ESI Manual of Clinical Endocrinology RV Jayakumar, Nihal Thomas, Sarita Bajaj, Sanjay Kalra, Rakesh Sahay, Nalini S Shah, Ambrish Mithal, GR Sridhar, Anil Bhansali, KM Prasanna Kumar, Nikhil Tandon, Shashank R Joshi, AC Ammini, Subhankar Chowdhury
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1Diabetes and Metabolic Syndrome
Section Editors: GR Sridhar, Sanjay Kalra, Rakesh Sahay
Associate Editors: Manash P Baruah, Manoj Chadha, Krishna G Seshadri2

The Diversity of DiabetesChapter 1

Sanjay Kalra,
Vishal Gupta
Diabetes mellitus is perhaps the most common endocrinopathy today. The diabetes epidemic has emerged as a global health problem, and Indian remains on the top of the list second only to China with 65.1 million patients as per recent IDF atlas, and keeping this in mind, the current manual of clinical endocrinology begins with a section on diabetes.
The term “diabetes mellitus”, however, does not denote a single disease or a single condition. It is composed of a wide spectrum of clinical conditions, all of which have in common a single pathophysiologic condition: carbohydrate intolerance.
The above statement too does not do justice to the multifaceted syndrome of diabetes. From a simplistic view point of insulin deficiency and insulin resistance, the understanding of diabetes has grown to include a number of other mechanisms.
These mechanisms and processes related to glucose regulation, insulin sensitivity/resistance, lipid metabolism, and body fat distribution vary among ethnic and racial groups as well as among different age groups.
There is also significant difference in the prevalence rates in various ethnic groups with as low as 0.1% in samburu tribes in Kenya to as high as 24% in Saudi Arabia.
This leads to varied clinical presentations as well as differing responses to medical therapy. There are cultural factors that impact the way in which patients view diabetes, its complications, and its treatment. Physicians also tend to treat diabetes differently at times, based on individual preferences and options, in spite of the availability f various guidelines. Current ADA and EASD consensus statement also recommends patient-centric approach and individualization of treatment as per patient needs.
It is the diversity of diabetes that makes it a dynamic and difficult to manage disease. It is also this diversity, which makes it a challenge, as well as a joy, to study diabetology.
This chapter, and this section, will try to address the diverse aspects of diabetes, and address the challenges of managing this important clinical condition.
Multiple pathophysiological conditions have been implicated in the development of type 2 diabetes mellitus. While earlier researchers had an insulin-centric approach to diabetes focusing on insulin deficiency and insulin resistance, recent workers have highlighted the role of the brain, kidney, gastrointestinal tract, and alpha cell in the natural history of diabetes. Along with the beta cell, liver skeletal muscle and adipose tissue form the Ominous Octet of DeFronzo.
This is not the final word, however. The forgotten felon, dopamine, has been proposed as an example of the role of the autonomic nervous system in glucose regulation.
Discovery of vitamin D hydroxylation and the renin–angiotensin system in the islets of Langerhans has added to the diversity of pathophysiologic mechanisms of diabetes. The role of sex steroids is also being considered in the development of metabolic syndrome.
Along with the ominous octet, testosterone, vitamin D, dopamine, and renin–angiotensin system form the Dirty Dozen of the metabolic syndrome. To add to this, various nontraditional associations of diabetes have been postulated.
4Chapters in this section deal with some of these aspects of diabetes, and help the reader understand the myriad associations of the syndrome.
Various races and ethnic groups demonstrate differences in glucose and lipid metabolism, as well as insulin sensitivity/resistance. In a study published by Fukushima, Japanese type 2 diabetic patients are characterized by a larger decrease in insulin secretion and show less attribution of insulin resistance. These factors, along with differences in dietary patterns, and attitude toward modern health care and disease, influence the response to therapy. Certain groups keep fasts or observe religious rituals that entail a change in management strategies at times.
These aspects of diabetes are especially important for a multiethnic country such as India. The chapter on ethnopharmacology focuses on these, as well as other aspects of ethnocentric diabetes care, in order to sensitize physicians to the need for India-specific treatment guidelines.
Diabetes has subtle differences when it occurs in the young, in the elderly, in women, and especially in pregnancy. While conventional classifications of diabetes include type 1, type 2, gestational and “other” diabetes, the clinical diabetologist sees a much wider spectrum of disease. Unfortunately, poor documentation and lack of complete investigations often hamper them from publishing their experiences.
The current manual includes chapters on diabetes in the young, type 1.5 diabetes, geriatric diabetes, type 3 diabetes, diabetes in women, and gestational diabetes. These chapters should encourage readers to appreciate the various forms of diabetes encountered in clinical practice.
Diabetes mellitus is feared because of its multiple complications. While the acute complications can be classified as hypoglycemia and hyperglycemia (with or without ketoacidosis), the chronic complications are divided into macrovascular and microvascular conditions. There are also “Cinderella” complications, including the manifestations of diabetes in the oral cavity, on malignancy, the musculoskeletal system, and the liver. The psychological and psychiatric morbidity associated with diabetes is included in this group of neglected Cinderella complications. Various authors try to focus on these aspects of diabetology in this section, while highlighting the easily preventable and manageable aspects of diabetes.
The section also covers the acute management of hyperglycemia in the intensive care unit as well as in the setting of acute coronary syndromes.
The management strategies for diabetes are as diverse as the clinical presentation is. Therapeutic diabetes education, nonpharmacological management, psychological therapy, oral drugs, and insulin are all used to manage the condition. The addition of incretin-based therapies and recently approved SGLT 2 inhibitors has further increased the treatment options. The section tries to do justice to the clinically relevant aspects of diabetes therapy.
Four distinct patterns of outdoor patient management can be discerned in diabetology. The classic picture of upgradation is seen in patients who need and are prescribed gradual intensification of therapy as their disease progresses.
The second scenario is seen in patients who present with acute comorbidity or hyperglycemia, receive initial intensive therapy, and then experience a reduction in requirement of drugs, due to correction of glucotoxicity, lipotoxicity, and other factors.
A third situation is known as the yo-yo pattern or see-saw pattern. Patients present with high glucose levels respond to therapy and then discontinue it for a period of time, for various reasons, before returning to the physician with uncontrolled hyperglycemia. This see-saw or yo-yo pattern implies inadequate patient and community education related to diabetes.
A fourth pattern, known as the linear pattern, describes a situation where the patient continues to be prescribed almost the same drugs, irrespective of glycemic levels or other comorbid developments, over long period of time. This indicates lack of proactivism on part of the diabetes care provider.
The diverse patterns of diabetes management should be understood by physicians and endocrinologists, as they grapple with the public health impact of diabetes. These patterns also help understand the various types 1.5 diabetes and their natural history.
Different communities perceive diabetes, its complications, and its management in different ways. This aspect 5 of science, known as medical anthropology, impacts the choice of therapy as well as the compliance and persistence with suggested therapy. The diversity of diabetes is obvious from the fact that different societies have varying opinions about inevitability of the disease or its complications. They also differ in their acceptance of modern therapy. This aspect of medicine is covered in the chapter on ethnopharmacy.
Conventional medical training enjoined a medical student to learn everything there was possible to learn, about his or her specialty. The recent rapid advances in science, however, have made it impossible to do so.
Diabetes has emerged as a diverse specialty, with diverse manifestations, requiring diverse skills for management. Appreciating this, the current manual has welcomed contributions from allied specialties such as gynecology, dentistry, psychiatry, psychology, and radiology, which will help improve our understanding of diabetes.
The diversity of diabetes is an undeniable part of the pandemic. Understanding and appreciating this diversity, while learning how to manage it, is of utmost importance. This will make the practice of diabetology an intellectually fulfilling exercise for the medical practitioner, and ensure a healthy life for his or her patients as well. The first section of the manual of clinical endocrinology hopes to achieve just this.
  1. Bajaj S, ed. Endocrine Society of India Manual of Clinical Endocrinology. 1st ed. Endocrine Society of India.  Hyderabad: 2012.
  1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2012; 55: 1577–96.
  1. International Diabetes Federation. IDF Diabetes Atlas, 6th edn. International Diabetes Federation,  Brussels,  Belgium: 2013.