Seventh Edition
Editors
Nihal Thomas
MBBS MD MNAMS DNB (Endo) FRACP (Endo) FRCP (Edin) FRCP (Glasg)
Professor and Head Department of Endocrinology Vice Principal (Research) Christian Medical College Vellore, Tamil Nadu, India
Professor and Head Department of Endocrinology Vice Principal (Research) Christian Medical CollegeVellore, Tamil Nadu, India
Nitin Kapoor
MBBS MD (Med) DM (Endo) ABBM (USA) Post-Doctoral Fellowship (Endo) Assistant Professor
Department of Endocrinology, Diabetes and Metabolism Christian Medical College Vellore,Tamil Nadu, India
Jachin Velavan
MBBS DNB (Fam Med) MRCGP (Int) Coordinator
Department of Distance Medical Education Christian Medical College Vellore, Tamil Nadu, India
Senthil Vasan K
MBBS PhD
Post-Doctoral Researcher Center for Molecular Medicine Karolinska Institute Stockholm, Sweden
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A Practical Guide to Diabetes Mellitus
First Edition: 2004
Second Edition: 2005
Third Edition: 2007
Fourth Edition: 2008
Fifth Edition: 2010
Sixth Edition: 2012
Seventh Edition: 2016
9789351528531
Printed at:
Advisory Board
Asha HS DNB (Med) DNB (Endo)
Associate Professor
Department of Endocrinology,
Diabetes and Metabolism
Christian Medical College, Vellore, Tamil Nadu, India
Dukhabandhu Naik MD (Med) DM (Endo)
Associate Professor
Department of Endocrinology,
Diabetes and Metabolism
Christian Medical College, Vellore, Tamil Nadu, India
Mahesh DM MD (Med) DM (Endo)
Assistant Professor
Department of Endocrinology,
Diabetes and Metabolism
Christian Medical College, Vellore, Tamil Nadu, India
Thomas V Paul MD DNB (Endo) PhD (Endo)
Professor
Department of Endocrinology,
Diabetes and Metabolism
Christian Medical College, Vellore, Tamil Nadu, India
Simon Rajaratnam MD MNAMS PhD (Endo) FRACP (Endo)
Professor and Head Unit-II
Department of Endocrinology,
Diabetes and Metabolism
FM7Contributors
Department of Endocrinology, Diabetes and Metabolism
Christian Medical College, Vellore, Tamil Nadu, India
Authors
Asha HS DNB (Med) DNB (Endo)
Bharathi S BSc (N) RN
Dukhabandhu Naik MD DM (Endo)
Mahesh DM MD DM (Endo)
Nihal Thomas MD MNAMS DNB (Endo) FRACP (Endo) FRCP (Edin) FRCP (Glasg)
Nitin Kapoor MD DM (Endo) ABBM (USA) Post Doc. Fellowship (Endo)
Ruth Ruby Murray BSc (N) RN
Sunitha R RN
Thomas V Paul MD, DNB (Endo), PhD (Endo)
Contributors from other Departments
in Christian Medical College, Vellore, Tamil Nadu, India
Abraham OC MD MS
Anna Simon MD DCH
Bobeena Rachel Chandy MD (PMR) DNB (PMR)
Edwin Stephen MS
Elizabeth Tharion DO MD (Physio)
Flory Christina RN
Geethanjali Arulappan MSc PhD
George M Varghese MD DNB DTMH FIDSA
Georgene Singh MD (Anes)
Hasna Rajesh BE
Inian Samarasam MS FRCS FRACS
Judy Ann John MD (PMR) DNB (PMR)
Mercy Jesudoss MSc (N)
Niranjan Thomas MD (Ped)
NV Mahendri MSc MHRM
Padma Paul DO MS Ophthal MPh
Ravikar Ralph MD (Med)
Saban Horo MS (Ophthal)
Samuel Vinod Kumar BPT
Sanjith Aaron MD DM (Neuro)
Santosh Varghese MD DM (Nephro)
Solomon Sathish Kumar MD
Subhrangshu Dey MD DM (Cardio)
Suceena Alexander MD DM (Nephro)
Viji Samuel MD DM (Cardio)
National Authors
Abraham Joseph MD DCH MS (Epid)
G Sai Mala PhD
Jubbin Jagan Jacob MD DNB (Endo)
Kishore Kumar Behera MD DNB (Endo)
Leepica Kapoor BSc MSc (Food and Nutrition) BEd.
Mathew John MD DM DNB (Endo)
Philip Finny MD DNB (Med) DNB (Endo)
Premkumar R PhD
Rajan P BOT
Ron Thomas Varghese MBBS
Ruchita Mehra Srivastava Hon (Psy) MSW (TISS)
Sudeep K MD Dip Diab DNB (Endo)
Veena V Nair MD PDCC (Ped Endo)
Vinod Shah MS MCh
International Authors
Charles Stephen MSc PhD
Hari Krishna Nair MD OSH (NIOSH) OHD (DOH) CMIA (MAL) CHM (USA) ESWT (Austria, Germany)
Kanakamani Jeyaraman MD DM (Endo) DNB (Endo)
Rahul Baxi MBBS MD PDF Diabetes (CMC, Vellore)
Ross Kristal
Senthil Vasan K MBBS PhD
Department of Endocrinology, Diabetes and Metabolism
Christian Medical College, Vellore, Tamil Nadu, India
Resource Persons
Aaron Chapla MSc (Bio-Chem)
Anil Satyaraddi MD
Chaitanya Murthy MBBS
Divya RN
Ezhilarasi RN
Felix Jebasingh MD
Haobam Surjitkumar Singh MBBS
Jansi Vimala Rani RN
Kaushiki Kirty MD
Kripa Elizabeth Cherian MD
Mercy Inbakumari BSc
Mini Joseph MSc (Diet) PhD
Padmapriya RN
Praveen MBBS
Riddhi Das Gupta MD
Sahana Shetty MD
Samantha MD
Sandip Chindhi MD
Shirley Jennifer RN
Shrinath Pratap Shetty MD
Simon Rajaratnam MD DNB (Endo) MNAMS PhD (Endo) FRACP (Endo) FRCP (Edin)
FM11Foreword
Copenhagen
Obesity and type 2 diabetes have become global epidemics affecting not only Western populations, but indeed to a highly worrying degree, the Asian populations including those of the Indian citizens. As for type 2 diabetes, there are currently an estimated number of more than 62,000,000 people suffering from this disease in India. Type 2 diabetes is associated with more than a two-fold excess mortality from cardiovascular disease, devastating microvascular complications affecting the eyes, kidneys and nerves, as well as with significant comorbidities including cancer, infections and psychosocial stress. If left untreated, the microvascular complications will ultimately lead to blindness, overt kidney failure, foot ulcers and amputations. There is an enormous challenge for the society and the healthcare system to organize treatment and management of people with diabetes to reduce its serious impact on health of the individual, as well as to reduce the otherwise extreme expenditure of society to compensate for lost working years as well as for managing blindness, dialysis, amputations, etc. Many landmark achievements within diabetes care have been obtained during recent years, including definitive knowledge that multifactorial pharmacological as well as nonpharmacological intervention targeting physical inactivity, overeating, smoking, reduction of blood pressure and lipids, as well as lowering glucose, significantly improves the most important clinical outcome variables in people with diabetes. Many novel drugs have been introduced targeting different distinct defects of metabolism in diabetes patients, leaving the clinical diabetes specialist with much better tools to tailor a more optimal and individualized treatment strategy in different diabetes patients. The fast generation of knowledge within the field of diabetes, as well as its significant quantitative impact on health within the society, makes it extremely important to have medical doctors with a proper and constantly updated scientific training in diabetes research, to lead the implementation of novel, better and more (cost-effective) treatment and care programs for patients with diabetes. I have had the great pleasure of working together with Professor Nihal Thomas and his team on clinical matters, as well as on important translational scientific projects, and in all of our interactions. I have been indeed very impressed about the dedication, level of knowledge as well as enthusiasm in general of Nihal Thomas and his team. I am therefore extremely happy hereby and with great confidence—to be able to give the doctors, councilors teams and patients associated with international community, the most sincere recommendations provided in this book, that would help in leading the fight against diabetes with the Seventh Edition of ‘A Practical Guide to Diabetes Mellitus’.
Allan Vaag MD PhD
Professor and Head
Department of Endocrinology
Riggs Hospital Copenhagen, Denmark
Adjunct Professor of Clinical Diabetes Research
Lund University, Sweden
FM13Foreword
New York
Diabetes mellitus has reached an astounding global prevalence of 343 million, according to recent estimates. While staggering, these numbers fall short of conveying the full magnitude of the problem. The human impact of diabetes includes devastating complications, economic hardships and reduction in the most creative and productive years of life. Though challenging to implement, optimal diabetes management has been proven to reduce the complications of diabetes. This underscores the vital need for training healthcare professionals in comprehensive diabetes management, particularly in settings that provide care to the poor.
Under the visionary leadership of Professor Nihal Thomas, Christian Medical College, Vellore, has developed a large-scale comprehensive diabetes education program. More than a hundred hospitals in rural and semi-urban parts of India have now been instructed in the medical management of diabetes. This program has promoted the creation of integrated diabetes clinics with an emphasis on close cooperation between diabetes nurse educators and doctors, thus favoring a very effective multidisciplinary approach to diabetes management.
Recently, in conjunction with the Global Diabetes Initiative of the Albert Einstein College of Medicine, New York, USA, this program has expanded its reach to over thirty countries, including many parts of Asia and Sub-Saharan Africa. The Seventh Edition of ‘A Practical Guide to Diabetes Mellitus’ offers a unique combination of rigorous pathophysiology with very practical approaches to diabetes prevention and control. This outstanding textbook will equip a cadre of doctors and other healthcare professionals to deliver high quality care to vulnerable populations around India and far beyond.
An ounce of practice is worth more than tons of preaching.
—Mahatma Gandhi
Meredith Hawkins MD MS FRCP (C)
Professor of Medicine
Endocrinology and Geriatrics
Director, Global Diabetes Initiative
Albert Einstein College of Medicine
New York, USA
FM15Foreword
Copenhagen
Diabetes mellitus is an emerging global health problem, not just in India. Fortunately, Indian physicians and researchers are also increasingly taking the lead, when it comes to doing something practical to stem the epidemic and to manage diabetes. Millions are affected by this chronic and potentially life-threatening disease. More than 3 million patients die from the disease on an annual basis. In some urban Indian societies, one out of five adults has diabetes.
The devoted team, editing the present as well as the previous editions of this important book, is headed by Professor Nihal Thomas. He and former Professor Abraham Joseph were partners in the renowned World Diabetes Foundation, and supported project entitled “Prevention and Control of Diabetes Mellitus in rural and semi-urban India through an established network of Hospitals,” which has successfully trained key-staff from more than 100 hospitals, many of these are situated in areas which are not easily accessible. The course material from this project makes up this book. Admirably, new versions are constantly evolving, including most recent knowledge on how to prevent, diagnose, care for and rehabilitate patients with diabetes. This book is soundly based on research as well as clinical practice, and it is a privilege and honor to write the foreword, while looking much forward to future editions from, and collaboration with Professor Nihal Thomas and his team.
Ib Chr. Bygbjerg MD DSCi
Professor of International Health
University of Copenhagen and
National University Hospital
Copenhagen, Denmark
FM17Preface
VELLORE
From Womb to Tomb: The Diabetes Cataclysm and Solutions Beyond
In the year 1995, when King et al, published an article in what is at times thought to be the clinical bible of diabetes (Diabetes Care1998)—he articulated for the very first time that India would house the largest number of patients with diabetes approaching around 20 million. The article had also prophesied that the number of diabetics in the country would stand at 57 million by the year 2025.
The prediction has not been false, but proven to be an underestimate. Today, in 2015, we stand at the precipice of reckoning and the predictions of Dr King have outlasted his own life. According to the findings of the ICMR sponsored INDIAB study, published in Diabetologia2011, India is faced with a galloping diabetes epidemic which is progressing at a speed which challenges the meanest and fastest on the F-1 circuit in a figurative sense. There are now an estimated 62 million patients with diabetes in India and this number is projected to explode beyond 85 million by the year 2030.
While diabetes in urban areas, with places like Cochin having figures in excess of 20% and Chennai at 17%, the epidemic is sweeping like a typhoon across the subcontinent and engulfing rural areas as well, and across terrains which were previously perceived as untouched. A study done by our group from rural Tripura, the first of its sort in the North-East part of the country and published in Journal of the Association of Physicians in India2007, demonstrated that a part of rural Tripura on the Indo-Bangladesh border, had a prevalence of diabetes of 9%. This was in contrast to parts of Himachal Pradesh which had a prevalence of 0.4% in the early 1990s. Similar trends have been shown in the state of Arunachal Pradesh, just South of China, published by our group (Ind J Endocrinol 2012). The changing patterns of disease in a country which still has a major proportion of the population in rural areas may be predictors of stories which may foretell a gloomy future.
The explosive growth of diabetes from across the country from the 1980s to till now is essentially multi-factorial which is very real and large. The real reasons would be inclusive of: (a) cable television, (b) economic liberalization (c) more processed food and fast food (d) increased academic competitiveness (thereby reducing physical activity) (e) mobile phones and computers (f) increased life expectancy—69 years for males now as opposed to 56 in 1980 and 66 for females, at present. I am indeed particularly fond of calling the jump in the prevalence of diabetes in the 1990s and their subsequent impact on teenage obesity in this millennium as the ‘Murdoch phenomenon,’ thanks to Rupert Murdoch for giving us cable television, which has perpetuated our populace to sit on their backsides for umpteen hours in a day adding to the catapult effect with regards to blood sugars. The hours of cricket being viewed on television, perpetuated unashamedly by mega-circuses like the Indian Premium League, not only serve to fatten the purses of those who run the industry, but also broaden the backsides and the waistlines of youngsters and elderly enhancing their propensity to develop diabetes! Surely our haloed film stars instead of munching bags of potato chips in voluminous quantities can show us how they manage to keep their figures trim and attractive by demonstrating methods of pumping iron or performing sessions of aerobics!
In the year 1998, wise men put their heads together and decided by consensus that the cut-off point for diabetes with regards to the fasting sugar should be reduced from 140 mg/dL to 126 mg/dL. This was a decision taken based on the fact that it appeared that ‘microvascular disease’ as generally gauged by diabetic involvement of the retina was present at much lower levels. From a scientific perspective, the decision was correct. However, many epidemiologists were not open about this fact when they published studies and data after 1998, mentioning the increasing prevalence of diabetes. In an ideal setting, they should have declared this in their publications—but they did not. They should have published ‘corrected’ figures taking into account the new definition. In any case, for the public, the ‘virtual effect’ added to the fuel provided for non-communicable disease awareness stakes, though some scientists gained a little extra mileage on the value of their publications.
There is an over representation of the phenomenon of impaired fasting glycemia and impaired glucose tolerance (measures of prediabetes) in screening surveys which does not necessarily indicate subsequent progression of disease. The newer cut-off of 100 mg/dL (well not so new!—instituted in 2002) for impaired fasting glycemia leads to earlier detection of the disease and enhancing the long-term prognostic outcome of pre-diabetes falsely causing another bias in the form of ‘lead time bias’.
Well—all in all, the disease is no doubt on the increase in geometric proportions, despite scientific interpretations that analyzing the situation. The evolution of the epidemic is a ‘womb to tomb’ phenomenon. Low birth weight is a precipitating factor for diabetes, cardiovascular disease, obesity, schizophrenia, osteoporosis and cancer, and perhaps more unperceived pestilences. This was a hypothesis proposed by Barker in the 1980s, which is no longer a hypothesis but a practical reality. Maternal malnutrition and the deficiency of micronutrients per se are responsible for the problem. The additive effect of poor lifestyle in childhood through adulthood therefore increases the chance of a low-birth weight child in subsequently developing diabetes. The mechanisms of this problem include a reduced secretion of insulin by the pancreas, increased peripheral resistance to insulin and an inability to burn calories when compared to the metabolism in a normal birth weight individual. Since low birth weight is present in almost 26% of the Indian population and in a larger proportion in rural areas, the impact is self-explanatory. From a scientific perspective, epigenetic changes or chemical changes in the uterus lead to changes in the genomic material which the child is born with.
The solutions are not simple, and essentially would involve proper counseling of the mothers and families of those children who are born low birth weight or preterm as to how over enthusiastic attempts to make the growth curve more steep in these children is probably likely to increase childhood obesity and lead to adverse consequences in adulthood. The ultimate solution of optimum feeding of mothers in pregnancy can be debated, but what is optimum and when? Research is on but the answer is unclear, and concepts are still evolving. Certainly, economic equity is a solution in improving birth weights, but is much more easily said than done.
So poverty may beget low birth weight and low birth weight begets diabetes. Unfortunately, to add to the complexity, when these children grow older they may have diabetes in pregnancy which may be inadequately treated due to poor awareness, finances or substandard medical care. This subsequently increases the risk of their offspring getting diabetes, particularly if FM19the diabetes in pregnancy is uncontrolled. Therefore, diabetes in pregnancy ends up being a continuous and depressing transgenerational phenomenon.
Thankfully, it appears that the effects of low birth weight can be blocked to a large extent by a healthy habitus, as suggested in our publication in Eur J Endocrinol 2012 and may indeed ameliorated by exercise interventions as simple as cycling (J Dev Health and Dis 2014), which are generally easily accessible and part of childhood recreation.
To add to the woes of those who are most affected by inflation, here is another quirk of fate which will increase the subsequent chances of the lower middle class and the poor in getting diabetes. Drewnowski and Specter in the American Journal of Clinical Nutrition 2004 have stated, that amongst subjects who belonged to the lower socioeconomic group, that there was a tendency to take more carbohydrate and fat rich food in greater abundance since it was cheaper than that of the food which was lower in calories and contained a larger quantum of free radicals and vitamins. Hence, the socioeconomically deprived, may in fact have a greater propensity to develop weight gain through the food which they eat, rather than those who are well-off. In other words, certainly cheaper oils are abundantly available and are not expensive compared to fresh fruits and vegetables. This lends further credence to the statement: ‘An apple a day keeps the doctor away’.
Vitamin D which is termed the ‘sunshine vitamin’, has its deficiency being associated with insulin resistance (the body's own lack of ability to respond to insulin). There is more evidence nowadays that though not entirely always with controversy, that since vitamin D deficiency has been shown by several groups including ours (Endocrine Practice 2008) to be fairly common owing to our propensity to avoid the sun for occupational and cosmetic reasons that this in itself may pose an added risk factor for the increasing prevalence of diabetes.
The magnitude of the disease in terms of its prevalence and the potential causes for the problem has now been discussed ad nauseum! The subsequent consequences of the disorder, with its impact on quality of life and even its economic impact cannot be overstated. Take for instance just one complication—the damage to the nerves (peripheral neuropathy). It is awfully common—according to an earlier study done in 4 centers across the country published in the Journal of Association of Physicians in India in 2005. Nerve damage was present in 15% of those who had diabetes who attended the outpatient clinics at these centers. What was probably more eerie is the fact that 3–4% of those patients with diabetes also had the amputation of at least a single toe, if not a whole limb.
Now try and visualize a situation that at least 1.5 million of your 70 million patients with diabetes have at least a toe or a limb that has been removed. This would impair not only their morale, but also their physical balance when attempting to walk and would lead to a number of those in the agrarian or laborer classes to be totally ineffective in their day-to-day work, without extensive rehabilitative therapy and prostheses.
The fact is that, as early as 2000, Lucini et al, pointed out in a study that was published in Pharmacoeconomics that if a patient with diabetes has one microvascular complication (that is peripheral nerve damage, retinal damage in the eye or early kidney disease) the cost of treatment goes up by 1.5 times. If a patient has one macrovascular complication (heart disease or stroke) the cost goes up by twice the amount that would normally be spent. However, if a patient has both 1 microvascular and 1 macrovascular complication, the cost of treatment goes up 3.5 times. This is totally unacceptable for the lower socioeconomic class in this country.FM20
A study conducted at Vellore published in Journal of Diabetes 2011, has shown that the commonest cause of death is cardiovascular disease (in general, a heart attack) or a stroke in 38% of the total number of hospitalized patients with diabetes. Urinary tract infections as a cause for death are far more common amongst the population with diabetes when compared to the non-diabetic population. There is an important public health message for administrators and also for the primary care physicians.
Indeed the number of pharmacological agents, on the other hand, that have emerged in the market over the last decade are significant, as opposed to the 1980s, when there were just 5 oral tablets for the management of diabetes, there are 18 at present! They may be used in a number of permutations and combinations. If used properly and up to maximal doses, the potential for delaying the usage of injectable products is certainly there. For the majority of the population in rural areas and amongst the lower socioeconomic classes, cost is a significant deciding factor. The harsh reality of incomplete and suboptimal therapy is a combination of the patient's financial inadequacy and at times the inability of the healthcare system to meet with the growing demands of and increasing patient load.
Going by the fact that prevention of complications is far more important than ultimately trying to treat or cure them, it brings us to a position where we would question ourselves as to where should we target our strategies, and who should we work on to improve the overall impact with regards to the prevention and treatment of diabetes in the community.
An editorial from the Lancet 2011 and some work from our center quoted in Heart Asia 2011 have both highlighted the fact that prediabetes, as documented as a fasting blood sugar of more than 100 mg/dL is present in 20% or more of high school children. They have a greater amount of subcutaneous fat (thicker skin) than their peers who do not have blood sugar or cholesterol problems. This is a strong signal that school programs are of primary importance in preventing obesity, diabetes and abnormalities of cholesterol which will wreck havoc on the individual and society later on as these children become adults.
Both at the central and state government levels, educational regulatory bodies should highlight the importance of compulsory physical training and games during school hours. There should be a compulsory assessment of physical fitness and period, self-assessment of physical abilities, weight and flexibility as a pre-requisite to pass before going to the next academic level. Radical thinking no doubt, but what if it were to help in preventing 80 million people or more from falling sick in the ensuing 40 years from now?
No doubt the growing number of endocrinologists and diabetologists appears to be a promising factor on the horizon. However, are they the ultimate solution for a disease that is going to affect 1 in 10 of the population of the country and 1 in 6 above the age of 20 years of age? Attempting to train large numbers of endocrinologists and diabetologists would be a time consuming, economically demanding and difficult to achieve solution for such a common disorder—an estimated 30,000 of them would be needed in our country—there are hardly 1,000 present at this point of time, almost all of them concentrated in urban areas. The concept of a competent family physician that has a better understanding of problems like diabetes, obesity, hypertension and other non-communicable problems are the way to go forward in tackling the problems of numerous clients with diabetes and prediabetes.
The role of councillors and educators who could be nurses, dieticians, physiotherapists and even school teachers in large numbers would be important in disseminating information FM21and supporting the role of public health physicians and family physicians in handling this pandemic. However, to sort out the problem of diabetes on a large-scale basis will require a megalithic vision spearheaded and encouraged by the government to develop teams to enhance physical activity and discourage unhealthy eating habits. It should involve a public health policy targeting schools, with primary health caregivers playing an important supplementary role.
There are other factors which play a role in the evolution of diabetes in India, and indeed, the genetic patterns do vary. Our recent studies in Maturity Onset Diabetes of the Young (MODY), have shown that the genetic forms which appear to be common in India (Clin Endocrinol 2015), differ from the patterns that are seen in the West. Moreover, it raises a possibility of other forms of diabetes also existing amongst the young, besides type 1 and type 2 diabetes. It also sets the foundation for a greater propensity of pharmacogenomic interventions in the years to come.
The current book is now into its 7th edition and has gone through a process of evolution starting with the World Diabetes Foundation Program which was initiated in 2004 to train doctors, nurses, foot care technicians and cobblers in the management of diabetes and set up integrated diabetes centers. Beyond that, what has resulted are comprehensive training programs for primary care doctors in diabetes and councillors in every corner on India, and parts of South-Asia and Africa as well.
Our role in handling the epidemic is to teach and to train those who can do their best in the periphery to handle diabetes to the extent they may be able to do well.
I would like to thank the number of authors who have performed their job so well to the extent that the current edition may be able to provide much more than what previous editions have for healthcare givers in both India as well as other parts of the world. I would like to specially thank Dr Nitin Kapoor, who has played a major role in the process of compiling the current edition of the book which has several new chapters including the ones on obesity, wound care, the elderly and epidemiology.
We are here to serve our patients directly, and in more ways than one through education of others to play their role better in countering the diabetic pestilence.
Nihal Thomas MBBS MD MNAMS DNB (Endo)
FRACP (Endo) FRCP (Edin) FRCP (Glasg)
Professor and Head
Department of Endocrinology
Vice Principal (Research)
Christian Medical College
Acknowledgments
We would like to thank Mr Jitendar P Vij (Group Chairman), Mr Ankit Vij (Group President), Ms Chetna Malhotra Vohra (Associate Director), Mr Umar Rashid (Development Editor) and production team of Jaypee Brothers Medical Publishers (P) Ltd., New Delhi, India.