Antonio Camargo1, Rosa Jimenez-Lucena1, Juan F Alcala-Diaz1, Oriol A Rangel-Zuñiga1, Sonia Garcia-Carpintero1, Javier Lopez-Moreno1, Ruth Blanco-Rojo1, Javier Delgado-Lista1, Pablo Perez-Martinez1, Ben van Ommen2, Maria M Malagon3, Jose M Ordovas4, Francisco Perez-Jimenez1, Jose Lopez-Miranda5. 1. Lipids and Atherosclerosis Unit, GC9 Nutrigenomics, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain. 2. Netherlands Institute for Applied Science (TNO), Research Group Microbiology & Systems Biology, Zeist, The Netherlands. 3. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Cordoba, Córdoba, Spain. 4. Nutrition and Genomics Laboratory, J.M.-US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; IMDEA Alimentacion, Madrid, Spain; CNIC, Madrid, Spain. 5. Lipids and Atherosclerosis Unit, GC9 Nutrigenomics, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Cordoba, Spain. Electronic address: jlopezmir@uco.es.
Abstract
BACKGROUND & AIMS: Insulin resistance (IR) and impaired beta-cell function are key determinants of type 2 diabetes mellitus (T2DM). Intestinal absorption of bacterial components activates the toll-like receptors inducing inflammation, and this in turn IR. We evaluated the role of endotoxemia in promoting inflammation-induced insulin resistance (IR) in the development of T2DM, and its usefulness as predictive biomarker. METHODS: We included in this study 462 patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months (Incident-DIAB group), whereas 355 patients did not developed it during this period of time (Non-DIAB group). RESULTS: We observed a postprandial increase in lipopolysaccharides (LPS) levels in the Incident-DIAB at baseline (P < 0.001), whereas LPS levels were not modified in the Non-DIAB. Disease-free survival curves based on the LPS postprandial fold change improved T2DM Risk Assessment as compared with the previously described FINDRISC score (hazard ratio of 2.076, 95% CI 1.149-3.750 vs. 1.384, 95% CI 0.740-2.589). Moreover, disease-free survival curves combining the LPS postprandial fold change and FINDRISC score together showed a hazard ratio of 3.835 (95% CI 1.323-11.114), linked to high values of both parameters. CONCLUSION: Our results suggest that a high postprandial endotoxemia precedes the development of T2DM. Our results also showed the potential use of LPS plasma levels as a biomarker predictor of T2DM development. CLINICAL TRIALS.GOV. IDENTIFIER: NCT00924937.
BACKGROUND & AIMS:Insulin resistance (IR) and impaired beta-cell function are key determinants of type 2 diabetes mellitus (T2DM). Intestinal absorption of bacterial components activates the toll-like receptors inducing inflammation, and this in turn IR. We evaluated the role of endotoxemia in promoting inflammation-induced insulin resistance (IR) in the development of T2DM, and its usefulness as predictive biomarker. METHODS: We included in this study 462 patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months (Incident-DIAB group), whereas 355 patients did not developed it during this period of time (Non-DIAB group). RESULTS: We observed a postprandial increase in lipopolysaccharides (LPS) levels in the Incident-DIAB at baseline (P < 0.001), whereas LPS levels were not modified in the Non-DIAB. Disease-free survival curves based on the LPS postprandial fold change improved T2DM Risk Assessment as compared with the previously described FINDRISC score (hazard ratio of 2.076, 95% CI 1.149-3.750 vs. 1.384, 95% CI 0.740-2.589). Moreover, disease-free survival curves combining the LPS postprandial fold change and FINDRISC score together showed a hazard ratio of 3.835 (95% CI 1.323-11.114), linked to high values of both parameters. CONCLUSION: Our results suggest that a high postprandial endotoxemia precedes the development of T2DM. Our results also showed the potential use of LPS plasma levels as a biomarker predictor of T2DM development. CLINICAL TRIALS.GOV. IDENTIFIER: NCT00924937.
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