Plasma levels of tumor necrosis factor-alpha, angiotensin II, growth hormone, and IGF-1 are not elevated in insulin-resistant obese individuals with impaired glucose tolerance

OBJECTIVE- To in investigate the relationship between insulin resistance an d plasma concentrations of free fatty acids (FFAs), leptin, and potential a gonists of the insulin receptor substrate (IRS) system, including tumor nec rosis factor-alpha (TNF-alpha), IGF-I, growth hormone (GH), and angiotensin II in individuals with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS- Because glucose toxicity per se leads to insul in resistance, the determination of the primary metabolic alterations leadi ng to insulin resistance is best accomplished in individuals who are at an increased risk to develop type 2 diabetes. Therefore, 48 subjects with IGT and insulin resistance (IR), characterized by hyper insulinemic-euglycemic clamps, were compared with 52 healthy insulin-sensitive (IS) control subjec ts with respect to the relationship between the plasma levels of TNF-alpha, IGF-I, GH, angiotensin II. FFA, leptin, and insulin resistance. RESULTS- Between the IR and the IS groups. there were no significant differ ences in the plasma concentrations of TNF-alpha, GH, angiotensin II, IGF-I, and leptin. However, plasma FFA levels were significantly elevated in the IR group compared with the IS group after matching for BMI. CONCLUSIONS- The plasma concentrations of FFA, but not TNF-alpha, IGF-I, GH , and angiotensin III are elevated in patients at an early stage of insulin resistance, suggesting that FFAs, but not the other modulators of the IRS system, may be a primary metabolic abnormality leading to insulin resistanc e.