title: 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.
  
  
  
  NCT00381134; Results.
authors.affiliation: Division of Renal Medicine, Brigham &Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Beverley
authors.initials: B
authors.lastname: Adams-Huet
authors.affiliation: Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Gloria L
authors.initials: GL
authors.lastname: Vega
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Toto
mesh_terms: D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
chemical_list: D008074:Lipoproteins; D014280:Triglycerides; C030087:lipoprotein triglyceride; D013148:Spironolactone; D019808:Losartan
keywords: Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Dyslipidemias; Proteinuria