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

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.

Conflict of interest statement

Competing Interests: This work was supported by the Research Foundation of the Italian Society of Diabetology (Fo.Di.Ri.) and the Diabetes, Endocrinology and Metabolism (D.E.M.) Foundation, and by unconditional grants from Eli-Lilly, Takeda, Chiesi Farmaceutici and Boehringer-Ingelheim. The sponsors had no role in design and conduct of the study; collection, management, and interpretation of the data; or preparation, review, and approval of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.”.

Figures

Fig 1. Adjusted risk of CKD Stages 1–2 (Panel A), CKD Stages 3–5 nonalbuminuric (Panel B) and CKD Stages 3–5 albuminuric (Panel C) (OR [95% CI]) according to deciles of triglyceride levels in subjects without (□) and with (●) statin treatment.

ORs are adjusted for age, male gender, smoking status, diabetes duration, HbA1c, BMI, HDL and LDL cholesterol, hypertension, and blockade of the renin-angiotensin system. Significant at * P<0.0001, † P at least <0.01, ‡ P at least <0.05.