PURPOSE: 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.
OBJECTIVE: The purpose of this study was to investigate whether adiponectin concentrations and biomarkers of inflammation, endothelial dysfunction, and insulin resistance mediate the association between alcohol consumption and diabetes.
RESEARCH DESIGN AND METHODS: In a nested case-control study of 705 women with incident diabetes and 787 matched control subjects, we examined the adjusted relationship between baseline alcohol consumption and risk of diabetes before and after adjustment for markers of inflammation/endothelial dysfunction (C-reactive protein, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, tumor necrosis factor-alpha receptor 2, and interleukin-6), fasting insulin, and adiponectin concentrations.
RESULTS: Alcohol consumption was associated with a decreased risk of diabetes (odds ratio per 12.5 g/day increment in alcohol use 0.58; 95% CI 0.49-0.69; P < 0.001). Adjustment for BMI attenuated the association by 25%. None of the markers of inflammation or fasting insulin appeared to account for >2% of the observed relationship. Without adjustment for BMI, these biomarkers individually explained slightly more of the association, but <10% in all cases. Adiponectin accounted for 25% in a fully adjusted model and for 29% without adjustment for BMI.
CONCLUSIONS: In this population of women, alcohol consumption was inversely associated with risk of type 2 diabetes. Adiponectin appeared to be a mediator of this association, but circulating biomarkers of inflammation, endothelial dysfunction, and fasting insulin did not explain this association. These results suggest that further research is needed into the potentially mediating roles of other biomarkers affected by alcohol consumption.
Moderate alcohol consumption is associated with reduced cardiovascular disease rates in nondiabetic populations. However, the effects of alcohol in people with diabetes are not well defined. Accordingly, we tested the hypothesis that alcohol would raise plasma high-density lipoprotein (HDL) cholesterol or have other beneficial metabolic effects in persons with type 2 diabetes mellitus. To assess the acute effects of alcohol on plasma glucose and serum insulin, subjects were inpatients for 2 days during which they received, in random order, 240 mL wine or grape juice with their evening meal. To assess the chronic effects of alcohol on fasting plasma lipids, subjects consumed, in random order, 120 to 240 mL wine daily for 30 days and abstained from alcohol for 30 days. Participants were 18 non-insulin-treated volunteers with type 2 diabetes mellitus. Acutely, 240 mL wine containing 24 g alcohol had no effect on plasma glucose or serum insulin. Chronically, wine consumption for 30 days (mean consumption, 18 g alcohol per day) compared with abstinence for 30 days resulted, respectively, in mean +/- SEM fasting plasma cholesterol of 160 +/- 6 and 160 +/- 8 mg/dL (P = .98), HDL cholesterol of 47 +/- 3 and 46 +/- 3 mg/dL (P = .87), low-density lipoprotein cholesterol of 82 +/- 5 and 82 +/- 6 mg/dL (P = .98), triglycerides of 157 +/- 19 and 159 +/- 19 mg/dL (P = .88), glucose of 128 +/- 6 and 128 +/- 7 mg/dL (P = .84), and serum insulin of 14 +/- 2 and 17 +/- 3 microU/mL (P = .03). Moderate consumption of alcohol in the form of wine did not raise plasma HDL cholesterol. However, alcohol did not have any harmful metabolic effect; and chronic consumption lowered fasting serum insulin. People with type 2 diabetes mellitus should not be discouraged from using alcohol in moderation.
Moderate alcohol consumption has been reported to be associated with lower risk for both cardiovascular disease and type 2 diabetes. An explanation for these epidemiologic observations is not entirely clear. Alcohol raises high-density lipoprotein (HDL) cholesterol levels. Other potential beneficial mechanisms have been proposed including anti-inflammatory and anti-thrombotic effects. The association between moderate alcohol consumption and insulin sensitivity is still under debate. Possible mechanisms include elevation of adiponectin level, reduction of C-reactive protein and suppression of free fatty acid release from adipose tissue.