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高甘油三酯血症与2型糖尿病患者的肾脏并发症独立相关,但与视网膜并发症无关:肾脏功能不全与心血管事件(RIACE)意大利多中心研究的横断面分析

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.

作者信息

Penno Giuseppe, Solini Anna, Zoppini Giacomo, Fondelli Cecilia, Trevisan Roberto, Vedovato Monica, Gruden Gabriella, Lamacchia Olga, Pontiroli Antonio E, Arosio Maura, Orsi Emanuela, Pugliese Giuseppe

机构信息

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Division of Endocrinology and Metabolic Diseases, University of Verona, Verona, Italy.

出版信息

PLoS One. 2015 May 5;10(5):e0125512. doi: 10.1371/journal.pone.0125512. eCollection 2015.

Abstract

OBJECTIVE

Atherogenic 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.

METHODS

Subjects 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.

RESULTS

HTG 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.

CONCLUSIONS

Triglycerides 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 REGISTRATION

www.ClinicalTrials.gov NCT00715481.

摘要

目的

致动脉粥样硬化性血脂异常似乎在微血管并发症以及他汀类药物治疗后残留的微血管风险中起主要作用,他汀类药物可使甘油三酯降低达40%。我们评估了2型糖尿病患者甘油三酯(TG)水平升高是否与微血管并发症负担增加相关。

方法

来自意大利多中心肾脏功能不全与心血管事件(RIACE)研究(n = 15773)的受试者根据血浆甘油三酯水平是否低于(正常甘油三酯组,NTG,67.8%)或高于(高甘油三酯组,HTG,32.2%)1.7 mmol/L以及是否接受(42.4%)或未接受(57.6%)他汀类药物治疗被分为4组。根据血清肌酐计算估算肾小球滤过率(eGFR),通过免疫比浊法或免疫散射比浊法测量蛋白尿,通过眼底检查评估视网膜病变。

结果

与NTG组相比,HTG组受试者无论是否使用他汀类药物,蛋白尿患病率更高,eGFR降低,慢性肾脏病(CKD)尤其是蛋白尿型CKD的患病率更高,但视网膜病变患病率无差异。相比之下,无论甘油三酯水平如何,接受他汀类药物治疗的受试者心血管疾病和晚期糖尿病视网膜病变(DR)的患病率均高于未接受治疗者。逻辑回归分析证实,无论是否使用他汀类药物,HTG均与微量和大量蛋白尿、轻度至重度eGFR降低以及所有CKD表型独立相关,但与视网膜病变无关。甘油三酯水平每升高0.26 mmol/L(约十分之一),CKD的校正比值比呈线性增加。随着蛋白尿严重程度、eGFR降低程度和CKD表型的增加以及接受他汀类药物治疗的受试者,这种增加更为明显。

结论

在2型糖尿病患者中,甘油三酯与CKD相关,但与视网膜病变无关,且与他汀类药物治疗无关。这些数据表明高甘油三酯血症在CKD发生发展中可能起作用,尽管仍有待证明糖尿病个体通过他汀类药物降低甘油三酯以及最终联合贝特类药物治疗是否有益。

试验注册

www.ClinicalTrials.gov NCT00715481

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7175/4420503/5b7701568de0/pone.0125512.g001.jpg

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