Thomas Merlin C, Rosengård-Bärlund Milla, Mills Vashti, Rönnback Mats, Thomas Stephen, Forsblom Carol, Cooper Mark E, Taskinen Marja-Riitta, Viberti Giancarlo, Groop Per-Henrik
The Baker Heart Research Institute, Melbourne, Australia.
Diabetes Care. 2006 Feb;29(2):317-22. doi: 10.2337/diacare.29.02.06.dc05-0809.
Dyslipidemia contributes to the progression of microvascular disease in diabetes. However, different lipid variables may be important at different stages of nephropathy. This study examines the pattern of dyslipidemia associated with the progression of nephropathy in patients with type 1 diabetes.
A total of 152 patients with type 1 diabetes were recruited in order to represent various phases of nephropathy. Patients were followed for 8-9 years, during which time they received standard care. Renal progression was defined a priori as a doubling in albumin excretion (in patients with normo- or microalbuminuria) or a decline in creatinine clearance (in those with macroalbuminuria). A panel of lipid variables was determined and correlated with indexes of progression.
In patients with normoalbuminuria (n = 66), progression was associated with male sex (P < 0.05), borderline albuminuria (P = 0.02), and LDL-free cholesterol (P = 0.02). In patients with microalbuminuria (n = 51), progression was independently associated with triglyceride content of VLDL and intermediate-density lipoprotein (both P < 0.05). In patients with macroalbuminuria (n = 36), a significant decline in the renal function (>3 ml x min(-1) x year(-1)) was independently associated with poor glycemic control, hypertension, and LDL size (P < 0.05). When all patients with progressive nephropathy were analyzed together, only LDL cholesterol was predictive on multivariate analysis (P < 0.05), which masked the importance of triglyceride enrichment in microalbuminuria.
Lipid variables are associated with progression of diabetic kidney disease, but the relationship is not the same at all stages. This finding has implications for the design of renoprotective strategies and the interpretation of clinical trials in type 1 diabetes.
血脂异常会促进糖尿病微血管病变的进展。然而，不同的血脂变量在肾病的不同阶段可能具有重要意义。本研究探讨了1型糖尿病患者中与肾病进展相关的血脂异常模式。
共招募了152例1型糖尿病患者，以代表肾病的各个阶段。患者随访8 - 9年，在此期间接受标准治疗。肾进展预先定义为白蛋白排泄量翻倍（正常白蛋白尿或微量白蛋白尿患者）或肌酐清除率下降（大量白蛋白尿患者）。测定一组血脂变量并将其与进展指标相关联。
在正常白蛋白尿患者（n = 66）中，进展与男性性别（P < 0.05）、临界白蛋白尿（P = 0.02）和无低密度脂蛋白胆固醇（P = 0.02）相关。在微量白蛋白尿患者（n = 51）中，进展与极低密度脂蛋白和中间密度脂蛋白的甘油三酯含量独立相关（均P < 0.05）。在大量白蛋白尿患者（n = 36）中，肾功能显著下降（>3 ml·min⁻¹·年⁻¹）与血糖控制不佳、高血压和低密度脂蛋白大小独立相关（P < 0.05）。当对所有进展性肾病患者进行综合分析时，多变量分析显示只有低密度脂蛋白胆固醇具有预测性（P < 0.05），这掩盖了微量白蛋白尿中甘油三酯富集的重要性。
血脂变量与糖尿病肾病进展相关，但在各个阶段的关系并不相同。这一发现对1型糖尿病肾脏保护策略的设计和临床试验的解读具有重要意义。
