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Diabetes Publish Ahead of Print published online ahead of print August 8, 2007
DOI: 10.2337/db07-0784
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Original Research

Evidence of Increased Inflammation and Monocytic Activity in Patients with Type 1 Diabetes: plausible role in Microvascular Complications

Sridevi Devaraj, PhD1, Anthony T. Cheung, PhD1, Ishwarlal Jialal, MD, PhD1,2, Steven C. Griffen, MD2, Danh Nguyen, PhD3, Nicole Glaser, MD2, and Thomas Aoki, MD2

Laboratory for Atherosclerosis and Metabolic Research, Departments of Pathology1 and
Internal Medicine2 and
Biostatistics3, UCDavis Medical Center, Sacramento CA

Correspondence: sdevaraj{at}ucdavis.edu

Background and Objectives:Type I diabetes (T1DM) is associated with increased microvascular complications and inflammation. The monocyte-macrophage is a pivotal cell in atherogenesis. There are scanty data on non-invasive measures of microvascular abnormalities and inflammation in T1DM with microvascular complications. Thus, we examined systemic and cellular biomarkers of inflammation in patients with T1DM with (T1DM-MV) and without microvascular complications (T1DM) compared to matched controls (C) and determined the microcirculatory abnormalities in T1DM and T1DM-MV using computer assisted intravital microscopy (CAIM).

Research Design and Methods:Fasting blood, 24 hr urine and CAIM measurements were obtained from T1DM and T1DM-MV and matched controls (C).

Results:CRP, E-selectin, nitrotyrosine, monocyte superoxide, cytokines were elevated in T1DM and T1DM-MV compared to C (p<0.01). Severity index, as assessed by CAIM, was significantly increased in T1DM and T1DM-MV compared to C (p<0.001). There was a significant increase in CRP, nitrotyrosine, VCAM and monocyte superoxide anion release, IL-1 release in T1DM-MV compared to T1DM (P<0.05). T1DM-MV had significantly increased CAIM severity index and microalbumin:creatinine ratio compared to T1DM (p<0.05). Furthermore, pp38MAPK, pp65 and pERK activity were significantly increased in monocytes from T1DM and T1DM-MV compared to C and pp38MAPK and pp65 activity were significantly increased in T1DM-MV compared to T1DM (p<0.01).

Conclusions:T1DM-MV have increased inflammation compared to T1DM. CAIM provides an effective biomarker of microvascular complications since it is significantly elevated in T1DM-MV compared to T1DM and can be monitored following therapies targeted at improving inflammation and/or microvascular complications of T1DM.


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