Studies have shown that obese patients have a lower tissue response to insulin than lean individuals, suggesting that obesity promotes the development of insulin resistance. The mechanisms linking obesity and insulin resistance are not known. Obese patients have decreased glucose oxidation and increased lipid oxidation compared with lean individuals, and are hyperinsulinemic, which may result in downregulation of insulin receptors. Studies in healthy subjects have shown that increased plasma levels of nonesterified free fatty acids resulted in a decrease in peripheral insulin-induced glucose uptake. Obese patients have increased plasma levels of nonesterified free fatty acids, which may be involved in the development of insulin resistance. Patients with central obesity have a greater degree of peripheral insulin resistance and higher plasma insulin levels than patients with lower body obesity. Patients with non-insulin-dependent diabetes mellitus (NIDDM) who become obese have a further reduction in insulin sensitivity. Studies in Pima Indians have shown that adiposity is the most important predictor for NIDDM in children with at least one parent who have diabetes. Insulin sensitivity improves with weight loss in obese patients.