Postprandial endotoxemia may influence the development of type 2 diabetes mellitus: from the CORDIOPREV study

Authors: CAMARGO, ANTONIO - UNIVERSITY HOSPITAL REINA SOFIA; JIMENEZ-LUCENA, ROSA - UNIVERSITY HOSPITAL REINA SOFIA; ALCALA-DIAZ, JUAN - UNIVERSITY HOSPITAL REINA SOFIA; RANGEL-ZUNIGA, ORIOL - UNIVERSITY HOSPITAL REINA SOFIA; GARCIA-CARPINTERO, SONIA - UNIVERSITY HOSPITAL REINA SOFIA; LOPEZ-MORENO, JAVIER - UNIVERSITY HOSPITAL REINA SOFIA; BLANCO-ROJO, RUTH - UNIVERSITY HOSPITAL REINA SOFIA; DELGADO-LISTA, JAVIER - UNIVERSITY HOSPITAL REINA SOFIA; PEREZ-MARTINEZ, PABLO - UNIVERSITY HOSPITAL REINA SOFIA; VAN OMMEN, BEN - THE NETHERLANDS ORGANISATION FOR APPLIED SCIENTIFIC RESEARCH (TNO); MALAGON, MARIA - INSTITUTO DE SALUD CARLOS III; ORDOVAS, JOSE - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; LOPEZ-MIRANDA, JOSE - UNIVERSITY HOSPITAL REINA SOFIA

Submitted to: Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/28/2018
Publication Date: 4/11/2018
Citation: Camargo, A., Jimenez-Lucena, R., Alcala-Diaz, J.F., Rangel-Zuniga, O.A., Garcia-Carpintero, S., Lopez-Moreno, J., Blanco-Rojo, R., Delgado-Lista, J., Perez-Martinez, P., Van Ommen, B., Malagon, M.M., Ordovas, J.M., Lopez-Miranda, J. 2018. Postprandial endotoxemia may influence the development of type 2 diabetes mellitus: from the CORDIOPREV study. Clinical Nutrition. 38(2):529-538. https://doi.org/10.1016/j.clnu.2018.03.016.
DOI: https://doi.org/10.1016/j.clnu.2018.03.016

Interpretive Summary: Type 2 diabetes (T2D) is a chronic disease that prevents the proper use of insulin by the body, and patients are said to have insulin resistance (IR). There are about 27 million people in the US with T2D, and they are at an increased risk of cardiovascular events, especially in myocardial infarction patients. There are many risk factors associated with the development of T2D, but knowledge is still incomplete, compromising prediction and effective prevention of T2D. We evaluated the role of postprandial endotoxemia (presence of endotoxins of intestinal origin in the bloodstream) in promoting inflammation-induced IR and its usefulness as a T2D predictive biomarker. For this purpose, we included in our study 462 patients from the CORDIOPREV study without T2D at baseline. Of these, 107 patients developed T2D after five years of follow-up. We measured lipopolysaccharides (LPS) levels, a well-known endotoxin, following a standard meal and our results showed that after a meal endotoxemia was higher in those patients who developed T2D, and this increase precedes the development of T2D. These results showed the potential use of LPS plasma levels as a biomarker predictor of T2DM development.

Technical 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 less than 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.