Incident type 2 diabetes is associated with HDL, but not with its anti-oxidant constituent - paraoxonase-1: The prospective cohort PREVEND study

Objective High-density lipoprotein cholesterol (HDL-C) is an established risk marker for cardiovascular disease and consistently associated with type 2 diabetes risk. Serum paraoxonase-1 (PON-1) - an anti-oxidant constituent of HDL - is inversely associated with cardiovascular disease risk, but its relationship with incident type 2 diabetes is uncertain. We aimed to investigate the prospective association between PON-1 and type 2 diabetes risk. Methods PON-1 was measured as its arylesterase activity at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) prospective study of 5947 predominantly Caucasian participants aged 29–76 years with no pre-existing diabetes, that recorded 500 type 2 diabetes cases during a median follow-up of 11.2 years. Results Serum PON-1 was positively correlated with HDL-C (r = 0.17; P < 0.001). In analyses adjusted for conventional diabetes risk factors, the hazard ratio (95% CI) for type 2 diabetes per 1 standard deviation increase in PON-1 was 1.07 (0.98 to 1.18; P = 0.13), which remained non-significant (1.02 (0.93 to 1.12) P = 0.65) after additional adjustment for potential confounders. The association was unchanged on further adjustment for HDL-C (1.05 (0.96 to 1.15; P = 0.29). However, in subsidiary analyses in the same set of participants, serum HDL-C concentration was inversely and independently associated with risk of type 2 diabetes. Conclusions Incident type 2 diabetes is associated with HDL cholesterol but not with its anti-oxidant constituent - PON-1 - in a large cohort of apparently healthy men and women. The current data question the importance of PON-1 activity for the development of diabetes.