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Increased Expression of Monocyte CD11b (Mac-1) in Overweight Recent-Onset Type 1 Diabetic Children
Vincenza Cifarelli1, Ingrid M Libman, Angela Deluca
1Division of Immunogenetics, Department of Pediatrics, Children´s Hospital of Pittsburgh, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.
Insights
Type 1 diabetes mellitus (T1DM) patients exhibit heightened monocyte activation and adhesion, indicating a proinflammatory state. Obesity exacerbates this monocyte activation in T1DM.
Area of Science:
- Immunology
- Endocrinology
- Metabolic Diseases
Background:
- Inflammation is implicated in type 1 diabetes mellitus (T1DM) pathogenesis and vascular complications.
- Obesity is associated with low-grade systemic inflammation.
Purpose of the Study:
- To characterize the inflammatory response in T1DM by analyzing monocyte activation markers.
- To investigate the effects of glycemic control and BMI on monocyte phenotype in T1DM.
Main Methods:
- Flow cytometry was used to analyze monocyte surface antigens (CD11b, CD49d, CD54, CD62L, CD64) in 51 T1DM patients.
- Monocyte adhesion capacity to human umbilical vein endothelial cells (HUVEC) was assessed.
Main Results:
- Monocytes from T1DM patients showed higher CD11b expression at disease onset compared to 2 months post-diagnosis.
- Elevated CD11b levels correlated with HbA1c < 8% and were significantly correlated with HbA1c.
- Overweight T1DM children (BMI >/= 85th percentile) exhibited higher monocyte activation.
- T1DM monocytes displayed increased adhesion to HUVEC.
Conclusions:
- T1DM patients present with circulating immune cells in a proinflammatory state, characterized by primed or activated monocytes.
- Obesity is a significant factor contributing to monocyte activation in diabetes.
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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