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

Context: Postprandial hyperinsulinemia might be an important cardiometabolic risk determinant in black compared with white women. However, the contributions of insulin clearance and ß-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 ß-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 ß-cell function assessed using the insulin secretion rate and ß-cell responsivity indexes. Results: Black pre-menopausal and postmenopausal women had a greater insulin response and lower insulin clearance and greater dynamic ß-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 ß-cell capacity to rapid changes in glucose, but not to higher insulin secretion. The relationship of increased ß-cell secretory capacity, reduced insulin clearance, and ambient hyperinsulinemia to the development of cardiometabolic disease requires further investigation.

Gluconeogenesis and risk for fasting hyperglycemia in Black and White women.

Black women, compared with White women, have high rates of whole-body insulin resistance but a lower prevalence of fasting hyperglycemia and hepatic steatosis. This dissociation of whole-body insulin resistance from fasting hyperglycemia may be explained by racial differences in gluconeogenesis, hepatic fat, or tissue-specific insulin sensitivity. Two groups of premenopausal federally employed women, without diabetes were studied. Using stable isotope tracers, [2H2O] and [6,62-H2]glucose, basal glucose production was partitioned into its components (gluconeogenesis and glycogenolysis) and basal whole-body lipolysis ([2H5]glycerol) was measured. Indices of insulin sensitivity, whole-body (SI), hepatic (HISIGPR), and adipose tissue, were calculated. Hepatic fat was measured by proton magnetic resonance spectroscopy. Black women had less hepatic fat and lower fractional and absolute gluconeogenesis. Whole-body SI, HISIGPR, and adipose tissue sensitivity were similar by race, but at any given level of whole-body SI, Black women had higher HISIGPR. Therefore, fasting hyperglycemia may be a less common early pathological feature of prediabetes in Black women compared with White women, because gluconeogenesis remains lower despite similar whole-body SI.

Time to glucose peak during an oral glucose tolerance test identifies prediabetes risk.

CONTEXT: Morphological characteristics of the glucose curve during an oral glucose tolerance test (OGTT) (time to peak and shape) may reflect different phenotypes of insulin secretion and action, but their ability to predict diabetes risk is uncertain. OBJECTIVE: To compare the ability of time to glucose peak and curve shape to detect prediabetes and ß-cell function. DESIGN AND PARTICIPANTS: In a cross-sectional evaluation using an OGTT, 145 adults without diabetes (age 42±9 years (mean±SD), range 24-62 years, BMI 29.2±5.3 kg/m2 , range 19.9-45.2 kg/m2 ) were characterized by peak (30 minutes vs >30 minutes) and shape (biphasic vs monophasic). MAIN OUTCOME MEASURES: Prediabetes and disposition index (DI)-a marker of ß-cell function. RESULTS: Prediabetes was diagnosed in 36% (52/145) of participants. Peak>30 minutes, not monophasic curve, was associated with increased odds of prediabetes (OR: 4.0 vs 1.1; P<.001). Both monophasic curve and peak>30 minutes were associated with lower DI (P≤.01). Time to glucose peak and glucose area under the curves (AUC) were independent predictors of DI (adjR2 =0.45, P<.001). CONCLUSION: Glucose peak >30 minutes was a stronger independent indicator of prediabetes and ß-cell function than the monophasic curve. Time to glucose peak may be an important tool that could enhance prediabetes risk stratification.

Multiplexed Lipid Bilayers on Silica Microspheres for Analytical Screening Applications.

Most druggable targets are membrane components, including membrane proteins and soluble proteins that interact with ligands or receptors embedded in membranes. Current target-based screening and intermolecular interaction assays generally do not include the lipid membrane environment in presenting these targets, possibly altering their native structure and leading to misleading or incorrect results. To address this issue, an ideal assay involving membrane components would (1) mimic the natural membrane environment, (2) be amenable to high-throughput implementation, and (3) be easily multiplexed. In a step toward developing such an ideal target-based analytical assay for membrane components, we present fluorescently indexed multiplexed biomimetic membrane assays amenable to high-throughput flow cytometric detection. We build fluorescently multiplexed biomimetic membrane assays by using varying amounts of a fluorescently labeled lipid, NBD-DOPE [1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl)], incorporated into a phospholipid membrane bilayer supported on 3 µm silica microspheres. Using flow cytometry, we demonstrate this multiplexed approach by measuring specific affinity of two well-characterized systems, the fluorescently labeled soluble proteins cholera toxin B subunit-Alexa 647 and streptavidin-PE/Cy5, to membranes containing different amounts of ligand targets of these proteins, GM1 and biotin-DOPE, respectively. This work will enable future efforts in developing highly efficient biomimetic assays for interaction analysis and drug screening involving membrane components.