Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) and future risk of type 2 diabetes: Results from the Cardiovascular Health Study

Introduction: Lipoprotein-associated phospholipase A2 (Lp-PLA₂) has been consistently associated with cardiovascular disease (CVD) risk factors and predictive of CVD outcomes; furthermore, it is consistently higher among type 2 diabetics than nondiabetics. However, the relationships of circulating Lp-PLA₂ mass and activity with incident type 2 diabetes mellitus have not been examined. Therefore, the purpose of this study was to determine the association of Lp-PLA₂ mass and activity with type 2 diabetes among older adults. Methods: We conducted analyses of Lp-PLA₂ and prevalent and incident diabetes among 5474 men and women from the Cardiovascular Health Study (1989-2007). Lp-PLA₂ mass and activity were measured in baseline plasma. Diabetes status was ascertained annually with medication inventories and repeated blood glucose measurements. Generalized linear and Cox proportional hazards models were used to adjust for confounding factors including body mass index and inflammation. Results: At baseline, the top two quintiles of Lp-PLA₂ activity were significantly associated with prevalent type 2 diabetes with a multivariable relative risk = 1.35 [95% confidence interval (CI) = 1.11-1.63] for quintile 4, and relative risk = 1.33 (95% CI = 1.07-1.66) for quintile 5. Among participants free of diabetes at baseline, we found a significant positive association with both the homeostatic model assessment for insulin resistance and β-cell function per sd increase in Lp-PLA₂ activity (P values for both <0.01). In prospective analyses, the risk of incident type 2 diabetes was significantly higher among those in the highest quintile of Lp-PLA₂ activity [multivariable hazard ratio = 1.45 (95% CI = 1.01-2.07)] compared with the lowest quintile. Lp-PLA₂ mass was not significantly associated with incident type 2 diabetes. Discussion: Lp-PLA₂ activity is positively associated with insulin resistance and predicts incident type 2 diabetes among older adults independent of multiple factors associated with diabetes pathogenesis.