Huang Yao, Dou Xiuping, He Man, Su Yang, Lin Hualiang, Yang Yin
Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
Int J Mol Sci. 2025 Aug 14;26(16):7855. doi: 10.3390/ijms26167855.
Although the single nucleotide polymorphism rs10830963 has been strongly associated with the onset of type 2 diabetes (T2D), its association with the progression and prognosis of T2D has been understudied. We conducted this prospective analysis based on the UK Biobank cohort study. Microvascular complications (MIC) of T2D in this study included diabetic retinopathy, diabetic neuropathy, and diabetic kidney disease. Macrovascular complications (MAC) of T2D included diabetic coronary artery disease, diabetic cerebrovascular disease, and diabetic peripheral vascular disease. The multi-state model was used to analyze the association between the polymorphism of rs10830963 and the trajectory of T2D. The accelerated failure time (AFT) model was used to assess the association between rs10830963 and the onset of T2D and T2D comorbidities. A total of 283,531 middle- and old-age participants were included. During a median follow-up of 13.7 years, 11,947 participants developed T2D, 1556 participants developed MIC, 1797 participants developed MAC, and 618 participants died. In the additive model, the G risk allele of rs10830963 was significantly associated with an increased risk of the transition from T2D-free to T2D (HR = 1.050, 95% CI: 1.020, 1.079) and a decreased risk of the transition from T2D to MIC (HR = 0.918, 95% CI: 0.850, 0.992), particularly from T2D to diabetic retinopathy (HR = 0.882, 95% CI: 0.782, 0.995). Besides, the G risk allele of rs10830963 accelerated the transition from T2D-free to T2D (Time Ratio [TR] = 0.966, 95% CI: 0.947, 0.986) and slowed down the transition from T2D to MIC (TR = 1.067, 95% CI: 1.030, 1.105). The single nucleotide polymorphism rs10830963 was associated with an increased risk of T2D and a decreased risk of MIC, particularly diabetic retinopathy among T2D individuals. Our results highlight that rs10830963 might play differential roles in the onset and progression of T2D.
尽管单核苷酸多态性rs10830963与2型糖尿病（T2D）的发病密切相关，但其与T2D进展及预后的关联研究较少。我们基于英国生物银行队列研究进行了这项前瞻性分析。本研究中T2D的微血管并发症（MIC）包括糖尿病视网膜病变、糖尿病神经病变和糖尿病肾病。T2D的大血管并发症（MAC）包括糖尿病冠状动脉疾病、糖尿病脑血管疾病和糖尿病周围血管疾病。采用多状态模型分析rs10830963多态性与T2D病程的关联。采用加速失效时间（AFT）模型评估rs10830963与T2D发病及T2D合并症的关联。共纳入283,531名中老年参与者。在中位随访13.7年期间，11,947名参与者患T2D，1556名参与者发生MIC，1797名参与者发生MAC，618名参与者死亡。在加性模型中，rs10830963的G风险等位基因与从无T2D转变为T2D的风险增加显著相关（HR = 1.050，95%CI：1.020，1.079），而与从T2D转变为MIC的风险降低相关（HR = 0.918，95%CI：0.850，0.992），尤其是从T2D转变为糖尿病视网膜病变（HR = 0.882，95%CI：0.782，0.995）。此外，rs10830963的G风险等位基因加速了从无T2D到T2D的转变（时间比[TR] = 0.966，95%CI：0.947，0.986），并减缓了从T2D到MIC的转变（TR = 1.067，95%CI：1.030，1.105）。单核苷酸多态性rs10830963与T2D风险增加及MIC风险降低相关，尤其是T2D个体中的糖尿病视网膜病变。我们的结果表明，rs10830963可能在T2D的发病和进展中发挥不同作用。
