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Heterogeneity in effects of genetically determined adiposity on insulin resistance and type 2 diabetes: The atherosclerosis risk in communities study.

ABSTRACT: BACKGROUND:A recent genome-wide association study has identified 12 genetic variants robustly associated with body fat percentage (BF%) with diverse cardiometabolic consequences. We developed three genetic risk scores (GRSs) according to the associations of the 12 individual variants with type 2 diabetes (T2D) and test the GRSs' associations with insulin resistance and T2D in the Atherosclerosis Risk in Communities Study. METHODS:In 6895 European-American participants, we calculated GRS-I as the number of BF%-increasing alleles from variants associated with increased risk of T2D, GRS-D from variants associated with decreased risk of T2D, and GRS-ALL from all 12 variants. Linear and logistic regression models were used to evaluate associations of the GRSs with insulin resistance and risk of T2D, respectively, adjusted for age, sex, smoking, and drinking, and additionally for body mass index (BMI). RESULTS:GRS-D was significantly associated with decreased levels of fasting insulin (P?=?0.014) and homeostasis assessment of insulin resistance (P?=?0.023). While GRS-I was not associated with insulin resistance measures, it was with T2D (P?=?0.002). Further adjustment for BMI did not substantially change the above associations. GRS-ALL was inversely associated with insulin resistance after controlling for covariates including BMI; GRS-ALL was not associated with T2D. CONCLUSION:Genetically determined BF% has differential effects on cardiometabolic risk, which may partly explain the heterogeneity in obesity-induced cardiometabolic risk and have implications for developing new strategies mitigating obesity-induced cardiometabolic consequences.

SUBMITTER: Liu T

PROVIDER: S-EPMC5820121 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Heterogeneity in effects of genetically determined adiposity on insulin resistance and type 2 diabetes: The atherosclerosis risk in communities study.

Liu Tingting T Li Changwei C Shen Luqi L Shen Ye Y Mao Weibo W Li Shengxu S

Journal of diabetes and its complications 20180103 3

<h4>Background</h4>A recent genome-wide association study has identified 12 genetic variants robustly associated with body fat percentage (BF%) with diverse cardiometabolic consequences. We developed three genetic risk scores (GRSs) according to the associations of the 12 individual variants with type 2 diabetes (T2D) and test the GRSs' associations with insulin resistance and T2D in the Atherosclerosis Risk in Communities Study.<h4>Methods</h4>In 6895 European-American participants, we calculat ...[more]

PMID: 29395842

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Project description:IntroductionTobacco use is associated with insulin resistance and incident diabetes. Given the racial/ethnic differences in smoking patterns and incident type 2 diabetes our objective was to evaluate the association between tobacco use and insulin resistance (IR) as well as incident type 2 diabetes mellitus in a contemporary multiethnic cohort.Methods and resultsWe studied 5,931 Multi- Ethnic Study of Atherosclerosis (MESA) participants who at baseline were free of type 2 diabetes (fasting glucose ≥7.0 mmol/l (126 mg/dl) and/or use of insulin or oral hypoglycemic medications) categorized by self-reported tobacco status and reclassified by urinary cotinine (available in 58% of participants) as never, current or former tobacco users. The association between tobacco use, IR (fasting plasma glucose, insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR)) and incident diabetes over 10 years was evaluated using multivariable linear regression and Cox proportional hazards models, respectively. Mean age of the participants was 62 (±10) years, 46% were male, 41% Caucasian, 12% Chinese, 26% African American and 21% Hispanic/Latino. IR biomarkers did not significantly differ between current, former, and never cigarette users (P >0.10) but showed limited unadjusted differences for users of cigar, pipe and smokeless tobacco (All P <0.05). Fully adjusted models showed no association between dose or intensity of tobacco exposure and any index of IR. When stratified into participants that quit smoking vs. those who continued smoking during the 10-year study there was no difference in serum glucose levels or frequency of diabetes. In fully adjusted models, there was no significant difference in diabetes risk between former or current cigarette smokers compared to never smokers [HR (95% CI) 1.02 (0.77,1.37) and 0.81 (0.52,1.26) respectively].ConclusionIn a contemporary multi-ethnic cohort, there was no independent association between tobacco use and IR or incident type 2 diabetes. The role smoking plays in causing diabetes may be more complicated than originally thought and warrants more in-depth large contemporary multi-ethnic studies.

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Heterogeneity in effects of genetically determined adiposity on insulin resistance and type 2 diabetes: The atherosclerosis risk in communities study.

Publications

Heterogeneity in effects of genetically determined adiposity on insulin resistance and type 2 diabetes: The atherosclerosis risk in communities study.

Similar Datasets

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