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Insulin Secretion and Action in Subjects With Impaired Fasting Glucose and Impaired Glucose Tolerance

Results From the Veterans Administration Genetic Epidemiology Study

From the Diabetes Division, University of Texas Health Science Center, San Antonio, Texas

Address correspondence and reprint requests to Ralph A. DeFronzo, Diabetes Division, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78229. E-mail: albarado{at}uthscsa.edu

Abbreviations: AUC, area under the curve; CGI, combined glucose intolerance; EGP, endogenous glucose production; FPI, fasting plasma insulin; IFG, impaired fasting glucose; HGP, hepatic glucose production; HOMA-IR, homeostasis model assessment of insulin resistance; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; OGIS, oral glucose insulin sensitivity; OGTT, oral glucose tolerance; TGD, total glucose disposal

This study was conducted to observe changes in insulin secretion and insulin action in subjects with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). A total of 319 subjects were studied with an oral glucose tolerance test (OGTT). Fasting plasma glucose and insulin concentrations were measured at baseline and every 30 min during the OGTT. Fifty-eight subjects also received a euglycemic-hyperinsulinemic clamp. Insulin sensitivity was calculated as the total glucose disposal (TGD) during the last 30 min of the clamp. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting plasma glucose and insulin concentrations. Subjects with IFG had TGD similar to normal glucose-tolerant subjects, while subjects with IGT and combined IFG/IGT had significantly reduced TGD. HOMA-IR in subjects with IFG was similar to that in subjects with combined IFG/IGT and significantly higher than HOMA-IR in subjects with IGT or NGT. Insulin secretion, measured by the insulinogenic index (I_0–30/G_0–30) and by the ratio of the incremental area under the curve (AUC) of insulin to the incremental AUC of glucose (0–120 min), was reduced to the same extent in all three glucose-intolerant groups. When both measurements of ß-cell function were adjusted for severity of insulin resistance, subjects with IGT and combined IFG/IGT had a significantly greater reduction in insulin secretion than subjects with IFG. Subjects with IGT and IFG have different metabolic characteristics. Differences in insulin sensitivity and insulin secretion may predict different rates of progression to type 2 diabetes and varying susceptibility to cardiovascular disease.

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