Rooney Mary R, Wallace Amelia S, Echouffo Tcheugui Justin B, Fang Michael, Hu Jiaqi, Lutsey Pamela L, Grams Morgan E, Coresh Josef, Selvin Elizabeth
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Welch Center for Prevention, Epidemiology, & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Diabetologia. 2025 Feb;68(2):357-366. doi: 10.1007/s00125-024-06315-0. Epub 2024 Nov 12.
AIMS/HYPOTHESIS: Prediabetes (HbA 39-47 mmol/mol [5.7-6.4%] or fasting glucose 5.6-6.9 mmol/l) is associated with elevated risks of microvascular and macrovascular complications. It is unknown to what extent these risks in prediabetes remain after accounting for progression to diabetes.
In 10,310 participants from the Atherosclerosis Risk in Communities (ARIC) Study (aged 46-70 years, ~55% women, ~20% Black adults) without diabetes at baseline (1990-1992), we used Cox regression to characterise age- and sex-adjusted associations of prediabetes with ~30 year incidence of complications (composite and separately), including atherosclerotic CVD (ASCVD), heart failure, chronic kidney disease (CKD) and all-cause mortality before and after accounting for intervening incidence of diabetes, modelled as a time-varying variable. We calculated the excess risk of complications in prediabetes remaining after accounting for progression to diabetes.
Of the 60% of adults with prediabetes at baseline, ~30% progressed to diabetes (median time to diabetes, 7 years). Over the maximum follow-up of ~30 years, there were 7069 events (1937 ASCVD, 2109 heart failure, 3288 CKD and 4785 deaths). Prediabetes was modestly associated with risk of any complication (HR 1.21 [95% CI 1.15, 1.27]) vs normoglycaemia. This association remained significant after accounting for progression to diabetes (HR 1.18 [95% CI 1.12, 1.24]) with 85% (95% CI 75, 94%) of the excess risk of any complication in prediabetes remaining. Results were similar for the individual complications.
CONCLUSIONS/INTERPRETATION: Progression to diabetes explained less than one-quarter of the risks of clinical outcomes associated with prediabetes. Prediabetes contributes to the risk of clinical outcomes even without progression to diabetes.
目的/假设：糖尿病前期（糖化血红蛋白39 - 47 mmol/mol[5.7 - 6.4%]或空腹血糖5.6 - 6.9 mmol/l）与微血管和大血管并发症风险升高相关。在考虑进展为糖尿病的因素后，糖尿病前期的这些风险在多大程度上仍然存在尚不清楚。
在社区动脉粥样硬化风险（ARIC）研究的10310名参与者中（年龄46 - 70岁，约55%为女性，约20%为黑人成年人），他们在基线时（1990 - 1992年）无糖尿病，我们使用Cox回归来描述糖尿病前期与约30年并发症发生率（综合及分别计算）的年龄和性别调整后的关联，包括动脉粥样硬化性心血管疾病（ASCVD）、心力衰竭、慢性肾脏病（CKD）以及在考虑糖尿病的干预发生率（作为一个随时间变化的变量进行建模）前后的全因死亡率。我们计算了在考虑进展为糖尿病的因素后糖尿病前期并发症的额外风险。
在基线时患有糖尿病前期的60%成年人中，约30%进展为糖尿病（糖尿病的中位时间为7年）。在最长约30年的随访中，有7069例事件（1937例ASCVD、2109例心力衰竭、3288例CKD和4785例死亡）。与血糖正常者相比，糖尿病前期与任何并发症风险存在适度关联（风险比1.21[95%置信区间1.15, 1.27]）。在考虑进展为糖尿病的因素后，这种关联仍然显著（风险比1.18[95%置信区间1.12, 1.24]），糖尿病前期任何并发症的额外风险中有85%（95%置信区间75, 94%）仍然存在。个体并发症的结果相似。
结论/解读：进展为糖尿病所解释的糖尿病前期相关临床结局风险不到四分之一。即使不进展为糖尿病，糖尿病前期也会增加临床结局的风险。
