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Rev Diabet Stud, 2007, 4(2):112-120 DOI 10.1900/RDS.2007.4.112

Increased Expression of Monocyte CD11b (Mac-1) in Overweight Recent-Onset Type 1 Diabetic Children

Vincenza Cifarelli1, Ingrid M. Libman2, Angela DeLuca3, Dorothy Becker2, Massimo Trucco1, Patrizia Luppi1

1Division of Immunogenetics, Department of Pediatrics, Children´s Hospital of Pittsburgh, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.
2Division of Endocrinology, Department of Pediatrics, Children´s Hospital of Pittsburgh, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.
3Department of Experimental Medicine, Section of Human Anatomy, University of Palermo, School of Medicine, Italy.
Address correspondence to: Patrizia Luppi, e-mail: luppip+@pitt.edu

Keywords: monocytes, adhesion molecules, type 1 diabetes, obesity, inflammation

Abstract

AIM: Compelling evidence implicates inflammation in the pathogenesis of type 1 diabetes mellitus (T1DM) and associated vascular complications. Obesity is also characterized by low-grade systemic inflammation. In this study, we characterized the inflammatory response in diabetes by analyzing the expression of a panel of activation markers on the surface of peripheral blood monocytes in recently-diagnosed T1DM patients. The potential effects of glycemic control and body mass index (BMI) on monocyte phenotype were also investigated. METHODS: Using flow cytometry, we analyzed the expression of CD11b, CD49d, CD54, CD62L and CD64 antigens on monocytes in a cohort of 51 T1DM patients (≤ 2 months after diagnosis). To test whether phenotype change in monocytes was associated with abnormal cellular function, we studied the adhesive capacity of monocytes to human umbilical vein endothelial cells (HUVEC). RESULTS: We found that circulating monocytes from T1DM patients tested at the clinical onset of the disease (i.e. within 1 week of diagnosis) had higher CD11b expression compared to patients analyzed 2 months after diagnosis (p = 0.02). The highest CD11b levels were detected in patients with HbA1c > 8% (p = 0.04 vs. patients with HbA1c < 8%). In T1DM children analyzed 2 months after diagnosis, we found that those who were overweight (BMI ≥ 85th percentile) had higher levels of monocyte activation than those who were not (BMI ≤ 85th percentile) (p = 0.03). CD11b and HbA1c were significantly correlated (correlation coefficient 0.329, p = 0.02). Finally, monocytes from T1DM patients showed higher adhesion to HUVEC compared to controls. CONCLUSIONS: Circulating immune cells from T1DM patients display many aspects of a proinflammatory state, as indicated by primed or activated monocytes. Obesity is an important factor in monocyte activation during diabetes.

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