Hypertriglyceridemia Is Independently Associated with Renal, but Not Retinal Complications in Subjects with Type 2 Diabetes: A Cross-Sectional Analysis of the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study

ObjectiveAtherogenic dyslipidemia seems to play a major role in microvascular complications and in residual microvascular risk after statin therapy, which reduces triglycerides up to 40%. We assessed whether raised TG levels are associated with an increased burden from microvascular complications in patients with type 2 diabetes.MethodsSubjects from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study (n=15,773) were divided in 4 groups depending on whether they had plasma triglycerides below (NTG, 67.8%) or above (HTG, 32.2%) 1.7 mmol/L and were (42.4%) or not on (57.6%) statin therapy. Estimated GFR (eGFR) was calculated from serum creatinine, albuminuria was measured by immunonephelometry or immunoturbidimetry, and retinopathy was evaluated by fundus examination.ResultsHTG subjects, either with or without statin, had higher prevalence of albuminuria, reduced eGFR and chronic kidney disease (CKD), especially the albuminuric forms, but not of retinopathy, than NTG subjects. In contrast, cardiovascular disease and advanced DR were more prevalent in subjects on statin than in those not, independently of triglyceride levels. Logistic regression analysis confirmed that HTG, without or with statin, was independently associated with micro and macroalbuminuria, mildly to severely reduced eGFR, and all CKD phenotypes, but not with retinopathy. The adjusted odd ratios for CKD increased linearly for every 0.26 mmol/L increase (approximately one decile) in triglyceride levels. The increase was higher with increasing severity of albuminuria, eGFR loss and CKD phenotype as well as in subjects receiving than in those not receiving statin treatment.ConclusionsTriglycerides are associated with CKD, but not retinopathy in subjects with type 2 diabetes, independently of statin treatment. These data point to a possible role of hypertriglyceridemia in the development of CKD, though it remains to be demonstrated that diabetic individuals might benefit from triglyceride reduction with statins and eventually with combination therapy with fibrates.Trial Registrationwww.ClinicalTrials.gov NCT00715481【研究背景】致动脉粥样硬化性血脂异常（atherogenic dyslipidemia）在微血管并发症以及他汀类药物治疗后的残余微血管风险中发挥关键作用，而他汀类药物可使甘油三酯（triglycerides, TG）水平降低达40%。本研究旨在探讨2型糖尿病患者中，升高的TG水平是否与微血管并发症负担增加相关。 【研究方法】本研究纳入意大利多中心肾功能不全与心血管事件（Renal Insufficiency And Cardiovascular Events, RIACE）队列的15773名受试者，根据其血浆TG水平是否低于1.7mmol/L（正常TG组，NTG，67.8%）或高于1.7mmol/L（高TG组，HTG，32.2%），以及是否接受他汀类药物治疗（42.4%接受治疗，57.6%未接受治疗），将受试者分为4组。采用血清肌酐计算估算肾小球滤过率（estimated GFR, eGFR），通过免疫比浊法或免疫散射比浊法检测白蛋白尿，通过眼底检查评估视网膜病变。 【研究结果】无论是否接受他汀类药物治疗，高TG组受试者的白蛋白尿、估算肾小球滤过率降低以及慢性肾脏病（chronic kidney disease, CKD）患病率均高于正常TG组，其中以白蛋白尿型CKD更为显著，但两组视网膜病变患病率无明显差异。与之相反，无论TG水平如何，接受他汀类药物治疗的受试者其心血管疾病与增殖性糖尿病视网膜病变（advanced DR, diabetic retinopathy）患病率均高于未接受治疗者。Logistic回归分析证实，无论是否联合他汀类药物治疗，高TG均与微量白蛋白尿、大量白蛋白尿、轻至重度估算肾小球滤过率降低以及所有类型CKD独立相关，但与视网膜病变无关联。随着TG水平每升高0.26mmol/L（约一个十分位间距），校正后的CKD比值比（odd ratios, OR）呈线性升高。这种升高幅度随着白蛋白尿严重程度、估算肾小球滤过率下降程度以及CKD分型的加重而增加，且在接受他汀类药物治疗的受试者中更为显著。 【研究结论】在2型糖尿病患者中，TG水平与CKD相关，但与视网膜病变无关，且这一关联不受他汀类药物治疗的影响。本研究结果提示高甘油三酯血症（hypertriglyceridemia）可能参与CKD的发生发展，但仍需进一步研究证实糖尿病患者通过他汀类药物（联合贝特类药物）降低TG水平是否可获益。 【试验注册】ClinicalTrials.gov NCT00715481