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Published by markgarimella, 2017-10-23 12:22:04

Cardio Diabetes_2017 book

Cardio Diabetes_2017 book

Cardio Diabetes Medicine 2017 I

Cardio Diabetes
Medicine-2017

Theme: Liberate Heart Monitor Diabetes

“Cardiodiabetes acknowledges the inter-relationship be-
tween diabetes and cardiovascular disease and the term
creates a meaningful label for both physicians and pa-
tients. It also denotes a need to consider risk factors be-
yond glycaemic control and weight management”

- Doug Robertson

Editor in Chief

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

Chairman, Commonwealth Medical Association Trust, UK
Chief Physician and Intensivist.

GCDC 2017, Chennai, India

Cardio Diabetes Medicine

II CONTENTS

No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by means
electronic, mechanical, photocopying, recording or otherwise without prior permission of the copyright owner

This publication contains views or opinions of experts in field of Cardio Diabetology Published by Prof. Dr. S. Arulrhaj,
MD, FRCP (G) on behalf of Indo Global Cardio Diabetes Academy, Mumbai.

Date of Publishing : September 2017

Print: 1000 Nos

Editor in Chief

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

Chairman, Commonwealth Medical Association Trust, UK
Chief Physician and Intensivist.

Editorial Board – : Dr. D. Selvaraj

Dr. E.Prabhu

Dr. Aarathy Kannan

Editorial Assistants : Dr. Kiran Palsania

Dr. Bhuvaneshwar

Designed by:
Daksha Kumar TL, Graphic Designer
DTF Division, Micro Labs Limited

Published by:
MICRO LABS LIMITED
# 27, Race Course Road,
Bangalore - 560001

Disclaimer
The editors have checked the information provided in this publication to the best of their knowledge. However in view of
possibility of human errors and changes in medical science, neither the authors nor the publisher or any other person/s
who has/have been involved in the preparations of this work warrants that the information contained herein is in every
respect accurate or complete and therefore disclaim all the responsibility for any errors or omissions or for the results
that may be obtained from use of the information contained in this publication.

GCDC 2017

Cardio Diabetes Medicine 2017 III

FOREWORD Dr. K. K. Aggarwal

Padma Shri Awardee
National President Indian Medical Association

As doctors, we not only look after the health of our pa-
tients, but also that of the community. Doctors are there-
fore “Brand Ambassadors of Health”, a role which puts
a responsibility on all of us to practice what we teach
our patients about healthy habits and lifestyle. Patients
particularly will not heed any such advice unless doctors
themselves are seen to be following the same. There is a
general perception among the public that doctors are nev-
er ill. But, this is not true. Doctors often neglect their health
because of the increasing demands of their profession. The medical profession by
itself is a health hazard. Lack of exercise, poor sleep quality or sleep deprivation,
work-related stress are potential health risks of the medical profession.

“Charity begins at home” is a phrase well-known to each one of us. Doctors should
also take care of their own health. This is important not only for themselves but
also for their patients.Today, the dynamics of doctor-patient relationship has shifted
from ‘paternilstic’ to ‘patient-centric’ with more autonomy to the patients, who now
are more likely than before to question what their doctors have to say. If doctors
have poor health behaviors, they are poor role models for their patients. When doc-
tors practice what they preach, they lead by example. This improves their credibility
including their ability to motivate patients to make healthy lifestyle choices about
diet, physical activity, smoking etc.

Lifestyle diseases or non communicable diseases such as type 2 diabetes, hyper-
tension, heart disease, stroke have become a major public health concern. Most
risk factors for these diseases are lifestyle-related behaviors. By practicing a health
personal lifestyle, doctors can influence a healthy lifestyle in their patients to prevent
lifestyle diseases.

Regards,

Dr. K K Agarwal

Recipient of Padma Shri, Vishwa Hindi Samman,
National Science Communication Award and Dr B C Roy National Award.
Hony. Prof. of Bioethics SRM Medical College Hospital & Research Centre.
Sr. Consultant Medicine & Cardiology, Dean Board of Medical Education, Mool-
chand.
President Heart Care Foundation of India.
Editor in Chief IJCP Group of Publications, eMedinewS

Cardio Diabetes Medicine

IV CONTENTS

GCDC 2017

Cardio Diabetes Medicine 2017 V

FOREWORD Dr B R Bansode

President Association of Physicians of India

Welcome Delegate to the Global
Cardio-Diabetes Conclave - 2017

I, Dr B R Bansode on behalf of Association of Physicians of
India would like to congratulate Prof. Sundaram Arul Rhaj
for organising the Global Cardio-Diabetes Conclave-2017
at the cultural and intellectual capital of India, Chennai
from September 29, 2017 to October 1, 2017.

We appreciate his efforts for providing a platform for luminaries from across the
world to exchange their ideas and experiences of managing cardio-diabetic chal-
lenges.

Endothelial dysfunction promotes vascular complication by secreting several medi-
ators and the interplay of other pathways at cellular levels in Cardio-Diabetes. This
results in the abnormal functioning of the heart, brain and kidneys. Intellectuals
and experts are trying to decipher the molecular / cellular mechanisms involved
in endothelial functions. There is an urgent need to protect the heart in diabetic
patients to reduce the cardio-vascular morbidity and mortality.

I feel great pride that Prof. Sundaram Arul Rhaj, a very active individual is part of
the Association of Physicians of India as an executive committee member.

I would like to urge you to contribute to the conclave by actively participating in
discussions and sharing your experience so as to better understand the challenges
of Cardiodiabetology.

Lastly, I would like to congratulate Prof. Sundaram Arul Rhaj and his active team
for organising the GCDC – 2017.

Dr. B. R. Bansode

President Association of Physicians of India

Cardio Diabetes Medicine

VI CONTENTS

GCDC 2017

Cardio Diabetes Medicine 2017 VII

FOREWORD Dr Shirish (M.S.) Hiremath

Director, Cath Lab, Ruby Hall, Pune
President - CSI

From the Desk of (President CSI)

It’s a great pleasure to be associated with Global Diabetes Conclave 2017 at
Chennai
The conference planning has been in great detail with emphasis on Cardiology
and Diabetes
An interesting discussion would happen on many sub topics in this field.
A very detailed scientific program has been planned and thus would interest you
immensely.
On the whole we are looking forward to a very exciting scientific flow.

Dr Shirish (M.S.) Hiremath

Director, Cath Lab, Ruby Hall, Pune
President - CSI

Cardio Diabetes Medicine

VIII CONTENTS

GCDC 2017

Cardio Diabetes Medicine 2017 IX

FOREWORD Dr. Sarita Bajaj

MD (Med), DM (Endocrinology, AIIMS) FRCP(Glasg),
FRCP (Edinburgh) FRCP (London)

Medical science is a rapidly advancing field where yes-
terday’s facts may become matter for the archives and
today’s facts may not find agreement with experts of to-
morrow.

Rapid growth of knowledge in all branches of Medicine
makes constant updating essential. Global Cardio Diabetes Conclave 2017 being
organized under the dynamic leadership of Prof S Arulrhaj along with Dr D Selvaraj,
Dr E Prabhu and Dr Aarathy Kanan aims to provide an opportunity to exchange
new ideas and technology trying to keep abreast with the latest developments in
the ever expanding field of Diabetes and Cardiology.

The theme “Liberate Heart, Monitor diabetes” is most innovative and appropriate.
It will create a platform to discuss both common and uncommon problems which
Physicians can adapt in their practice.

Participants can enrich their knowledge through interaction with eminent Profes-
sors, Scientists and Scholars.

The well planned scientific programme has been designed to explore newer thera-
peutic options available in Clinical Diabetology and Cardiology.

The hard work, enthusiasm and spirit of the organizing team will be reflected in
this megaevent.

With best wishes and regards to all the distinguished participants,

Dr. Sarita Bajaj

President RSSDI
President API (UP Chapter)
Founder President SAFES
Director-Professor and Head of Medicine, MLN Medical College, Allahabad

Cardio Diabetes Medicine

X CONTENTS

GCDC 2017

Cardio Diabetes Medicine 2017 XI

FOREWORD Dr. A. Muruganathan, MD., FACP

Governor

Dear Brothers and Sisters, Greetings!

I am very pleased to know that you are organizing the “Glob-
al Cardio Diabetes Conclave” (GCDC) on 29th, 30th Septem-
ber & 1st October, 2017 at Chennai and releasing a souvenir
on that occasion. Dr. S. Arulrhaj (Executive Chairman) Dr.
D. Selvaraj (Org. Chairman), Dr. E. Prabhu (Org. Secretary),
Dr. Aarathy Kannan (Scientific Committee) and their team
are known for their organizing capacity and Chennai is well
known for hospitality.

The forthcoming GCDC Conclave is going to be a mind-blowing, and an interesting
one. Real Knowledge is timeless with no boundaries. Knowledge is accumulation of
facts while wisdom is the synthesis of knowledge with insightful experience over
time, increasing the depth of knowledge. Meeting seniors and your own pals is an
experience at a different level more vibrant and colorful. Interacting with wise ones
is a pleasant experience, hearing facts from them in real life is more powerful than
distance learning.

Many young speakers will get an opportunity to present their research papers. You
can also learn about the new drugs and devices which have come to the market,
in the conference. Free papers and posters will be additional advantage to you and
will kindle your research interest.

I congratulate you and other organizers for your effort and wish you all the best.

I wish you all to have a happy learning.

For ACP India Chapter

Dr. A. Muruganathan, MD., FACP

Governor

Cardio Diabetes Medicine

XII CONTENTS

GCDC 2017

Cardio Diabetes Medicine 2017 XIII

FOREWORD We are all aware of the twin epidemics namely Diabetes and Coronary artery heart
disease in our country and similar phenomenon is spreading to rest of the world. We
are struggling to cope with the burden imposed by the epidemics. Cardio diabetolo-
gy or Vascular medicine has been trying to take shape as an interrelated speciality
to set focus on the dual issue, which is an evolving agenda of public health world
wide. The Global cardio diabetic conclave exactly addresses the issue and provide
a platform for the experts to converge in the related specialities namely cardiology
and diabetology in our country.

The first attempt of this kind of conference will make relevant doctors like GPs,
Physicians, Diabetologists, Endocrinologists, and Cardiologists to come together to
share their knowledge and experiences . The scientific topics has been thoughtfully
prepared by the scientific committee which I am sure will be appreciated by the
participants. It will also help the research minded people to do collaborative research
and to network with their peers. The innovative aspect of GCDC 2017 is its book
release. The compilation of the topics presented in the conference will be a torch
bearer of future books on Cardiodiabetology.

Dr. D.Selvaraj Dr. E.Prabhu Dr. Arul Prakash Dr. Aarathy Kannan
Org. Chairman Org. Secretary Finance Officer Scientific Committee

Cardio Diabetes Medicine

XIV CONTENTS

GCDC 2017

Cardio Diabetes Medicine 2017 XV

FROM THE EDITORS DESK Dear Colleagues,
Warm greeting from Global Cardio Diabetes Con-
clave Board
Indo Global Cardio Diabetes Academy is the front-
liner in the Academics of Cardio Diabetes Medicine,
Globally.
We have well developed Cardiology & Diabetology.
System Globally running parallely Patients have
both. Hence the Knowledge & Skills of Practicing
Clinicians are to be well updated in the field of Car-
dio Diabetology which is the key objective of Global
Cardio Diabetes Conclave.
This monogram “Cardio Diabetes Medicine 2017” is a compendium of the Scientific
proceeds of GCDC 2017 at Chennai on 29th, 30th September & 1st October 2017.
As the Editor in Chief of this monogram I convey my sincere thanks to all our col-
leagues who by their timely Academic contribution have made this Book possible.
Support rendered by the members of the Editorial Board especially Dr.Aarathy Kan-
nan is remarkable and memorable.
Our post Graduates Dr. Bhuvaneshwar and Dr.Kiran Palsania need to be thanked
for their untiring efforts to make this Book a reality.
Secretarial assistance by Ms. Valli Karthika is highly appreciable.
Microlab Ltd needs Special Appreciation and thanks for undertaking the responsi-
bility of support, quality printing & timely completion of the book.
Dear Colleagues, Cardio Diabetes Medicine 2017 will be a Guiding force on our table
to offer the Best Cardio Diabetes Medical Care to our needy Cardio Diabetic patients.

Prof. Dr. S. Arulrhaj

Chief Physician & Intensivist,Tuticorin
Chairman Commonwealth Medical Association Trust ,UK

Cardio Diabetes Medicine

XVI CONTENTS

GCDC 2017

Cardio Diabetes Medicine 2017 XVII

LIST OF AUTHORS 1. Prof. Dr. S. Arulrhaj 54. Dr.Mugundhan
2. Dr. Aarathy Kannan 55. Dr.Murthy
3. Dr.Abraham Oomman 56. Dr.Muruganathan
4. Dr.K.K.Aggarwal 57. Dr.Muthukumaran Jayapaul
5. Dr.Akhilesh Verma 58. Dr.S.N.Narasingan
6. Dr.Alexander Thomas 59. Dr.Narendranath Jena
7. Dr.Ambady Ramachandran 60. Dr.Neelambujan
8. Dr.Ameya Udyavar 61. Dr.Palaniappen
9. Prof.Amuthan 62. Dr.Periyakaruppan
10. Dr.Anand Moses 63. Dr.Prayaag Kini
11. Dr.Anjana 64. Dr.S.Prakash
12. Dr.Anju Virmani 65. Prof.Preetam Arthur
13. Dr.Archana Ambujan 66. Dr.Prema Tirou
14. Dr.Arulprakash 67. Dr.Pritam Gupta
15. Dr.Ashok Kumar Das 68. Dr.Puvi Seshiah
16. Dr.A.J.Asirvatham 69. Dr.Raja Selvaraj
17. Dr.Avijit Lahiri 70. Dr.Rajan
18. Dr.Avinash De Sousa 71. Dr.Sudhir
19. Dr.Balamurugan 72. Dr.Rajavelmurugan
20. Dr.Balasubramanian 73. Dr.Rajesh Upadhyay
21. Dr.Cecily Mary Majella 74. Dr.Rakesh Kumar Sahay
22. Dr.Davis Prabhakar 75. Prof.Ram Dhillon
23. Dr.Deep Chandh Raja 76. Dr.Ramamoorthy
24. Prof.Deepak K Jumani 77. Dr.Ramasami Nandakumar
25. Dr.Deepanjan Mitra 78. Dr.Ramasubramanian
26. Dr.Devaki Nair 79. Prof.Russell Dsouza
27. Dr.Dhanushkodi 80. Prof.Sandeep Bansal
28. Dr.Dhinakaran 81. Dr.Sankar
29. Dr.Dina Nagodra 82. Dr.S.Saravanan
30. Prof.Elango 83. Dr.R.Saravanan
31. Dr.Ezhilian 84. Dr.Selvaraj
32. Prof.Geetha 85. Dr.Senthilkumar Nallusamy
33. Dr.Georgi Abraham 86. Dr.Senthilkumaran
34. Dr.Gurpreet S Wander 87. Prof.Seshiah
35. Dr.Hari Hara Krishnan 88. Dr.A.Sethuramashankaran
36. Prof.Hariharan 89. Dr.Shirish Hiremath
37. Dr.Isaac Christian Moses 90. Dr.Shrikant Solav
38. Prof.J.A.Jayalal 91. Dr.Shunmugavelu
39. Dr.Joy M Thomas 92. Prof.Sidharthadas
40. Dr.Justinpaul 93. Dr.Siva Somana Rajasekar
41. Prof.Jyotirmoy Pal 94. Dr.Solaiman Juman
42. Dr.Kader Sahib 95. Prof.Soundarajan
43. Dr.Kannan 96. Dr.Sudhir Mehta
44. Dr.Kevin Shotliff 97. Dr.Sundararaman
45. Prof.Kutikuppala Surya Rao 98. Dr.Thamilpavai
46. Prof.Lakshminarasimhan Ranganathan 99. Dr. Thilak P Weerarathna
47. Dr.Liviu Klein 100. Dr.Ulhas M. Pandurangi
48. Prof.Luigi Gnudi 101. Dr.Vajira Dissanayake
49. Dr.G.N.Mahapatra 102. Dr.Vetrivel
50. Dr.Manoria 103. Dr.Vimala Paul
51. Dr.Meenakshi Bajaj 104. Dr.Vijay Viswanathan
52. Dr.Meenakshi Sundaram 105. Dr.Virendra Kumar Goyal
53. Prof.Mohan 106. Dr.Vinoth Ram Kumar

Cardio Diabetes Medicine

XVIII CONTENTS

GCDC 2017

Cardio Diabetes Medicine 2017 XIX

Table of contents

No. Topic Page
3
1 Genesis Growth And Future Of Cardiodiabetic Medicine - Review Article
- Prof. Dr. S. Arulrhaj 23
26
01. Epidemiology 30

1. Addressing the Twin Epidemics of Diabetes and Heart Disease in India - Dr.V. Mohan 36
42
2. Glucose is not Always Sweet - Dr.Luigi Gnudi 44
48
3. The New Brave World of Dyslipidemia Ready to Target ASCVD after Statins -
Dr. P.C. Manoria 52
58
4. Diabetes and Hypertension-Common Soil Hypothesis -Dr. A. Muruganathan
63
5. The Sugary Mind and the Burdended Heart - A View Point - Dr. Avinash De Sousa 66

6. Diabetes and Ethical Issue - Professor Dr Russell Dsouza 70
74
7. Gender and Outcomes in Type 2 Diabetes Mellitus and Cardiovascular Disease - Dr Prema 79
Tirou 82
83
8. Cardiogenic Shock: Etiopathogenesis and Clinical Recognition - Dr. Deep Chandh Raja
87
9. Progressive Heart Failure –Etiopathogenesis, Invasive and Noninvasive Evaluation - 93
Dr. G. Justinpaul 97
105
10. CVD in India - Dr. Ramasami Nandakumar 112

11. Childhood and Youth Onset Diabetes in India: Profile, Changes,Progress and Future? - 116
Dr. Anju Virmani 121
126
12. The Applied Biochemical and Metabolic aspects of Diabetes and Heart - Dr. Siva Somana
128
13. Diabetes and Heart are Inseparable Partners-How & Why - Prof. Dr. Elango 131
136
14. Gestational Diabetes Mellitus and Cardiovascular Disease - Prof. Dr. Sidhartha Das 141
146
15. Diabetes Retina Screening Project in Sudan - Dr. Dina Nagodra

16. Pre Diabetes- Beyond the Tip of the Iceberg - Dr. Arulprakash

02.Clinical Presentation

1. Peripheral Vascular Disease - Dr. J. Ezhilan

2. Stress Hyperglycaemia or Diabetes – Which is Bad in ICU? - ? Dr. M. Jayapaul

3. Resistant Hypertension in Clinical Practice - Dr Virendra Kumar Goyal

4. Diabetic Cardiovascular Autonomic Neuropathy - Dr. Ulhas M. Pandurangi

5. Erectile Dysfunction: Endothelial Dysfunction; Emotional Disturbance -
Prof Dr Deepak K Jumani

6. Regression of Atherosclerosis- In Diabetics - Dr Joy M Thomas

7. Triglyceride and Cardiovascular Risk-Whats New??? - Dr.Aarathy Kannan

8. Impaired Glucose Tolerance and Coronary Artery Disease and Peripheral Artery Disease -
Dr D. Selvaraj

9. Atypical Presentation of Acute Coronary Syndrome in Diabetics - Dr. T. Neelambujan

10. Cardiovascular Risk in Diabetes: Known vs Unknown - Dr. T.P. Weerarathna

11. Effect of Stroke on Heart, Diabetes and Hypertension - Prof. Dr. Lakshminarasimhan

12. Thyroid dysfunction, Diabetes and the Cardiac Link - Dr. Muthukumaran Jayapaul

13. Mechanism , Clinical Presentation and Treatment of Diabetic Kidney Diseases - Prof.
Soundarajan

Cardio Diabetes Medicine

XX CONTENTS

14. DKD is Coronary Equivalent (Evidence And Remedy) - Dr. T. Dhinakaran 149

15. Stroke in Cardiodiabetic Syndrome – How Different is it? - Dr. K. Mugundhan 153

16. Management of Cardioembolic Stroke - Dr. N. Thamilpavai 156

17. Stemi in Young - Dr. Joy M Thomas 162

18. Cardiomegaly in Diabetes Mellitus - Dr. T. Geetha 165

19. Clinical Presentation and Management of Acute Heart Failure - Dr. Prayaag Kini 168

20. Non-Infarct Related Artery Intenvention in ST-Elevation Myocardial Infarction with Multives- 181
sel Disease - Dr. Shirish Hiremath

21. Obstructive Sleep Apnoea (OSA): Cardiodiabetic issues - Professor. Dr. Ram Dhillon 188

22. Diabetes and Systemic Complications in Immune Deficiency Syndrome - Prof. Kutikuppala 190
Surya Rao

23. Low Body Weight T2DM and Macro Vascular Disease - Prof. Dr .Sidhartha Das 194

24. Alcohol – Heart, Diabetes and Lipids -Dr. Meenakshi Sundaram 200

25. Anxiety and Diabetes - Dr. Avinash De Sousa 204

26. Diabetes Melitus and Tuberculosis - Double Jeopardy - Dr. Prof. Preetam Arthur 207

27. Eating Disorders in Diabetes Mellitus - Dr. Davis Prabhakar 212

28. Obstructive Sleep Apnoea Syndrome and Cardio Metabolic Risk - Dr. Solaiman Juman 215

29. Pre Diabetes as Risk Factor for Coronary Artery Disease and Peripheral Vascular Disease - 220
Dr. Arulprakash

30. Bradyarrhythmias - Dr. Kader Sahib 222

31. Congestive Heart Failure in Diabetic ....! How It is Different? - Dr. Dhanushkodi 227

32. Remnant Lipo Proteins - Residual Vascular Risk - Dr. R. Sarvanan 234

33. Treatment of Acute Ischemic Stroke - Dr B. Kannan 238

34. Hypoglycemic Heart- Cardiologist Perspective - Dr. Senthil Kumar 244

35. Listening to our Gut: Microbiomes and NCD /CVD - Dr. Rajesh Upadhyay 248

36. Diabetic Dysrhythmias - Dr. Ulhas Pandurangi 250

37. Cardiac Complications in Diabetic Ketoacidosis - Dr. Sankar 255

38. Role of Oxygen Insufficiency in the Onset and Development of Vascular Complications of 258
Diabetes - Dr. R. Sudhir

39. Heart Rate Variability in Ischemic Heart Disease and Diabetes - Dr. R. Hari Hara Krishnan 261

40. Hypoglycemia How Critical It is? - Prof. Dr. S. Arulrhaj 265

41. Diabetes and Genitalia - Dr. M. Balasubramanian 278

42. Diabetic Kidney Disease: When to Refer to a Nephrologist & Why? - Dr. Pritam Gupta 279

43. Role of Nerve Conduction Study in Diabetic Patients - Dr. B. Kannan 282

44. South Asians with PCOS - Metabolic Risk in Future Generation - Dr. Aarathy Kannan 287

45. Hypertension in Elderly Population - Prof. Dr. Jyotirmoy Pal 290

46. CVD in Diabetes - Is it only Macrovascular? - Dr.Arulprakash 294

47. Double Trouble - Diabetes And Heart Disease - Dr Preetam Arthur 296

48. Diabetic Cardiomyopathy: Mechanisms, Diagnosis and Treatment - Dr. A. K. Das 301

49. International Lipid Guidelines : What is Needed for Indians ? - Dr. S. N. Narasingan 311

50. Maternal obesity & Pregnancy outcomes - Dr. Archana Ambujan 318

GCDC 2017

Cardio Diabetes Medicine 2017 XXI

03. Investigations

1. Risk Stratification in Asymptomatic Diabetics :Role of Selective Imaging with Cardiac CT 325
and Myocardial Perfusion Imaging - Dr. Avijit Lahiri

2. Monitoring in Diabetes - Dr. Kevin Shotliff 328

3. Post Revascularisation Status - Myocardial Perfusion Imaging - Dr.Shrikant Solav 331

4. Role of Nuclear Imaging in the Evaluvationof Non-Coronary Artery Disease - 333
Dr. Deepanjan Mitra

5. Evaluvation of Cardiac Syncope and ECG Markers of Sudden Cardiac Arrest - Dr. Ameya 339
Udyavar

6. Myocardial Imaging Products : Continuing Evolution for the Better - Dr.N. Ramamoorthy 343

7. Pitfalls in Computer ECG Interpretations - Dr. V. Balchandran 347

8. Echocardiographic Evaluvation of a Diabetic Patient - Prof. Dr. V. Amuthan 350

9. Biochemical Evaluation of Dyslipidaemia - Dr. Devaki Nair 355

10. ECG Evaluation in Patients with Acute Coronary Syndrome - Dr.Senthilkumar Nallusamy 358

11. Strain and Strain Rate Imaging in Early Detection of Ventricular Systolic Dysfunction - Is 362
this the Best Investigation? - Dr. R. Balamurugan

12. Cardiac MRI vs PET Scan - Dr. G. N. Mahapatra 367

13. Mechanical Circulatory Support for Advanced Heart Failure - Dr. Liviu Klein 377

04. Invasive Procedure

1. Role of Percutaneous Intervention in Cardiovascular Diseases in Diabetes - 389
Prof. Dr. R. S. Hariharan

2. Percutaneous Coronary Intervention in the Management of Multi-Vessel CAD in Diabetics- 391
Is there Still a Role after Freedom Trial - Dr. Puvi Seshiah

3. Percutaneous Heart Repair- Can We Replace Open Heart Surgery - Dr. Puvi Seshiah 396

05. Therapeutics Options

1. Real World Effect of Type 2 Diabetes Therapies on HbA1c and Weight - Dr. Kevin Shotliff 403

2. Raising the Standard of Care in Cardiodiabetes Post Graduate Diploma in 408
Cardiodiabetes - Professor Ram Dhillon

3. DM Management in Special Situations - Post Renal Transplant & Post CABG– - 410
Prof. Dr. Sandeep Bansal

4. Cardiac Emergencies in Diabetes Mellitus - Dr. Arvinth Soundarrajan 414

5. Don’t Let Diabetes Pull Down our Foot - Prof. Dr. J. A. Jayalal 418

6. Glycemic Control- How Tight it Should Be? - Dr. R. M. Anjana 425

7. New Armamentarium in Combined dyslipidemia Management – Current Evidences - 430
Dr Sudhir Mehta

8. Cardiovascular Outcomes with Antihyperglycemic Therapy: Past , Present And Future 435
Impact on Practice - Dr. V. Balachandran

9. Obesity- Pharmacotherapy - Dr. Rakesh Kumar Sahay 443

10. Bariatric Surgery In Diabesity : What is Endocrinologist’s Perspective? - Dr. S. Murthy 449

11. Idnetifying the Right Patients Who Benefits from AICD Implantation - Dr. Raja Selvaraj 454

12. Heart Failure: Drug Therapies and Revascularization Strategies - Dr Abraham Oomman 457

13. When to Use ? When Not to Use ? - Antiplatelets - Prof. Dr. A. S. Mohan 464

14. Nutrient Manipulation for Obesity, Metabolic Syndrome and Diabetes - 467
Dr. Sethuramashankaran. A

Cardio Diabetes Medicine

XXII CONTENTS

15. Cardio Vascular Safety of Antidiabetic Drugs –Do we know Enough? - Dr. S. Saravanan 471

16. NAFLD And CVD - Importance and Therapies - Dr. R. Ramasubramanian 475

17. Foot Care in Type 2 Diabetes - Dr.Vijay Viswanathan 479

18. Newer Guidelines on Cardiac Arrest in Nutshell - Dr. S. Senthilkumaran 483

19. Stable Ischaemic Heart Disease in Diabetics: Medical Therapy vs Revascularization - 486
Dr. Gurpreet S Wander

20. New Lipid Lowering Therapies - Dr. Devaki Nair 491

21. Drugs on Pipeline For Management of Diabetes- An Overview - Dr .P. Rajavel Murugan 494

22. Hyperglycemia & Glycemic Control In ICU - Prof. Dr. S. Arulrhaj 497

23. Stroke Thrombectomy - Dr. A. L. Periyakaruppan 507

24. Obesity and Weight Management-Current concepts - Dr. Isaac Christian Moses 509

25. Convertible Visceral Fat as a Therapeutic Target to Curb Obesity - Dr. P.G. Sundararaman 514

26. Inotropes and Heart : When to Use and When Not to Use - Dr. J. Cecily Mary Majella 516

27. Integrated Management of Diabetes Through Novel Therapies - Dr. Dina Nagodra 524

28. Initiation & Intensification of Insulin Therapy in T2DM - Dr. Palaniappen 529

29. Cardio Diabetic Therapeutics – When to Use? When Not to Use –OHA - Dr. A. J. Asirvatham 550

30. Novel Oral Anti Coagulants in Chronic Kidney Disease - Dr. Georgi Abraham 553

31. Sulfonylureas and Cardiovascular Mortality? - Dr. Vimala Paul 556

32. Glucose Lowering Strategies and Cardiovascular Outcomes - Dr. Rakesh Sahay 560

06. Prevention

1. Tight Glycemic Control Decreases Cardio Vascular Mortality - Dr. M. Shunmugavelu 567

2. Diabetes and Exercise - Dr. S. Rajan 571

3. Exercise and Physical Activity in Diabetes Mellitus - Dr. N. Vetrivel 574

4. Medical Nutrition Therepy in Cardiodiabetes - Dr. Akhilesh Verma 585

5. Prevention of Non-Communicable Diseases - Whom to Focus? - Prof. Dr. Seshiah 588

6. Medical Nutritional Therapy in Gestational Diabetes - Dr. Meenakshi Bajaj 595

7. Medical Nutrition Therapy in Heart Failure - Dr. Meenakshi Bajaj 599

8. Primary Prevention of Type 2 Diabetes – Make in India - Dr. Ambady Ramachandran 605

9. Medical Nutrition Therapy in Chronic Kidney Disease - Dr. Meenakshi Bajaj 612

10. The Role of Lifestyle Modification in the Prevention of Diabetes and 617
Cardiovascular Disease - Prof. Dr. Anand Moses

11. Lifestyle & Noncommunicable Diseases: My ‘Formula of 80’ to Live Up to 80 Years With- 623
out a Lifestyle Disease - Dr. K. K. Aggarwal

07. Future

1. An Overview of Legal Issues in Hypertensive and Diabetic Patients. - Dr .T. Ravi Shankar 629

2. Susceptible and Prognostic Genetic Factors associated with Diabetic Peripheral 631
Neuropathy: A Literature Review - Dr. VHW Dissanayake

3. Can the Projected World Center of Chronic Disease be Converted to the Worlds Control 638
Centre of Chronic Disease? - Dr. Alexander Thomas

4. Health Insurance – A Comprehensive Study - Dr. S. Prakash 640

GCDC 2017

Cardio Diabetes Medicine 2017 1

GENESIS GROWTH AND
FUTURE OF CARDIODIABETIC

MEDICINE - Review Article

Prof. Dr. S.Arulrhaj

Chief Physician & Intensivist,Tuticorin
Chairman Commonwealth Medical Association Trust ,UK

Cardio Diabetes Medicine

2 Genesis Growth And Future of Cardiodiabetic Medicine

GCDC 2017

Cardio Diabetes Medicine 2017 3

Genesis Growth And Future of
Cardiodiabetic Medicine

Prof. Dr. S. Arulrhaj,MD,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 Physicians of India

Formerly Adjunct Professor of Medicine, Dr.MGR Medical University, Chennai
Co-Author

Dr.Aarathy Kannan,MD,Dip.Diab

Consultant Physician & Diabetologist, Sundaram Arulrhaj Hospiatls,Tuticorin

Dr.Bhuvaneshwar, Dr.Kiran Palsania

Postgraduate Students, Sundaram Arulrhaj Hospiatls,Tuticorin

Cardio Diabetes Medicine patients with diabetes and cardiovascular disease
may be obese, ‘cardiodiabesity’ was suggested
Cardio-Diabetology is a multi-disciplinary as an appropriate catch-all term. Further, the
subspeciality / Interdisciplinary Speciality and high risk for renal complications in patients with
encompasses diabetologists, non – invasive convergent diabetes and cardiovascular disease led
cardiologists, interventional cardiologists, cardio- to the suggestion of ‘cardiorenaldiabetes’ as another
thoracic surgeons, pathologists and general descriptor.
physicians in its spectra. An interplay of specialists
of above fields is mandatory for a comprehensive “The term ‘cardiodiabetes’ is a useful reminder for
approach towards management of cardiac clinicians to assess multiple risk factors’
complications of diabetes. Besides treatment,
special emphasis should also be laid on prevention The fusion of the prefix cardio with the suffix diabetes:
/ modulation of complications and this indeed is
possible in the present scenario. -Reminds diabetologists to assess blood pressure,
lipids, weight and glucose management.
Is the term cardiodiabetes really
meaningful? -Prompts cardiologists to consider diabetes-related
risk factors in patient assessment and management
A number of terms are used to describe the
convergence of cardiovascular disease and type 2 -The combination of cardio with diabetes tells patients
diabetes in a patient. more about their condition

The term cardiodiabetes was preferred by the Group Cardiodiabetes what’s in a name?
over the word ‘cardiobetes’, which was considered
too truncated a term. In recognition that many ‘Physicians must communicate and collaborate
to combine the best of specialist experience with
primary care expertise’

Cardio Diabetes Medicine

4 Genesis Growth And Future of Cardiodiabetic Medicine

Metabolic Medicine CAD in Diabetics is not only frequent and occurs at a
younger age and women and the involvement is also
Metabolic Medicine is a sub-specialty within Internal more extensive. Triple vessel disease and left main
medicine which can be defined as a group of stem lesion are more common. Intramural arteries are
overlapping areas of clinical practice with common also involved producing, coronary microangiopathy.
dependence on detailed understanding of basic Silent myocardial ischemia and silent infarcts are
biochemistry and metabolism.  It therefore falls more common. Pump failure, cardiogenic shock and
within the areas of expertise of both the physician reinfarction following acute myocardial infarction
and chemical pathologist.  (AMI) are distinctly higher in diabetes. Diabetic state
does not come in way of providing benefit by catheter
Metabolic Syndrome interventions or by bypass surgery but the necessity
of a repeat procedure is higher in the long run.
The metabolic syndrome may be more useful when
considering prevention of the continuum from obesity DC is another manifestation of cardiac involvement.
through diabetes to cardiovascular disease, whereas It is a consequence of involvement of intramural
the term cardiodiabetes is more applicable to the arteries without affection of epicardial coronary
particular spectrum of cardiovascular disease, plus arteries, but it also has extravascular component like
more diffuse peripheral vascular and renal disease, interstitial fibrosis and metabolic control of diabetes
that is associated with diabetes. also play an important part. In individuals after 35-
40 years, CAD may closely mimic DC and coronary
Diabetologists, cardiologists, lipidologists and renal angiography is necessary to discriminate between
physicians joint specialist clinics run at hospital them. On occasions both may co-exist in the same
centres, Primary Care Trust (PCT) one-stop clinics. patients.

Life Style Medicine Sudden cardiac death (SCD) is the most dreadful
complication and it is 1.8 times more common in men
Lifestyle medicine is a scientific approach to and 3 times common is women compared to non-
decreasing disease risk and illness burden by utilizing Diabetics. CAD, DC and autonomic cardiovascular
lifestyle interventions such as nutrition, physical neuropathy contribute to it. The availability of
activity, stress reduction, rest, smoking cessation, powerful antiarrhythmic drugs like Amiodarone and
and avoidance of alcohol abuse. Lifestyle medicine Automatic implantable cardiovertor defibrillator has
is the recommended foundational approach to greatly improved the prospects of survival.
preventing and treating many chronic diseases.
Recognition of Hypertension in Diabetics is
Concept Note of crucial importance because -

Cardio-Diabetology is fast emerging as a sub- 1.It is a major risk factor for development and progress
speciality throughout the globe to tackle the menace of diabetic microangiopathy.
of cardiac related mortality in Diabetes, particularly
NIDDM. 2.It is also a greater risk factor for the development
of macrovascular disease in a diabetic than in
Cardiac involvement in Diabetes commonly manifests nondiabetics.
as coronary artery disease (CAD) and less commonly
as dilated cardiomyopathy (DC) and autonomic 3.Diabetics with hypertension are prone for
cardiovascular neuropathy. CAD alone accounts, for development of coronary heart disease. especially
the major chunk of mortality in diabetes. when there is associated left ventricular hypertrophy

CAD is the leading cause of mortality in Diabetics. It
not only involves the epicardial coronary arteries but
also the intramural coronary arteries. Silent ischemic
events constitute a special feature of presentation.

CAD in Diabetics is multifactorial but dyslipidemia
has a major impact on it. The lipid profile in Indian’s
is different compared to the West and comprises
of normal or near normal total cholesterol and LDL
cholesterol with raised triglycerides and low HDL
cholesterol.

GCDC 2017

Cardio Diabetes Medicine 2017 5

(LVH) and other coronary risk factors. from the Fragigham Heart (FHS) to identify diabetes
as a major cardio vascular risk factor.3 It was also
The development of hypertension in a diabetic is an one of the first atusies to demonstrate the higher
intricate issue because of potential of development risk of CVD in women with Diabetes compared to
of intraglomerular hypertension (IGH) consequent to men with diabetes. Kannel et al used a cohort of
diabetic nephropathy, so that two concurrent circuits 13,8361 men and 18,928 women of 45 to 74 years of
of hypertension may develop in the same patient. age at the time of the study who had been followed
biennially over a twenty year time period. In the 20
These two circuits of hypertension, namely systemic years of Follow- Up there were 957 cases of CVD,
hypertension and IGH may not and go hand in hand. which included 732 cases of coronary artery Disease
Reduction of blood pressure in the systemic circuit (CAD), 138 strokes,179 intermittent claudication.4 (IC),
may not be associated with reduction of IGH with and 219 cases of congestive heart Failure (CHF).
consequent vicious circle of progressive nephron Looking at the results comprehensively, men had a
loss. Thus, caution must be exercised in selecting higher incidence of CVD than women.
an appropriate drug for hypertension in a diabetic. It
is important to bear in mind that reduction of blood Multiple stidied have followed the original Kannel
pressure in the systemic circuit will only provide publication in 1979 to better defined the role of
protection to the heart, brain, retina and peripheral Diabetes as a risk factor in cardiovascular Disease.
vascular system, but not to the kidneys The kidneys Re-Examination of the contribution of diabetes
will only be protected if IGH is lowered. isespecially important since the defination of
diabetes has changed since publication of the
Genesis of Cardio Diabetology original study, and the prevalence of Diabetes has
increased dramatically fox et al. in 2006 showed
Cardiovascular Epidemiology began in the 1930s as that the incidence of the diabetes has also almost
a consequence of observed changes in the causes doubted between 1970 and 1990 further more even
of mortality in 1932,Whilem Raab Described the though there has been a 50 % reduction in the rate
Relationship between diet and coronary and heart of CVD among participants with diabetes from the
disease (CHD) in different region and in 1953 an FHS the relative risk of diabetis as a risk factor foe
association between cholesterol levels and CHD CVD has been unchanged.5
mortality was reported in Various Populations.
Additionaly since the kannel article other studies
In 1949 it was noted that “ the proper control of have also looked at how the attributed risk (AR) has
Diabetes is obiviously describe even though there is changed overtime for diabetes and CVD. The AR for
uncertainty as to wheather coronary atherosclerosis diabetes as a risk factor for CVD has increased from
is more frequent to severe in the uncontrol diabetic.” 5.4 % between 1952 and 1974 to 8.7 % between 1975
and 1998. The importance of this finding is highlighted
In 1951 735 Finish men and women aged 25-74 when other factors are observed as well; the AR for
years, who where followed for an average 17 years, other factor has either decreased or remained stable.6
and comprising 9201 deaths, That combined hazards
ratio for coronary mortality, adjusted for other risk Preis et al were able to utilize data from 1950 to 2005
factors,49 among men with MI only and with both to look at trends in all – cause and CVD mortality in
diseases, were 2.1,4.0, and 6.4 respectively compared both men and women with and without Diabetes . In
with men without either disease. The corresponding contrast to the NHANES study , this study showed
Hazards ratio for women were 4.9,2.5, and 9.4 haz- a decline in all – cause and CVD mortality in both
ards ratios for total mortality were 1.8,2.3,and 3.7 in men and women with diabetes. It also Showed that
men and 3.2,1.7, and 4.4 in women Diabetic men and men and women in the Diabetes continued to be
women had comaparable mortality rates. Whereas at higher risk of CVD and all – cause mortality than
coronary Mortality among men was markedly high- those without Diabetes. These findings have been
er. Thus,a History of Diabetes and MI Markedely in- supported and replicated in other studies as well as
creased CVD and all – cause mortality2 showing a decrease in CVD mortality in men and
women with diabetes.7
Relationship between Diabetes & CVD
1998 Haffner et al were able to show that Diabetic
The role of Diabetes in CVD had been uncertain patient without prior myocardial infarction (MI) were at
until the prominent article published by kannel et a similar risk of developing MI those patient without
al in 1979 identified it as a major risk factor based Diabetes and history of MI. 8Further more in 2005
on evidence from the FHS, the seminal prospective
study CVD and its determinants .Kannel et used data

Cardio Diabetes Medicine

6 Genesis Growth And Future of Cardiodiabetic Medicine

whitely et al were able to show that middle- aged pathogenesis of CVD in patients with Diabetes has
men and women with diabetes but no CAD were at improved, the incidence and prevalence of Diabetes
a lifetime vascular risk as high as individuals with has increased significantly as well. Shaw et al
CAD but no diabetes.9 However one of the most showed that the burden of Diabetes will increase
important studies identifying diabetes as a CAD risk significantly from 2010 to 2030, with a 69% increase
conducted by schramm et al in 3.3 million Danish in adult Diabetes in developing countries, and a
residents, which showed that patients with diabetes 20% increase in developed countries; the associated
had a CVD risk comparable to those individuals populations increase is expected to be 36% and
without diabetes. All of these studies highlighted the 2% respectively. Based on these figures, the
notion that Diabetes should be considered a CAD risk diabetes burden will lead to increasing morbidity
equivalent. , mortality, stress on healthcare providers, and
healthcare –associated costs. A joint statement
The Framingham Offspring studies(FOS) have also by the American Heart Association and American
provided further insight into Insulin resistance as well Diabetes Associations in 2007 said that a multi-
as Diabetes as CVD risk factors.10 In 2002 Meigs et faceted approach including risk factor control as well
al examined 3370 subjects from the Framingham as aggressive life-style changes must be employed
Offspring Cohort and found post-challenge to prevent the development of Diabetes and its
hyperglycemia as an independent risk factor for complications, most importantly CVD .12
CVD .This is especially important since fasting
hyperglycemia has largely replaced post-challenge Incidence of CAD in General Population in
hyperglycemia for diagnosing diabetes and several india
studies have shown that fasting hyperglycemia
overlooks a significant number of people at risk The Registrar General of India reported that CHD led
for CVD who are identified using post –challenge to 17% of total deaths and 26% of adult deaths in
hyperglycemia. 2001-2003, which increased to 23% of total and 32%
of adult deaths in 2010-2013. In India, studies have
Additionally, other FOS have used data to identify reported increasing CHD prevalence over the last 60
surrogate markers for CVD in Diabetics. Meigs et years, from 1% to 9%-10% in urban populations and
al found that participants with diabetes had more <1% to 4%-6% in rural populations13
coronary artery calcification than those without
diabetes ,indicating a higher burden of subclinical Incidence of CAD in Diabetics: According to
CVD not detected by conventional testing . Similary, Cardiovascular diseases and Diabetes Association
other studies have shown that elevated levels there is a Definite Correlation of CAD in Diabetics,
of C-Reactive protein and Homocysteine are both The Prevalence is 68% of People with Diabetes of
associated with insulin resistance and an increased More than 10 years duration.14
risk of CVD.
Presentation of CAD in Diabetics: Diabetics patients
Since the inception of the FHS, researchers have frequently present with silent myocardial infarction
tried to devise a score that would help predict the with absence of imperative warning symptoms.
risk of developing CAD based on risk factors. Truett ln regards to type of lesion involved in diabetics
et al were the first to utilize data from the FHS to compared with nondiabetic PTCA patients,
develop a risk score for men and women based diabetic patients have more extensive and diffuse
on seven risk factors: age, systolic blood pressure, atherosclerotic disease,most common being LAD
relative weight , hemoglobin, cigarette smoking ,and followed by RCA and Left circumfiex.
EKG evidence of LVH.11 Overtime, hemoglobin and
LVH were removed glucose intolerance was Complications of Diabetes in CAD: Diabetes is
added, and the AHA published a book of risk associated independently with a 2-5 fold increased
tables in 1973. Eventually, in the 1991 a point scoring risk and incidence of Heart failure compared
system was developed to help clinicians risk – with those without Diabetes. The Increased
stratify patients and in 2008 a tool was developed for risk of Diabetes is multifactorial caused by
primary care physicians. Data from the Framingham ischemic metabolic and functional myocardial
Heart Study , therefore, were crucial in devising perturbation. Myocardial insulin resistance
the Framingham Risk Score to determine the 10- and cardiac complications of diabetes EDAbel 
year risk of developing CAD. Current Drug Targets-Immune, Endocrine 2005
ingentaconnect.com
Even though our understanding of the

GCDC 2017

Cardio Diabetes Medicine 2017 7

Mortality in DM with CAD: from endothelial cells (EC) in the late stages of

Mortality was twice as high in Diabetic Patients atherosclerosis.

(35.9% versus 17 9%) influence of Diabetes Mellitus Cardio Diabetology growth in india :
on heart failure risk and outcome Christophe Bauters
corresponding author1 Nicolas Lamblin,1 Eugéne Prof. Sam G P Moses, Chennai formed the
P Mc Fadden,1 Eric Van Belle,1 Alain Millaire,1  Cardiodiabetology study group in 1988 along with
and Pascal de roote1Cardiovasc Diabetol. 2013;2: 1. Prof.Dr.Anantha subramaniam & Dr.J.K.Ramanakumar

Pathogenic Link between Diabetes and -On 28th July 1988 – API HYD Chapter & DAI Southern
Cardiovascular disease Chapter National Seminar on Cardio Diabetology –
Prof.BK Sahay Hyderabad – President

Type 2 Diabetes and Cardiovascular diseases could be -In 1988, Dr.J.K Ramanakumar, Chennai – Actively
considered different aspects of the same syndrome: Conducted the Cardiodiabetology Meetings
i.e. the metabolic syndrome. Metabolic syndrome
is a cluster of metabolic abnormalities which -In 1991 – Prof.Dr.Sam GP Moses Brought out the First
includes obesity, insulin resistance, dyslipidemia, Cardiodiabetology Book and Presented a Copy to
hypertension, endothelial dysfunction. Endothelial Prof.Dr.S.Arulrhaj.
dysfunction, which represents a common trait of
the type 2 diabetes and cardiovascular diseases, is -1998 – PC Manoria Past President API – APICON – PG
characterized by a reduction of the bioavailability of Medicine. Cardio Diabetology, Book Published
vasodilators, mainly nitric oxide, which causes an
impairment of endothelium-dependent vasodilation. History Of Cardio Diabetology Journal
Endothelium-derived nitric oxide is a potent
endogenous vasodilator that plays a major role in Cardiovascular Diabetology is a peer-reviewed open
vascular tone; it is synthesized by endothelial nitric access medical journal covering the intersection
oxide synthase in a multistep reaction from L-arginine. of cardiology and diabetology, meaning the
Genetic variants on eNOS gene are associated to type connection between diabetes, metabolic syndrome
2 diabetes, cardiovascular diseases and metabolic and cardiovascular diseases. It is published by
syndrome. BioMed Central and was established in 2002, with
Enrique Fisman (Tel-Aviv University) and Alexander
In 2015 we completed a 9 year follow-up in subjects Tenenbaum (Sheba Medical Center) as founding
treated for 18 months with L-arginine orally1. It has editors-in-chief. A printed version is periodically
been estimated that it is possible to maintain a better distributed in India by Panacea Biotec Ltd.
sensitivity and insulin secretion, while complying with
a type 2 diabetes reduced the incidence in treated The journal is abstracted and indexed in Current
subjects. The result seems to demonstrate the Contents, EMBASE, MEDLINE/PubMed, Science
ability of L-arginine to induce a positive metabolic Citation Index, and Scopus. According to the Journal
memory capable of delaying the onset of diabetes Citation Reports, the journal has a 2016 impact factor
mellitus. Moreover, the presence of a greater number of 4.752.[1]
of progenitor endothelial cells, the reduction in
markers of oxidative stress also seems to indicate Cardio Diabetes Medicine Today
the presence of a vascular memory. As vascular
memory can affect the metabolic memory will be the Cardiometabolic Medicine Foundation, UK founded
aim of future in vitro and in vivo studies in human by a Respected throughout leader in metabolic
endothelial cell line and in progenitor cells. medicine

These findings, together with the The Cardiometabolic Medicine Foundation will
Hyperhomocysteinemia reported in diabetic provide a resource for patients and healthcare
patients, strongly suggest that homocysteine might profesionas who wish to pursue and individualized
be considered a risk factor in the development of and comprehensive approach to the prevention and
cardiovascular complications associated to type 2 management of common vascular and metabolic
Diabetes mellitus. disorders including heart diseases, stroke, diabetes
and dementia.
Subendothelial accumulation of extracellular lipids
leads to the formation of foam cells primarily The Foundation encourages an evidence –based
derived from monocytes/ macrophages, but also approach to cardiometabolic disease.

Cutting edge clinical science will be integrated with
emerging complementary therapies to move beyond

Cardio Diabetes Medicine

8 Genesis Growth And Future of Cardiodiabetic Medicine

GCDC 2017

Cardio Diabetes Medicine 2017 9

speciality.

It provides care regarding the prevention of one
(Diabetes) and will also prevent from other (CAD)

All speciality care regarding Diabetes and Cardiac
disease is available under single roof.

It helps in giving special attention to high risk
population.

Speciality will provide detailed knowledge regarding
diseases, pathology outcome and help in reducing
morbidity and mortality.

Some Examples are: Cardio Diabetic clinic

Dr.Soumya Sengupta
Jharkhand.

freedom from disease to a sustainable state of Dr.Mahendra Tilkar Cardio Diabetic clinics, Indore.
optimal physical and psychological functioning.
Cardio Diabetes Clinic (Eden Doctors’s Chamber),
It is anticipated that the Foundation will offer the Kolkata.
opportunity for personal clinical consultations with
Professor Krentz in London UK and via the internet Life Span Diabetes & Cardiometabolic Clinic,
later in 2015(see link below to DEMOS healthcare). Kolkatta

In Developing Countries: Dr. Rajeev Bansal’s Cardiodiabetic Clinic , Delhi.
Cardio Diabetic clinics-
Dr.Shende Cardio-Diabetic Clinic, Pune.
Cardio Diabetic clinic is consist of Specialists consists
of Diabetologist, Physician , Cardiologists. -Facilities provided in clinic are :-

It provides Preventive and Management care to the Current Progress:
patients under single roof.
In association with the Public Health Foundation of
Why there is need? India (PHFI) New Delhi

To improving awareness of Correlation between Center for Chronic Disease control (CCDC) New Delhi.
these two diseases.
World Heart Foundation (WHF) , Geneva
To make available more Doctors who work in this
Chellaram Diabetes Institue (CDI), Pune is the
National Academic Partner and a collaborator for

For Diabetes For Heart Patients

-Arterio Flow Machine -Echocardiogr Aphy & Colour Doppler

-Vibratometery I Biothesiometery -Stress Echocardiography

-Podio Scan(Digital) -Paediatric Echocardiography

-Abi (Ankle Brachial Index) -Dobutamine Stress Echocardiography

- Urine For Acr(Albumin Creatinine Ratio) -Contrast Echocardiography

-Hba1c -Tmt (Tredmill Test)

- Angiography & Stentsurgery

-Pacemaker

-Bypass Surgery

-Valve Surgery

Cardio Diabetes Medicine

10 Genesis Growth And Future of Cardiodiabetic Medicine

Curriculum development of ACMDC –an Advanced of the TNF superfamily is the TNF-like weak inducer
certificated Course in the Prevention and Management of apoptosis (TWEAK/ TNFS12) and its receptor
of Diabetes and Cardiovascular Disease. Fn14. We have observed that Fn14 and TWEAK are
expressed in macrophages and smooth muscle cells
Diabetologists, cardiologists, lipidologists and renal in carotid atherosclerotic plaques, and could be novel
physicians joint specialist clinics run at hospital mediators of atherosclerosis. In addition, we have
centres, Primary Care Trust (PCT) one-stop clinics. observed that soluble TWEAK (sTWEAK) is released
in lower amount by carotid plaques than normal
The Future of Cardiovascular Medicine endarteries. Subsequent measurement of sTWEAK in
plasma showed a reduced concentration in subjects
Novel Biomarkers Of Cardiovascular with carotid stenosis compared with healthy subjects.
Diseases Furthermore, in a test population of 106 asymptomatic
subjects, we showed that sTWEAK concentrations
JESUS EGIDO, JOSE LUIS MARTIN-VENTURA, LUIS negatively correlated with the carotid intima-media
MIGUEL BLANCO-COLIO Fundación Jiménez Diaz, thickness, suggesting that sTWEAK could be a
Autonoma University, Madrid, Spain potential biomarker of subclinical atherosclerosis.
The identification of novel biomarkers along with
Assessment of vascular risk in asymptomatic traditional risk factors and imaging techniques, could
patients is a major challenge for prevention of help to target vulnerable patients and monitor the
cardiovascular events. These events arise from the beneficial effects of pharmacological agents.
disruption of atherosclerotic plaques that contain
Cardio-diabetology research reports and training Genomics of Cardiovascular Disease &
unit 25 numerous inflammatory cells. Inflammatory Diabetes Mellitus
and resident cells (endothelial and vascular smooth
muscle cells) release different proteins that can The most studied and replicated locus associated
generate a chronic inflammatory response in the with MI and CAD is locatedon chromosome 9p21.3 .
injured artery. This locus is near the CDKN2A and CDKN2B genes,
contains no annotated genes, and is not associated
Measurement of circulating markers of inflammation with established CVD risk factors such as plasma
may provide some insights into this process. lipoproteins, or hypertension. Interestingly, it has also
Interaction between members of the tumor necrosis been associated with diabetes.
factor (TNF) superfamily and their receptors
elicits diverse biologic actions that participate in Diabetes can be classified as type 1 diabetes (T1D),
atherosclerosis development. Fas and its ligand are type 2 diabetes (T2D), latent autoimmune diabetes
typical members of the TNF superfamily. Proteins in adults (LADA), mature onset diabetes of the
secreted by cells implicated in atherosclerotic lesions, young (MODY). For T1D, the major susceptibility
including soluble Fas (sFas) and soluble Fas ligand locus is related to HLA class II genes at 6p21, which
(sFasL), circulate in small, but detectable, amounts. accounts for more than 30%-50% of the genetic risk
We have observed that sFas concentrations are of T1D. Also, more than 40 non-HLA susceptibility
increased and sFasL are decreased in subjects at high gene markers have been associated with the trait .
cardiovascular risk, suggesting that these proteins
may be novel markers of vascular injury. 15 T2D involves complex genetics. There is an intricate
interaction between the environment and genetic
In addition, patients with familial combined background, understood as the contribution of many
hyperlipidemia or carotid atherosclerosis have different genes.
decreased circulating sFasL levels, probably
indicating endothelial dysfunction. To confirm this Susceptibility loci:  Genome-wide association studies
hypothesis, we have recently analyzed whether the (GWAS). successfully identified approximately 75
forearm vasodilatory response to reactive hyperemia susceptibility loci related to T2DM. Examples of
(an indicator of endothelial function), is associated candidate genes are KCNJ11 (potassium inwardly
with soluble sFasL plasma concentrations in subjects rectifying channel, subfamily J, member 11), TCF7L2
with coronary artery disease. (transcription factor 7-like 2, the strongest T2D locus
identified to date), IRS1 (insulin receptor substrate
There was a linear trend for the increase of sFasL 1), MTNR1B (melatonin-receptor gene), PPARG2
and forearm reactive hyperemia which suggest that (peroxisome proliferator-activated receptor gamma
sFasL plasma concentrations could be a potential 2), IGF2BP2 (insulin-like growth factor two binding
biomarker of endothelial function. Another member

GCDC 2017

Cardio Diabetes Medicine 2017 11

protein 2), CDKN2A (cyclin-dependent kinase inhibitor PCSK9 on both the risk of cardiovascular events
2A), HHEX (hematopoietically expressed homeobox) and the risk of diabetes. We constructed genetic
and FTO (fat mass and obesity associated) gene. scores that mimic the effect of PCSK9 inhibitors
vanExel and his group found that low IL-10 production and the effect of statins (which target 3-hydroxy-3-
capacity is also associated with T2D methylglutaryl–coenzyme A reductase [HMGCR]) and
compared the effect of these scores on the risk of
Susceptibility loci associated with T2DM discovered cardiovascular disease and the risk of diabetes to
with GWAS. make inferences about the potential clinical benefit
and safety of treatment with a PCSK9 inhibitor as
Risk of cardiovascular disease and diabetes affected compared with treatment with a statin.
by PCSK9 and HMGCR genetic variations.
GENE Therapy
Monoclonal antibodies and other therapies that
inhibit proproteinconvertasesubtilisin–kexin type 9 Gene therapy is designed to introduce genetic
(PCSK9) have been shown to reduce low-density material into cells to compensate for abnormal genes
lipoprotein (LDL) cholesterol levels by approximately or to make a beneficial protein.
50 to 60% in several randomized trials.
Gene therapy may be classified into two types:
Because PCSK9 inhibitors are designed to recapitulate
the phenotype of loss-of-function mutations, we used 1.Somatic gene therapy - the therapeutic genes are
the presence of LDL cholesterol–lowering variants transferred into the somatic cells, or body, of a patient.
in PCSK9 to estimate the biologic effect of inhibiting Any modifications and effects will be restricted to the

Cardio Diabetes Medicine

12 Genesis Growth And Future of Cardiodiabetic Medicine

Gene Gene Population disease, drug and food interactions, comorbidity, as
Region SNPs well as genetic factors. Large variability related to
hypoglycemic drug therapy response is often
KCNQ1 11p15.4 rs2237897 Japanese
encountered in the clinic. Poor therapeutic
11p15.4 rs2237895 Chinese outcomes may be caused by variability of individual
characteristics. Personalized medicine is an emerging
11p15.4 rs231362 European concept for treating diseases, which involves
determining specifi c information of a particular
11p15.4 rs2237892 Japanese patient and then prescribing specific treatment.
Pharmacogenetics holds the promise of bringing
TCF7L2 10q25.2 rs7903146 European personalized medicine to drug dosing decisions, to
reduce morbidity and mortality, and to improve life
KCNJ11 11p15.1 rs5219 European quality for T2DM patients.

11p15.1 rs5215 UK Digital Cardiac Health

IRS1 2q36.3 rs7578326 European Solutions that exist currently are portable ECG
recorders and Holter monitors but none provide real-
MTNR1B 11q14.3 rs1387153 European time, beat-by-beat event information and have very
less recording time. They are very expensive and
IGF2BP2 3q27.2 rs4402960 European are heavy for the patient to attach to their body for
extended period of time. Sensory Health Systems use
3q27.2 rs6769511 European latest advances in mobile technology and sensors to
provide a digital healthcare platform to keep patients
CDKN2A/B 9p21.3 rs564398 UK with heart conditions out of hospitals.

9p21.3 rs2383208 Japanese Remote Monitoring

9p21.3 rs10811661 European India being the cardiac disease capital of the world
and CVD’s being leading cause of deaths in the
HHEX 10q23.33 rs1111875 European country makes it first target market for the company.
The company’s platform consists of wearable
10q23.33 rs5015480 European wireless health sensors that provide continuous
monitoring outside clinical settings with acceptable
PPARG2 3p25.2 rs1801282 European accuracy. The sensors and electrodes are designed
keeping the patients comfort, convenience and other
3p25.2 rs17036101 European environment conditions in mind. It can be used at
home and on the go. It uses advanced data analytics
individual patient only, and will not be inherited by to provide real time diagnosis on the smart phone
the patient’s offspring or later generations based on the sensed data and patient’s digital health
record.
2.Germ line gene therapy - sperm or eggs, are
modified by the introduction of functional genes, Vocal biomarkers: the future of diagnostic
which are integrated into their genomes. This would medicine
allow the therapy to be heritable and passed on to
later generations Not long ago, scientists discovered vocal features
in every way imperceptible to humans. They also
Clinical Success since 2006 upon treatment of Retinal found that the identification of such distinctive
Disease, Inherited disorders & various Leukemias. characteristics might have a huge impact on setting
up a diagnosis. Researchers labelled these features
IDDM also responds well. Future will be for NIDDM “vocal biomarkers”. These can serve as a diagnostic
& Coronary Heart Disease. tool for your physician to indicate signs of illnesses
ranging from stress and depression to cardiovascular
Pharmacogenomics and Personalised diseases. 16
Medicine
Vocal biomarkers will gain ground in 2017. Instead
Type 2 diabetes mellitus (T2DM) has reached
epidemic proportions worldwide and poses a
considerable concern for public health. Although a
variety of pharmacological treatments is available,
but response, doses, and tolerability to drugs are
highly variable and monotherapy often failed. A large
interindividual variability in drug response has been
noticed and contributing factors include age, sex,

GCDC 2017

Cardio Diabetes Medicine 2017 13

of focusing only on biomarkers measured in blood version of the organ does on its own; and it enables
or genomic markers analysed by geneticists, vocal diabetes patients to live an easier life in a sustainable
biomarkers which are easy to detect, record and way. It is the biggest step towards a new are in
analyse will be used more and more for detecting diabetes management in years.The breakthrough
and preventing diseases. happened years after the #wearenotwaiting
movement started to campaign for the introduction
What if coronary artery disease could be of such artificial pancreas on the market. One of the
identified over a phone call? leading figures of the movement, Dana Lewis also
told me how an artificial pancreas eases everyday
An Israeli company, Beyond Verbal deals with emotion life. In 2017, this new way of diabetes management
analytics and provides voice analysis software. It will spread around; and it will become a life-changing
has announced that its algorithms were successful milestone in many patients’ lives when they first start
in helping to detect the presence of coronary artery to use the device.
disease (CAD) in a group of patients.
The development of Diabetes care does not end
The research was presented at the American Heart there. Google patented a digital contact lens that can
Association Scientific Sessions in New Orleans, measure blood glucose levels from tears as an added
Louisiana in December 2016; carried out in cooperation benefit. Google launched a partnership with the
with Mayo Clinic. It involved a double-blind study with pharmaceutical company Novartis; and while there is
120 patients undergoing both an angiography and rather silence around the state of the developments,
a voice analysis; and a group of controls. Beyond there are rumors about it becoming available for trials
Verbal used a smartphone app to measure their in 2017.
voice signal prior to a coronary angiograph. One
voice characteristic in particular indicated an almost Digital Health and the Future of Diabetes
20-fold increase in the likelihood of CAD. Yuval Mor, Management
CEO of Beyond Verbal said that these vocal features
are not audible by the human ear alone !. Future of diabetes management, patient engagement
and interaction, and clinical practice.
Digital Diabetic Health
A new era in diabetes care Mobile devices, Wearable devices

In 2016, the US Food and Drug Administration 10,000 health and wellness and medical apps
approved the world’s first artificialpancreas. The available across the Apple and Google app stores
device monitors blood sugar and supplies insulin
automatically. It basically replicates what a healthy Roche’s Accu-Check Connect diabetes

Cardio Diabetes Medicine

14 Genesis Growth And Future of Cardiodiabetic Medicine

susceptible to infection, meaning that nanosensors
monitoring levels of bacteria could have a significant
impact on their care.

management app New service in nutrigenomics

SMBGs Nutrigenomics, is going to become a hit in 2017.

Smart-contact lens Nutrigenomics is a brand-new cross-field combining
genetics and nutrition science. The basic idea behind
A doctor inside the body - Nano Technology nutrigenomics is that our genome reveals valuable
information about our organism’s needs. We should
“Ideally, we want to create sensors that behave a lot map out this data and utilize in order to lead a long
like natural cells in the body,” Prof. Webster explained and healthy life. After having your DNA sequenced
to MNT. “Many of us would say the human body is (perhaps already at home), a smart app could let you
the ultimate sensor. We can sense things much better know which food you should eat and what you should
than anything we have made synthetically so far.” avoid at all cost. There is already a California-based
start-up dealing with nutrigenomics. The inventive
Constructing a sensor using nanotechnology company,  Habitplans to use genetic markers to
to mimic human immune cells that circulate identify the ideal meal for each of its customers, and
around the body, indicating when something is send that meal directly to their doors.
wrong and responding positively to any problems
that surface may be possible one day in the Next generation Capsules
future, but for now, it remains a big step to take.
So far, the team has trialed their nanosensors by The Silicon Valley startup’s “Smart pill” platform,
growing them on titanium hip implants and catheters. discover, helps Doctors track patients’ biometrics
&whether or not they are sticking to drug protocol-
As well as hip implants, the team has tested their with help of ingestible and on the body sensors that
nanosensors on catheters using the same approach. communicate with a smart phone app. This way,
People who receive indwelling catheters are patients with chronic diseases like hypertension &
diabetes & their physician can figure out the most
effective dosing regimens.

Regenerative Medicine

GCDC 2017

Cardio Diabetes Medicine 2017 15

Putative stem cells found in the pancreas, liver, Besides monitoring and notification, wearable medical
spleen, central nervous system, and bone marrow devices also have the potential to provide automated
could either be induced to differentiate into insulin- or remote treatment.
producing cells in vitro and then be transplanted, or
be injected into the circulation along with stem cell The OmniPod is an example of a wearable insulin
stimulators to differentiate into a permanent self-
renewing b-cell population .

Mesenchymal Stem cells combined with IV ozone
therapy and orthomolecular supplements.

Administration of Nerve Growth Factor and
recombinant Human Insulin like Growth Factor-1.

Wearable Healthcare

Wearable devices have been life-changing for those
with chronic disease like diabetes. Smart glucose
monitors like the Dexcom G5 can be placed on the
body and link wirelessly with smartphones to provide
continuous blood-sugar monitoring. An app can alert

users to low or high blood-sugar events, and can pump that coordinates with a glucose monitor to
share data with loved ones or caregivers. automatically administer correct dosage.

Personalised DM Care More drastically, ZOLL’s LifeVest is a wearable
defibrillator worn by patients at risk of a heart attack.
Quell is another example of wearable technology It monitors heart rhythms and in the event of a heart
that’s changing the lives of those with chronic health attack, releases conductive gel from its electrodes
issues. Using electrical nerve stimulation to relieve and administers a life-saving electrical shock to
pain, it tracks activity and sleep patterns to adjust restore normal heart rhythms.
its pain-management intensity, as well as provide
proactive relief throughout the night to improve Remote Monitoring in Heart Failure
sleep quality for patients dealing with chronic pain.
For elderly populations, wearables are improving Why Is This Important?
quality of life by providing greater independence
while ensuring safety. • Despite current therapies and disease management

approaches, the rate of heart failure hospitalization
remains

unacceptably high

- > 1.1 million heart failure hospitalizations annually

-#1 cause of hospitalization for those ≥ 65 years

‒ #1 cause of hospital readmission

‒ > $18 billion in annual direct costs of hospitalization

Cardio Diabetes Medicine

16 Genesis Growth And Future of Cardiodiabetic Medicine



Current methods for monitoring and managing heart DiabNext’s JARVIS interface is designed to allow
failure doctors and patients alike to “tap into the power of
patients have not adequately addressed this problem AI and supercomputing from any internet connected
MEMS-microelectromechanical system that measure tool.”
instantaneous pressure and velocity of flow
ReDS-Remote dielectric sensing The officially description states: “In particular,
physicians logged in... can for the first time visualize
DiabNext’s ‘Personal Diabetes Assistant’ the patients’ insulin injection therapy metrics, oral
medicine intake, blood glucose levels, meals and
precise carbs intake calculation, diabetes standard

GCDC 2017

Cardio Diabetes Medicine 2017 17

diagnostics test results, A1C trends, diabetes-related generation and our children.”
genes sequencing profile, and even workout and
weight data trends to better assess what drives D1NAMO
patients’ highs and lows. Physicians, Nutritionists,
Caregivers, Researchers and Patients are ONE TEAM The D1NAMO acronym stands for Diabetes type
in DIABNEXT® A.I., designing together the therapies 1 Non-invasive Activity MOnitoring and aims at
of the future to prevent and cure Diabetes for our providing to type 1 diabetic patients a non-invasive
way to manage their chronic disease. Several studies

Cardio Diabetes Medicine

18 Genesis Growth And Future of Cardiodiabetic Medicine

have shown that hypoglycemias are causing some Track ‘A’ (1979-to-date)
modifications in the PQRST characteristics of ECGs,
especially a prolongation in the QT intervals . One of Protein energy malnutrition in early infancy, with or
these studies also suggests that this may allow the without a deficiency of other essential micronutrients.
development of an hypoglycemia detection device .
The D1NAMO project aims at using such technology Track ‘B’ (1988 – to- date)
to monitor type 1 diabetes in a non-invasive way.
The PQRST characteristics with the QT interval The Low birth weight (less than 2.5Kg) and lower body
D1NAMO concept is the following: Diabetic patients weight at one year
are wearing an ECG sensor which is connected
by Bluetooth to their smartphones. An Android Track ‘C’ (1992-to-date)

The growth of the fetus (and possibly infant) is
quantitatively and qualitatively altered.

Poor insulin secretion and insulin resistance can
result from these adaptive processes, include loss
of glucose tolerance and hypertension.

Early Nutritional deprivation : Impact on Cell
Programming

Thus, the concept of malnutrition-related cellular
programming (MRCP) provides a rational basis
of such diverse metabolic syndromes as MRDM,
NIDDM, hypertension, obesity and CAD and offers
a unifying hypothesis. A conceptual model of such
a hypothesis.

Unifying Hypothesis: MRDM, NIDDM, Syndrome ‘X’

application acts there as a controller to 31 start/
stop data transmission, as an helper to manage the
disease by offering an interface to manually keep
track of events, and as a buffer to store data while
dealing with connectivity issues. The application send
the data to a server that will analyze them on arrival,
and then store them in a database for visualization.
In case of a detected event, an alert is sent to the
patient’s phone, warning him about a potential event
and asking him to take further measurements. Finally
a web interface allows Medical Doctors to see their
patients’ data.

The In-Utero Connection

Evidence is coming up that the roots of Cardio-
Diabetology start building up even in-utero.

The Three-Track Hypothesis :

Three TRAC

TRAC A TRAC B TRAC C

GCDC 2017

Cardio Diabetes Medicine 2017 19

Implication:- Let us adopt advances in Medicine to Prevent &
Control Diabetes in Men & Women.
* Diet and Lifestyle to target Inutero Nutrition and
Growth In Utero Intervention is a key Message.

* Gene Therapy References:-

Conclusion:- 1. Qazi MU, Malik S. Diabetes and Cardiovascular Disease: Insights from the
Framingham Heart Study. Global heart. 2013 Mar 31;8(1):43-8.
Cardiodiabetes – is a joint approach the way forward?
2. Friedberg CK. Diseases of the heart. WB Saunders Company; Philadelphia:
Diabetes and serious cardiovascular disease 1949. p. 939.
are frequently observed together, the term
‘cardiodiabetes’ is increasingly applied to describe 3. Kannel WB, McGee DL. Diabetes and Cardiovascular Disease. JAMA.
the convergence of these conditions. 1979;241:2035–2038

The European Society of Cardiology – European 4. Kannel WB, McGee DL. Diabetes and Cardiovascular Disease. JAMA.
Association for the Study of Diabetes (ESC-EASD) 1979;241:2035–2038
Task Force guidelines of 2007 acknowledge
the inter-relationship between diabetes and 5. Fox CS, Pencina MJ, Meigs JB, et al. Trends in the incidence of type 2
cardiovascular disease and call for an early, diabetes mellitus from the 1970s to the 1990s: the Framingham Heart
multidisciplinary approach to the recognition and Study. Circulation. 2006;113:2914–2918
intensive management of all cardiodiabetes risk
factors. The Key to Cardiodabetology is a focuson 6. Fox CS, Coady S, Sorlie PD, et al. Increasing cardiovascular disease bur-
a Multidisciplinary approach to ensure that the den due to diabetes mellitus: the Framingham Heart Study. Circulation.
numerous Global ASCVD Risk factors.17The evidence 2007;115:1544–1550
that Diabetes is a key factor in cardiovascular disease
is also highlighted by the National Institute for Health 7. Preis SR, Pencina MJ, Hwang SJ, et al. Trends in cardiovascular disease risk
and Clinical Excellence (NICE) clinical guidelines factors in individuals with and without diabetes mellitus in the Framingham
on lipid modification and type 2 diabetes, which Heart Study, 1950–2005. Circulation. 2009;119(13):1728–1735. 2009a
recommend treatment of serum lipids in patients with
type 2 diabetes mellitus and those with established 8. Haffner SM, Lehto S, Rönnemaa T, et al. Mortality from coronary heart
cardiovascular disease (CVD). disease in subjects with type 2 diabetes and in nondiabetic subjects with
and without prior myocardial infarction. N Engl J Med. 1998;339:229–34.
‘Prevention of cardiovascular disease must focus
equally on patients with established atherosclerotic 9. Whiteley L, Hole D, Padmanabhan S, et al. Should diabetes be considered
disease and on people with Diabetes’18 a coronary heart disease risk equivalent? Diabetes Care. 2005;28:1588–
1593
India is the Diabetes Capital of the World.
10. Meigs JB, Jacques PF, Selhub J, et al. Fasting plasma homocysteine levels
India is the Cardiac Disease Capital of the World. in the insulin resistance syndrome. Diabetes Care. 2001;24(8):1403–1410

11. Truett J, Cornfield J, Kannel W. A multivariate analysis of the risk of
coronary heart disease in Framingham. J Chronic Dis. 1967;20:511–524

12. Buse JB, Ginsberg HN, Bakris G. Primary prevention of cardiovascular dis-
eases in people with diabetes mellitus. Diabetes Care. 2007;30:162–172

13. Gupta R, Mohan I, Narula J. Trends in coronary heart disease epidemiology
in India. Annals of global health. 2016 Apr 30;82(2):307-15.

14. Coronary Angioplasty in Diabetic Patients.Current and Future Perspective
Joaquin J Alonso a,Juan M Duran a, Federico Gimeno a, Benigno Ramos
a, Ana Serrador a, Franscisco Fernandez- Aviles

15. Cheng J, Zhou T, Liu C, Shapiro JP, Brauer MJ, Kiefer MC, Barr PJ,Mountz
JD. Protection from Fas-mediated apoptosis by a soluble form of the Fas
molecule.Science. 1994;263:1759–1762

16. h t t p : / / m e d i c a l f u t u r i s t . c o m / t h e - m o s t - e x c i t i n g - m e d i c a l - t e c h n o l o -
gies-of-2017

17. The Emergence of Cardiodiabetology, paul D.Rosenblita ,Norman E.Leporc
and Nathan D.Wongb cardiovascular Endocrinology, 2017,6:3-7

18. National Institute for Health and Clinical Excellence. Clinical Guideline 67.
Lipid Modification. Cardiovascular risk assessment and the modification
of blood lipids for the primary and secondary prevention of cardiovascular
disease. May 2008

19. PC.Manoria, cardiodiabetology The Inutero connection, vol XII(Part-I),1998

20. Sam.G.P.Moses , G.Anantha subramaniam,T.K.Ramana kumar,Manual on
Cardiodiabetology,1991

Cardio Diabetes Medicine

20 Genesis Growth And Future of Cardiodiabetic Medicine

GCDC 2017

Cardio Diabetes Medicine 2017 21

2. Epidemiology

1. Addressing the Twin Epidemics of Diabetes and Heart Disease in India - Dr.V. Mohan

2. Glucose is not Always Sweet - Dr.Luigi Gnudi

3. The New Brave World of Dyslipidemia Ready to Target ASCVD after Statins -
Dr. P.C. Manoria

4. Diabetes and Hypertension-Common Soil Hypothesis -Dr. A. Muruganathan

5. The Sugary Mind and the Burdended Heart - A View Point - Avinash De Sousa

6. Diabetes and Ethical Issue - Professor Dr Russell Dsouza

7. Gender and Outcomes in Type 2 Diabetes Mellitus and Cardiovascular Disease - Dr Prema
Tirou

8. Cardiogenic Shock: Etiopathogenesis and Clinical Recognition - Dr. Deep Chandh Raja

9. Progressive Heart Failure –Etiopathogenesis, Invasive and Noninvasive Evaluation -
Dr. G.justinpaul

10. CVD in India - Dr. Ramasami Nandakumar

11. Childhood and Youth Onset Diabetes in India: Profile, Changes,Progress and Future? - Dr.
Anju Virmani

12. The Applied Biochemical and Metabolic aspects of Diabetes and Heart - Dr. Siva Somana

13. Diabetes and Heart are Inseparable Partners-How & Why - Prof. Dr. Elango

14. Gestational Diabetes Mellitus and Cardiovascular Disease - Prof. Dr. Sidhartha Das

15. Diabetes Retina Screening Project in Sudan - Dr. Dina Nagodra

16. Pre Diabetes- Beyond the Tip of the Iceberg - Dr. Arulprakash

Cardio Diabetes Medicine

22 Addressing the Twin Epidemics of Diabetes
and Heart Disease in India

GCDC 2017

Cardio Diabetes Medicine 2017 23

Addressing The Twin Epidemics of
Diabetes and Heart Disease In India

Dr. V. MOHAN

M.D., FRCP (London, Edinburgh, Glasgow & Ireland), Ph.D., D.Sc.
D.Sc (Hon. Causa), FNASc, FASc, FNA, FACE, FTWAS, MACP

Chairman & Chief of Diabetology, Dr. Mohan’s Diabetes Specialities Centre,
President & Director, Madras Diabetes Research Foundation, Chennai

INTRODUCTION : most important gene implicated in type 2 diabetes is
the TCF7L2 gene. Recently, our Genome Wide Asso-
Diabetes, which is already a huge global health prob- ciation Studies (GWAS) done with UK collaborators
lem (1), is now spreading its wings to low and middle in individuals of South Asian ancestry published in
income countries like India. Earlier, many epidemi- NATURE GENETICS identified six novel type 2 dia-
ological studies have reported that migrant Asian betes in South Asians (predominantly Indians) which
Indians living in other countries like UK, USA, Fiji, were not seen among Europeans or other races (4).
Singapore, Malaysia and Middle East countries in the Our findings thus provide support for possible novel
Gulf region have much higher prevalence rates of di- associations with type 2 diabetes in our population.
abetes compared to native Indians within the Indian
subcontinent (2). According to the International Diabe- However, although genetic factors undoubtedly play
tes Federation (IDF), Diabetes Atlas Seventh Edition a major role in the predisposition of diabetes in Indi-
(2015), India had 69.2 million people with diabetes in ans, environmental factors contributes to over 50% of
the year 2015 and this is expected to increase to 123.5 the risk and indeed the epidemic is driven by envi-
million by the year 2040 (1). The epidemic of diabe- ronmental factors as our genes did not change in 40
tes in India is still spiraling upwards and the Indian years. Rapid economic growth in India has resulted in
Council of Medical Research, India Diabetes (ICMR– rapid nutritional transition contributing to excess cal-
INDIAB) study, the largest epidemiological study on ories mainly from refined carbohydrates in both rural
the prevalence of diabetes published in Lancet Di- and urban population (high dietary glycemic load) (5,6)
abetes & Endocrinology showed wide variation in along with decreased physical activity. Recently, we
prevalence of diabetes in India (3). The prevalence showed that consumption of white rice was strongly
of diabetes across all 15 states from the ICMR–INDI- associated with risk of type 2 diabetes in our popula-
AB study was 7.3%. When we looked at the GDP of tion (7). A recent study from our centre has shown that
various states in relation to prevalence of diabetes, replacing white rice with brown rice could improve 24
there was a fairly good correlation between diabetes hour blood glucose and insulin levels (8). Therefore,
prevalence and the GDP of the different states. Over it is logical to assume that adopting a diet that is
50% of people who participated in the study were rich in whole grains along with increasing physical
unaware of their condition indicating low awareness activity could be a cost-effective, feasible and sus-
about the disease. The prevalence of the disease in tainable approach to diabetes prevention and control
urban India is twice that of rural India. In most states, in India. However, our studies (9,10) the promotion of
the rate of pre-diabetes exceeded the rate of diabe- whole grains also revealed the challenges in doing
tes, a forewarning that the epidemic is far from over. so such as colour and texture of the cooked brown
Thus, effective preventive programmes need to be ur- rice having low acceptability in society. Hence, we
gently implemented to tackle the diabetes epidemic further engaged in research to lower the white rice
in our country. This will also indirectly help stem the digestibility (lower GI than high GI of white rice) using
coronary heart disease epidemic also. classical hybridization techniques. Recently, we have
pioneered and produced an innovative High Fibre
The first question is, why the pandemic of diabetes? White Rice which has 5 times higher fibre content and
- Is it due to genetic or environmental factors?. The lower glycemic index. This is a “first of its kind among

Cardio Diabetes Medicine

24 Addressing the Twin Epidemics of Diabetes
and Heart Disease in India

white rice varieties”. Studies with this rice show that of Indians live in rural areas whereas 80% of doctors
it has much lower glycemic index than conventional practice in urban areas. Large cohort studies, like the
white rice .(11) Prospective Urban Rural Epidemiologic (PURE) cohort
study, reported higher rates of major cardiovascular
The big question is how do we take diabetes preven- events and the rates of death from any cause in ru-
tion to the masses. I want to share our success story ral communities than in urban communities in mid-
of Asiad Colony experience. We had carried out the dle-income countries and low-income countries, sug-
Chennai Urban Population study (CUPS), in two urban gesting that the health care systems (the access to
residential colonies one representing the middle in- and quality and affordability of health care) are likely
come group (Asiad colony in Tirumangalam) and the to have a large impact on cardiovascular disease out-
other representing the low income group (Bharathi comes .(17) Hence, we had to innovate and develop
Nagar in T.Nagar) in Chennai city, in southern India. a rural diabetes model called as the “Chunampet
The study was conducted from 1996 to 1998 and as Rural Diabetes Prevention Project (CRDPP)”. CRDPP
expected, showed a significantly higher prevalence was developed with the aim of not only providing
of diabetes in the middle income group (12.4%) com- diabetes health care, but also to take up diabetes
pared to the lower income group (6.5%) .(12) The results prevention through the use of telemedicine. With the
of the study were discussed with the residents of help of a tele medicine van, 27,014 individuals (86.5%
both colonies. After these awareness campaigns, the of the adult population) were screened in 42 villages
middle income residents realized the value of physi- of Kancheepuram District in Tamil Nadu. As a result
cal activity and built a beautiful park adjacent to their of the follow up treatment given, the mean glycated
colony, by raising funds through their own resources hemoglobin levels among the diabetic subjects in
thus increasing not just their physical activity but also the community decreased from 9.3 ± 2.6% to 8.5±2.4%
people in the neighborhood. The question was did within a year .(18) We also found that less than 5% of
this help to reduce or at least slow down the rapidly patients needed referral for further management to
escalating the diabetes rates. A follow up study was the tertiary diabetes hospital in Chennai. Thus, the
done after 10 years which showed that in the middle CRDPP can be used as a model for diabetes pre-
income group, the prevalence of diabetes increased vention and health care delivery in undeserved rural
from 12.4 to 15.4% (24% increase), while in the lower areas of developing countries like India .(19) It is clear
income group, it increased from 6.5 to 15.3% (135% that to tackle the menace of the diabetes epidemic
increase) (13). This study is the first of its kind in In- in India, we all have to work together. The time for
dia to introduce a “real-world” lifestyle intervention in action is NOW!
prevention of diabetes through community empow-
erment. REFERENCES

Recently, we have carried out a unique ten-year lon- 1. International Diabetes Federation. Diabetes Atlas Seventh Edition 2015,
gitudinal follow-up of the Chennai Urban Rural Epide- IDF 2015. Available at URL: http://www.idf.org/idf-diabetes-atlas-sev-
miology Study (CURES). Our results show that more enth-edition [Accessed on 15th December 2016].
than 80% of cases of diabetes can be prevented in
this Asian Indian population just by modifying five 2. Unnikrishnan R, Anjana RM, Mohan V. Diabetes mellitus and its compli-
risk factors (14). Modifying diet and physical activity cations in India. Nature Reviews Endocrinology. 2016;12:357-70.
alone will reduce over half (52%) of risk for diabetes
.(15) 3. Anjana RM, Deepa M, Pradeepa R, Mahanta J, Narain K, Das HK,

We also published the results of the Diabetes Com- Adhikari P, Rao PV, Saboo B, Kumar A, Bhansali A, John
munity Lifestyle Improvement Program (DCLIP) in
people with prediabetes. We found that there is the M, Luaia R, Reang T, Ningombam S, Jampa L, Budnah RO,
reduction of incidence of diabetes by a third in com-
munity settings. The reduction was more impressive Elangovan N, Subashini R, Venkatesan U, Unnikrishnan R, Das
in those with combined IGT and IFG whereas in those
with isolated IFG, there was only a 12% reduction in AK, Madhu SV, Ali MK, Pandey A, Dhaliwal RS, Kaur T, Swaminathan S,
progressive to diabetes. This suggests that different
prevention strategies are needed in different sub- Mohan V, for the ICMR–INDIAB Collaborative Study Group. Prevalence of
types of pre-diabetes .(16)
diabetes and prediabetes in 15 states of India: results from the
The next huge challenge is how to provide special-
ized diabetes care to rural India. Unfortunately, 72% ICMR–INDIAB population- based cross-sectional study. Lancet

Diabetes Endocrinology. 2017. Published Online. June 7, 2017

4. Jaspal SK, Saleheen D, Sim X, Sehmi J, Zhang W, Frossard P, Radha

V, Mohan V, Chidambaram M, et al. Genome-wide association study in

people of South Asian ancestry identifies six novel susceptibility loci for
Type 2 Diabetes. Nature Genetics. 2011;43:984-989.

5. Radhika G, Sathya RM, Ganesan A, Sudha V, Mohan V et al., Dietary

profile of urban adult population in South India in the context of non-com-
municable disease epidemiology. Public Health Nutrition. 2010;14:

591-96.

GCDC 2017

Cardio Diabetes Medicine 2017 25

6. Sowmya N, Lakshmipriya N, Vijayalakshmi P, Ruchi V, Sudha V, Mohan V
et al. Comparison of the dietary profile of a rural South Indian population
with the dietary recommendations for prevention of non-communicable
diseases. Indian Journal of Medical Research. 2016;144:112-119.

7. Mohan V, Radhika G, Sathya RM, Tamil SR, Ganesan A, Sudha V. Dietary
carbohydrates, glycaemic load, food groups and newly detected type 2
diabetes among urban Asian Indian population in Chennai, India (Chennai
Urban Rural Epidemiology Study 59). British Journal of Nutrition.
2009; 102: 1498-1506.

Cardio Diabetes Medicine

26 Cardio Diabetes Medicine 2017

Glucose is Not Always Sweet
Diabetic Kidney Disease: Can we Make it

“SWEET” Again?

Prof. Luigi Gnudi, MD., PhD., FRCP., FASN.,

Head, Unit for Metabolic Medicine,
Cardiovascular Division, King’s College London School of Medicine & Life Sciences,

Department of Diabetes and Endocrinology,
Guy’s and St Thomas Hospital NHS Foundation Trust, London, UK

Abstract on metabolic (glycaemic and lipid control) and hae-
modynamic (blood pressure) control.
Diabetic nephropathy (DN) is currently the most
feared chronic microvascular complication of diabe- In some patients, the diabetes-driven renal damage
tes. DN is characterised by a progressive decline in is so minimal that clinically these individuals do not
glomerular filtration rate, that ultimately leads to end experience any evidence of kidney disease during
stage renal disease (ESRD) and is often paralleled by their lifetime.
an increase in cardiovascular morbidity and mortality.
The prevention and management of diabetes and its This supports the idea that hyperglycaemia alone is
chronic complications remains a huge global chal- not sufficient to cause renal damage and other fac-
lenge, as the global number of diabetic patients is tors should be required for its clinical presentation.
expected to increase from 415 million (today) to 642
million by 2040. The epidemic of type 2 diabetes, The interaction between metabolic (hyperglycaemia)
particularly in newly industrialized and developing and haemodynamic (hypertension) perturbations is
countries, translates into a dramatic increase of di- an important driver of DN. Hyperglycaemia-mediat-
abetic renal disease and its related increase in car- ed increase in vascular nitric oxideand reactive oxy-
diovascular morbidity and mortality, that results in an gen species, have been implicated in vasodilation of
unbearable growth of social and economic burden. both afferent and efferent glomerular arteriolae. Hy-
perglycaemia also stimulates the local (e.g. glomeru-
To face this health-related catastrophe enormous ef- lar) excess production of angiotensin-2. In diabetes,
forts have been devoted to implement new tools to the documented higher sensitivity (likely related to
prevent/treat this disease. Optimized metabolic and a more abundance of angiotensin-2 receptors) of
blood pressure controls remain the cornerstone of the efferent (versus the afferent) glomerular arteri-
treatment. Renin Angiotensin Aldosterone System ole to the vasoconstrictive action of angiotensin-2,
(RAAS) inhibitors have proven very successful in contributes to the imbalance in arteriolar tone which
delaying the progression of kidney disease and in then results in higher glomerular capillary pressure.
preventing ESRD. Data have shown that diabetic kid- As a result, in diabetes, a disproportionate systemic
ney disease can be reversed and recent studies have pressure is transmitted to the glomerular circulation
suggested a potential renoprotective role of different resulting in glomerular hypertension and activation
new molecules (e.g. SGLT2 inhibitors and GLP-1 ago- of the cellular mechanisms that lead to glomerular
nists). Future studies will answer whether these new damage.
therapeutic approaches can improve renal outcome
in patients with diabetes. In diabetes, the severity of insulin resistance relates
to the development and progression of kidney dis-
Diabetic kidney disease: pathophysiology(1) ease. Patients withtype 1 diabetes (T1DM)and microal-
buminuria are characterised by increased insulin re-
Chronic kidney disease (CKD) presents in approxi- sistance,and in patients with type 2 diabetes(T2DM)
mately 40% of patients with diabetes, and patients and normal renal function, insulin resistance relates
with diabetes and CKD are at increased risk for car- with the development of microalbuminuria. Insulin re-
diovascular disease. Current treatments rely mainly sistance has been implicated in the development of

GCDC 2017

Glucose is Not Always Sweet Diabetic Kidney Disease: 27
Can we Make it “SWEET” Again?

glomerular hypertension and hyperfiltration as seen In old subjects, however, too aggressive metabolic
in the initial phase of diabetic kidney disease, when control would offer no appreciable advantages in
the interaction between metabolic and haemody- terms of long-term prevention of complications and
namic perturbations plays an important role in the would expose the patient to potentially catastroph-
pathophysiologyof kidney disease. In both T1DM and ic consequences of hypoglycaemic episodes, that
T2DM, insulin resistance per secontributes to higher become more dangerous as chronic kidney disease
salt sensitivity, which closely associates with increase progresses. In those with concomitant renal vascu-
in blood pressure, albuminuria, and renal function de- lar disease -that will be the vast majority-, intensified
cline. blood pressure control and/or RAAS inhibitor therapy
might evenaccelerate renal disease progression and
In the early phase of diabetic kidney disease, insu- expose the patient to the risk of life-threatening hy-
lin resistance and the associated poor glycaemic potension episodes, during concomitant diseases of
control also associate with upregulation of the Na+/ other nature or dehydration, an event not uncommon
glucose transporter sGLT2 that in turns leads to an in the elderly. Compliance and treatment-related hy-
increase in proximal tubular salt (Na+) reabsorption perkalemia may also be a concernin those on dual
and secondary worsening of hyperfiltration through RAAS blockade. No evidence is available so far that
the physiologic action of the tubule-glomerular feed- combined ACE inhibitor and ARB therapy may offer
back system. any advantage over single RAAS blockade in patients
with type 2 diabetes with overt nephropathy, whereas
The increased glucose reabsorption appears to also this approach might reasonably provide major reno-
contributes to the interstitial inflammatory processes protection to younger patients with less advanced
that characterize the renaltubulo-interstitial changes. renal disease. A response-driven approach titrated
to both efficacy and tolerability, and combined with
Tubular damage occurs early during the disease as close monitoring and patient counselling, will be the
suggested by presence of liver-type fatty acid-bind- key component of effective intervention to minimise
ing protein (L-FABP), a marker of tubulo-interstitial harm in the frailest patients.
damage, in the urine; L-FABP has been shown to
correlates closely with renal dysfunction in diabetic Novel recent treatment approaches have been trying
subjects. to target different aspects of the pathophysiology of
CKD in diabetes, and their future use is tested on top
Increase exposure to elevated glucose levels results of current standard of care for metabolic control and
in the activation of the local angiotensin-2 system hypertension with RAAS inhibition.
and growth factors (e.g. CTGF, TGFβ1) resulting in
early tubular cells proliferation, tubular hypertrophy The most promising treatments, currently under in-
and fibrosis.Tubular hypertrophy and glucose/Na+ vestigations, have been investigating inflammation
hyper-reabsorption contribute to glomerular hyperfil- inhibitors (CCR2/CCR5 antagonist), oxidative stress
tration in the initial stages of diabetic nephropathy. inhibitors (allopurinol, Nox1-4 inhibitors, N-acetyl-
Hyperfiltration, in turns, participate with the glomer- cysteine, Nrf2 activators), novel endothelin and al-
ular capillary dysregulation towards the development dosterone/renin receptor system inhibitors, vitamin
of glomerular hypertension. D activators, inhibitors of advanced glycation end
products (AGE) and their receptor (RAGE), Jak1-2 in-
Diabetic nephropathy is known as an irreversible hibitors, Transforming Growth Factor-α (TGF-α) and
disease and the current treatments are been able Epidermal Growth Factor Receptor (“EGFR”) blockers,
to slow its progression; only one report suggest a phosphodiesterase inhibitors, Apoptosis Signal-regu-
reversibility of diabetic nephropathy(2) and hopefully lating Kinase 1 (ASK1) inhibitors, and TGFβ1 and CTGF
future treatments will be able to improve the outcome inhibitors.Tie-2 activators are currently being tested in
of this devastating diabetic complication. diabetic eye disease and might, in a near future, be
explored also in diabetic kidney disease.
Diabetic kidney disease: current and future
treatments In the past few years, many failures have charac-
terized the search for new agents for the treatment
The current treatment strategies are not sufficient to of chronic kidney disease (CKD) in diabetes. One of
completely prevent progression of diabetic kidney the main problems is patients’ phenotype; despite we
disease to ESRD. Intensive metabolic and haemody- can usually obtain a pretty clear phenotypic charac-
namic control has proven to be efficacious in delaying terization in patients with T1DM, in the T2DM popu-
the progression of chronic kidney disease in diabe- lation we encounter a huge phenotypic heterogene-
tes in younger and relatively uncomplicated subjects.

Cardio Diabetes Medicine


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