Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
J Diabetes Investig. 2023 Apr;14(4):503-515. doi: 10.1111/jdi.13970. Epub 2023 Jan 14.
Type 2 diabetes results from a complex interaction between genetic and environmental factors. Precision medicine for type 2 diabetes using genetic data is expected to predict the risk of developing diabetes and complications and to predict the effects of medications and life-style intervention more accurately for individuals. Genome-wide association studies (GWAS) have been conducted in European and Asian populations and new genetic loci have been identified that modulate the risk of developing type 2 diabetes. Novel loci were discovered by GWAS in diabetic complications with increasing sample sizes. Large-scale genome-wide association analysis and polygenic risk scores using biobank information is making it possible to predict the development of type 2 diabetes. In the ADVANCE clinical trial of type 2 diabetes, a multi-polygenic risk score was useful to predict diabetic complications and their response to treatment. Proteomics and metabolomics studies have been conducted and have revealed the associations between type 2 diabetes and inflammatory signals and amino acid synthesis. Using multi-omics analysis, comprehensive molecular mechanisms have been elucidated to guide the development of targeted therapy for type 2 diabetes and diabetic complications.
2 型糖尿病是遗传和环境因素复杂相互作用的结果。利用遗传数据进行 2 型糖尿病精准医学有望更准确地预测个体发生糖尿病和并发症的风险，并预测药物和生活方式干预的效果。全基因组关联研究（GWAS）已在欧洲和亚洲人群中进行，发现了新的遗传位点，这些遗传位点调节 2 型糖尿病的发病风险。随着样本量的增加，GWAS 发现了新的与糖尿病并发症相关的遗传位点。利用生物库信息进行大规模全基因组关联分析和多基因风险评分，使得预测 2 型糖尿病的发生成为可能。在 2 型糖尿病 ADVANCE 临床试验中，多基因风险评分有助于预测糖尿病并发症及其对治疗的反应。还进行了蛋白质组学和代谢组学研究，揭示了 2 型糖尿病与炎症信号和氨基酸合成之间的关联。通过多组学分析，阐明了综合分子机制，为 2 型糖尿病和糖尿病并发症的靶向治疗的发展提供了指导。
