Plasma Levels of Tumor Necrosis Factor-α, Angiotensin II, Growth Hormone, and IGF-I Are Not Elevated in Insulin-Resistant Obese Individuals With Impaired Glucose Tolerance
- Matthias Blüher, MD,
- Juergen Kratzsch, PHD and
- Ralf Paschke, MD
- From the III Medical Department (M.B., R.P.), Faculty of Medicine, and the Institute of Clinical Chemistry and Pathobiochemistry (J.K.), University of Leipzig, Leipzig, Germany.
- Address correspondence and reprint requests to Prof. R. Paschke, University of Leipzig, III. Medical Department, Philipp-Rosenthal-Straβe 27, D-04103 Leipzig, Germany. E-mail: pasr{at}medizin3.uni-leipzig.de .
Abstract
OBJECTIVE— To investigate the relationship between insulin resistance and plasma concentrations of free fatty acids (FFAs), leptin, and potential agonists of the insulin receptor substrate (IRS) system, including tumor necrosis factor-α (TNF-α), 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 insulin resistance, the determination of the primary metabolic alterations leading 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 hyperinsulinemic-euglycemic clamps, were compared with 52 healthy insulin-sensitive (IS) control subjects with respect to the relationship between the plasma levels of TNF-α, IGF-I, GH, angiotensin II, FFA, leptin, and insulin resistance.
RESULTS— Between the IR and the IS groups, there were no significant differences in the plasma concentrations of TNF-α, 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-α, IGF-I, GH, and angiotensin II, 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 resistance.
Footnotes
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M.B. is currently affiliated with the Research Division, Joslin Diabetes Center, Boston, Massachusetts.
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Abbreviations: ELISA, enzyme-linked immunosorbent assay; FFA, free fatty acid; GH, growth hormone; HOMA, homeostasis model assessment; IGFBP-3, IGF binding protein 3; IGT, impaired glucose tolerance; IR, insulin-resistant; IRS, insulin receptor substrate; IS, insulin-sensitive; OGTT, oral glucose tolerance test; PI3K, phosphatidylinositol 3-kinase; RIA, radioimmunoassay; SDS, SD score; TNF-α, tumor necrosis factor-α.
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted November 1, 2000.
- Received August 9, 2000.
- by the American Diabetes Association, Inc.
