C-Reactive Protein Is an Independent Predictor of Risk for the Development of Diabetes in the West of Scotland Coronary Prevention Study
- Dilys J. Freeman1,
- John Norrie2,
- Muriel J. Caslake3,
- Allan Gaw3,
- Ian Ford2,
- Gordon D.O. Lowe4,
- Denis St. J. O’Reilly3,
- Chris J. Packard3,
- Naveed Sattar3 and
- for the West of Scotland Coronary Prevention Study Group
- 1Department of Obstetrics and Gynaecology, University of Glasgow, Glasgow, U.K.
- 2Robertson Centre for Biostatistics, University of Glasgow, Glasgow, U.K.
- 3Department of Pathological Biochemistry, University of Glasgow, Glasgow, U.K.
- 4Department of Medicine, University of Glasgow, Glasgow, U.K.
Accumulating evidence implicates inflammation as a potential pathway in the pathogenesis of type 2 diabetes. The objective of the present study was to assess the ability of C-reactive protein (CRP) to predict the development of diabetes in middle-aged men in the West of Scotland Coronary Prevention Study. Baseline plasma samples for CRP measurement were available for 5,245 men of whom 127 were classified as having a transition from normal glucose control to overt diabetes during the study, based on American Diabetes Association criteria. Baseline CRP was an important predictor of the development of diabetes in univariate analysis (hazard ratio [HR] for an increase of 1 SD = 1.55; 95% CI 1.32–1.82; P < 0.0001). In multivariate analysis, CRP remained a predictor of diabetes development (HR 1.30; 95% CI 1.07–1.58; P = 0.0075) independent of other clinically employed predictors, including baseline BMI and fasting triglyceride and glucose concentrations. Moreover, there was a graded increase in risk across CRP quintiles throughout the study, evident at even 1 year of follow-up. The highest quintile (CRP >4.18 mg/l) was associated with a greater than threefold risk of developing diabetes (HR 3.07; 95% CI 1.33–7.10) in a multivariate analysis at 5 years. Thus, CRP predicts the development of type 2 diabetes in middle-aged men independently of established risk factors. Because CRP, the most commonly used acute-phase protein in clinical practice, is very stable in serum, our observations have clinical potential in helping to better predict individuals destined to develop type 2 diabetes. They also add to the notion that low-grade inflammation is important in the pathogenesis of type 2 diabetes.
Address correspondence and reprint requests to Dr. Dilys Freeman, Department of Obstetrics and Gynaecology, Royal Infirmary, Queen Elizabeth Building, 10 Alexandra Parade, Glasgow, G31 2ER, U.K. E-mail:.
A.G. has received honoraria for lectures from Bristol-Myers Squibb, AstraZeneca, MSD, Pfizer, and Sankyo. I.F. has received honoraria for speaking engagements from Bristol-Myers Squibb.
Received for publication 12 November 2001 and accepted in revised form 15 February 2002.
ADA, American Diabetes Association; CRP, C-reactive protein; HR, hazard ratio; WCC, white cell count; WOSCOPS, West of Scotland Coronary Prevention Study.