Postprandial Insulin Response and Clearance Among Black and White Women: The Federal Women's Study

Abstract

Context: Postprandial hyperinsulinemia might be an important cardiometabolic risk determinant in black compared with white women. However, the contributions of insulin clearance and β-cell function to racial differences in postprandial insulin response are unknown.

Objective: To compare, by race and menopause, early insulin response to oral and intravenous glucose and to measure postprandial intact glucagon-like peptide 1 (GLP-1) concentrations, insulin clearance, and β-cell function.

Design and participants: 119 federally employed women without diabetes [87 premenopausal (52 black, 35 white) and 32 postmenopausal (19 black, 13 white)] underwent an oral glucose tolerance test, insulin-modified frequently sampled intravenous glucose test (IM-FSIGT), and mixed meal tolerance test (MMTT).

Outcome measures: Early insulin response was measured as follows: (i) insulinogenic index (oral glucose tolerance test); (ii) acute insulin response to glucose (IM-FSIGT); and (iii) ratio of incremental insulin/glucose area under the curve in the first 30 minutes of the MMTT. Insulin clearance was assessed during the IM-FSIGT and MMTT. During the MMTT, intact GLP-1 was measured and β-cell function assessed using the insulin secretion rate and β-cell responsivity indexes.

Results: Black pre-menopausal and postmenopausal women had a greater insulin response and lower insulin clearance and greater dynamic β-cell responsivity (P ≤ 0.05 for all). No differences were found in the total insulin secretion rates or intact GLP-1 concentrations.

Conclusions: Greater postprandial hyperinsulinemia in black pre-menopausal and postmenopausal women was associated with lower hepatic insulin clearance and heightened β-cell capacity to rapid changes in glucose, but not to higher insulin secretion. The relationship of increased β-cell secretory capacity, reduced insulin clearance, and ambient hyperinsulinemia to the development of cardiometabolic disease requires further investigation.

Trial registration: ClinicalTrials.gov NCT01809288.

Figures

Figure 1.

The change in (a, b) glucose, (c, d) insulin, and (e, f) C-peptide concentrations during the MMTT in black (solid squares and lines) and white (white circles and dotted lines) pre-menopausal and postmenopausal women. Data presented as mean ± SEM.

Figure 2.

Early insulin response to three different glucose stimuli. Early response was defined as (a) insulinogenic index during OGTT, (b) AIRg during IM-FSIGT, and (c) insulin iAUC30/glucose iAUC30 during MMTT. Data are presented as Tukey box and whiskers plots. Black circles represent any value that lie outside the range of the whiskers.

Figure 3.

Basal and total fractional hepatic insulin extraction during IM-FSIGT and MMTT in black (black bars) and white (white bars) women. Data presented as mean ± SEM.

Figure 4.

Model estimates of insulin secretion and β-cell function during the MMTT. ISR in black (blue lines) and white (green lines) (a) premenopausal and (b) postmenopausal women. β-cell responsivity in black (gray boxes) and white (white boxes) women by menopausal status: (c) dynamic and (d) static. (e) The total insulin secretion AUC rate during the MMTT partitioned into its components: ISRbasal (black box), ISRstatic (gray box) and ISRdynamic (white box). Data presented as (a, b) line graphs, (c, d) Tukey Box and whisker plots, and (e) bar graphs. Black circles represent any value that lie outside the range of the whiskers. *P < 0.01 premenopausal white vs black women.

Figure 5.

The relationship of basal fractional hepatic insulin extraction during the MMTT and hepatic fat in (a) black and (b) white women. Data presented as individual data points for black (black squares) and white (white circles) women with the corresponding regression line.