Diabetes Susceptibility Polymorphisms and Risk of Prediabetes and Diabetes Complications in the Atherosclerosis Risk in Communities (ARIC) Study Public Deposited

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  • March 20, 2019
Creator
  • Yan, Yu
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Transcription factor 7-like 2 (TCF7L2) has emerged as a consistently replicated susceptibility gene for type 2 diabetes, however, its association with prediabetes as quantified by impaired fasting glucose (IFG), and diabetes complications such as retinopathy has not been well characterized in population-based studies. Thus, we investigated the association between the TCF7L2 rs7903146 polymorphism and two types of diabetes-related outcomes, IFG and retinal microvascular signs, in the Atherosclerosis Risk in Communities cohort. The incident IFG analysis was conducted among 1,377 African American and 5,152 Caucasian participants without diabetes and IFG at baseline. IFG was defined as fasting glucose levels of 100-125 mg/dl. After adjusted for age, sex, and study center, the rs7903146 T risk allele was significantly associated with higher risk of IFG over 9 years of follow-up in Caucasians. Moreover, the association was stronger in Caucasians with obesity or high triglycerides. No association of the rs7903146 polymorphism and incident IFG was noted in African Americans, although we had limited power to assess this association. We also evaluated the association between the rs7903146 polymorphism and retinal microvascular signs in 2,199 African American and 8,121 Caucasian participants in the ARIC cohort. After adjusting for age, sex, study center, and other covariates, TCF7L2 rs7903146 T risk allele was associated with increased risk of focal arteriolar narrowing in Caucasians with hypertension or without diabetes. No significant association of the rs7903146 polymorphism and retinal vascular signs was noted among African American individuals, although, again, we were limited in power to detect these associations. In summary, our study replicates the association between the rs7903146 polymorphism and IFG risk in Caucasians and provides new evidence for interactions between TCF7L2 and metabolic risk factors on the occurrence of IFG in Caucasians. Moreover, our study is the first to report an association with focal arteriolar narrowing in Caucasians with hypertension or without diabetes. Our study results contribute knowledge about the etiology of type 2 diabetes, and could be important for public health initiatives to encourage lifestyle changes in patients at risk of diabetes. Further research in other larger population-based studies will be needed to replicate our results.
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  • North, Kari
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