Expediente Clinico Pediatrico

Phagocytic Activity Is Impaired in Type 2 Diabetes Mellitus and Increases after Metabolic Improvement
´ ´ ´ Albert Lecube1., Gisela Pachon1,2., Jordi Petriz2, Cristina Hernandez1, Rafael Simo1*
´ 1 Diabetes and Metabolism Research Unit, CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Vall d’Hebron Institut ´ ` de Recerca (VHIR),Hospital Universitari Vall d’Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain, 2 Research Unit in Biomedicine and Translational and ` Pediatrics Oncology, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain

Abstract
Objective: 1) To evaluate whether peripheral blood mononuclear cells (PBMCs) from type 2 diabetic patients present an impairment ofphagocytic activity; 2) To determine whether the eventual impairment in phagocytic activity is related to glycemic control and can be reversed by improving blood glucose levels. Methods: 21 type 2 diabetic patients and 21 healthy volunteers were prospectively recruited for a case-control study. In addition, those patients in whom HbA1c was higher than 8% (n = 12) were hospitalized in order tocomplete a 5-day intensification treatment of blood glucose. Phagocytic activity was assessed by using a modified flow cytometry procedure developed in our laboratory based on DNA/RNA viable staining to discriminate erythrocytes and debris. This method is simple, highly sensitive and reproducible and it takes advantage of classic methods that are widely used in flow cytometry. Results: Type 2 diabeticpatients showed a lower percentage of activated macrophages in comparison with non-diabetic subjects (54.00618.93 vs 68.53612.77%; p = 0.006) Significant negative correlations between phagocytic activity and fasting glucose (r = 20.619, p = 0.004) and HbA1c (r = 20.506, p = 0.019) were detected. In addition, multiple linear regression analyses showed that either fasting plasma glucose or HbA1c wereindependently associated with phagocytic activity. Furthermore, in the subset of patients who underwent metabolic optimization a significant increase in phagocytic activity was observed (p = 0.029). Conclusions: Glycemic control is related to phagocytic activity in type 2 diabetes. Our results suggest that improvement in phagocytic activity can be added to the beneficial effects of metabolicoptimization.
´ ´ndez C, Simo R (2011) Phagocytic Activity Is Impaired in Type 2 Diabetes Mellitus and Increases after Metabolic ´ Citation: Lecube A, Pachon G, Petriz J, Herna Improvement. PLoS ONE 6(8): e23366. doi:10.1371/journal.pone.0023366 Editor: Giorgio Sesti, Universita Magna-Graecia di Catanzaro, Italy Received May 6, 2011; Accepted July 13, 2011; Published August 18, 2011 Copyright: ß 2011Lecube et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ´ Funding: This study was supported by the CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM). CIBERDEM is an initiative of theInstituto de Salud Carlos III (ISCIII). This work was also supported by grants to Jordi Petriz from the Spanish Ministry of Health (PI081132). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: rsimo@ir.vhebron.net . These authorscontributed equally to this work.

Introduction
Patients with type 2 diabetes mellitus (T2DM) are immunocompromised and have an increased incidence of infections, mainly in the bone and skin, as well as in the respiratory, enteric and urinary tracts [1,2]. In a Canadian retrospective cohort study that included 513,749 people with T2DM matched to an equal number of nondiabetic subjects the risk ratio...