High genetic risk scores for impaired insulin secretory capacity doubles the risk for type 2 diabetes in Asians and is exacerbated by W estern‐type diets

BACKGROUND: Asians have among the highest incidence of type 2 diabetes (T2DM) in the world, partly due to low β-cell function, causing them to rapidly develop T2DM when insulin resistant. This study tested the hypothesis that genetic polymorphisms are responsible for the low β-cell function and that dietary factors interact with the genes to exacerbate their risk of T2DM. METHODS: We selected 10 genetic variants of 5 genes involved in insulin secretion (CDKAL1, KCNQ1, IDE, HHEX, and ABCA1) from the genome-wide association studies to calculate the genetic risk scores (GRSs) in 8842 Korean adults in the Ansan/Ansung cohort in the Korean Genome Epidemiology Study. The genetic risk score were divided into low, medium, and high groups, and the association between T2DM and the genetic risk score was measured using logistic regression. We also analysed the interaction between the genetic risk score and the nutrition intakes. RESULTS: The individual genetic variants were positively associated with T2DM even when adjusted for covariates. Individuals with medium and high genetic risk score had higher T2DM risk by 1.68 and 2.17 folds compared to those with the low genetic risk score after adjusting for covariates. The increased risk was mainly associated with lower HOMA-B, an indicator of insulin secretion capacity, but not HOMA-IR, an indicator of insulin resistance. Subjects with high carbohydrate intakes and a medium genetic risk score did not have a higher risk of T2DM, and the risk was partially mitigated in the high genetic risk score group. CONCLUSION: Seventy-two percent of the Korean population had either medium or high genetic risk scores for impaired insulin secretion, which approximately doubled their risk of type 2 diabetes, and the risk was exacerbated by consuming a low carbohydrate Western-style diets.