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Contribution of Insulin Secretion and Clearance to Glucose-Induced Insulin Concentration in African-American and Caucasian Children

Department of Nutrition Sciences and Clinical Nutrition Research Center (B.A.G., F.F.), Department of Critical Care (W.M.G.), Department of Pediatrics (F.F.), and Department of Health Services Administration (R.M.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294-3360; and Departments of Preventive Medicine and Physiology and Biophysics, University of Southern California, and Institute for Prevention Research (M.I.G.), Los Angeles, California 90033

Address all correspondence and requests for reprints to: Dr. Barbara A. Gower, Department of Nutrition Sciences and Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294-3360. E-mail: . bgower{at}uab.edu

Abstract

Relative to Caucasians (C), African-American (AA) children and adults have lower indices of insulin sensitivity (S_i) and a higher acute insulin response to glucose (AIR_g). Among AA children, AIR_g is greater than that which would be predicted based on lower S_i. The objectives of the present study were 1) to determine whether insulin secretory parameters differ in AA vs. C children and adolescents using C-peptide modeling, 2) to determine whether hepatic insulin extraction differs with ethnicity/race using the C-peptide to insulin molar ratio, and 3) to determine whether the relatively greater AIR_g among African-Americans is due to greater insulin secretion or lesser clearance. Subjects (n = 76) were AA and C children (mean age, 11 yr). A 3-h tolbutamide-modified iv glucose tolerance test and minimal modeling were used to determine S_i and AIR_g. First phase C-peptide/insulin secretion and basal, first, and second phase ß-cell sensitivity to glucose were determined using C-peptide modeling with standard kinetic parameters developed in adults. The incremental C-peptide to insulin molar ratio over the 3-h test period, an index of hepatic insulin extraction, was calculated with the trapezoidal method. S_i was lower and AIR_g was higher in AA vs. C children. First phase C-peptide/insulin secretion and first phase ß-cell sensitivity to glucose were approximately 2-fold greater in AA vs. C children (P < 0.001); there were no between-group differences in basal or second phase ß-cell sensitivity to glucose. Hepatic insulin extraction was lower in AA vs. C (3.77 ± 1.78% vs. 5.99 ± 2.18%; P < 0.001). Multiple linear regression modeling indicated that first phase C-peptide/insulin secretion and hepatic insulin extraction contributed independently to AIR_g; however, it was only first phase C-peptide/insulin secretion that explained the significant independent contribution of ethnicity/race to AIR_g after adjusting for S_i. The results of this study suggest that greater AIR_g among AA is due to both greater insulin secretion and lesser hepatic insulin extraction, and that AIR_g above that predicted based on lower S_i is due to greater insulin secretion. The insulin secretion data await verification that the kinetic parameters used apply to children and AA.

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