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Nested Study: Identifying Risk for Diabetes and Heart Disease in Women: A Study of African-American, African and White Federal Employees and Contractors

$55,373ZIAFY2022DKNIH

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

The Federal Women nested study was designed to help unravel the complex association of race/ ethnicity, hepatic insulin resistance and the pathway to diabetes. This project evaluated the components of hepatic glucose production (gluconeogenesis and glycogenolysis) and the contribution of hepatic to total body insulin resistance by race and ethnicity. Eligible women (30 African descent and 30 white) who participated in the primary protocol (13-DK-0090) were invited to participate in the nested study to measure glucose and fat metabolism and energy expenditure. In 46 pre-menopausal federally-employed women, without diabetes: 24 black and 22 white; age 371 (meanSEM), range 25-49 y; BMI 321, range 24-45 kg/m2 we found lower gluconeogenesis (new glucose made by the liver) despite similar rates of whole-body insulin resistance and prediabetes. In addition, there was less insulin resistance in the liver in black women but no difference in insulin resistance in adipose (fat) tissue. These findings provided mechanistic insight to help understand why the fasting blood glucose test has lower sensitivity for detecting prediabetes/ diabetes in black women. Our findings have been published in major peer-review journals (The Journal JCI Insight and The Journal of Clinical Endocrinology and Metabolism, Circulation Research) two additional manuscripts are in preparation. One manuscript, LPIR in African ancestry populations is being prepared. Secondary analyses will also examine the relationship of comprehensive dietary assessments with nutritional metabolomics will provide critical insights into how to tailor precision nutrition prescriptions. We applied for a grant to test the hypothesis that nutrient and food pattern data from food records will be associated with plasma food metabolome markers and genetic variants of fatty acid metabolism regardless of race/ ethnicity. Analysis of genetic variants of fatty acid metabolism has been completed and the metabolomic and lipidomic fatty acid profile analysis is underway.

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