title: Lipoprotein-associated phospholipase A2 (Lp-PLA2) and future risk of type 2 diabetes: results from the Cardiovascular Health Study.
abstract: BACKGROUND
  Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) 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-PLA(2) 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-PLA(2) mass and activity with type 2 diabetes among older adults.
  
  
  METHODS
  We conducted analyses of Lp-PLA(2) and prevalent and incident diabetes among 5474 men and women from the Cardiovascular Health Study (1989-2007). Lp-PLA(2) 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-PLA(2) 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-PLA(2) 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-PLA(2) activity [multivariable hazard ratio = 1.45 (95% CI = 1.01-2.07)] compared with the lowest quintile. Lp-PLA(2) mass was not significantly associated with incident type 2 diabetes.
  
  
  CONCLUSIONS
  Lp-PLA(2) activity is positively associated with insulin resistance and predicts incident type 2 diabetes among older adults independent of multiple factors associated with diabetes pathogenesis.
authors.affiliation: Colorado State University, Colorado School of Public Health and Department of Health and Exercise Science, 220 Moby Complex, Fort Collins, Colorado 80523-1582, USA. tnelson@cahs.colostate.edu
authors.forename: T L
authors.initials: TL
authors.lastname: Nelson
authors.forename: M L
authors.initials: ML
authors.lastname: Biggs
authors.forename: J R
authors.initials: JR
authors.lastname: Kizer
authors.forename: M
authors.initials: M
authors.lastname: Cushman
authors.forename: J E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: C D
authors.initials: CD
authors.lastname: Furberg
authors.forename: K J
authors.initials: KJ
authors.lastname: Mukamal
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase