Bacterial Endotoxin Activity in Human Serum Is Associated With Dyslipidemia, Insulin Resistance, Obesity, and Chronic Inflammation
- Mariann I. Lassenius, MSC1,2,
- Kirsi H. Pietiläinen, MD, DMSC3,
- Kati Kaartinen, MD, DMSC2,4,
- Pirkko J. Pussinen, PHD5,
- Jaana Syrjänen, MD, DMSC4,
- Carol Forsblom, MD, DMSC1,2,
- Ilkka Pörsti, MD, DMSC4,
- Aila Rissanen, MD, DMSC3,
- Jaakko Kaprio, MD, DMSC6,7,
- Jukka Mustonen, MD, DMSC4,
- Per-Henrik Groop, MD, DMSC1,2,8,
- Markku Lehto, PHD1,2⇓ and
- on behalf of the FinnDiane Study Group*
- 1Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
- 2Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
- 3Obesity Research Unit, Division of Internal Medicine, Department of Medicine and Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
- 4Department of Internal Medicine, Tampere University Hospital, and University of Tampere Medical School, Tampere, Finland
- 5Institute of Dentistry, University of Helsinki, Helsinki, Finland
- 6Department of Public Health, Hjelt Institute, and Centre of Excellence in Complex Disease Genetics, Institute for Molecular Genetics, University of Helsinki, Helsinki, Finland
- 7National Institute for Health and Welfare, Helsinki, Finland
- 8Baker International Diabetes Institute, Heart and Diabetes Institute, Melbourne, Victoria, Australia
- Corresponding author: Markku Lehto, .
OBJECTIVE To investigate whether bacterial lipopolysaccharide (LPS) activity in human serum is associated with the components of the metabolic syndrome (MetS) in type 1 diabetic patients with various degrees of kidney disease and patients with IgA glomerulonephritis (IgAGN).
RESEARCH DESIGN AND METHODS Serum LPS activity was determined with the Limulus Amoebocyte Lysate chromogenic end point assay in type 1 diabetic patients with a normal albumin excretion rate (n = 587), microalbuminuria (n = 144), macroalbuminuria (n = 173); patients with IgAGN (n = 98); and in nondiabetic control subjects (n = 345). The relationships of the LPS/HDL ratio and MetS-associated variables were evaluated with Pearson correlation.
RESULTS The MetS was more prevalent in type 1 diabetic patients (48%) than in patients with IgAGN (15%). Diabetic patients with macroalbuminuria had a significantly higher serum LPS/HDL ratio than patients with IgAGN. In the normoalbuminuric type 1 diabetic group, patients in the highest LPS/HDL quartile were diagnosed as having the MetS three times more frequently than patients in the lowest quartile (69 vs. 22%; P < 0.001). High LPS activity was associated with higher serum triglyceride concentration, earlier onset of diabetes, increased diastolic blood pressure, and elevated urinary excretion of monocyte chemoattractant protein-1.
CONCLUSIONS High serum LPS activity is strongly associated with the components of the MetS. Diabetic patients with kidney disease seem to be more susceptible to metabolic endotoxemia than patients with IgAGN. Bacterial endotoxins may thus play an important role in the development of the metabolic and vascular abnormalities commonly seen in obesity and diabetes-related diseases.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc10-2197/-/DC1.
- Received November 22, 2010.
- Accepted April 28, 2011.
- © 2011 by the American Diabetes Association.
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