Dataset Information

Association between obesity phenotypes of insulin resistance and risk of type 2 diabetes in African Americans: The Jackson Heart Study.

ABSTRACT:

Objective

To determine whether insulin resistance (IR) measured by homeostasis model of insulin resistance (HOMA-IR) can further stratify diabetes risk in African Americans (AAs) beyond obesity and identify obese, low risk and non-obese, high risk individuals.

Methods

Using the Jackson Heart Study cohort, we categorized participants without diabetes into four phenotypes: non-obese/insulin-sensitive, non-obese/IR, obese/insulin-sensitive and obese/IR. Obesity was defined as BMI ? 30 or BMI 25-30 plus an increased waist circumference. IR was defined as HOMA-IR ? 2. We used modified Poisson regression models to estimate the incident risk-ratios (IRR) of diabetes across these phenotypes adjusting for potential confounders and HbA1c.

Results

Among 3219 AAs without diabetes, 14.0% were non-obese/insulin-sensitive, 24.6% non-obese/IR, 6.2% obese/insulin-sensitive, and 55.3% obese/IR. The overall crude incidence rate of diabetes was 29.91 cases/1000 person-years. In fully-adjusted models, compared to the non-obese/insulin-sensitive group, the relative risk of diabetes was highest in obese/IR (IRR = 2.35; 95% CI: 1.53, 3.60), followed by non-obese/IR (IRR = 1.59; 95% CI: 1.02, 2.46), and non-significant for the obese/insulin-sensitive (IRR = 1.70; 95% CI: 0.97, 2.99) group.

Conclusions

HOMA-IR can further stratify diabetes risk in AA adults beyond obesity, identifying non-obese high-risk and lower-risk obese individuals. However, diabetes risk should still be carefully monitored in obese populations despite insulin sensitivity.

SUBMITTER: Lee S

PROVIDER: S-EPMC6909037 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Association between obesity phenotypes of insulin resistance and risk of type 2 diabetes in African Americans: The Jackson Heart Study.

Lee Sean S Lacy Mary E ME Jankowich Mathew M Correa Adolfo A Wu Wen-Chih WC

Journal of clinical & translational endocrinology 20191120

<h4>Objective</h4>To determine whether insulin resistance (IR) measured by homeostasis model of insulin resistance (HOMA-IR) can further stratify diabetes risk in African Americans (AAs) beyond obesity and identify obese, low risk and non-obese, high risk individuals.<h4>Methods</h4>Using the Jackson Heart Study cohort, we categorized participants without diabetes into four phenotypes: non-obese/insulin-sensitive, non-obese/IR, obese/insulin-sensitive and obese/IR. Obesity was defined as BMI ≥ 3 ...[more]

PMID: 31871895

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Project description:Genome-wide association analysis in populations of European descent has recently found more than a hundred genetic variants affecting risk for common disease. An open question, however, is how relevant the variants discovered in Europeans are to other populations. To address this problem for cardiovascular phenotypes, we studied a cohort of 4,464 African Americans from the Jackson Heart Study (JHS), in whom we genotyped both a panel of 12 recently discovered genetic variants known to predict lipid profile levels in Europeans and a panel of up to 1,447 ancestry informative markers allowing us to determine the African ancestry proportion of each individual at each position in the genome. Focusing on lipid profiles -- HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglycerides (TG) -- we identified the lipoprotein lipase (LPL) locus as harboring variants that account for interethnic variation in HDL-C and TG. In particular, we identified a novel common variant within LPL that is strongly associated with TG (p = 2.7 x 10(-6)) and explains nearly 1% of the variability in this phenotype, the most of any variant in African Americans to date. Strikingly, the extensively studied "gain-of-function" S447X mutation at LPL, which has been hypothesized to be the major determinant of the LPL-TG genetic association and is in trials for human gene therapy, has a significantly diminished strength of biological effect when it is found on a background of African rather than European ancestry. These results suggest that there are other, yet undiscovered variants at the locus that are truly causal (and are in linkage disequilibrium with S447X) or that work synergistically with S447X to modulate TG levels. Finally, we find systematically lower effect sizes for the 12 risk variants discovered in European populations on the African local ancestry background in JHS, highlighting the need for caution in the use of genetic variants for risk assessment across different populations.

Dataset Information

Association between obesity phenotypes of insulin resistance and risk of type 2 diabetes in African Americans: The Jackson Heart Study.

Objective

Methods

Results

Conclusions

Publications

Association between obesity phenotypes of insulin resistance and risk of type 2 diabetes in African Americans: The Jackson Heart Study.

Similar Datasets

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