Moderate Alcohol Consumption, Risk of Cardiovascular Disease and Type 2 Diabetes: Influence of Alcohol Oxidation

Moderate Alcohol Consumption, Risk of Cardiovascular Disease and Type 2 Diabetes: Influence of Alcohol Oxidation

Effect of Moderate Alcohol Consumption on PPAR-γ Activity and Risk Markers of Metabolic Disease: Influence of Genetic Variation in Alcohol Oxidation

Moderate alcohol consumption is associated with a decreased risk of cardiovascular disease and type 2 diabetes. The association of alcohol consumption with cardiovascular disease is mediated by a functional polymorphism of alcohol dehydrogenase 1c, but the effect of this polymorphism on alcohol metabolism is only investigated in vitro. The risk reduction of moderate alcohol consumption for cardiovascular disease is explained largely by an increase of HDL cholesterol, but an increase of adiponectin concentrations after moderate alcohol consumption may also be involved. It seems likely that adiponectin is a mediator for the association of moderate alcohol consumption with type 2 diabetes. The mechanism by which moderate alcohol consumption increases adiponectin concentrations is unknown, but ppar-gamma activation may be involved. effects of this polymorphism on mediators of this relation are not known. This study therefore investigates the effect of moderate alcohol consumption and the influence of alcohol dehydrogenase 1c polymorphism on ppar-gamma activated gene expression and risk factors of cardiovascular disease and type 2 diabetes.

Objectives : To investigate the effect of moderate alcohol consumption and influence of genetic variation of ethanol oxidation on: PPAR-γ activated gene expression Markers of coronary heart disease or type 2 diabetes Postprandial changes of HPA-axis activity among 36 postmenopausal women with ADH1C genotype associated with slow or fast alcohol metabolism. Design : Randomized, controlled, not blinded crossover trial with 1 week wash-out preceding each treatment period Participants Description : Apparently healthy postmenopausal women Number : 36 Study substances Test substance : White wine (ca. 25 g alcohol/day) Reference substance : White grape juice Study treatments Treatment A: 250 ml white wine daily (ca. 25 g alcohol/day) Treatment B: 250 ml white grape juice daily Study period - Duration : two periods of 6 weeks preceded by 1 week wash-out period Test parameters: Adiponectin mRNA expression Expression of PPAR-gamma activated genes: CD36, lipoprotein lipase, AP2 Markers of cardiovascular disease (blood lipid profile, Lp-PLA2 activity, hs-CRP, fibrinogen) Markers of type 2 diabetes (adiponectin, adiponectin oligomers, insulin sensitivity) Parameters of alcohol oxidation (postprandial: blood alcohol and acetate, acetaldehyde) HPA-axis activity (postprandial & fasting: cortisol, ACTH, testosterone)

Moderate alcohol consumption, Alcohol dehydrogenase 1c polymorphism, PPAR-gamma activated gene expression

Inclusion Criteria: Healthy women aged 40 to 65 years Absence of menstrual period for at least 2 years Homozygotes for the ADH1C*1 or ADH1C*2 allele of ADH1C I349V polymorphism Alcohol consumption ≥ 5 and ≤ 21 units/week Exclusion Criteria: Smoking Family history of alcoholism History of medical or surgical events that may significantly affect the study outcome, particularly metabolic or endocrine disorders and gastrointestinal disorders Recent blood donation

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Joosten MM, Beulens JW, Kersten S, Hendriks HF. Moderate alcohol consumption increases insulin sensitivity and ADIPOQ expression in postmenopausal women: a randomised, crossover trial. Diabetologia. 2008 Aug;51(8):1375-81. doi: 10.1007/s00125-008-1031-y. Epub 2008 May 27.