Emerging Concepts in Pathophysiology of T2DM

Diabetes is the most common non-communicable disease globally and has assumed epidemic proportions both in developed and developing countries. The recent data IDF of global estimates shows that 387 million people were afflicted with diabetes by 2014, and this number is going to be ballooned to 592 million by 2035. Great number of the people having diabetes is between 40 and 59 years of age. Type 2 diabetes is characterized by two defects: insulin resistance and insulin deficiency. The growing prevalence of obesity, adaptation to sedentary life style, consumption of calorie-dense food and increasing longevity (increased adipose tissue mass) and possibly genetic factors have contributed to increasing insulin resistance. [beta] cells of the pancreas have a tremendous capacity to overcome this increasing insulin resistance, but eventually they exhaust and manifest as hyperglycemia due to decline in insulin secretion. However, after the onset of hyperglycemia, the decline in b cell function is rapid, progressive and inexorable. The ongoing glucotoxicity, lipotoxicity, oxidative stress and enhanced programmed b cell apoptosis leads to [beta] cell dysfunction. Last few years have witnessed and important role of incretins in the pathophysiology of T2DM. Progressive decline in incretins particularly in GLP1 and GIP results in decrease in insulin secretion and worsening of hyperglycemia. The uses of DPPIV inhibitor and GLP analogues have modulated the whole scenario. In addition, newer understandings in programmed [beta] cell death has also resulted in exploration of new therapeutic targets.