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Diabetes 55:1114-1120, 2006
DOI: 10.2337/diabetes.55.04.06.db05-1100
© 2006 by the American Diabetes Association
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The Natural Course of ß-Cell Function in Nondiabetic and Diabetic Individuals

The Insulin Resistance Atherosclerosis Study

Andreas Festa1,2, Ken Williams1, Ralph D’Agostino, Jr.3, Lynne E. Wagenknecht3, and Steven M. Haffner1

1 Department of Medicine, University of Texas Health Science Center, San Antonio, Texas
2 Eli Lilly Area Medical Center, Vienna, Austria
3 Wake Forest University School of Medicine, Winston-Salem, North Carolina

Address correspondence and reprint requests to Steven M. Haffner, MD, University of Texas Health Science Center, Department of Medicine (#7873), 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. E-mail: haffner{at}uthscsa.edu

Abbreviations: AIR, acute insulin response; FSIGTT, frequently sampled intravenous glucose tolerance test; IGT, impaired glucose tolerance; IRAS, Insulin Resistance Atherosclerosis Study; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; UKPDS, U.K. Prospective Diabetes Study

Data from the UKPDS (U.K. Prospective Diabetes Study) indicate a continuous decline in ß-cell function in patients with type 2 diabetes. We studied longitudinal changes in ß-cell function (follow-up of 5.2 years) in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes, using acute insulin response (AIR) and insulin sensitivity index (Si) from a frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40–69 years. At baseline, decreasing levels of both Si and AIR (either unadjusted or adjusted for Si) mirrored deteriorating glucose tolerance status at baseline and at follow-up. A different pattern was found with respect to longitudinal changes; Si declined in each glucose tolerance category, ranging from –0.81 x10–4 min–1 · µU–1 · ml–1 in NGT at baseline and NGT at follow-up (NGT/NGT) to –1.06 x10–4 in NGT/diabetes, whereas the directional change in AIR principally determined the glucose tolerance status at follow-up. In NGT/NGT Si decreased by 35% and AIR increased by 34%. Results were similar in each of the three ethnic groups. These data shed light on the natural course of ß-cell function; over 5.2 years, mean insulin sensitivity declined in each glucose tolerance category. The change in AIR, however, principally determined glucose tolerance status at follow-up; NGT was maintained by a compensatory increase in insulin secretion. Failure to increase insulin secretion led to IGT, and a decrease in insulin secretion led to overt diabetes. This data may have important implications for the prevention and treatment of type 2 diabetes.


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