The current obesity epidemic and its major sequelae, including type 2 diabetes, atherosclerosis, and cardiovascular diseases, threaten human health, productivity, and life quality. Recent studies, which continue to further clarify the molecular basis of these diseases, aim to ultimately provide a path to better diagnoses and therapies for disease prevention and reversal. Insulin resistance is a defining feature of obesity-linked type 2 diabetes and nearly always coexists with reduced plasma adiponectin levels and a constellation of other abnormalities that increase the risks for cardio- and cerebro-vascular diseases.