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Previous Volume 329:1988-1992 December 30, 1993 Number 27 Next

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ABSTRACT

Background The relative roles of obesity, insulin resistance, insulin secretory dysfunction, and excess hepatic glucose production in the development of non-insulin-dependent diabetes mellitus (NIDDM) are controversial. We conducted a prospective study to determine which of these factors predicted the development of the disease in a group of Pima Indians.

Methods A body-composition assessment, oral and intravenous glucose-tolerance tests, and a hyperinsulinemic-euglycemic clamp study were performed in 200 nondiabetic Pima Indians (87 women and 113 men; mean [±SD] age, 26 ±6 years). The subjects were followed yearly thereafter for an average of 5.3 years.

Results Diabetes developed in 38 subjects during follow-up. Obesity, insulin resistance (independent of obesity), and low acute plasma insulin response to intravenous glucose (with the degree of obesity and insulin resistance taken into account) were predictors of NIDDM. The six-year cumulative incidence of NIDDM was 39 percent in persons with values below the median for both insulin action and acute insulin response, 27 percent in those with values below the median for insulin action but above that for acute insulin response, 13 percent in those with values above the median for insulin action and below that for acute insulin response, and 0 in those with values originally above the median for both characteristics.

Conclusions Insulin resistance is a major risk factor for the development of NIDDM. A low acute insulin response to glucose is an additional but weaker risk factor.

Source Information

From the Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Ariz. (S.L., D.M.M., M.S., R.F., E.R., W.C.K., P.H.B., C.B.), and the Sandoz Research Institute, East Hanover, N.J. (J.E.F.).

Address reprint requests to Dr. Bogardus at the Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, 4212 N. 16th St., Rm. 541, Phoenix, AZ 85016.

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