Evidence of increased inflammation and microcirculatory abnormalities in patients with type 1 diabetes and their role in microvascular complications.
OBJECTIVE
Type 1 diabetes is associated with increased microvascular complications and inflammation. The monocyte-macrophage is a pivotal cell in atherogenesis. There are scanty data on noninvasive measures of microvascular abnormalities and inflammation in type 1 diabetic subjects with microvascular complications. Thus, we examined systemic and cellular biomarkers of inflammation in type 1 diabetic patients with microvascular complications (T1DM-MV patients) and type 1 diabetic patients without microvascular complications (T1DM patients) compared with matched control subjects and determined the microcirculatory abnormalities in the T1DM and T1DM-MV patients using computer-assisted intravital microscopy (CAIM).


METHODS
Fasting blood, 24-h urine, and CAIM measurements were obtained from the T1DM and T1DM-MV patients and matched control subjects. C-reactive protein, E-selectin, nitrotyrosine, monocyte superoxide, and cytokines were elevated in the T1DM and T1DM-MV patients compared with control subjects (P < 0.01).


RESULTS
Severity index, as assessed by CAIM, was significantly increased in the T1DM and T1DM-MV patients compared with the control subjects (P < 0.001). There was a significant increase in C-reactive protein, nitrotyrosine, vascular cell adhesion molecule and monocyte superoxide anion release, and interleukin-1 release in T1DM-MV compared with T1DM patients (P < 0.05). T1DM-MV patients had significantly increased CAIM severity index and microalbumin-to-creatinine ratio compared with T1DM patients (P < 0.05). Furthermore, pp38MAPK, pp65, and pERK activity were significantly increased in monocytes from the T1DM and T1DM-MV patients compared with those from the controls subjects, and pp38MAPK and pp65 activity were significantly increased in the T1DM-MV compared with the T1DM patients (P < 0.01).


CONCLUSIONS
T1DM-MV patients have increased inflammation compared with T1DM patients. CAIM provides an effective biomarker of microvascular complications, since it is significantly elevated in T1DM-MV compared with T1DM patients and can be monitored following therapies targeted at improving inflammation and/or microvascular complications of type 1 diabetes.
Department of Pathology, Laboratory for Atherosclerosis and Metabolic Research, UCDavis Medical Center, Sacramento, CA 95817, USA. sdevaraj@ucdavis.edu
Sridevi
S
Devaraj
Anthony T
AT
Cheung
Ishwarlal
I
Jialal
Steven C
SC
Griffen
Danh
D
Nguyen
Nicole
N
Glaser
Thomas
T
Aoki
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000503:physiopathology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology*; D008264:Macrophages / Q000502:physiology; D008833:Microcirculation / Q000503:physiopathology*; D009000:Monocytes / Q000502:physiology; D015398:Signal Transduction; D013481:Superoxides / Q000097:blood
D015415:Biomarkers; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D013481:Superoxides