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

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. Grant Support: NIH K24AT00596, NIH R21DK69801, NIH UL1 RR024146