Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy

Abstract

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ΔUACR differed among treatment arms (placebo -24.6%, los -38.2%, spiro -51.6%, p=0.02). No correlation existed between ΔUACR and ΔTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (-20.9% vs +34.3%, p<0.01), V+I C(-18.8% vs +21.3%, p<0.01), and V+I-ApoB (-13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins.

Trial registration number: NCT00381134; Results.

Keywords: Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Dyslipidemias; Proteinuria.

Figure 1

(A) Per cent change of plasma triglycerides by treatment group triglyceride per cent change at week 48: +34.3% (placebo), 20.9% (losartan), −5.1% (spironolactone). (B). Absolute change in plasma triglyceride/HDL-cholesterol ratio by treatment group triglyceride/HDL per cent change at week 48: +2.9% (placebo), −1.4% (losartan), +0.8% (spironolactone). (C) Per cent change of very-low-density lipoprotein cholesterol (VLDL-C)+intermediate-density lipoprotein cholesterol (IDL)-C V+I-C by treatment group. Per cent change at week 48: +34.3% (placebo), −18.8% (losartan), −14.4% (spironolactone). (D) Per cent change of very-low-density lipoprotein ApoB (V-ApoB)+intermediate-density lipoprotein ApoB (I-ApoB) by treatment group. Per cent change at week 48: +21.0% (placebo), −13.2%, (losartan), −9.2% (spironolactone). The figures depict geometric mean (95% CI). p Values are from mixed-model repeated-measures analysis comparing treatment groups. Apo-B, apolipoprotein B.