title: Estimating the mediating effect of different biomarkers on the relation of alcohol consumption with the risk of type 2 diabetes.
abstract: OBJECTIVE
  Moderate alcohol consumption is associated with a reduced type 2 diabetes risk, but the biomarkers that explain this relation are unknown. The most commonly used method to estimate the proportion explained by a biomarker is the difference method. However, influence of alcohol-biomarker interaction on its results is unclear. G-estimation method is proposed to accurately assess proportion explained, but how this method compares with the difference method is unknown.
  
  
  METHODS
  In a case-cohort study of 2498 controls and 919 incident diabetes cases, we estimated the proportion explained by different biomarkers on the relation between alcohol consumption and diabetes using the difference method and sequential G-estimation method.
  
  
  RESULTS
  Using the difference method, high-density lipoprotein cholesterol explained the relation between alcohol and diabetes by 78% (95% confidence interval [CI], 41-243), whereas high-sensitivity C-reactive protein (-7.5%; -36.4 to 1.8) or blood pressure (-6.9; -26.3 to -0.6) did not explain the relation. Interaction between alcohol and liver enzymes led to bias in proportion explained with different outcomes for different levels of liver enzymes. G-estimation method showed comparable results, but proportions explained were lower.
  
  
  CONCLUSIONS
  The relation between alcohol consumption and diabetes may be largely explained by increased high-density lipoprotein cholesterol but not by other biomarkers. Ignoring exposure-mediator interactions may result in bias. The difference and G-estimation methods provide similar results.
authors: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands. J.Beulens@umcutrecht.nl
authors: Joline W J
authors: JW
authors: Beulens
authors: Yvonne T
authors: YT
authors: van der Schouw
authors: Karel G M
authors: KG
authors: Moons
authors: Hendriek C
authors: HC
authors: Boshuizen
authors: Daphne L
authors: DL
authors: van der A
authors: Rolf H H
authors: RH
authors: Groenwold
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D005260:Female; D006306:Health Surveys; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D002097:C-Reactive Protein