Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, OH, 44195, USA.
Hum Genomics. 2024 Jun 22;18(1):70. doi: 10.1186/s40246-024-00639-z.
We previously identified a genetic subtype (C4) of type 2 diabetes (T2D), benefitting from intensive glycemia treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Here, we characterized the population of patients that met the C4 criteria in the UKBiobank cohort.
Using our polygenic score (PS), we identified C4 individuals in the UKBiobank and tested C4 status with risk of developing T2D, cardiovascular disease (CVD) outcomes, and differences in T2D medications.
C4 individuals were less likely to develop T2D, were slightly older at T2D diagnosis, had lower HbA1c values, and were less likely to be prescribed T2D medications (P < .05). Genetic variants in MAS1 and IGF2R, major components of the C4 PS, were associated with fewer overall T2D prescriptions.
We have confirmed C4 individuals are a lower risk subpopulation of patients with T2D.
我们之前确定了 2 型糖尿病（T2D）的一种遗传亚型（C4），在糖尿病心血管风险控制行动（ACCORD）试验中，该亚型从强化血糖治疗中获益。在此，我们在 UKBiobank 队列中对符合 C4 标准的患者人群进行了特征描述。
我们使用多基因评分（PS）在 UKBiobank 中确定了 C4 个体，并检测了 C4 状态与 T2D 发病风险、心血管疾病（CVD）结局以及 T2D 药物治疗差异之间的关系。
C4 个体发生 T2D 的可能性较低，T2D 诊断时年龄稍大，HbA1c 值较低，并且不太可能开 T2D 药物（P < 0.05）。C4 PS 的主要成分 MAS1 和 IGF2R 中的遗传变异与总体 T2D 处方数量减少有关。
我们已经证实 C4 个体是 T2D 患者的低风险亚人群。
