Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Diabetes. 2013 Sep;62(9):3218-23. doi: 10.2337/db13-0256. Epub 2013 Jun 12.
Many patients with type 1 diabetes develop renal disease despite moderately good metabolic control, suggesting other risk factors may play a role. Recent evidence suggests that the haptoglobin (HP) 2-2 genotype, which codes for a protein with reduced antioxidant activity, may predict renal function decline in type 1 diabetes. We examined this hypothesis in 1,303 Caucasian participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. HP genotype was determined by polyacrylamide gel electrophoresis. Glomerular filtration rate was estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and albumin excretion based on timed urine samples. Participants were followed up for a mean of 22 years. HP genotype was significantly associated with the development of sustained estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) and with end-stage renal disease (ESRD), with HP 2-2 having greater risk than HP 2-1 and 1-1. No association was seen with albuminuria. Although there was no treatment group interaction, the associations were only significant in the conventional treatment group, where events rates were much higher. We conclude that the HP genotype is significantly associated with the development of reduced GFR and ESRD in the DCCT/EDIC study.
许多 1 型糖尿病患者尽管代谢控制较好，但仍会出现肾脏疾病，这表明可能存在其他危险因素。最近的证据表明，触珠蛋白（HP）2-2 基因型编码一种抗氧化活性降低的蛋白质，可能预测 1 型糖尿病患者的肾功能下降。我们在糖尿病控制和并发症试验/糖尿病干预和并发症的流行病学（DCCT/EDIC）研究的 1303 名白种人参与者中检验了这一假设。HP 基因型通过聚丙烯酰胺凝胶电泳确定。肾小球滤过率（GFR）通过慢性肾脏病流行病学合作（CKD-EPI）方程和基于定时尿样的白蛋白排泄来估计。参与者的平均随访时间为 22 年。HP 基因型与持续估计肾小球滤过率（GFR）<60mL/min/1.73m(2)和终末期肾病（ESRD）的发生显著相关，与 HP 2-2 相比，HP 2-1 和 1-1 的风险更高。与白蛋白尿无关。尽管没有治疗组间的相互作用，但这些关联仅在常规治疗组中显著，常规治疗组的事件发生率更高。我们的结论是，在 DCCT/EDIC 研究中，HP 基因型与 GFR 降低和 ESRD 的发生显著相关。
