Apolipoprotein C-III and High-Density Lipoprotein Subspecies Defined by Apolipoprotein C-III in Relation to Diabetes Risk

Apolipoprotein C-III (apoC-III) is a potentially novel biomarker that may play an important role in the pathogenesis of diabetes, particularly when present on the surface of high-density lipoprotein (HDL). In a case-cohort study carried out among 434 incident diabetes cases occurring before 2007 and 3,101 noncases in the Danish Diet, Cancer, and Health Study, we examined associations of baseline (1993-1997) plasma concentrations of apoC-III and subspecies of HDL defined by the presence or absence of apoC-III with risk of diabetes using Cox regression. ApoC-III was strongly associated with risk of diabetes (for top quintile vs. bottom quintile, hazard ratio (HR) = 3.43, 95% confidence interval (CI): 1.75, 6.70; P-trend < 0.001). The cholesterol concentration of HDL (HDL cholesterol (HDL-C)) without apoC-III was inversely associated with risk of diabetes (HR = 0.48, 95% CI: 0.27, 0.85; P-trend = 0.002), more so than total HDL-C (HR = 0.60, 95% CI: 0.35, 1.03; P-trend = 0.04), whereas HDL-C with apoC-III was not associated (HR = 1.05, 95% CI: 0.50, 2.21; P-trend = 0.44) (for HDL-C with apoC-III vs. HDL-C without apoC-III, P-heterogeneity = 0.002). ApoC-III itself is a strong risk marker for diabetes, and its presence on HDL may impair the antidiabetogenic properties of HDL. ApoC-III has potential to be a therapeutic target for the prevention of diabetes.