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

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, approximately 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 beta-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 beta-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 beta-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.

Difference in dietary intake between women with polycystic ovary syndrome and healthy controls

“…Within the PCOS group, we observed that black women demonstrated higher ␤-cell function than did their white counterparts, although this difference did not reach statistical significance. It is well established within healthy populations that insulin secretion is higher among blacks vs. whites (41,42). It is likely that a larger sample size in the present study would have yielded a significant difference between races in insulin secretion among subjects with PCOS as well.…”

Longitudinal Changes in Insulin Sensitivity, Insulin Secretion, and β-Cell Function During Puberty

“…29 It is possible that other measures would be able to provide a more detailed assessment of insulin secretory dynamics. Although our research group has previously characterized differences in insulin secretory measures among whites, blacks, and Hispanics using C-peptide modeling, 23 we were unable to perform similar analyses in the present study. C-peptide modeling would help to identify both insulin secretion and clearance and whether differences in these variables are evident during puberty.…”

“…However, insulin secretion and extraction are known to differ by race. Gower and colleagues 23 have shown that AIRg is higher in blacks versus whites, and this may be the result of either increased insulin secretion or decreased insulin clearance. The underlying physiology is still unknown, but group differences may relate to lower hepatic tissue mass or a conservation of b-cell function in blacks.…”

“…Stratified mixed models for SI, AIRg, and DI were run for whites and blacks separately because black children are known to have lower SI and higher insulin secretion compared with white children. 16,23,24 Both linear and quadratic models were fitted for SI variables because a curvilinear U-shape was expected based on earlier cross-sectional reports in which SI was lowest at Tanner stage III versus Tanner stage I (pre-puberty) and Tanner stage V (post-puberty). 5 Linear models were fitted for AIRg and DI.…”

Racial and etiopathologic dichotomies in insulin hypersecretion and resistance in obese children

“…[16][17][18][19] These alterations of insulin dynamics can present in the first decade of life before the onset of weight gain 20 and tend to worsen during puberty. 16,21,22 However, despite their insulin resistance, black children paradoxically have greater subcutaneous and less visceral fat, 23 and black adults, for any level of body mass index (BMI), exhibit decreased incidence of the Metabolic Syndrome, both in adults 24 and children.…”