Associations between inflammatory markers, traditional risk factors, and complications in patients with type 2 diabetes mellitus.
OBJECTIVE
Inflammatory markers predict cardiovascular events in a wide range of patients. Two factors, fibrinogen (FIB) and high-sensitivity C reactive protein (CRP), are currently entering clinical practice as cardiovascular risk predictors. In patients with type 2 diabetes mellitus, we sought to examine the relationship between macrovascular disease, urinary albumin/creatinine ratio (ACR), and FIB or CRP, as well as the relationship of FIB and CRP with traditional risk predictors of these complications of diabetes.


METHODS
In 202 consecutive patients with type 2 diabetes mellitus from a diabetes clinic, clinical and biochemical data were obtained and a cross-sectional analysis was performed.


RESULTS
Patients with macrovascular disease had higher FIB (P=.02) but not higher CRP. They were older, more likely to have retinopathy or elevated serum creatinine, had higher ACR and lower HDL cholesterol. They were more likely to be treated with statins, beta-blockers, and ASA. Adjustment for statin therapy did not result in significant differences in CRP levels according to macrovascular disease status. Both FIB (P=.01) and CRP (P=.02) were significantly higher in patients with ACR whose values were in the proteinuria range. In multivariate analysis, both FIB (P=.001) and CRP (P=.03) were positively correlated with ACR, but no association was seen between CRP and ACR when FIB was entered in the model. Other factors positively associated with ACR were age, diastolic blood pressure, retinopathy, and hemoglobin A1c (HbA1c). FIB and CRP were strongly correlated (R=.49, P< or =.001) and this effect was independent of statin therapy. CRP was positively associated with body mass index (BMI), serum triglycerides, and sulfonylurea therapy and negatively associated with metformin therapy. Patients on statin therapy had significantly higher FIB and lower CRP. Women on hormone replacement therapy (HRT) had significantly lower FIB and higher CRP.


CONCLUSIONS
In patients with diabetes: (1) the two markers, FIB and CRP, are interrelated; (2) FIB is significantly associated with presence of microvascular disease, independent of CRP; (3) CRP is strongly associated with metabolic factors but not with complications of diabetes, independently of FIB; (4) statins and HRT were divergently associated with CRP and FIB as HRT was associated with lower FIB and higher CRP, while statins showed the reverse association; and (5) CRP and FIB provide different information about the characteristics and consequences of diabetes mellitus because of divergent associations with biological indicators and therapeutic agents.
Streja
Dan
D
Department of Medicine, UCLA, School of Medicine, Los Angeles, CA, USA. dstreja@ucla.edu
Cressey
Pamela
P
Rabkin
Simon W
SW
D000328:Adult; D000368:Aged; D000419:Albuminuria; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000032:analysis*; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000652:urine; D003925:Diabetic Angiopathies / Q000097:blood / Q000652:urine; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D015415:Biomarkers; D001786:Blood Glucose; D005340:Fibrinogen; D002097:C-Reactive Protein; D003404:Creatinine