High-sensitive C-reactive protein and risk of incident type 2 diabetes: a case–control study nested within the Singapore Chinese Health Study

BACKGROUND The liver-derived C-reactive protein (CRP) is a sensitive and systemic biomarker of inflammation, and has been associated with increased risk of developing type 2 diabetes in populations other than Chinese. Therefore, we prospectively examined the relation between plasma levels of CRP and risk of type 2 diabetes (T2D) among a Chinese population. METHODS Plasma high-sensitive CRP (hs-CRP) concentrations were assayed among 571 T2D cases and 571 controls nested in the prospective cohort of the Singapore Chinese Health Study. Both cases and controls were free of physician-diagnosed diabetes, cardiovascular disease and cancer at blood collections (1999-2004). Incident physician-diagnosed T2D cases were self-reported during the follow-up visits (2006-2010), and controls were matched for age (±3 years) and date (±6 months) of blood collection and gender. Multivariable logistic regression models were used to compute the odds ratio (OR) and the corresponding 95% confidence intervals (CIs). RESULTS The mean (SD) concentrations of hs-CRP were 2.79 (2.65) and 1.86 (2.03) mg/L, respectively, in cases and controls (P < 0.001). After multivariate adjustment for T2D risk factors such as lifestyle, body mass index, plasma triglycerides and HDL cholesterol, the OR comparing the extreme quartiles of hs-CRP was 1.74 [95% CI 1.12-2.70; P for trend = 0.016]. When the analysis was limited to 279 cases who had HbA1c ≥6.5% at the time of blood collection and their controls, the OR comparing the extreme quartiles of hs-CRP was 2.43 (95% CI 1.25-4.71; P for trend = 0.003). When confined to the other 292 subjects with HbA1c <6.5% and their controls, the corresponding OR was 1.24 (95% CI 0.64-2.39; P for trend = 0.93). CONCLUSIONS We found that CRP was not associated with increased risk of incident diabetes in this cohort of Chinese in Singapore. Previous positive findings from prospective studies might be partly due to undiagnosed T2D among the cases during blood collection.