Bui Thu Hien, Kaga Hideyoshi, Kakehi Saori, Someya Yuki, Tabata Hiroki, Yoshizawa Yasuyo, Naito Hitoshi, Tajima Tsubasa, Ito Naoaki, Kadowaki Satoshi, Nishida Yuya, Kawamori Ryuzo, Watada Hirotaka, Tamura Yoshifumi
Department of Metabolism and Endocrinology, Sportology Center, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan.
Sports Medicine and Sportology, Sportology Center, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan.
J Endocr Soc. 2025 Jan 28;9(2):bvaf019. doi: 10.1210/jendso/bvaf019. eCollection 2025 Jan 6.
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.
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.
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.
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.
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.
全基因组关联研究已经确定了许多与2型糖尿病（T2D）相关的单核苷酸变异（SNV，以前称为单核苷酸多态性），从而提高了遗传风险评分（GRS）预测T2D的准确性。
本研究旨在调查新型GRS与T2D患病率之间的关联，并阐明区分具有相似遗传风险的T2D患者和非T2D患者的特征。
这项横断面研究分析了1610名年龄在65至84岁之间的日本个体。使用与日本人群中T2D相关的110个SNV计算GRS，并将个体分为T2D低、中、高风险组。在每个风险水平下，按性别比较糖尿病患者和非糖尿病患者的特征。
低、中、高风险水平的T2D患病率分别为7.8%、14.7%和16.7%。即使在调整混杂因素后，高风险和中风险水平的比值比仍显著高于低风险水平。在所有风险水平上，糖尿病组的内脏脂肪面积（VFA）和胰岛素抵抗稳态模型评估（HOMA-IR）值均高于非糖尿病组，但胰岛素生成指数较低。在非糖尿病组中，随着GRS的增加，胰岛素生成指数显著降低，但HOMA-IR和松田指数值无相关性。在患有糖尿病的男性中，VFA往往随着GRS的升高而降低。
较高的GRS与老年日本个体中T2D患病率的增加显著相关。我们的数据表明，VFA对糖尿病发展的影响因遗传风险而异。
