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.
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.


BACKGROUND
www.ClinicalTrials.gov NCT00715481.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Giuseppe
G
Penno
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Anna
A
Solini
Division of Endocrinology and Metabolic Diseases, University of Verona, Verona, Italy.
Giacomo
G
Zoppini
Diabetes Unit, University of Siena, Siena, Italy.
Cecilia
C
Fondelli
Endocrinology and Diabetes Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
Roberto
R
Trevisan
Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy.
Monica
M
Vedovato
Department of Internal Medicine, University of Turin, Turin, Italy.
Gabriella
G
Gruden
Department of Medical Sciences, University of Foggia, Foggia, Italy.
Olga
O
Lamacchia
Department of Medicine, Surgery and Odontoiatrics, San Paolo Hospital, University of Milan, Milan, Italy.
Antonio E
AE
Pontiroli
Endocrinology Unit, San Giuseppe Hospital, University of Milan, Milan, Italy.
Maura
M
Arosio
Diabetes Unit, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, Milan, Italy.
Emanuela
E
Orsi
Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy.
Giuseppe
G
Pugliese
D000419:Albuminuria / Q000209:etiology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D015228:Hypertriglyceridemia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D007558:Italy; D008297:Male; D016017:Odds Ratio; D051437:Renal Insufficiency / Q000209:etiology* / Q000503:physiopathology*; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000503:physiopathology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors