Kristensen Frederik P B, Domazet Sidsel L, Nielsen Jens S, Stidsen Jacob V, Højlund Kurt, Beck-Nielsen Henning, Vestergaard Peter, Jessen Niels, Olsen Michael H, Hansen Torben, Brøns Charlotte, Vaag Allan, Sørensen Henrik T, Thomsen Reimar W
Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark.
Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark.
Diabetologia. 2025 Mar;68(3):576-587. doi: 10.1007/s00125-024-06342-x. Epub 2024 Dec 11.
AIMS/HYPOTHESIS: A better understanding of the mechanisms underlying an elevated infection risk in individuals with type 2 diabetes is needed to guide risk stratification and prevention. We investigated the risk of infection in subgroups of individuals with type 2 diabetes according to indices of insulin sensitivity and beta cell function.
We classified 7265 individuals with recently diagnosed type 2 diabetes (median duration 1.4 years, IQR 0.5-2.9 years) into hyperinsulinaemic (high beta cell function [HOMA 2-beta-cell function, HOMA2-B], low insulin sensitivity [HOMA 2-insulin sensitivity, HOMA2-S]), classical (low HOMA2-B, low HOMA2-S) and insulinopenic (low HOMA2-B, high HOMA2-S) type 2 diabetes. Individuals were followed until first hospital-treated infection or first prescription for an anti-infective agent (community-treated infection). We used Cox regression analysis to estimate HRs adjusted for age, sex, index year, diabetes duration and treatment, lifestyle behaviours and comorbidities.
Among study participants, 28% had hyperinsulinaemic, 63% had classical and 9% had insulinopenic type 2 diabetes. The 10 year risks of hospital-treated infections were 42.3%, 36.8% and 31.0% in the three subgroups, respectively. Compared with the insulinopenic subgroup, adjusted HRs for hospital-treated infections were elevated for hyperinsulinaemic (1.38 [95% CI 1.16, 1.65]) and classical type 2 diabetes (1.20 [95% CI 1.02, 1.42]). The 10 year risks of community-treated infections were high in all three subgroups at 91.6%, 90.1% and 88.3%, respectively, corresponding to adjusted HRs of 1.20 (95% CI 1.08, 1.33) for the hyperinsulinaemic and 1.10 (95% CI 1.00, 1.21) for the classical subgroup. Infection risk in the hyperinsulinaemic subgroup decreased substantially when further adjusted for abdominal obesity, metabolic derangements and low-grade inflammation.
CONCLUSIONS/INTERPRETATION: The risk of severe infections is clearly elevated in individuals with type 2 diabetes characterised by a higher degree of insulin resistance/hyperinsulinaemia.
目的/假设：为了指导风险分层和预防，需要更好地理解2型糖尿病患者感染风险升高的潜在机制。我们根据胰岛素敏感性和β细胞功能指标，研究了2型糖尿病亚组人群的感染风险。
我们将7265例新诊断的2型糖尿病患者（中位病程1.4年，四分位间距0.5 - 2.9年）分为高胰岛素血症型（高β细胞功能[稳态模型评估2 - β细胞功能，HOMA2 - B]，低胰岛素敏感性[稳态模型评估2 - 胰岛素敏感性，HOMA2 - S]）、经典型（低HOMA2 - B，低HOMA2 - S）和胰岛素缺乏型（低HOMA2 - B，高HOMA2 - S）2型糖尿病。对患者进行随访，直至首次因感染住院治疗或首次开具抗感染药物处方（社区治疗的感染）。我们使用Cox回归分析来估计经年龄、性别、索引年份、糖尿病病程和治疗、生活方式行为及合并症校正后的风险比（HR）。
在研究参与者中，28%为高胰岛素血症型，63%为经典型，9%为胰岛素缺乏型2型糖尿病。三个亚组中因感染住院治疗的10年风险分别为42.3%、36.8%和31.0%。与胰岛素缺乏型亚组相比，高胰岛素血症型（1.38[95%置信区间1.16，1.65]）和经典型2型糖尿病（1.20[95%置信区间1.02，1.42]）因感染住院治疗的校正后HR升高。三个亚组中社区治疗感染的10年风险均较高，分别为91.6%、90.1%和88.3%，高胰岛素血症型亚组的校正后HR为1.20（95%置信区间1.08，1.33），经典型亚组为1.10（95%置信区间1.00，1.21）。当进一步调整腹部肥胖、代谢紊乱和低度炎症后，高胰岛素血症型亚组的感染风险大幅降低。
结论/解读：以胰岛素抵抗/高胰岛素血症程度较高为特征的2型糖尿病患者发生严重感染的风险明显升高。
