METHODS: Fructosamine, advanced glycation end products (AGEs), and methylglyoxal-modified hydro-imidazolone (MG-H1) were measured from baseline serum samples in the FinnDiane study (n = 575). Kidney disease progression was defined as steep eGFR decline (> 3 mL/min/1.73 m2/year) or progression of albuminuria (from lower to higher stage of albuminuria). MACE was defined as acute myocardial infarction, coronary revascularization, cerebrovascular event (stroke), and cardiovascular death.
RESULTS: Fructosamine was independently associated with steep eGFR decline (OR 2.15 [95% CI 1.16-4.01], p = 0.016) in the fully adjusted model (age, sex, baseline eGFR). AGEs were associated with steep eGFR decline (OR 1.58 per 1 unit of SD [95% CI 1.07-2.32], p = 0.02), progression to end-stage kidney disease (ESKD) (HR 2.09 per 1 unit of SD [95% CI 1.43-3.05], p < 0.001), and pooled progression (to any stage of albuminuria) (HR 2.72 per 1 unit of SD [95% CI 2.04-3.62], p < 0.001). AGEs (HR 1.57 per 1 unit of SD [95% CI 1.23-2.00], p < 0.001) and MG-H1 (HR 4.99 [95% CI 0.98-25.55], p = 0.054) were associated with incident MACE. MG-H1 was also associated with pooled progression (HR 4.19 [95% CI 1.11-15.89], p = 0.035). Most AGEs and MG-H1 associations were no more significant after adjusting for baseline eGFR.
CONCLUSIONS: Overall, these findings suggest that protein glycation products are an important risk factor for target organ damage in type 1 diabetes. The data provide further support to investigate a potential causal role of serum protein glycation in the progression of diabetes complications.
方法:果糖胺,糖基化终产物(AGEs),和甲基乙二醛修饰的氢咪唑酮(MG-H1)从FinnDiane研究中的基线血清样品中测量(n=575)。肾脏疾病进展定义为eGFR急剧下降(>3mL/min/1.73m2/年)或蛋白尿进展(从低至高蛋白尿阶段)。MACE定义为急性心肌梗死,冠状动脉血运重建,脑血管事件(中风),心血管死亡。
结果:果糖胺与eGFR急剧下降独立相关(OR2.15[95%CI1.16-4.01],p=0.016)在完全调整的模型中(年龄,性别,基线eGFR)。AGEs与eGFR急剧下降相关(每1单位标准差为1.58[95%CI1.07-2.32],p=0.02),进展为终末期肾病(ESKD)(每1单位SD的HR2.09[95%CI1.43-3.05],p<0.001),合并进展(至任何阶段的白蛋白尿)(每1单位SDHR2.72[95%CI2.04-3.62],p<0.001)。年龄(每1单位标准差为1.57HR[95%CI1.23-2.00],p<0.001)和MG-H1(HR4.99[95%CI0.98-25.55],p=0.054)与事件性MACE相关。MG-H1也与合并进展相关(HR4.19[95%CI1.11-15.89],p=0.035)。调整基线eGFR后,大多数AGEs和MG-H1关联没有更显著。
结论:总体而言,这些发现表明,蛋白质糖基化产物是1型糖尿病靶器官损害的重要危险因素。这些数据为研究血清蛋白糖基化在糖尿病并发症进展中的潜在因果作用提供了进一步的支持。