Clinical Research Unit, Khoo Teck Puat Hospital, 768828 Singapore.
Diabetes Centre, Admiralty Medical Centre, 730676 Singapore.
Diabetes Metab. 2021 Nov;47(6):101238. doi: 10.1016/j.diabet.2021.101238. Epub 2021 Feb 23.
To study the relationship between genetic risk of beta cell dysfunction, young onset age and glycaemic progression in individuals with type 2 diabetes (T2D).
1385 T2D outpatients were included in cross-sectional sub-study and 730 insulin-naïve outpatients were followed for 3 years in prospective sub-study. Genetic risk score (GRS) was derived from 24 beta cell dysfunction-related single nucleotide polymorphisms, with lower and upper 25 percentiles defined as low and high genetic risk. Glycaemic progression was defined as requirement for sustained insulin therapy.
388 participants in cross-sectional and 128 in prospective sub-study experienced glycaemic progression. Young onset age (T2D diagnosis below 40 year-old) was associated with high risk of glycaemic progression as compared to usual-onset counterparts (adjusted OR 1.64 [95% CI 1.14-2.36], and 2.92 [95% CI 1.76-4.87] in cross-sectional and prospective sub-study, respectively). As compared to those with intermediate risk, a low GRS was associated with lower risk for glycaemic progression (adjusted OR 0.72 [95% CI 0.49-1.06], and 0.51 [95% CI 0.29-0.90]) whereas a high GRS was not significantly associated with glycaemic progression. Notably, the association of young-onset T2D with high risk of glycaemic progression was independent of known clinical risk factors and beta cell dysfunction GRS (P interaction > 0.10).
Young onset age and low genetic risk of beta cell dysfunction are independently associated with risk of glycaemic progression. Our data do not support that genetic risk modulates the risk of glycaemic progression in individuals with young-onset T2D.
研究 2 型糖尿病（T2D）患者β细胞功能障碍的遗传风险、发病年龄早和血糖进展之间的关系。
纳入了 1385 名 T2D 门诊患者进行横断面亚研究，730 名新诊断为 T2D 的且未接受胰岛素治疗的门诊患者进行了前瞻性亚研究。遗传风险评分（GRS）是由 24 个与β细胞功能障碍相关的单核苷酸多态性衍生而来，将最低和最高 25%的 GRS 定义为低和高遗传风险。血糖进展定义为需要持续胰岛素治疗。
横断面亚研究中有 388 名患者和前瞻性亚研究中有 128 名患者发生了血糖进展。与常规发病的患者相比，发病年龄早（T2D 诊断年龄<40 岁）与高血糖进展风险相关（横断面亚研究和前瞻性亚研究中的校正比值比分别为 1.64[95%可信区间 1.14-2.36]和 2.92[95%可信区间 1.76-4.87]）。与中危患者相比，低 GRS 与较低的血糖进展风险相关（校正比值比分别为 0.72[95%可信区间 0.49-1.06]和 0.51[95%可信区间 0.29-0.90]），而高 GRS 与血糖进展无显著相关性。值得注意的是，T2D 发病年龄早与血糖进展高风险之间的关系独立于已知的临床危险因素和β细胞功能障碍 GRS（P 交互作用>0.10）。
发病年龄早和β细胞功能障碍的低遗传风险与血糖进展风险独立相关。我们的数据不支持遗传风险调节早发 T2D 患者血糖进展风险。
