Factors Associated With Type 2 Diabetes in Older Japanese With Similar Genetic Risk Scores: The Bunkyo Health Study.

Abstract

Context: Genome-wide association studies have identified numerous single-nucleotide variations (SNVs, formerly single-nucleotide polymorphisms) linked to type 2 diabetes (T2D), thus improving the accuracy of genetic risk scores (GRS) in predicting T2D.

Objective: This study aimed to investigate the association between the novel GRS and the prevalence of T2D and clarify the characteristics that differentiate individuals with and without T2D with similar genetic risk.

Methods: This cross-sectional study analyzed 1610 Japanese individuals aged 65 to 84 years. GRS were calculated using 110 SNVs associated with T2D in Japanese, and GRS classified individuals as having low, average, or high risk for T2D. The characteristics of participants with or without diabetes were compared by sex at each risk level.

Results: The prevalences of T2D were 7.8%, 14.7%, and 16.7% at low-, average-, and high-risk levels, respectively. The odds ratios at the high- and average-risk levels were significantly higher than those at the low-risk level, even after adjusting for confounding factors. The diabetes group had a higher visceral fat area (VFA) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) value, but a lower insulinogenic index, than the nondiabetes group across all risk levels. In the nondiabetes group, the II decreased significantly as GRS increased, but the HOMA-IR and Matsuda index values showed no association. In men with diabetes, VFA tended to decrease with higher GRS.

Conclusion: A higher GRS was significantly associated with increased T2D prevalence in older Japanese individuals. Our data demonstrated that the contribution of VFA to the development of diabetes varies with genetic risk.