Serum Lipopolysaccharide Activity Is Associated With the Progression of Kidney Disease in Finnish Patients With Type 1 Diabetes
- Mariann Nymark, MSC1,
- Pirkko J. Pussinen, PHD2,
- Anita M. Tuomainen, MSC2,
- Carol Forsblom, MD, DMSC1,
- Per-Henrik Groop, MD, DMSC1,
- Markku Lehto, PHD1 and
- on behalf of the FinnDiane Study Group*
- 1Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, and Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland;
- 2Institute of Dentistry, Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
- Corresponding author: Markku Lehto, markku.lehto{at}helsinki.fi.
Abstract
OBJECTIVE The aim of the study was to investigate whether serum lipopolysaccharide (LPS) activities are associated 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 6 years. At the baseline visit, 239 patients had a normal albumin excretion rate (normoalbuminuria) and 238 patients had macroalbuminuria. Patients were further divided into nonprogressors and progressors 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 the Limulus amoebocyte lysate chromogenic end point assay.
RESULTS Serum LPS activity was significantly higher in the macroalbuminuric group than in the normoalbuminuric group (P < 0.001). Notably, normoalbuminuric progressor patients had a significantly higher LPS activity at baseline than normoalbuminuric nonprogressor patients (median 49 [interquartile range 34–87] vs. 39 [29–54] EU/ml; P = 0.001). The normoalbuminuric progressor patients exhibited features of the metabolic syndrome with higher triglyceride concentrations and lower estimated glucose disposal rate. A high LPS-to-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 A1C 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.
Footnotes
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↵*A list of participating centers in the FinnDiane Collection is available in the online appendix at http://care.diabetesjournals.org/cgi/content/full/dc09-0467/DC1.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received March 10, 2009.
- Accepted May 29, 2009.
- © 2009 by the American Diabetes Association.
