Introduction
Endocrinology is that branch of medicine that focuses on the study of the endocrine system in the human body. It comprises of glands that have the ability to secrete hormones. These hormones are chemical agents that affect the actions/reactions of different organ systems in the body for its normal functioning. The most common disorder in hormones is glucose homeostasis disorder and in this category diabetes is well known. The latter is a group of metabolic diseases characterized by hyperglycemia that results from defects in insulin secretion, insulin action, or both. (1) Those patients who have diabetes undoubtedly have a higher risk of acquiring many of the life threatening health issues that comes with more medical care expenditure, poor/moderate quality of life and higher mortality rate. (2) The rapid change in diabetes prevalence in many countries and regions has been increased by rapid urbanization and major changes in one’s sedentary lifestyle. (3)
Global burden of diabetes
The global prevalence of diabetes and impaired glucose tolerance has been multiplying over the past decennium. (4) Diabetes is one of the major leading causes of morbidity and mortality in the world. This up-growing diabetes epidemic endeavors a major challenge to public health. (5) In a recent study it was estimated that in 2017 there were 451 million (age 18–99 years) people with diabetes worldwide. These figures are presumably expected to rise in number to 693 million by 2045. Furthermore it was also assumed that almost half of all people (49.7%) living with diabetes are still not diagnosed. According to WHO approximately 5 million deaths worldwide were directly or indirectly related to diabetes in the 20–99 years age range. It was the seventh foremost cause of death. The global healthcare expenditure for patients with diabetes was estimated to be USD 850 billion in 2017. (6) It has been also observed that seven out of top ten countries with the largest number of diabetic patients are low or middle-income countries, including India, China, Russia, Brazil, Pakistan, Indonesia, and Bangladesh, among which the prevalence rates are 12.1% and 9.7% in India and China, respectively. (7)
Prevalence in china
The estimated prevalence of diabetes among a representative sample of Chinese adults was 11.6% and the prevalence of prediabetes was 50.1%. Projections based on sample weighting suggest this may represent up to 113.9 million Chinese adults with diabetes and 493.4 million with prediabetes. Unfortunately these findings indicate that diabetes is a major public health problem in China. (8)
Complications of diabetes
The complications of diabetes mellitus affect mostly every tissue of the body and diabetes mellitus is a leading causative factor of cardio- vascular morbidity and mortality, blindness, renal failure, and amputations. (9) This can be broadly classified as micro vascular and macro vascular complications. The micro vascular one can be further divided into diabetic retinopathy/nephropathy/neuropathy and the macro vascular one into stroke, cardiovascular disease.
A brief history of anti diabetic drugs
During the last 90 years, there are around 11 different categories of medications used for the treatment of hyperglycemia in diabetic patients. In the last 30 years, new insulin analogs, glucagon-like peptide 1 agonists, and valuable oral hypoglycemic agents have been introduced. (10) In 1993, the results of the Diabetes Control and Complications Trial (DCCT) were released, followed by the publication of the United Kingdom Prospective Diabetes Study (UKPDS) in 1998. These trials gave in to the consequence that a regulation on the glycemic level contributed to reduce incidence of some of diabetic complications in type 1 DM (T1DM) and T2DM, respectively. Another important aspect was to explore the effect of rapidly securing tight glycemic control in patients with T2DM and high cardiovascular risk. This was the aim of 3 trials, the Action to Control Cardiovascular Risk in Diabetes (ACCORD), the Veterans Administration Diabetes Trial (VADT) and the Action in Diabetes and Vascular Disease (ADVANCE). (11)
Another important issue is the fact that rosiglitazone was associated with an increase in the risk of myocardial infarction and in the risk of death from cardiovascular causes that had borderline implication. (11) Furthermore due to this, in 2008, FDA published a guidance for the drug industry recommending that new drug applications (NDAs) for diabetes should include evidence that the therapy does not increase the risk of cardiovascular events.
Pathogenesis of diabetes: Triumvirate and ominous octet
The triumvirate of hyperglycemia constitutes of the three factors namely impaired insulin secretion, increased HGP, and decreased glucose uptake. It is henceforth perceived that the β-cell failing occurs much prior to the actual diagnosis and is more serious than previously anticipated. In addition to the muscle, liver, and β-cell, the fat cell (accelerated lipolysis), gastrointestinal tract (incretin deficiency/resistance), α-cell (hyperglucagonemia), kidney (increased glucose reabsorption), and brain (insulin resistance) all perform meaningful roles in the progression of glucose intolerance in type 2 diabetic individuals. Simultaneously, these eight components amount to the ominous octet and dictate that: 1) amalgamation of multiple drugs used will be imperative for the correction of the multiple pathophysiological defects, 2) treatment should be comply to ease upon the reversal of known pathogenic abnormalities and not only on reducing the A1C, and 3) therapy must be initiated earlier to prevent/slow the progressive β-cell failure that previously is well established in IGT subjects. A treatment paradigm shift is essential in which combination therapy is initiated with diet/exercise, metformin (which improves insulin sensitivity and has anti atherogenic effects), a thiazolidinedione (TZD) (which boost insulin sensitivity, conserves β-cell function, and strive anti atherogenic effects), and exenatide (which preserves β-cell function and promotes weight loss). Sulfonylureas are not recommended because, after an initial improvement in glycemic control, they are co related with a progressive rise in A1C and gradual loss of β-cell function. (12)