The Obese Patient with Diabetes Mellitus: From Research Targets to Treatment Options

Abdominal obesity is a recognized risk factor for both type 2 diabetes mellitus and cardiovascular disease. The metabolic consequences of obesity, such as insulin resistance and impaired glucose tolerance, are primarily attributable to visceral, rather than to subcutaneous, adipose tissue. As a result, liposuction, which mainly removes subcutaneous fat, has no significant effect on insulin sensitivity; by contrast, weight loss resulting from bariatric surgical procedures is associated with resolution of type 2 diabetes in almost 80% of patients. Even modest weight loss in overweight or obese individuals is associated with significant reductions in the risk of diabetes and increased survival. Recent studies have suggested that the renin-angiotensin system (RAS) functions in the regulation of adipogenesis. Activation of this system is increased in obese individuals and angiotensin II, acting via angiotensin type 1 receptors, inhibits the differentiation of preadipocytes into mature adipocytes. This might be expected to result in ectopic storage of fat in tissues such as skeletal muscle and liver, thereby decreasing insulin sensitivity. Evidence from animal studies suggests that angiotensin-receptor blockers can promote redistribution of excess fat from these ectopic sites to mature adipocytes, resulting in improved insulin sensitivity. Clinical trials with telmisartan are currently investigating the effects of RAS blockade on insulin sensitivity in humans.