UNASSIGNED: We examined trajectories of tubular biomarkers in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC Study) of type 1 diabetes (T1D). Biomarkers were measured in a subset of 220 participants across 7 time points over 26 years. Measurements included the following: kidney injury molecule 1 (KIM-1), soluble tumor necrosis factor 1 (sTNFR1) in serum or plasma, epidermal growth factor (EGF), monocyte chemoattractant protein-1 (MCP1) in timed urine, and a composite tubular secretion score. We described biomarker trajectories and examined how these were affected by intensive glucose-lowering therapy and glycemia.
UNASSIGNED: At baseline, participants had a mean age of 28 years, 45% were women, and 50% were assigned to intensive glucose-lowering therapy. The mean estimated glomerular filtration rate (eGFR) was 125 ml/min per 1.73 m2 and 90% of participants had a urinary albumin excretion rate (AER) <30 mg/24h. Mean changes in biomarkers over time (percent/decade) were: KIM-1: 27.3% (95% confidence interval [CI]: 21.4-33.5), sTNFR1: 16.9% (14.5-19.3), MCP1: 18.4% (8.9-28.8), EGF: -13.5% (-16.7 to -10.1), EGF-MCP1 ratio: -26.9% (-32.2 to -21.3), and tubular secretion score -0.9% (-1.8 to 0.0), versus -12.0% (CI: -12.9 to -11.1) for eGFR and 10.9% (2.5-20.1) for AER. Intensive versus conventional glucose-lowering therapy was associated with slower increase in sTNFR1 (relative difference in change: 0.94 [0.90-0.98]). Higher HbA1c was associated with faster increases in sTNFR1 (relative difference in change: 1.06 per 1% higher HbA1c [1.05-1.08]) and KIM-1 (1.09 [1.05-1.14]).
UNASSIGNED: Among participants with T1D and normal eGFR at baseline, kidney tubular biomarkers changed significantly over long-term follow-up. Hyperglycemia was associated with larger increases in serum or plasma sTNFR1 and KIM-1, when followed-up longitudinally.
■我们检查了1型糖尿病(T1D)的糖尿病控制和并发症试验以及糖尿病干预和并发症流行病学研究(DCCT/EDIC研究)中肾小管生物标志物的轨迹。在26年的7个时间点,对220名参与者的子集中的生物标志物进行了测量。测量包括:肾损伤分子1(KIM-1),血清或血浆中的可溶性肿瘤坏死因子1(sTNFR1),表皮生长因子(EGF),定时尿液中的单核细胞趋化蛋白-1(MCP1),和复合肾小管分泌评分。我们描述了生物标志物的轨迹,并检查了这些轨迹如何受到强化降糖治疗和血糖的影响。
■在基线时,参与者的平均年龄为28岁,45%是女性,50%被分配到强化降糖治疗.平均估计肾小球滤过率(eGFR)为每1.73m2125ml/min,90%的参与者尿白蛋白排泄率(AER)<30mg/24h。生物标志物随时间的平均变化(百分比/十年)为:KIM-1:27.3%(95%置信区间[CI]:21.4-33.5),sTNFR1:16.9%(14.5-19.3),MCP1:18.4%(8.9-28.8),EGF:-13.5%(-16.7至-10.1),EGF-MCP1比率:-26.9%(-32.2至-21.3),和肾小管分泌评分-0.9%(-1.8至0.0),eGFR为-12.0%(CI:-12.9至-11.1),AER为10.9%(2.5-20.1)。强化降糖治疗与常规降糖治疗相比,sTNFR1增加较慢(变化的相对差异:0.94[0.90-0.98])。较高的HbA1c与sTNFR1的较快增加相关(变化的相对差异:HbA1c每1%升高1.06[1.05-1.08])和KIM-1(1.09[1.05-1.14])。
■在基线时具有T1D和正常eGFR的参与者中,肾小管生物标志物在长期随访期间发生显著变化.纵向随访时,高血糖与血清或血浆sTNFR1和KIM-1的增加有关。