As the first speaker has reviewed the epidemiology of diabesity, it is clear that the epidemic of obesity is the driving force for the prevalence of diabetes mellitus. For the pathogenesis of obesity, the imbalance between energy intake and energy expenditure is the primary cause. Through evolution, living organisms, including humans have developed “thrifty” genes that effectively conserve surplus energy for the need for the period of food scarcity. It is the mismatch between these thrifty genes and modern affluent environment in the presence of sufficient insulin secretion that generate the positive energy balance in the obesogenic conditions. The possible environmental factors include excessive dietary intake, decreased physical activity, change in intestinal microbiota, and metabolic endotoxemia. Insulin resistance, dysfunctional endocrine function of the adipose tissues, lipotoxicity to pancreatic beta cells and many other physiological derangements following obesity lead to gradual decline in insulin secretory capacity of the islet beta cells. As the result, hyperglycemia occurs eventually into the diabetic range. Some of the pathogenic mechanisms may be shared by both obesity and diabetes. However, it should be noted that it is the decreased insulin secretion from the failing islet beta cell that can not meet the needs of the peripheral tissues to take up glucose and produces the subsequent pathophysiology of diabetes mellitus.