mild elevations in TG dian time of initiation of 3 days after symptom
levels do not affect the severity of AP. The role of onset. There was no significant difference in
TG elevation of >500 mg/dl on the clinical course mortality and local or systemic complications
of AP is unclear. Future studies using adequate between the two time periods or among pa-
sample size should compare outcomes in pa- tients with severe AP (defined by Ranson’s score
tients with HTG (>500 and >1,000 mg/dl) with >3) who did (n=10) or did not (n=19) get plas-
other major causes of AP. mapheresis60. The limitations of this study are
its retrospective design, experience from
Management of HTG pancreatitis: a single center and small sample size.
Apheresis is expensive and is not without risk.
Initial treatment of AP includes pancreas rest It requires central intravenous access and
by limiting oral intake, aggressive intravenous transient anti-coagulation with associated com-
hydration, and analgesia. Other etiologies plications of line-associated bacteremia, deep
of AP should be quickly ascertained with a venous thrombosis, and bleeding. Potential
thorough history and physical examination, ba- candidates for apheresis may be patients with
sic laboratory testing, imaging as indicated, predicted severe or severe AP who continue
and medication review. As mentioned previous- to have TG levels above 1000 mg/dl after the
ly, serum TG level should be checked shortly first 24-48 hours. However, given the lack of
after admission given rapid decline in levels proven efficacy, a firm recommendation for
with fasting. If there is evidence of severe AP apheresis cannot be made at this time and the
and need for prolonged fasting, pancreat- treatment should be highly individualized. In
ic rest via post-ligament of Treitz nasojejunal fact, the recent American Society for Apher-
enteral feeding tube (preferred) or total par- esis (ASFA) guidelines placed apheresis in
enteral nutrition (TPN) should be entertained. patients with HTG pancreatitis as 2C grade
For obvious reasons, if TPN is chosen, lip- (weak recommendation) and that other
ids should be avoided. Once HTG is the alternatives may be equally reasonable based
established cause of AP, multiple mostly ex- on data from observational studies or cases
perimental therapies including insulin, heparin, series (category III evidence) Infusion of insulin
and apheresis have been studied in the acute and heparin has been utilized to treat HTG in the
setting. Apheresis has been repeatedly shown in acute setting and in patients with HTG pancre-
cases reports and series to be effective in quickly atitis. Insulin leads to an increase in peripheral
removing TG from the serum of patients with LPL activity and helps to reverse hepatic effects
HTG pancreatitis of different causes. The of insulin resistance. Insulin infusion is especially
premise of using apheresis is that it removes helpful in patients with poorly controlled dia-
available TG in VLDL and chylomircons from betes who have hyperglycemia in addition to
serum and prevents generation of FFA severe HTG. Enthusiasm for heparin has
which cause local and systemic effects. In waned, as it has been shown that although it

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 21

results in an increases in serum LPL activity, Highlights:
this effect is transient and is quickly followed
by reduced activity of LPL, which may ulti- •Hypertriglyceridemia is a well established and
mately lead to a rise in TG. Therefore, in- underestimated cause of pancreatitis
sulin infusion should be considered in se- •Pancreatitis secondary to HTG is typically seen
lect patients while the use of heparin is in the presence of one or
controversial and should be avoided. more secondary factors (uncontrolled diabetes,
A multi-faceted approach is required in pa- alcoholism, medications, pregnancy) in a patient
tients with HTG pancreatitis to prevent with an underlying common genetic abnormality
recurrences. Lifestyle modifications directed of lipoprotein metabolism.
at weight loss, limiting intake of fat and simple •HTG >1000mg is a definitite risk factor for pan-
carbohydrates, abstinence from alcohol, con- creatitis while HTG level between 500 and 1000
trol of secondary risk factors such as diabetes, mg is likely.
and discontinuation of offending medication •Infusion of insulin and heparin has been utilized
is integral to the management. In conjunction, to treat HTG in the acute setting, but fibrates
lipid lowering medications are often required. should be the first line of treatment in non acute
Patients should seek formal consultation with setting.
a dietitian to discuss food choices and an endo-
crinologist to help control TG levels and diabe- References:
tes. Although TG levels close to normal may be
preferable, levels <500 mg/dl represents a safe 1. Saligram S, Lo D, Saul M, et al. Analyses of hos-
therapeutic target for prevention of recurrences. pital administrative data that use diagnosis codes
Fibrates are the first line medications for treat- overestimate the cases of acute pancreatitis.
ing HTG6. HMG-CoA reductase inhibitors, i.e. Clin Gastroenterol Hepatol. 2012; 10:805–11 e1.
statins have a weak TG lowering effect, and [PubMed: 22504004]
should not be used as monotherapy for HTG.
Statins can have a synergistic lipid-lowering 2.BerglundL,BrunzellJD,GoldbergAC,etal.Eval-
effect in combination with fibrates and should uation and treatment of hypertriglyceridemia: an
be considered in patients in whom severe HTG Endocrine Society clinical practice guideline.
is not controlled on fibrates alone. Fibrates J Clin Endocrinol Metab. 2012; 97:2969–89.
are generally well-tolerated but caution should [PubMed: 22962670]
be exercised when used with statins given the
increased, albeit small risk of myopathy or 3. Lindkvist B, Appelros S, Regner S, et al. A pro-
rhabdomyolysis. This risk is mainly attributed spective cohort study on risk of acute pancreatitis
to older fibrates such as gemfibrozil and ap- related to serum triglycerides, cholesterol and
pears to be much less with newer fibrate fasting glucose. Pancreatology. 2012; 12:317–24.
derivatives such as fenofibric acid. Nicotin- [PubMed: 22898632]
ic acid, or niacin, is considered a second-line
agent. However, its efficacy is often limit- 4. Bessembinders K, Wielders J, van de Wiel A.
ed by side effects such as facial flushing, Severe hypertriglyceridemia influenced by alcohol
gastrointestinal intolerance, and hepatotox- (SHIBA). Alcohol Alcohol. 2011; 46:113–6.
icity. Omega-3 fatty acids can be used in [PubMed: 21245063]
combination with other agents such
as fibrates but not as monotherapy 5. Sandhu S, Al-Sarraf A, Taraboanta C, et al. In-
cidence of pancreatitis, secondary causes, and
treatment of patients referred to a specialty lip-
id clinic with severe hypertriglyceridemia: a
retrospective cohort study. Lipids Health
Dis. 2011; 10:157. [PubMed: 21906399]

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 22

6. Girman CJ, Kou TD, Cai B, et al. Patients with
type 2 diabetes mellitus have higher risk for acute
pancreatitis compared with those without dia-
betes. Diabetes Obes Metab. 2010; 12:766–71.
[PubMed: 20649628]
7. Noel RA, Braun DK, Patter-
son RE, et al. Increased risk of acute
pancreatitis and biliary disease
observed in patients with type 2 diabetes: a ret-
rospective cohort study. Diabetes Care. 2009;
32:834–8. [PubMed: 19208917]
8. Lai SW, Muo CH, Liao KF, et al. Risk of acute
pancreatitisintype2diabetesandriskreductionon
anti-diabetic drugs: a population-based cohort
study in Taiwan. Am J Gastroenterol. 2011;
106:1697–704. [PubMed: 21577242]
9. Van de Wiel A. The effect of alcohol on post-
prandial and fasting triglycerides. Int J Vasc Med.
2012; 2012:862504. [PubMed: 21961068]

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 23

MATERNAL HEALTH IS THE LINK TO THE
NON-COMMUNICABLE DISEASES EPIDEMICS

Prof Dr V. Seshiah MD FRCP DSc

Abstract: from the last meal. A venous blood sample is to
be collected at 2 hours for estimating plasma

Preventive measures against Type 2Diabetes glucose by the GOD-POD method. GDM is diag-

Mellitus (T2DM) and associated cardio vascular nosed if 2-hour PG is ≥ 140 mg/dL(7.8 mmol/L).

complications should start during intra-Uterine In case 75 g glucose packet is not available,

period and continue throughout life from early remove and discard five level teaspoons (not

childhood. Preventive medicine starts before heaped) of glucose from a 100g packet which

birth. In this aspect, Gestational Diabetes Melli- is freely available. In hospitals where glucose is

tus(GDM) offers an important opportunity for the supplied in bulk, a cup or container of 75 g may

development, testing and implementation of the be used. The marketed glucose is available in

clinical strategies for prevention of diabetes and anhydrous form. As glucose concentrations are

Non-Communicable Diseases(NCDs). Gesta- affected little by the time since the last meal in

tional Diabetes Mellitus (GDM) is defined as a normal glucose tolerant woman, it makes it a

glucose intolerance of varying severity first de- rationale to perform this test in the non fasting

tected during the present pregnancy. GDM may state. After a meal, a normal glucose tolerant

play a crucial role in the increasing prevalence woman would be able to maintain euglycemia

of diabetes and obesity. Insulin resistance, in- due to brisk insulin response against glucose

creased atherogenic lipid profile, inflammatory challenge. Whereas, a woman with GDM would

markers, hypertension and endothelial dysfunc- not be able to do so due to impaired insulin se-

tion lead to increased risk for Cardio Vascular cretion that leads to increase in her glycemic

Diseases(CVD). GDM is associated with short levels with glucose challenge and the glyce-

term maternal, fetal, neonatal consequences for mic excursion may exaggerate further. There

both mother and the offspring. In most instanc- are several advantages of the DIPSI procedure

es the glucose intolerance reverts to normal but such as: Pregnant women need not be fasting,

substantial number of women with GDM have it causes least disturbance in routine activities

increased lifetime risk of developing diabetes at of a pregnant woman, and it serves as both

over three times compared to control after six- screening and diagnostic procedure. This sin-

teen years of index pregnancy. By 17 years of gle-step procedure has been approved by Min-

age one third of children born to GDM mothers istry of Health, Government of India. It is also

have had evidence of pre-diabetes, T 2 DM, recommended by WHO, Federation of Gyne-

Metabolic syndrome, impaired insulin sensitiv- cologist and Obstetrician and Ministry of Health

ity and secretion. The underlying pathogenic Government of India and International Diabetes

mechanism for the abnormal metabolic profile Federation.

could be due to epigenetic changes induced by Hence timely action taken now in screening

fetal exposure to hyperglycemia, intrauterine all pregnant women for glucose intolerance,

milieu Interior. achieving euglycemia in them may prevent in all

Diagnostic procedure recommended by Diabe- probability the epidemic of non communicable

tes in pregnancy study group in India(DIPSI) is, diseases. Female gender is key to prevention of

after completing preliminary clinical examina- non communicable diseases. The Postpartum

tion of pregnant woman, she should be given 75 follow up is very essential and pre GDM women

g oral glucose load, irrespective of her fasting/ should be advised against gaining weight, simi-

non fasting status and without regard to the time larly their off-springs should also follow a

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 24

healthy lifestyle pattern. “GDM is the mother of Impact of maternal hyperglycemia
Non communicable Diseases”
It has been now recognized that GDM may be
Key Words: Non-communicable Diseases, playing an important role in increasing prev-
alence of diabetes. Also, causing insulin re-
Gestational Diabetes Mellitus, Cardio-vascular sistance, obesity, dyslipidemia, increased in-
diseases flammatory markers , endothelial dysfunction ,
hypertension and ultimately leading to increased
INTRODUCTION risk of cardiovascular diseases. Maternal hyper-
glycemia in pregnancy is an independent risk
The prevalence of diabetes is increasing global- factor for putting the offspring at increased risk
ly and India is no exception. The concern is that of IGT, obesity , hypertension at 7 years of age,
India would be having the highest population of while CV risk continues to increase from adoles-
diabetes by 2025.The increased prevalence is cent to adulthood. There is also effect on child-
attributed to the aging population structure, ur- hood adiposity which is only evident in girls and
banization, the obesity epidemic, and physical not boys .There has been an association of ma-
inactivity. While all these factors contribute to ternal hyperglycemia with offspring’s adiposity
the epidemic of diabetes, early life exposures and insulin resistance. Intrauterine exposure to
are emerging as potential risk factors. The ‘‘fetal hyperglycemia has deleterious effects that are
origin of disease’’ hypothesis proposes that ges- in addition to those related to genetic predispo-
tational programming may critically influence sition5 Also, in utero exposure to hyperinsulin-
adult health and disease. Gestational program- emia is an independent predictor of abnormal
ming is a process whereby stimuli or stress- glucose tolerance in later childhood. Maternal
es that occur at critical or sensitive periods of hyperglycaemia in pregnancy predisposes both
development, permanently change structure, mother and child at future risk of developing di-
physiology, and metabolism, which predispose abetes and cardiovascular diseases.
individuals to disease in adult life. Traditional- Glucose that normally acts as fuel for devel-
ly and convincingly, lifestyle modifications and oping fetus, in hyperglycemic state becomes
drug interventions have proved to delay or post- deleterious for growing fetus. That gave rise to
pone the development of overt diabetes in per- hypothesis called, “The fuel-mediated terato-
sons diagnosed to have impaired glucose toler- genesis”, that first proposed the explanation for
ance. This is a post primary prevention strategy. the association of excessive growth of fetus with
The primary prevention of Type 2 DM at best maternal hyperglycemia. Maternal insulin does
would mean to keep genetically or otherwise not cross placenta freely while maternal glucose
susceptible individuals normoglycemic and not does and in response to that fetal pancreas tries
only preventing Type 2 DM from developing. to balance by producing more insulin. This in
The primary prevention is more important than turn acts as fetal growth hormone and becomes
post primary prevention, as this effort is likely to responsible for promoting growth and adiposity.
reverse or halt the epidemic of disease. Women
with Gestational Diabetes Mellitus (GDM) are Role of AdipoInsular axis
an ideal group for the primary prevention of di-
abetesas they are at increased risk of develop- An endocrine feedback loop called as adipoin-
ing diabetes predominantly Type 2 DM as are sularaxis connects the endocrine pancreas with
their children. Gestational Diabetes Mellitus is adipose tissue and the brain. This axis regulates
defined as carbohydrate intolerance of variable hunger and fat storage through the hormones
severity with onset or first recognition during the named insulin and leptin. Insulin is responsi-
present pregnancy. Women with GDM have an ble for promoting development of fat mass and
increased lifetime risk of developing diabetes, at leptin production. Leptin reduces energy intake
over 3 times compared to controls at 16 years and suppresses the insulin secretion via leptin
after index pregnancy. By 17 years of age one- receptors on pancreatic β-cells. Abnormal func-
third of children born to GDM mothers have had tioning of this adipoinsular axis may lead to hy-
evidence of IGT or T 2 DM. perphagia, dysregulation of the energy balance
and excessive adiposity Fig-1

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 25

Fig 1

Maternal Obesity and It’s Influence on Mellitus: gives an opportunity where in devel-
opment of T2DM and cardiovascular Disease
Off-Spring and CVD in young Women can be prevented. Women

Exposure to maternal hyperglycemia in intra- with previous gestational diabetes (pGDM),are
uterine life confersan additional risk of devel- at increased risk of developing Type 2 diabetes.
oping cardiovascular disease in later part of life. Sometimes GDM may represent an early stage
This risk is independent of any genetic predis- in the natural history of Type 2 diabetes. Also
position or adiposity. Studies are required to ex- in subsequent years after the index pregnancy,
plain the mechanisms of maternal hyperglyce- these women with pGDMshow deranged car-
mia conferring the cardiovascular risk . There is diovascular profile with an increased incidence
an increasing interest in another hypothesis on of cardiovascular disease.

maternal obesity that leads to metabolic conse-

quences in offspring’s. This can add up to accel- Diagnostic Tests Procedure:

erate the obesity epidemic too which is indepen- Women of Asian origin and more so ethnic Indi-

dent to genetic or environmental factors.9 The ans, are at a higher risk of developing GDM and

glycemic index of diets also has an influence on subsequent type 2 diabetes. Universal screen-

birth weight of offspring’s. Exposure to high-gly- ing for GDM is essential and early screening

cemic index diets led to higher birth weight and should be done in population where there is a

skinfold thickness compared to exposure to a higher prevalence of T2DM. As per new recom-

low glycemic diet. mendations all women should be screened for

GDM even if there are no symptoms. Compared

It can be safely concluded that exposure to a to selective screening universal screening of

hyperglycemic environment in the intrauterine GDM detects more cases and ultimately im-

life is associated with increased occurrence of proves maternal and neonatal outcomes.

impaired glucose tolerance and a defective in- >Based on the Hyperglycemia and Adverse

sulin secretary responses. Gestational Diabetes Pregnancy Outcome (HAPO) study, Internation-
Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 26

al Association of the Diabetes and Pregnancy the antenatal clinic and that too in fasting state.
Study Groups (IADPSG) has suggested the Hence, it was important to have a test that de-
guidelines. Predominantly HAPO study was tects the glucose intolerance at first visit itself,
performed in Caucasian population and popu- irrespective of fasting or fed state.
lation from India, China, South Asian countries
(except city of Bangkok, Hong Kong), Middle Procedure In the antenatal clinic should include
East and Sub Saharan countries were not in- ,after completing preliminary clinical examina-
cluded. The IADPSG recommendations include; tion of pregnant women, she should be given 75
that diagnosis of GDM is made when any of g oral glucose load*, irrespective of her fasting/
the following plasma glucose values meet or nonfasting status and without regard to the time
exceed: Fasting: 92 mg/dL, (≥ 5.1 mmol/L), from the last meal. A venous blood sample is to
1-hour: 180 mg/dL ( ≥ 10.0 mmol/L) , 2-hour: be collected at 2 hours for estimating plasma
153 mg/dL (≥ 8.5 mmol/L) with 75 g OGTT. The glucose by the GOD-POD method. GDM is diag-
IADPSG also suggests: nosed if 2-hour PG is ≥ 140 mg/dL(7.8 mmol/L).
In case 75 g glucose packet is not available,
Fasting plasma glucose (FPG); 126 mg/dL(> remove and discard five level teaspoons (not
7.0 mmol/L) and A1C > 6.5% in the early weeks heaped) of glucose from a 100 g packet which
of pregnancy is diagnostic of overt diabetes. is freely available. In hospitals where glucose is
Fasting >92mg/dL and <126 mg/dL is diagnosed supplied in bulk, a cup or container of 75 g may
as GDM. be used. The marketed glucose is available in
anhydrous form.
Disadvantages of the IADPSG recommenda-
tions are: • Most of the time pregnant women As glucose concentrations are affected little by
do not come in the fasting state because of be- the time since the last meal in a normal glucose
lief that they should not fast for long hours. The tolerant woman, it makes it a rationale to per-
dropout rate is very high if they are asked to form this test in the nonfasting state. After a
come back for repeat test for glucose tolerance. meal, a normal glucose tolerant woman would
In many situations attending the first prenatal be able to maintain euglycemiadue to brisk insu-
visit in the fasting state is almost impractical. • lin response against glucose challenge. Where-
The hall mark of GDM is that In all cases FPG as, a woman with GDM would not be able to do
values do not reflect the 2-hour post glucose so due to impaired insulin secretion that leads
with 75 g oral glucose [2-hour plasma glucose to increase in her glycemic levels with glucose
(PG)]. Two hour PG values are much higher in challenge and the glycemic excursion may ex-
ethnically Asian Indians compared to Cauca- aggerate further. There are several advantages
sians as they have high insulin resistance. The of the DIPSI procedure such as: Pregnant wom-
insulin resistance during pregnancy is further in- en need not be fasting, it causes least distur-
creased,hence FPG is not an appropriate option bance in routine activities of a pregnant woman,
to diagnose GDM in Asian Indian women. About and it serves as both screening and diagnostic
76% of pregnant women would have missed the procedure. This single-step procedure has been
diagnosis of GDM made by WHO criterion by approved by Ministry of Health, Government of
following FPG > 5.1 mmol/L as cut-off value, in India. It is also recommended by WHO, Federa-
this population. tion of Gynecologist and Obstetrician and Minis-
try of Health Government of India.
Diabetes in Pregnancy Study Group India (DIP-
SI), has recommended single step procedure The chances of detecting unrecognized type 2
for diagnosing GDM in community. DIPSI diag- diabetes before pregnancy (pre-GDM) is like-
nostic criteria of 2-hour PG ≥ 140 mg/dL is simi- ly to be missed if usual recommendation for
lar to WHO criteria 2-hour PG ≥ 140 mg/dL. This screening between 24 weeks and 28 weeks of
was developed due to the practical difficulty in gestation is followed. In case where 2-hour PG
performing glucose tolerance test in the fasting is > 200 mg/dL in the early weeks of pregnancy,
state, challenge of women revisiting she may be a pre-GDM and in this case A1C of

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 27

≥ 6.5 becomes confirmatory. A pregnant woman 5) KrishnaveniGV ,Hill JC, Leary SD, etal. Intra-
found to have normal glucose tolerance (NGT), uterine exposure to maternal diabetes is associ-
in the first trimester, should be tested again for ated with higher adiposity and insulin resistance
GDM around 24th–28th week and finally around and clustering of cardiovascular risk markers
32nd–34th week. in Indian children. Diabetes Care 33;402-404,
2010
CONCLUSION 6)V.Seshiah,David McIntyre, Moshe hod et al.
FEMALE GENDER: THE KEY TO DIA- Matching diagnosis and management of diabe-
BETES PREVENTION and thus Maternal tes in pregnancy to local prioritis and resources:
An international approach.2009. IJGO.
health is the link to the NCD epidemic. GDM 7) Maternal Environment and the Transgener-
is the mother of non communicable disease. ational Cycle of Obesity and Diabetes - Dana
Hence preventive measures against Type 2 DM Dabelea and Tessa Crume – Diabetes, Volume
should start right from intrauterine period and 60 – July 2011 – P 1849-1855
continue throughout life from early childhood. 8) McMillen IC, Edwards LJ, Duffield J, Muhl-
GDM offers an important opportunity for the de- hausler BS. Regulation of leptin synthesis and
velopment, testing and implementation of clini- secretion before birth: implications for the ear-
cal strategies for diabetes prevention and NCD. ly programming of adult obesity. Reproduction
Public Health Priority is to initiate the action in 2006;131:415–427
screening all pregnant women for glucose in- 9) Catalano PM. Obesity and pregnancy-the
tolerance, achieving euglycemia in them and propagation of a viscous cycle? J ClinEndocri-
ensuring adequate nutrition. This in turn in all nolMetab 2003;88:3505-3506
probability, will help in preventing the epidem- 10) Strategies for Implementing the WHO Diag-
ic of diabetes and CVD.DuringPostpartum pe- nostic Criteria and Classification of Hypergly-
riod, women should be screened periodically caemia First Detected in Pregnancy. Stephen
for glucose intolerance and advised proper diet Colagiuri, MaiconFalavigna, Mukesh M. Agar-
plan and physical activities. Their off-springs wal, Michel Boulvain, Edward Coetzee, Moshe
shouldalso be advised to follow the healthy diet Hod, Sara Meltzer, Boyd Metzger, Yasue Omori,
and healthy lifestyle. Ingvars Rasa, Maria Inês, Veerasamy Seshiah,
David Simmons, Eugene Sobngwi, Maria Re-
REFERENCES gina Torloni, Hui-xia Yang. DRCP. 103 (2014)
364-372
1) Hunt KJ, Schuller KL. The increasing preva- 11) C. Anjalakshi, V.Balaji, MadhuriBalaji, Et Al.
lence of diabetes in pregnancy.ObstetGynecol- A Single test procedure to diagnose gestation-
Clin North Am 2007;34:173-99. al diabetes mellitus.ActaDiabetologia (2009)
46:51-54
2) Henry OA, Beischer NA. Long-term impli- 12) Thomas A Buchanan, Anny Xiang, Siri L
cations of gestational diabetes for the mother. Kjos, Richard Watanabe. “What is gestational
BaillieresClinobstetGynaecol 1991;5:461-83. diabetes?” Diabetes Care 30(2): S105-111, July
2007
3) Bernard L Silvermen, Nam H Cho, et al. Long-
term effects of the intrauterine Environment . Di-
abetes care 1998;21:B142.

4) Wing Hung Tam, Ronald Ching Wan Ma,
Risa Ozaki, et al. In Utero Exposure to Mater-
nal Hyperglycemia Increases Childhood Car-
diometabolic Risk in Offspring. Diabetes care
2017;40:679-686.

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 28

DIABETIC CARDIOVASCULAR AUTONOMIC NEUROPATHY

Dr.Ulhas M.Pandurangi
Chief – Cardiac Electrophysiology & Pacing
The Madras Medical Mission

Introduction: asymptomatic CAN, whereas 100% of those with

Diabetic cardiovascular autonomic neuropathy symptomatic DCAN present classical PNP.

(DCAN) is a neuro-humoral regulation distur- Pathogenesis:
bance due to malfunction of autonomic nervous

system (ANS). DCAN represents a significant DCAN is widely believed and largely proven

cause of morbidity and mortality in patients with to be to be the result of complex interactions

diabetes mellitus (DM) and is associated with among degree of glycemic control, disease du-

a high risk of cardiac arrhythmias and sudden ration, age-related neuronal attrition, and systol-

death. It is one of the most insidious complica- ic and diastolic blood pressure. Hyperglycemia

tions of DM especially if it is long standing and plays the key role in the activation of various bio-

poorly controlled. DCAN is often overlooked chemical pathways related to the metabolic and/

both in terms of diagnosis and treatment simply or redox state of the cell, which, in concert with

because there is no widely accepted single ap- impaired nerve perfusion, contribute to the de-

proach to its diagnosis and management1,2,3. This velopment and progression of diabetic neuropa-

review covers the epidemiology, pathophysiolo- thies.

gy, clinical presentation, and diagnosis of DCAN

and discusses current evidence on approaches Pathophysiology:
to prevention and treatment. It has been shown that chronic hyperglycemia

Epidemiology: promotes progressive autonomic neural dys-

function (Fig.1) in a manner that parallels the

Diabetic neuropathies, including DCAN, are a development of peripheral neuropathy, e.g., be-

common chronic complication of type 1 and type ginning distally and progressing proximally. The

2 DM and confer high morbidity and mortality. vagus nerve, the longest autonomic nerve, medi-

The reported prevalencevaries greatly depend- ates 75% of all parasympathetic activity (Fig.2).

ing on the criteria used to identify DCAN and the Because neuropathy is seen first in the longest

population studied. DCAN prevalence ranges fibers, the earliest manifestations of autonomic

from as low as 2.5% of the primary prevention neuropathy in diabetes tend to be associated

cohort in the Diabetes Control and Complications with parasympathetic denervation. As such, the

Trial (DCCT)4 to as high as 90% of patients with initial development of DCAN is characterized by

long-standing type 1 diabetes who were poten- early augmentation of sympathetic tone. The ini-

tial candidates for a pancreas transplantation5. tial augmentation in cardiac sympathetic activity

In a large cohort of patients with type 1 and type with subsequent abnormal norepinephrine sig-

2 diabetes, Ziegler et al.using predefined heart nalling and metabolism, increased mitochondri-

rate variability (HRV) tests and spectral analysis al oxidative stress, and calcium- dependent ap-

of the R-R intervals, found that 25.3% of patients optosis may contribute to myocardial injury and

with type 1 diabetes and 34.3% of patients with may explain the high risk of cardiac events and

type 2 diabetes had abnormal findings. Age, sex, sudden death in these patients. The sympathetic

and other risk factors may also influence DCAN imbalance associated with DCAN may critically

development. DCAN is more often seen in pa- influence myocardial substrate utilization and

tients with polyneuropathy (PNP). Approximately contribute to mitochondrial uncoupling, regional

50% of the diabetic patients with PNP have ventricular motion abnormalities, functional defi-

cits, and cardiomyopathy.
Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 29

Fig1: Mechanisms that relate hyperglycemia to neuropathy

Fig2: Cardiac Innervation

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 30

Clinical Signs and Symptoms: Autonomic dysfunction may impair exercise tol-
erance and has been shown to reduce heart rate,
Great majority of diabetic patients with DCAN blood pressure, and cardiac output responses to
remain asymptomatic for decades. Since clinical exercise. It is generally recommended that pa-
history and physical examination are ineffective tients suspected to have DCAN be tested with a
for its early detection, it is of crucial importance cardiac stress test before undertaking an exer-
to perform quantitative tests in order to diagnose cise program.
DCAN in its initial and still reversible stages2,4.
Subclinical DCAN, manifested as changes in Abnormal blood pressure regulation:
Heart rate variability (HRV), may be detected
within 1 year of diagnosis in type 2 DM and with- At night, nondiabetic subjects exhibit a predom-
in 2 years of diagnosis in type 1 DM9. DCAN is inance of vagal tone and decreased sympathet-
also accompanied very often by ANS malfunction ic tone, associated with reduction in nocturnal
seen in other organs-gastroparesis, constipation blood pressure. In DCAN this pattern is altered,
and diarrhoea (gastro-intestinal) and urinary in- resulting in sympathetic predominance during
continence, neurogenic bladder and erectile dys- sleep and subsequent nocturnal hypertension.
function (genitourinary system). Fig.3 illustrates These are associated with a higher frequency
natural progression of DCAN and correlation of left ventricular (LV) hypertrophy and both fatal
with clinical signs and symptoms. and severe nonfatal cardiovascular events in di-
abetic CAN subjects.
Impaired HRV:
Orthostatic hypotension:
In a normal individual, the heart rate has a high
degree of beat- to-beat variability and HRV fluc- Orthostatic hypotension occurs largely as a con-
tuates with respiration increasing with inspiration sequence of efferent sympathetic vasomotor
and decreasing with expiration. The earliest clin- denervation, causing reduced vasoconstriction
ical indicator of DCAN is a decrease in HRV. of the splanchnic and other peripheral vascular
beds. Symptoms associated with orthostatic hy-
Resting tachycardia: potension include: light-headedness, weakness,
faintness, dizziness, visual impairment, and, in
Resting heart rates of 100 bpm with occasional most severe cases, syncope on standing. These
increments up to 130 bpm usually occur later in symptoms can be aggravated by several drugs
the course of the disease and reflect a relative including: vasodilators, diuretics, phenothi-
increase in the sympathetic tone associated with azines, insulin (through endothelium-dependent
vagal impairment. A fixed heart rate that is unre- vasodilatation), and tricyclic antidepressants, a
sponsive to moderate exercise, stress, or sleep class of drugs commonly used for symptomat-
indicates almost complete cardiac denervation ic relief of pain associated with painful diabetic
and is indicative of severe DCAN. neuropathy.

Exercise intolerance:

Fig.3: Natural progression of DCAN and correlation with clinical signs and symptoms.
Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 31

Clinical Evaluation and Diagnosis Cri- Orthostatic hypotension:
teria:
Orthostatic hypotension is documented by a fall
There is no widely accepted single approach to 30 mmHg in systolic or 10 mmHg in diastolic
the diagnosis of DCAN. Assessment of HRV, or- blood pressure in response to a postural change
thostatic hypotension, and 24-hr blood pressure from supine to standing.
profiles provide indexes of both parasympathet-
ic and sympathetic autonomic function and can The rapid postural changes that are part of head-
be used in clinical settings. Other methods such up-tilt-table testing, with or without pharmaco-
as cardiac sympathetic imaging, microneurogra- logical provocation, can be used for the inves-
phy, occlusion plethysmography, and baroreflex tigation of DCAN or of predisposition to neurally
sensitivity are currently used predominantly in mediated (vasovagal) syncope due to the wide
research settings but may find a place in the clin- range of changes in the autonomic input to the
ical assessment of DCAN in the future. heart and in the R-R intervals.

HRV: Imaging techniques for DCAN:

Quantitative scintigraphic assessment of sympa-

Simple bedside tests to detect HRV us- thetic innervation of the human heart is possible
with positron emission tomography (PET) and
ing ECG in DCAN are: either [123I] metaiodobenzylguanidine (MIBG)

a) changes in R-R intervals with deep breath- or [11C]-meta-hydroxy-ephedrine ([11C] HED).
ing, which measures sinus arrhythmia during Quantitative regional measurements of myo-
quiet respiration which primarily reflects para- cardial-adrenoreceptor density can also be as-

sympathetic function sessed using PET and the high-affinity–adreno-

receptor radioligand [11C] CGP-12177.
b) R-R response to standing, which induces re-

flex tachycardia followed by bradycardia and Baroreflex sensitivity:
is jointly vagal and baroreflex mediated
Baroreflex sensitivity (BRS) is a technique that

c) Valsalva ratio, which evaluates vagal function evaluates the capability to reflexively increase

in response to increase in intrathoracic pres- vagal activity and decrease sympathetic activity
sure during Valsalva manoeuvre
in response to a sudden increase in blood pres-

HRV can also be evaluated using statistical in- sure. It is calculated from the measurement of
dexes in the time and frequency domains. 24 the heart rate– blood pressure relation after an
hour R-R recordings allow calculation of more intravenous bolus of phenylephrine.

complex statistical time domain measures, such Microneurography:
as standard deviation (SD) of all normal R-R in-
tervals (SDNN), SD of 5-min average of normal This technique is based on recording electri-
R-R intervals (SDANN), root-mean square of the cal activity emitted by peroneal, tibial, or radial
difference of successive R-R intervals (rMSSD), muscle sympathetic nerves and identification of
and the number of instances per hour in which sympathetic bursts. Bursts have a characteristic
two consecutive R-R intervals differ by 50 ms shape consisting of a gradual rise and fall that is
over 24 h (pNN50). SDNN is thought to represent usually constrained by the cardiac cycle and at
joint sympathetic and parasympathetic modula- least twice the amplitude of random fluctuations.
tion of HRV, and rMSSD and pNN50 are specific Recently available fully automated sympathetic
for the parasympathetic limb. Spectral analysis neurogram techniques provide a rapid and ob-
of HRV is another tool to evaluate DCAN. It de- jective method that is minimally affected by sig-
composes the R-R signal into a set of sine and nal quality and preserves beat-by-beat sympa-
cosine waves and estimates the magnitude of thetic neurograms.

variability as a function of frequency.
Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 32

Clinical Implications: Further studies are needed to clarify the complex
interactions between CAN, silent myocardial is-
Mortality risk: chemia, and cardiomyopathy in diabetes.

DCAN is associated with a high risk of cardiac Intraoperative and perioperative cardi-
arrhythmias and with sudden death. Longitudi- ovascular instability:
nal studies of subjects with DCAN have shown
5-year mortality rates 16–50% in type 1 and type Observations in diabetic patients undergoing
2 DM, with a high proportion attributed to sud- general anaesthesia reported that individuals
den cardiac death18. In the EURODIAB Prospec- with DCAN required vasopressor support more
tive Cohort Study of 2,787 type 1 DM patients, often than those without CAN. Individuals with
DCAN was the strongest predictor for mortality DCAN may experience a greater decline in heart
during a 7-year follow-up, exceeding the effect rate and blood pressure during induction of an-
of traditional cardiovascular risk factors19. The aesthesia and more severe intraoperative hypo-
mechanisms proposed to account for this in- thermia resulting in decreased drug metabolism
creased mortality are: difficulty in recognizing and impaired wound healing.
angina (atypical manifestations such as nausea,
shortness of breath and tiredness are common), Stroke:
asymptomatic ischemia or MI, dysfunction of the
coronary flow autoregulation, increased heart A recent study in 1,458 patients with type 2 di-
rate, LV systolic and diastolic dysfunction, in- abetes reported that presence of DCAN, as-
creased risk of arrhythmias (prolonged QT inter- sessed by standard HRV testing, was one of the
val), decreased nocturnal protection against MI, strongest predictors of ischemic stroke in this co-
changes in BP circadian cycle, increased car- hort together with age and hypertension. Earlier
diac mass, increased risk of microalbuminuria reports showed similar associations.
and, lastly, apnea1,2. The death in bed syndrome,
in which the triad CAN + sympathetic-adrenergic Therapeutic Approaches
discharge + nocturnal hypoglycemia plays a key
role, is also well-known. Glycaemic control:

Silent myocardial ischemia and diabet- The DCCT demonstrated that intensive insulin
ic cardiomyopathy: therapy for type 1 DM reduced the incidence of
DCAN by 53% compared with conventional ther-
In a meta-analysis of 12 published studies, Vin- apy. The Epidemiology of Diabetes Interventions
ik et al1. reported a consistent association be- and Complications (EDIC) study, the prospec-
tween DCAN and the presence of silent myo- tive observational study of the DCCT cohort, has
cardial ischemia, measured by exercise stress shown persistent beneficial effects of past glu-
testing, with point estimates for the prevalence cose control on microvascular complications de-
rate ratios from 0.85 to 15.53. In the Detection spite the loss of glycaemic separation24. In type
of Ischemia in Asymptomatic Diabetics (DIAD) 2 DM, the effects of glycaemic control are less
study of 1,123 patients with type 2 diabetes, conclusive. The VA Cooperative Study demon-
DCAN was a strong predictor of silent ischemia strated no difference in the prevalence of au-
and subsequent cardiovascular events20. The tonomic neuropathy in type 2 DM after 2 years
presence of DCAN was also linked to the devel- of tight glycaemic control compared with those
opment of diabetic cardiomyopathy in type 1 DM without tight control25. On the other hand, the
because in these patients ventricular dysfunction Steno-2 Trial reported that a targeted, intensive
often precedes or occurs in the absence of signif- intervention involving glucose control and multi-
icant coronary artery disease or hypertension21. ple cardiovascular risk factors reduced the prev-
alence of DCAN among patients with type 2 DM

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 33

and microalbuminuria. plasma expansion and may enhance the sensi-
tivity of blood vessels to circulating catechola-
Other therapies: mines28. The effects usually occur over a 1- to
2-week period. Supine hypertension, hypokal-
Data regarding the impact of lifestyle interven- aemia, and hypomagnesemia may occur. Cau-
tions in preventing progression of DCAN are tion must be used, particularly in patients with
emerging. Strictly supervised endurance training congestive heart failure, to avoid fluid overload.
combined with dietary changes was associated Treatment with fludrocortisone should begin with
with weight loss and improved HRV in patients 0.05 mg at bedtime and may be titrated gradually
with minimal abnormalities. In the Diabetes Pre- to a maximum of 0.2 mg/day. Doses up to 0.3–
vention Program, indexes of DCAN improved 0.4 mg used in refractory cases are associated
most in the lifestyle modification arm compared with high risk for hypokalaemia, excessive fluid
with the metformin or placebo arm. ACE inhibi- retention, hypertension, and congestive heart
tors, angiotensin receptor blockers, or aldose re- failure.
ductase inhibitors appear promising but are yet
to be validated. Erythropoietin:

Orthostatic hypotension: Erythropoietin may improve orthostatic hypoten-
sion, but the mechanism of action for this pres-
The treatment of orthostatic hypotension is chal- sor effect is still unresolved. Possibilities include
lenging. Nonpharmacological treatments include the increase in red cell mass and central blood
avoidance of sudden changes in body posture to volume, correction of the normochromic normo-
the head-up position; avoiding medications that cytic anaemia that frequently accompanies se-
aggravate hypotension, such as tricyclic antide- vere CAN, and direct or indirect neuro- humoral
pressants and phenothiazines; eating small, fre- effects on the vascular wall and vascular tone
quent meals to avoid postprandial hypotension; regulation mediated by the interaction between
and avoiding activities that involve straining, haemoglobin and the vasodilator nitric oxide.
since increased intra-abdominal and intra-tho- Erythropoietin is administered subcutaneously
racic pressure decrease venous return. Several or intravenously at doses of 25–75 units/kg three
physical counter manoeuvres, such as leg cross- times a week until the haematocrit level ap-
ing, squatting, and muscle pumping can help proaches normal followed by lower maintenance
maintain blood pressure during daily activities by doses (25 units/kg three times/week).
inducing increased cardiac filling pressures and
stroke volume. Non-selective Beta-blockers:

Pharmacological Treatment Nonselective beta-blockers, particularly those
Midodrine: with intrinsic sympathomimetic activity, may
have a limited role in the treatment of orthostat-
Midodrine, a peripheral-selective alpha 1- ic hypotension. The suggested mechanism of
adrenoceptor agonist is widely tested agent for action of these agents is the blockade of vas-
the treatment of orthostatic hypotension in doses odilating beta-2 receptors allowing unopposed
of 2.5–10 mg three times/day. It does not cross alpha-adrenoceptor–mediated vasoconstriction.
the blood-brain barrier, resulting in fewer central To date there is no clear efficacy evidence in di-
side effects. The main adverse effects are pilo- abetic DCAN.
erection, pruritis, paraesthesia, urinary retention,
and supine hypertension. Clonidine:

Fludrocortisone acetate: Clonidine, an alpha-2 antagonist, produces a
central sympatholytic effect and a consequent
Fludrocortisone acetate, a synthetic mineralo- decrease in blood pressure. Patients with severe
corticoid with a long duration of action, induces DCAN have little central sympathetic efferent

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 34

activity, and the use of clonidine (0.1– 0.6 mg/ 3. Tesfaye S, Boulton AJM, Dyck PJ. Diabetic
day) could result in an increase in venous re- neuropathies: update on definitions, diagnos-
turn without a significant increase in peripheral tic criteria, estimation of severity, and treat-
vascular resistance. Its use is limited by the in- ments. Diabetes Care 2010;33(10):2285–93.

consistent hypertensive effect and serious side 4. The Diabetes Control and Complications Tri-
effects. al Research Group. The effect of intensive

Somatostatin analogs: diabetes therapy on measures of autonom-
ic nervous system function in the Diabetes
Somatostatin analogs (25–200 g/day) may at- Control and Complications Trial (DCCT). Dia-
betologia. 1998; 41: 416-23.
tenuate orthostatic hypotension in patients with

DCAN by inhibiting the release of vasoactive

gastrointestinal peptides, enhancing cardiac 5. Kennedy WR, Navarro X, Sutherland DE.
output, and increasing forearm and splanchnic Neuropathy profile of diabetic patients in a
vascular resistance. However, severe cases of pancreas transplantation program. Neurolo-
hypertension were reported with their use in pa- gy 1995;45:773–780
tients with DCAN.
6. Ziegler D, Dannehl. Prevalence of cardio-
Conclusions vascular autonomic dysfunction assessed by
spectral analysis, vector analysis, and stand-
DCAN is one of the most clinically significant ard tests of heart rate variation and blood
complications of diabetes mellitus (DM), but one pressure responses at various stages of di-
of the least frequently diagnosed. It also is one abetic neuropathy. Diabet Med 1992;9: 806
of the most obscure and controversial topics in – 814
current diabetology. DCAN is an independent

predictor of cardiovascular disease mortality. It 7. Edwards JL, Vincent AM, Cheng HT, Feld-
is associated with a poor prognosis and poor man EL. Diabetic neuropathy: mechanisms to
quality of life. Conclusive clinical evidence from management. PharmacolTher2008;120:1–34
randomized prospective trials supports a central

role for hyperglycaemia in the pathogenesis of 8. Paulson DJ, Light KE. Elevation of serum
DCAN, although other metabolic and vascular and ventricular norepinephrine content in the

factors contribute to the disease state. The clini- diabetic rat. Res CommunChemPatholPhar-

cal presentation of DCAN comprises a broad con- macol1981;33:559 –562

stellation of symptoms and deficits. Assessment 9. Pfeifer MA, Weinberg CR, Cook DL, Reenan
of HRV is an easily available tool to document A, Halter JB, Ensinck JW, Porte D Jr. Au-
the presence of DCAN. Cardiac scintigraphic im- tonomic neural dysfunction in recently di-
aging with sympathetic analogs offers more sen- agnosed diabetic subjects Diabetes Care
sitive diagnostic alternatives for research use. 1984;7:447– 453
The treatment of DCAN is challenging. Recent

clinical evidence continues to prove the benefits 10. Spallone V, Bernardi L, Ricordi L, Solda` P,
of glycemic control, while the benefits of lifestyle Maiello MR, Calciati A, Gambardella S, Fra-
and pharmacologic interventions are emerging. tino P, Menzinger G. Relationship between

References: the circadian rhythms of blood pressure and
sympathovagal balance in diabetic autonom-
1. Vinik AI, Ziegler D. Diabetic cardiovas- ic neuropathy. Diabetes 1993;42:1745–1752
cular autonomic neuropathy. Circulation
2007;115:387–97.Ziegler D. Cardiovascular 11. Consensus Committee of the American Au-
autonomic neuropathy: tonomic Society and the American Academy
of Neurology. Consensus statement on the
2. clinical manifestations and measurement. Di- definition of orthostatic hypotension,
abetes Rev. 1999; 7: 300-15.
Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 35

pure autonomic failure, and multiple system the EURODIAB Prospective Complications
atrophy. Neurology 1996;46:1470 Study (PCS). Diabetes Care 2008;31:1360
–1366
12. Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feld- 20. Young LH, Wackers FJ, Chyun DA, Davey
man EL, Freeman R, Malik RA, Maser RE, JA, Barrett EJ, Taillefer R, Heller GV, Is- kan-
Sosenko JM, Ziegler D, American Diabetes drian AE, Wittlin SD, Filipchuk N, Ratner RE,
Association. Diabetic neuropathies: a Inzucchi SE, DIAD Investigators. Cardiac
statement by the American Diabetes Associ- outcomes after screening for asymptomatic
ation. Diabetes Care 2005;28:956 –962 coronary artery disease in patients with type
2 diabetes: the DIAD study: a randomized
13. Task Force of the European Society of Car- controlled trial. JAMA 2009;301:1547–1555
diology and the North American Society of 21. Cardiac Autonomic Neuropathy in Diabetes:
Pacing and Electrophysiology. Heart rate Clinical Perspective. Rodica Pop-Busui. Dia-
variability: standards of measurement, physi- betes care2010;33:434-441
ological interpretation and clinical use. Circu-
lation 1996;93:1043–1065

14. Raffel DM, Wieland DM. Assessment of 22. Ko SH, Song KH, Park SA, Kim SR, Cha BY,
cardiac sympathetic nerve integrity with Son HY, Moon KW, Yoo KD, Park YM, Cho
positron emission tomography. Nucl Med JH, Yoon KH, Ahn YB. Cardiovascular auto-
Biol2001;28:541–559 nomic dysfunction predicts acute ischaemic
stroke in patients with Type 2 diabetes mel-
15. Stevens MJ, Raffel DM, Allman KC, Dayanikli litus: a 7-year follow-up study. Diabet Med
F, Ficaro E, Sandford T, Wieland DM, Pfeif- 2008;25:1171–1177
er MA, Schwaiger M. Cardiac sympathetic
dysinnervation in diabetes: implications for 23. The effect of intensive diabetes therapy on
enhanced cardiovascular risk. Circulation measures of autonomic nervous system func-
1998;98:961–968 tion in the Diabetes Control and Complica-
tions Trial (DCCT). Diabetologia 1998;41:416
16. La Rovere MT, Bigger JT, Jr, Marcus FI, Mor- – 423
tara A, Schwartz PJ. Baroreflexsensi- tivity
and heart-rate variability in prediction of total 24. Writing Team for the Diabetes Control and
cardiac mortality after myocardial infarction. Complications Trial/Epidemiology of Dia-
ATRAMI (Autonomic Tone and Reflexes After betes Interventions and Complications Re-
Myocardial Infarction) Investigators. Lancet search Group. Sustained effect of intensive
1998;351:478 – 484 treatment of type 1 diabetes mellitus on de-
velopment and progression of diabetic ne-
17. Hamner JW, Taylor JA. Automated quantifi- phropathy: the Epidemiology of Diabetes In-
cation of sympathetic beat-by-beat activity, terventions and Complications
independent of signal quality. J ApplPhysi- (EDIC) study. JAMA 2003;290: 2159 –2167
ol2001;91:1199 –206
25. Azad N, Emanuele NV, Abraira C, Hen- der-
18. O’Brien IA, McFadden JP, Corrall RJ. The son WG, Colwell J, Levin SR, Nuttall FQ,
influence of autonomic neuropathy on mor- Comstock JP, Sawin CT, Silbert C, Rubino
tality in insulin-dependent diabetes. Q J Med FA. The effects of intensive glycaemic control
1991;79:495–502 on neuropathy in the VA cooperative study on

19. Soedamah-Muthu SS, Chaturvedi N, Witte type II diabetes mellitus (VA CSDM). J Diabe-
DR, Stevens LK, Porta M, Fuller JH, EU- tes Complications 1999;13:307–313

RODIAB Prospective Complications Study 26. Gaede P, Vedel P, Larsen N, Jensen GV,
Group. Relationship between risk factors and Parving HH, Pedersen O. Multifactorial in-
mortality in type 1 diabetic patients in Europe: tervention and cardiovascular disease in

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 36

patients with type 2 diabetes. N Engl J Med
2003;348:383–393

27. Vinik AI, Maser RE, Mitchell BD, Freeman R.
Diabetic autonomic neuropathy. Diabetes
Care 2003;26:1553–1579

28. Freeman R. Treatment of orthostatic hypo-
tension. SeminNeurol2003;23:435– 442

29. Pop-Busui R, Chey W, Stevens MJ. Severe
hypertension induced by the long-acting so-
matostatin analogue sandostatin LAR in a pa-
tient with diabetic autonomic neuropa-
thy. J ClinEndocrinolMetab2000;85:943–946

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 37

Management of Symptomatic IHD in Type 2 Diabetes Mellitus

Dr.Pravin Kahale, M.D,DM(Cardio)
Consultant Interventional Cardiolagist & Heart Failure Cardiolagist
Kokileben Dhirubai Ambhani Hospital & Medical Research Institute, Mumbai.

Abstract Diabetes Mellitus (DM)
Ischemic Heart Disease (IHD)
Diabetes mellitus (DM) is a common medical Coronary Artery Disease (CAD)
problem and a major risk factor for the develop- Percutaneous Coronary Intervention (PCI)
ment of atherosclerotic coronary artery disease Coronary Artery Bypass Grafting (CABG)
(CAD). Coronary artery disease is highly preva- Percutaneous Transluminal Coronary Angioplas-
lent and is the major cause of morbidity and mor- ty (PTCA)
tality in diabetic patients. Patients with CAD and Myocardial Infarction (MI)
prediabetic states should undergo lifestyle mod- Optimum Medical Therapy (OMT)
ifications aimed at preventing DM. In patients Clinical Outcomes Utilizing Revascularization
with CAD and DM, routine use of aspirin and an and Aggressive Drug Evaluation (COURAGE)
angiotensin-converting enzyme inhibitor (ACE-I) Bypass Angioplasty Revascularization Investiga-
unless contraindicated or not tolerated are tion 2 Diabetes (BARI 2D)
strongly recommended. Strict glycaemic, blood Future Revascularization Evaluation in Patients
pressure, and lipid control are of prime impor- with Diabetes Mellitus: Optimal Management of
tance. Intense insulin therapy might be needed Multivessel Disease (FREEDOM)
for glycaemic control, and high-dose statin ther-

apy might be needed for lipid control. For blood Introduction
pressure control, ACE-Is and angiotensin recep-
tor blockers are considered as first-line therapy. Diabetes mellitus is the most potent risk factor
In patients with stable or no symptoms with doc- for coronary artery disease (CAD). Patients with
umented ischemia, the results from COURAGE diabetes are two to four times more likely to have
and BARI 2D provide a rationale for intensive cardiovascular disease. This increased risk is
medical therapy and lifestyle intervention, and seen in both type I and type II diabetes. Patients
a strong justification for delaying revasculariza- with diabetes but no CAD have the same inci-
tion in patients. These studies indicate that PCI dence of myocardial infarction (MI) as patients
is vital when symptoms become unstable and with CAD but no diabetes. Other risk factors such
may be useful to relieve burdensome symptoms as hypertension, smoking, and hyperlipidaemia
in other situations. BARI 2D provides important carry a worse prognosis in patients with diabetes
new evidence that CABG is preferred over med- than in those who do not have diabetes. More-
ical therapy alone for patients with diabetes and over, there is an increased prevalence of these
severe coronary disease not only for symptom risk factors in patients with diabetes. This article
relief but also for reducing the rate of myocardial reviews the prevention and management of CAD
infarction. FREEDOM (Future Revascularization in patients with diabetes .

Evaluation in Patients with Diabetes Mellitus: CAD Prevention in Diabetic Patients
Optimal Management of Multivessel Disease)
trial showed a similar benefit of CABG over PCI, Screening for CAD in Diabetic Patients
including reductions in myocardial infarction (MI) Diabetes is commonly considered as a CAD risk
and all-cause mortality. In this article, we will re- equivalent. High-risk diabetic patients include
view the various management aspects for symp- those with typical or atypical symptoms, those
tomatic IHD with diabetes. 55 years of age or older, those with peripheral
or carotid vascular disease, and those with 2 or

Abbreviations more of the following risk factors: hyperlipidae-
mia, hypertension, smoking, family history of

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 38

premature CAD, microalbuminuria, and progres- substudy, intensive therapy was associated with

sive retinopathy. Screening for CAD might be in- reduced risks of stroke and MI. Greater risk re-

dicated in younger individuals, with a relatively duction was achieved with lower BP levels, and

short duration of DM and few risks or diabetic there was no threshold for risk reduction. The ev-

complications, because most guidelines recom- idence for drug efficacy in reducing CV events in

mend more aggressive management of risk fac- high-risk patients with DM is largely derived from

tors in the presence of CAD. Detection of CAD subgroup analyses of trials. In the ASCOT (An-

involves the usual diagnostic methods, which glo- Scandinavian Cardiac Outcomes Trial), the

include exercise stress testing and, as indicat- benefits of the amlodipine-based regimen (with

ed, myocardial perfusion scintigraphy or stress or without perindopril) versus the atenolol-based

echocardiography. regimen on rates of nonfatal MI and fatal CAD

were similar for hypertensive patients with or with-

Pharmacological Interventions to Pre- out DM. In the diabetic patients randomized in the
vent CAD in Diabetes
MICRO-HOPE (Microalbuminuria, Cardiovascu-

The implementation of lifestyle modification, in- lar, and Renal Outcomes-Heart Outcomes Pre-

cluding dietary measures and aerobic exercise vention Evaluation) substudy, ramipril reduced

aiming at long-term weight loss, are even more the primary composite end point of MI, stroke, or

critical in patients with diabetic CAD than in those CV death. Diabetic patients derived similar risk

with DM alone, because of the higher risk of CV reductions with perindopril in the EUROPA (EU-

events in these patients. Ropean trial On reduction of cardiac events with

Perindopril in stable coronary Artery disease). In

Antiplatelet therapy the LIFE (Losartan Intervention For Endpoints)

Primary prevention therapy with aspirin is rec- study reduction in hypertension study, the prima-

ommended in diabetic patients >40 years of age, ry composite end point of CV death, stroke, or

with additional risk factors, and/or with diabetes MI occurred less often in patients assigned to lo-

>10 years’ duration. Contemporary guidelines sartan than in those assigned to atenolol. Thus,

recommend prophylactic therapy with aspirin for compared with a beta-blocker–based regimen,

diabetic patients with CAD. In patients who do losartan therapy conferred consistent CV risk re-

not tolerate or have a contra-indication to aspirin, duction in hypertensive diabetic patients.

clopidogrel can be used as an alternative anti-

platelet agent. Trimetazidine limits intracellular Clinical guidelines recommend primary preven-

acidosis, stabilizes ionic membranes and pre- tion measures with ACE-I therapy in diabetic pa-

vents free radicals. Ranolazine improves blood tients with 1 other CAD risk factor and secondary

flow by indirect action on calcium overload. prevention with these drugs in diabetic patients

with CAD. Recognizing that diabetic patients will

Optimization of glycaemic control usually need 3 or 4 antihypertensive drugs to

The goal of anti-diabetic drug therapy is to en- lower BP to the recommended level, ACE-Is and

sure optimal glycaemic control (HbA1c <7%) ARBs (along with long-acting calcium channel

with minimization of diabetes-related complica- blockers) are recommended as first-line therapy

tions. There is no specific threshold for glycemia

in relation to CV risk. Thus, optimal glycaemic Lipid-lowering therapy

control must be a clear objective in diabetic pa- Lipid lowering therapy is recommended for dia-

tients, not only for prevention of microvascular betic patients >40 years of age or subjects <40

but also of macrovascular events. years of age with additional risk factors. The

current lipid target ranges are LDL-C <100 mg/

Antihypertensive therapy dl or a reduction in LDL-C by 30% to 40%, tri-

The current anti-hypertension treatment targets glycerides <150 mg/dl, and HDL-C >40 mg/dl. In

are <130/80 mm Hg in diabetic patients (120/80 women, an HDL-C goal of 10 mg/dl higher (50

mm Hg after MI). In the UKPDS BP-lowering mg/dl) might be considered. On the basis of the

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 39

HPS and other trials, it is reasonable to target a Treatment Targets
LDL-C of 70 mg/dl for high-risk subjects such as
diabetic patients. Available treatment options, meant to preserve
and optimize myocardial functions, achieve sta-
CAD Management in Diabetic Patients bilisation of vulnerable plaques, prevent recur-
Managing CAD patients with DM requires spe- rent events by controlling prothrombotic activity,
cial attention. The majority of data on the man- and to counteract progression of atheroscle-
agement of CAD in DM are based on retrospec- rotic lesions, are summarized in table 1. Evi-
tive subgroup analysis of major clinical trials, dence-based recommendations for secondary
which on an average included 20%–30% dia- prevention are, in general terms, valid for pa-
betic patients. Patients with DM have a number tients as well as without diabetes. The manage-
of adverse clinical, angiographic and metabolic ment strategy should, if anything, be even more
features contributing to poor prognosis. Diabetic ambitious in the former category of patients.
patients with CAD are more often female, obese
and hypertensive. They usually have severe an- Hyperglycaemia and Acute Coronary
gina, history of previous MI or CABG and marked Syndrome
left ventricular failure. They have abnormal en-
dothelial function with reduced coronary flow re- Hyperglycaemia, on admission in patients with
serve. There is platelet activation with increased acute coronary syndrome (ACS) is common, and
thromboxane A2 secretion. The levels of fibrino- it is a powerful predictor of survival and increased
gen and factor VII are higher than normal, while risk of in-hospital complications in patients both
antithrombin III and plasma fibrinolytic activity with and without diabetes mellitus.
are lower. Angiographically, they have diffuse,
extensive involvement of smaller reference ves- Diabetes and Coronary Revasculariza-
sels, multivessel involvement, higher incidence tion
of left main coronary artery disease, poorer col-
laterals, lower ejection fraction and more throm- Revascularization procedures may be indicated
bus formation. in diabetic patients with stable or unstable coro-
nary syndromes, covering the whole spectrum of
ischemic heart disease from asymptomatic pa-
tient to ST- elevation MI, ACS, and prevention
of sudden cardiac death. The COURAGE and
BARI 2D trial results have important implications
for the way cardiologists approach clinical de-
cision-making and practice (4,5). Evaluation of
symptoms, risk factors and test results are first
used to risk stratify patients. In patients with sta-
ble or no symptoms with documented ischemia,
the results from COURAGE and BARI 2D pro-
vide a rationale for intensive medical therapy
and lifestyle intervention, and a strong justifica-
tion for delaying revascularization in patients with
the characteristics of those enrolled in the trials.
Intensive medical therapy aimed at treating dys-
lipidaemia, hypertension and glycaemia must be
available for all patients. These studies indicate
that PCI is vital when symptoms become unsta-
ble and may be useful to relieve burdensome
symptoms in other situations. BARI 2D provides
important new evidence that CABG is preferred
over medical therapy alone for

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 40

patients with diabetes and severe coronary dis-

ease not only for symptom relief but also for

reducing the rate myocardial infarction. Practi- 3. AHA scientific statement. Hyperglyce-
tioners must carefully consider generalization
of trial results to individual patients, and in the mia and acute coronary syndrome. Circulation.
case of CABG and BARI 2D risk stratification, 2008;117;1610-9.

knowledge of the patient’s coronary anatomy is

essential before applying the results to individual 4. Boden WE, O’Rourke RA, Teo KK, et al.,
patients. FREEDOM (Future Revascularization COURAGE Trial Research Group. Optimal med-
Evaluation in Patients with Diabetes Mellitus:
Optimal Management of Multivessel Disease) ical therapy with or without PCI for stable coro-
trial showed a similar benefit of CABG over PCI, nary disease. N Engl J Med 2007;356:1503–16.

including reductions in myocardial infarction (MI)

and all-cause mortality (6). Consequently, the 5. BARI 2D Study Group. A randomized trial
2014 American College of Cardiology/American of therapies for type 2 diabetes and coronary ar-
Heart Association guidelines and the 2014 Eu-
ropean Society of Cardiology/European Asso- tery disease. N Engl J Med 2009;360:2503–15.

ciation for Cardio-Thoracic Surgery guidelines Farkouh ME, Domanski M, Sleeper LA, et
recommend CABG over PCI in patients with dia- 6.

betes and multivessel disease al., for the FREEDOM Trial Investigators. Strate-

Conclusion of CAD in diabetic patients gies for multivessel revascularization in patients
with diabetes. N Engl J Med 2012;367:2375–84.
The management

poses a challenging problem. The risk factors
need to be vigorously controlled with tight man- 7. FihnSD, Blankenship JC, Alexander KP,

agement of lipids and blood pressure. Strict con- et al.2014 ACC/AHA/AATS/PCNA/SCAI/STS fo-
trol of hyperglycaemia should be ensured. In cused update of the guideline for the diagnosis
patients who are appropriate candidates for re-
vascularization, a thoughtful and transparent dis- and management of patients with stable ischemic
cussion between the cardiologist, surgeon, and heart disease: a report of the American College

patient should be undertaken to ensure that the of Cardiology/American Heart Association Task

goals of therapy are aligned with the scientific Force on Practice Guidelines, and the American
evidence that supports it, and that the decision Association for Thoracic Surgery, Preventive
to proceed with PCI or CABG is individualized in
the interests of what is best for the patient. Cardiovascular Nurses Association, Society for
Cardiovascular Angiography and Interventions,

References and Society of Thoracic Surgeons. J Am Coll

1. Berry C, Tardif JC, Bourassa MG. Cor- Cardiol 2014;64:1929–49

onary heart disease in patients with diabe-

tes. Part I: Recent advances in prevention and Highlights:

noninvasive management. J Am Coll Cardiol. • Diabetes is the most potent risk factor for
the development of coronary heart disease and
2007;49:631-42.

other risk factors like hypertension, smoking,
2. Bax JJ, Young LH, Frye RL, Bonow RO, and hyperlipidaemia carry a worse prognosis in

Steinberg HO, Barrett EJ. Screening for coro- patients with diabetes than in those who do not
nary artery disease in patients with diabetes. have diabetes.

Diab Care. 2007;30:2729-36.

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 41

• CAD can be detected through diagnostic
methods which include exercise stress testing
and, as indicated, myocardial perfusion scintig-
raphy or stress echocardiography

• The implementation of lifestyle modifica-
tion, including dietary measures and aerobic ex-
ercise aiming at long-term weight loss, are more
critical in patients with diabetic CAD than in those
with DM alone, because of the higher risk of CV
events in these patients.

• Medical management should include in-
tensive anti-diabetic, anti-platlet, hypolipidemic,
anti-hypertensive therapy in patients of CAD with
diabetes.

• Hyperglycaemia in patients with acute
coronary syndrome (ACS) is a powerful predic-
tor of survival and increased risk of in-hospital
complications in patients both with and without
diabetes mellitus

• CABG + OMT is the preferred treatment
strategy as it reduces the primary composite of
death, MI or stroke

• In the presence of factors that preclude
a CABG + OMT strategy, OMT alone is the next
best therapeutic approach

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 42

THE ‘OBESITY PARADOX’ IN SILENT CORONARY ARTERY
DISEASE AND DIABETES

Dr.Avijit Lahiri,MBBS,BS,MSc,FACC,FESC
Medical Director

British Cardiac Research Trust,London,United Kingdom

Abstract 3 times lower than in those of normal weight (<25
Objective kgs/m2)

Lower incidences of cardiovascular mor- Conclusions
tality and morbidity in overweight/obese patients
compared ‘normal’ BMI subjects have been re- Patients with higher BMI were associated
ported. We evaluated the relationship between with lower prevalence of coronary atherosclero-
BMI and coronary atherosclerosis in an asymp- sis in our cohort and those with normal BMI were
tomatic cohort of patients with diabetes. more likely to suffer an adverse cardiovascular
event compared to those with BMI > 25Kgs/m2.
Research Design and Methods

226 asymptomatic patients with type-2
diabetes and no known coronary artery disease
were recruited. All patients underwent CT coro-
nary angiograms (CTCA) at baseline.

Results

There were 58.3% males with median
BMI of 28.3 (IQR: 25.3-32.4), and median dura-
tion of diabetes of 13 years (IQR: 8-19). 55.5%
of the study population were south Asians, re-
flecting their high prevalence in the catchment
areas of the clinics. Four BMI categories, defin-
ing normal BMI (18-25 kgs/m2, overweight (25
– 30 kgs/m2), obese (30-35 kgs/m2) and grossly
obese (>35 kgs/m2) individuals were created.
In patients with BMI < 25 kgs/m2, 53% had at
least one significantly stenotic plaque whereas
in the two higher BMI categories (30-35 kgs/m2
and > 35 kgs/m2) only 26% of patients had sig-
nificant coronary plaque. Both the unadjusted
and adjusted analyses suggested a significant
association between BMI and significant plaque
(p=0.03 and 0.01 respectively). During a median
22-month follow up, the risk of an adverse event
in the overweight/obese group (> 25 kgs/m2) was

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 43

Real culprit of Cardiometabolic Disease

DR.Dina Nagodra
MBBS,MSC Public and Tropical Health UMST.,Sudan

1.Epidemiology: 3. Inflammation — NO —> decreased
thrombosis
Heart disease continues to be our
leading cause of death among both men and 4. Oxidation —> free radicals injure the endo-
women. Women actually outnumber men in the thelium by neutralizing NO (Antioxidants can
prevalence of cardiovascular disease (CVD) prevent this).
with about 53% of CVD related deaths occurring
in women. CVD claims as many lives each year Nerve cells in the erectile tissue of the penis can
as the next seven leading causes of death com- activate the enzyme “Neuronal NO synthetase”
bined. Up to 90% of all cases of impotence are that produces NO, which causes the smooth
now known to be due to “vascular insufficien- muscle of the penis to relax so that more blood
cy.” In fact, 80% of all humans die as a result of enters and increases the erection. (Nerve cells
some sort of cardio-metabolic disease. Adults in the brain and lung function in the same man-
with diabetes in the world have more than dou- ner.)
bled since 1980. Every 29 seconds an Ameri-
can has a heart attack. A death occurs once A prolonged period of sitting reduces critical en-
every minute. Every 53 seconds an American zymes essential for good health. Sitting is a big-
has a stroke. A death from stroke occurs every ger risk factor than smoking.
3 minutes. One out of two Americans will die of
cardiovascular disease – which in most cases 2.Aims:
could have been prevented. 75% of heart attack
victims have Diabetes or Pre-diabetes - the oth- To identify the real culprit of cardiometabolic dis-
er 25% according to Dr. Joseph Kraft have just ease.
not been properly diagnosed.
3.Method:
1.1 What is cardio-metabolic disease?
In depth analysis of causes of cardiometabolic
Cardio: Disease of the Heart and Blood Vessels. disease.
Metabolic: Disease of Metabolism including:
obesity, diabetes and metabolic syndrome. 4.Results:
Diabetes starts from the age of 20 years with
obesity, becomes discernible at 30 years with There are different causes of CVD but endo-
abnormal glucose tolerance, subclinical at thelial dysfunction is the main cause leading
the age of 40 with elevated FBG, outreached to inflammation, oxidative stress, immune dys-
threshold at 50 with glucose in urine, becomes function, abnormal growth, vasoconstriction, in-
severe at 60 with requirement of hypoglycemic creased permeability, thrombosis and ultimately
agents, results in complications of blindness, cardiovascular disease.
neuropathy and nephropathy at 70.
Inflammation effects both carbohydrate and lip-
Nitric Oxide (NO) production is very important id metabolism. The result is insulin resistance,
for a healthy heart. Endothelial cells are the glucose intolerance and atherogenic dyslipid-
power plants for NO production. NO plays a key emia characterized by low HDL-C, high TG and
role in 4 essential processes in the endothelium: the formation of small dense LDL prone to oxi-
dation.

1. Vascular tone — NO —> increased vasodi- High levels of certain endotoxins from abnormal
lation gut bacteria can increase inflammation that is
2. Coagulation — NO —> decreased thrombo- associated with insulin resistance and obesity.
sis

Cardio Diabetes Medicine

Real culprit of Cardiometabolic Disease 44

1:4 people have a subsequent major event with- When oestrogen levels are low, the enzyme LPL
in 2.5 years despite intensive statin therapy and is “upregulated” on fat cells,
optimum LDL levels.
7:10 cardiovascular events still occur on inten-
5.Discussion: sive statin therapy who have reached LDL < 80.
5.1Consequences of Insulin Resis-
tance and more fat is pulled from the circulation into
the cell. When oestrogen levels are
Sugar is the main reason for causing cardiomet- high, LPL activity is suppressed, and the fat
abolic syndrome causing: obesity, sarcopenia, cells accumulate less fat.
dyslipidemia, hypertension, atherosclerosis,
type 2 disease, cardiovascular disease, stroke, One reason men get fatter above the waist as
osteoporosis, GERD, fatty liver, gout, erectile they age is that they secrete less testosterone
dysfunction, malignancies, PCOs, sleep apnea and testosterone suppresses LPL activity on the
and alzheimer’s disease. abdominal fat cells. Less testosterone means
Fructose is the most “lipogenic” carbohydrate more LPL activity on the fat cells of the gut and
– not only does it cause fatty liver and insulin so more fat.
resistance but also causes muscle to become
insulin resistant. Cortisol also stimulates LPL to put fat into our
cells (with stress, lack of sleep) but it also re-
Rather than doing GTT, a 3-5hr insulin/sugar leases fat from our fat cells by stimulating HSL,
load need to be measured to diagnose “insu- just like other hormones. So cortisol can make
lin resistance”. By doing that 100% of people us fatter still when insulin levels are elevated but
with heart disease will show insulin resistance. can make us leaner, just like all other hormones,
when insulin levels are low. The bottom line is if
5.1.1 Hormonal effect on LPL and HSL we want to get leaner. If we want to get fat out of
our fat cells and burn it we must lower our insu-
With more secreted insulin, more active the lin levels by reducing the quantity and quality of
lipoprotein lipase (LPL) on the fat cells, and the the carbohydrates we eat.
more fat is diverted from the bloodstream into
the fat cells to be stored. Insulin also happens The more insulin we secrete the more likely our
to suppress LPL activity on the muscle cells, as- cells will become resistant to that insulin and
suring that they won’t have many fatty acids to the quicker you will develop cardio-metabolic
burn. This means that when fatty acids do es- disease.
cape from a fat cell, if insulin levels happen to
be high, these fatty acids won’t be taken up by 5.1.2 Hormonal effect on lipid profile
the muscle cells and used for fuel. They’ll end
up back in the fat tissue.

Just as LPL works to make fat cells (and us) Insulin also turns on a mechanism in the fat cells
fatter, hormone sensitive lipase (HSL) works to pump in glucose – just as it does in muscle
to make fat cells (and us) leaner. It does so by cells – and this increases the amount of glucose
working inside the fat cells to break down tri- the fat cells metabolize. This in turn increases
glycerides into their component fatty acids, so the amount of glycerol molecules (a by-prod-
that those fatty acids can then escape into the uct of glucose metabolism) floating around in
circulation. The more active this HSL, the more the fat cells, and these glycerol molecules can
fat can be liberated and can burn for fuel and now be bundled together with fatty acids into tri-
the less is stored. Insulin also suppresses this glycerides, and so more fat can be stored.
enzyme HSL and so it prevents triglycerides
from being broken down inside the fat cells and The insulin works on the fat cells to make us
keeps the outward flow of fatty acids from the fat accumulate fat, and the expanding fat cells then
cells to a minimum. release “inflammatory molecules” (“cytokines”),

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 45

that have adverse effects throughout the body. 6.Conclusion:

It works on the liver to convert carbohydrates Modern medicine has focused on treating symp-
into fat, and this fat (triglycerides) is sent off into toms like high cholesterol and high blood sugar
the bloodstream on the particles that eventu- but to really prevent chronic disease and live
ally become small, dense LDL. It works on the long healthy lives we need to treat the under-
kidney to raise blood pressure by reabsorbing lying causes of “leptin and insulin resistance” –
sodium (and so has the same effect as eating these are what fuel the global epidemic of car-
extreme amounts of salt) and by impairing the dio-metabolic disease.
secretion of uric acid, which also accumulates
to unhealthy levels in the blood stream. (High If TG/HDL ratio is greater than 3 = insulin resis-
uric-acid levels cause gout, which is also as- tance!
sociated with obesity and diabetes, and the in-
cidence of gout, too, is increasing in Western “Insulin-resistance” (prediabetes) begins 10-15
societies). The insulin also works on the artery years before the blood sugar goes up. If we wait
walls to stiffen them and cause the accumula- until this time the person has lost 60-70% of the
tion of triglycerides and cholesterol in the bud- Beta cells of their pancreas. Advanced lipid and
ding atherosclerotic plaques. lipoprotein studies (LDL-P) begins to shift very
early and provides us a “window” into the met-
LDL Particles is the better predictor of car- abolic health of the individual long before there
diometabolic disease than LDL or VLDL size. are significant health problems –
The LDL-P (particle number) is 20x more ac- Intermittent fasting is a great way to reduce in-
curate than an LDL-C level. Triglycerides are sulin levels and help the body move from burn-
6x more predictive than cholesterol in causing ing sugar to burning fat and decreasing inflam-
heart attacks. TG/HDL ratio is also an excellent mation.
predictor of heart disease and insulin resistance.
Goal is to keep the ratio of <1.5 Omega 3 FA increases insulin and leptin sensi-
tivity

5.1.3 Role of Leptin in CVD NO levels can be increased by a NO friendly
Paleo or Veleo Diet, supplements and moderate
Leptin is produced by fat cells and tells brain exercise. Bergamet from a citrus fruit increases
when to eat, how much to eat and most import- NO and is a great antioxidant with powerful an-
ant when to stop eating. It includes many oth- ti-inflammatory properties.
er important functions like temperature control,
reproduction and the prevention of blood clots. The key to health is the QUALITY and QUAN-
Leptin levels are also essential to see how well TITY of carbohydrates we consume each day!
we age. If leptin levels are high this indicates We need to do what we have learnt now. There
not only poor health but poor longevity – just like is big gap between “knowing” and “doing.”
“insulin resistance” leptin ages us! When we re-
store “leptin sensitivity” we will stop storing fat 7.References:
and begin to burn it off.
1.WHO Guidelines 2014
When our body continually uses sugar as its
primary fuel the resulting leptin resistance will 2.Cardiometabolic Manual, Eternity Academy,
lock us in the sugar burning mode, simulating Reversing Metabolic Disease
the stressed out “fight or flight” mode. As would
the car engine quickly wear out, if continually
revved, we would age, become diseased and
die. Intermittent fasting helps a lot in changing
this process.

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 46

METABOLIC SYNDROME IN PCOS – THE SOUTH ASIAN
PROFILE

Dr.Chandrika N Wijeyaratne
Professor in Reproductive Medicine
Faculty of Medicine, University of Colombo
Honorary Physician and Endocrinologist
De Soysa Hospital for Women, Colombo

Polycystic ovary syndrome (PCOS) is the com- was recognized to play a central role in the com-
monest endocrine disorder reported among plex pathophysiology of PCOS, and insulin was
women of reproductive age worldwide, and man- thereby identified as a co-gonadotrophin in caus-
ifests with a clinical spectrum of heterogeneity ing an excess of ovarian androgen production. It
that can vary even in a given woman’s life cycle. is noteworthy that within the milieu of insulin re-
The three fundamental diagnostic criteria include sistance, acanthosis nigricans is a common cu-
oligoamenorrhoea / oligo-anovulation, hyperan- taneous marker of insulin resistance, which was
drogenaemia / hyperandrogenism manifesting increasingly reported among women with PCOS
as hirsutism, acne, seborrhoea and frontal bald- since the 1990s. It is noteworthy that by the
ing and ultrasound evidence of polycystic ova- early 21st century, women with PCOS of South
ries (PCO). As per Rotterdam Criteria (2003), Asian descent were reported to manifest this cu-
the presence of two or more of these three major taneous feature of insulin resistance even more
features, with the exclusion of other pathologies overtly from their early adult years. Acanthosis
that can mimic PCOS, (such as primary hypothy- as an important metabolic clinical parameter
roidism, Cushing syndrome, non-classical con- was linked to the finding of significantly greater
genital adrenal hyperplasia, acromegaly, hyper- fasting insulin concentrations even in apparently
prolactinaemia and androgen producing tumors normoglycaemic women of South Asian ethnic-
of the adrenal gland or ovaries) can lead to four ity. The greater propensity to insulin resistance
possible clinical sub-phenotypes. The well char- among young women of South Asian descent,
acterized phenotype with all three criteria be- in both migratory and indigenous groups alike,
ing fulfilled accounts for the majority of affected brought forth the need to consider the ethnicity
women, the hyperandrogenic and oligo-amenor- of the afflicted as an important determinant of the
rhoeic women without overt PCO accounts for clinical expression and metabolic risks of PCOS.
around a quarter of women with PCOS, while Since our first observational report in 2002, there
yet another fifth comprises of predominantly hir- has been an escalation of reports supporting this
sute women with regular cycles and PCO. Such observation; where ethnicity plays a role in the
a phenotypic mix has been reported from many determination of the variable phenotypic expres-
geographic regions. However, the indigenous sion of one and the same disorder of PCOS.
and migrant South Asians were found to mani- This association of PCOS and insulin resistance
fest more severe symptoms and signs from their was in parallel with the increase in insulin resis-
adolescence and early adulthood that was quite tance observed among young adult populations
significantly different from white Europeans. of South Asia since the early 1990s with central
obesity rather than global BMI related obesity
Hyperinsulinemia, reflecting selective peripheral being the causative factor; that quite significantly
insulin resistance, was first recognized as an im- included women. The same pattern of greater in-
portant biochemical feature in PCOS by the mid- sulin resistance was reported even among other
1980s and was studied extensively by Dunaif ethnic groups at risk of obesity and metabolically
et al. Over the next decade, insulin resistance unhealthy body configurations such as Caribbe-

Cardio Diabetes Medicine

Cardio Diabetes Medicine 2018 47

an Hispanics, Pacific Islanders, indigenous pop- types), age and geographic region of the affected
ulations from Australia-New Zealand and Mex- subjects. Caucasian women with PCOS had a
ican Americans; where the metabolic problems greater prevalence of obesity than Asian women
of PCOS were reported as being more than an with PCOS, having taken into account the differ-
additive effect. The underlying pathophysiology ing diagnostic criteria for overweight and obesity
although being similar, the differing ethnicities based on ethnicity. What is different about the
have shown varying expressions of the phe- South Asian woman, is that she manifests the
notype of PCOS and particularly the link to the problems related to the metabolic syndrome and
clinical constellation of the metabolic syndrome its effects at a lower BMI, but with comparable or
among women with PCOS. The presence of the even greater central obesity for the given (low-
metabolic syndrome however, has been shown er) BMI. This phenomenon highlights the ethnic
among South Asian to be equally prevalent propensity to the thrifty phenotype possibly as a
among the four clinical sub-phenotypes; where result of fetal programming and genetic plastici-
even the slim hirsute women with PCOS had the ty that the South Asian populations have been
propensity for having the metabolic syndrome exposed to since the mid 1960s. The changing
in their 3rd decade of life; while white European demographics and epidemiologic transition over
women with PCOS have a greater risk for the the previous 4 decades of the propensity of the
metabolic syndrome among women with obesi- South Asian populations to the metabolic syn-
ty and hyperandrogenism representing the well drome, has unfolded the picture about PCOS
characterized phenotype. and its role among women and their short-term
pregnancy outcomes. Issues related to pregnan-
The complex pathophysiology and clinical het- cy induced hypertension / pre-eclampsia, ma-
erogeneity of PCOS has contributed to the lack of ternal hyperglycaemia, fetal growth retardation
a clear understanding of its clinical correlates ob- and macrosomia have been observed to have a
served over time, chiefly body fat. Weight gain is greater incidence among women with the PCOS.
a common presenting complaint of PCOS, while
reduction of body weight is accompanied by im- The great majority of women seeking treatment
provement of its main symptoms. Although the from all ethnic groups for PCOS are at risk of
increasing trend in the epidemiology of PCOS being overweight or obese. Obesity is a com-
worldwide appears to be in parallel with the glob- mon feature of PCOS, although not a diagnostic
al epidemic of obesity, the occurrence of PCOS criterion, with over half of afflicted women being
among lean populations clearly depicts it is not either overweight or obese. Obesity, particularly
caused solely by obesity. Nevertheless, PCOS central obesity, is well known to increase insulin
is closely associated with obesity. Lim et al. re- resistance and has a close causative relationship
port a comprehensive systematic review and me- with the metabolic syndrome. PCOS is currently
ta-analysis of the prevalence of overweight, obe- considered to be the foremost identifiable overt
sity and central obesity in women with and without endocrine-metabolic risk among young women
PCOS. They found that women with PCOS had for developing premature morbidity and mortal-
a significantly increased risk for adiposity when ity from the metabolic syndrome, pre-diabetes /
compared with controls. The pooled estimated overt type 2 diabetes mellitus, and atheroscle-
prevalence of overweight and obesity in PCOS rosis related generalized vascular dysfunction
was 61% (95% CI: 54 –68%) and 49% (95% CI: using criterial such as carotid intimal thickness
42–55%) respectively, and central obesity being and arterial calcification. In parallel as much as
54% (95% CI: 43– 62%). This increased risk was half the women with the metabolic syndrome
independent of the PCOS diagnostic criteria (ini- complicating PCOS have been reported to have
tial NIH that aimed only at recognizing the well non-alcoholic fatty liver disease to be present.
characterized phenotype versus. Rotterdam that Nevertheless, the occurrence of overt prima-
addressed the heterogeneity and all sub-pheno- ry outcomes such as coronary artery disease,

Cardio Diabetes Medicine


Click to View FlipBook Version