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Serum Lipids and the Progression of Nephropathy in Type 1 Diabetes

¹ The Baker Heart Research Institute, Melbourne, Australia
² Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland
³ Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
⁴ Cardiovascular Division, Guy’s Hospital, King’s College, London, U.K.

Address correspondence and reprint requests to Per-Henrik Groop, Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, PoB 63, FIN-00014, Finland. E-mail: per-henrik.groop{at}helsinki.fi

OBJECTIVE—Dyslipidemia contributes to the progression of microvascular disease in diabetes. However, different lipid variables may be important at different stages of nephropathy. This study examines the pattern of dyslipidemia associated with the progression of nephropathy in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—A total of 152 patients with type 1 diabetes were recruited in order to represent various phases of nephropathy. Patients were followed for 8–9 years, during which time they received standard care. Renal progression was defined a priori as a doubling in albumin excretion (in patients with normo- or microalbuminuria) or a decline in creatinine clearance (in those with macroalbuminuria). A panel of lipid variables was determined and correlated with indexes of progression.

RESULTS—In patients with normoalbuminuria (n = 66), progression was associated with male sex (P < 0.05), borderline albuminuria (P = 0.02), and LDL-free cholesterol (P = 0.02). In patients with microalbuminuria (n = 51), progression was independently associated with triglyceride content of VLDL and intermediate-density lipoprotein (both P < 0.05). In patients with macroalbuminuria (n = 36), a significant decline in the renal function (>3 ml · min^–1 · year^–1) was independently associated with poor glycemic control, hypertension, and LDL size (P < 0.05). When all patients with progressive nephropathy were analyzed together, only LDL cholesterol was predictive on multivariate analysis (P < 0.05), which masked the importance of triglyceride enrichment in microalbuminuria.

CONCLUSIONS—Lipid variables are associated with progression of diabetic kidney disease, but the relationship is not the same at all stages. This finding has implications for the design of renoprotective strategies and the interpretation of clinical trials in type 1 diabetes.

Abbreviations: AER, albumin excretion rate • apo, apolipoprotein • IDL, intermediate-density lipoprotein

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