Serum lipopolysaccharide (LPS) activity is associated with the progression of kidney disease in Finnish patients with type 1 diabetes

doi:10.2337/dc09-0467

Serum lipopolysaccharide (LPS) activity is associated with the progression of kidney disease in Finnish patients with type 1 diabetes

Mariann Nymark, MSC¹,²,
Pirkko J Pussinen, PhD³,
Anita M Tuomainen, MSC³,
Carol Forsblom, MD, DMSC¹,²,
Per-Henrik Groop, MD, DMSC¹,² and
Markku Lehto, PHD (markku.lehto{at}helsinki.fi) ON BEHALF OF THE FINNDIANE STUDY GROUP¹,²

From the ¹Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
²Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
³Institute of Dentistry, Department of Oral and Maxillofacial Diseases, Helsinki University Cental Hospital, University of Helsinki, Helsinki, Finland

Abstract

Objective: The aim of the study was to investigate whether serum lipopolysaccharide (LPS) activities associate with the progression of kidney disease in patients with type 1 diabetes.

Research design and methods: For this prospective study, we chose 477 Finnish patients with type 1 diabetes, who were followed for six years. At the baseline visit, 239 patients had a normal albumin excretion rate (NA) and 238 patients macroalbuminuria (MA). Patients were further divided into non-progressors (non) and progressors (prog) based on their albumin excretion rate at follow-up. Eighty normoalbuminuric patients had developed microalbuminuria, and 79 macroalbuminuric patients had progressed to end-stage renal disease. Serum LPS activity was determined with Limulus Amoebocyte Lysate (LAL) chromogenic endpoint assay.

Results: Serum LPS activity was significantly higher in the macroalbuminuric group than in the normoalbuminuric group (P<0.001). Notably, NAprog patients had a significantly higher LPS activity at baseline than NAnon patients [49 (IQR 34-87) vs. 39 (IQR 29-54) EU/ml; P=0.001]. The NAprog patients exhibited features of the metabolic syndrome with higher triglyceride concentrations and lower estimated glucose disposal rate (eGDR). A high LPS/HDL-ratio was associated with the progression of kidney disease in both groups. Insulin resistance (P<0.001) and serum LPS activity (P=0.026) were independent risk factors of disease development, when HbA_1c was removed from the regression analysis.

Conclusions: High serum LPS activity is associated with the development of diabetic nephropathy in Finnish patients with type 1 diabetes.