Can reduction in hypertriglyceridaemia slow progression of microalbuminuria in patients with non‐insulin‐dependent diabetes mellitus?

Abstract

The objective of this study was to investigate whether reduction in hypertriglyceridaemia is associated with a slower rate of progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus (NIDDM). Fifteen normotensive NIDDM patients with hypertriglyceridaemia (> 2.5 mmol L-1) and microalbuminuria were randomly selected to receive either placebo (eight patients) or gemfibrozil 600 mg b.i.d. (seven patients). Progression of microalbuminuria was assessed during a 12-month follow-up period with measurements, consisting of blood tests and triplicate 24-h urine collections, at 1, 3, 6, 9 and 12 months. All but one patient in the treatment group showed a favourable response (> or = 20% reduction) of hypertriglyceridaemia to gemfibrozil. One patient in the placebo group showed a spontaneous reduction in triglyceride levels. Progression of microalbuminuria was lower, although not statistically significantly so, in the treatment group (36%) than in the placebo group (65%). In the group with > or = 20% reduction in triglyceride levels, progression of MA was significantly lower than in the group with stable or increasing triglyceride levels (+1%, range -56% to +49% vs. +97%, range -35% to +202% respectively) (P = 0.03). Continued follow-up data of patients switching from placebo to gemfibrozil after the trial further support the role of serum triglyceride reduction in stabilizing albumin excretion. In conclusion, the results indicate that, in microalbuminuric NIDDM patients, effective treatment of dyslipidaemia could be associated with stabilization of urinary albumin excretion.

Accelerated Diabetic Nephropathy in Mice Lacking the Peroxisome Proliferator–Activated Receptor α

“…Cardiac-specific PPAR␣ overexpression increases fatty acid oxidation, elevates lipid storage droplets, and exacerbates cardiomyopathy in diabetes compared with wild-type controls (21). On the other hand, oral fibrates, PPAR␣ agonists that lower serum triglycerides, reduced proteinuria in a subset of diabetic patients (22,23). Our study consistently showed that diabetes increased PPAR␣ expression in diabetic wild-type mice and in vitro PPAR␣ activation in mesangial cells by fenofibrate-attenuated extracellular matrix production associated with reduced TGF-␤1 levels and leukocyte adherence to mesangial cells.…”

Peroxisome Proliferator-Activated Receptor Family and Its Relationship to Renal Complications of the Metabolic Syndrome

“…These findings raise a potential therapeutic concern for patients who have diabetic nephropathy and receive oral fibrate treatment, because a marked increase in PPAR-␣ gene expression has been evident in diabetic kidney (154). However, clinical evidence suggests a beneficial effect of fibrate treatment on type 2 diabetes and diabetic nephropathy (155,156). In normotensive patients with non-insulin-dependent diabetes, effective treatment of dyslipidemia by a PPAR-␣ activator gemfibrozil for 12 mo was associated with significant stabilization of urine albumin excretion (156).…”

Plasma lipoproteins and the incidence of abnormal excretion of albumin in diabetic American Indians: The Strong Heart Study

“…Two short-term controlled trials with simvastatin to reduce hypercholesterolaemia in participants with Type I [21] or Type II [22] diabetes did not show any improvement in kidney function. Two long-term randomized trials have, however, suggested a beneficial effect of hypolipidaemic treatment for microalbuminuria [23] or decreased glomerular filtration rate [24,25] in Type II diabetes.…”