Moderate Alcohol Consumption and Insulin Sensitivity: Observations and Possible Mechanisms

Alcohol and Diabetes 

The prevalence of type 2 diabetes is rising. Between 2000 and 2030, a 37% increase in the worldwide prevalence of diabetes is expected (1). Next to aging of the population, the lack of physical activity and high energy intake leading to overweight and obesity have been shown to be largely responsible for the so-called obesity epidemic. Moderate alcohol consumption has been suggested to be a lifestyle factor that may modify the risk of developing type 2 diabetes.

A meta-analysis was performed based on all epidemiologic studies available describing the association between moderate alcohol consumption and type 2 diabetes risk (2). The 15 original cohort studies that were included comprise 11,959 incident cases of type 2 diabetes in 369,682 individuals who, on average, were followed up for 12 years. A U-shaped association was obtained after pooling all data, suggesting a 30% reduced risk of type 2 diabetes in moderate alcohol consumers, whereas no risk reduction was observed in those consuming more than 48 g of alcohol per day. The lower type 2 diabetes risk was consistent over most included studies, but risk estimates differed more across studies than expected. This appeared not to be caused by multiple adjustments, the definition of type 2 diabetes used, or by differences between men and women and low and high body mass index. In the absence of long-term randomized intervention studies, a meta-analysis can be considered the best available evidence.

However, relatively few data were available in the meta-analysis on the association between moderate drinking and the incidence of type 2 diabetes in women. Therefore this association was studied in one of the Dutch Prospect-EPIC (European Prospective Investigation into Cancer and Nutrition) cohorts consisting of 16,330 women aged 49 to 70 years, who were free from diabetes and were followed up for 6.2 years (3). During follow-up, 760 new cases of type 2 diabetes were documented. A linear inverse association between alcohol consumption and type 2 diabetes risk was observed. The hazard ratio for type 2 diabetes risk varied between 0.9 and 0.6 up to consumption levels of 210 g of alcohol per week. Beverage type seemed not to affect the association. Lifetime alcohol consumption was associated with type 2 diabetes in a U-shaped fashion. These findings support the evidence of a decreased risk of type 2 diabetes with moderate alcohol consumption and expand the finding to a population of older women.

In an additional meta-analysis, the relationship between alcohol consumption and coronary heart disease and mortality in type 2 diabetic patients was investigated. Statistical pooling showed lower risks in those who consumed alcohol than in those who did not for total mortality, fatal and total coronary heart disease (4).

Possible Mechanisms in Type 2 Diabetes Reduction 

A reduced type 2 diabetes risk in moderate alcohol consumers may be explained by an increase in insulin sensitivity. Indeed, an association between alcohol consumption and insulin sensitivity is consistently reported in cross-sectional studies 5, 6.

Randomized controlled trials, however, report contradictory results. An alcohol intake reduction study (7) showed that high-density lipoprotein cholesterol and liver enzymes were reduced in healthy young men, but the intervention did not affect the insulin sensitivity index (assessed by clamp technique) or homeostatic model (HOMA) assessment, calculated on the basis of fasting insulin and glucose. A borderline increase in an insulin-resistant subgroup was observed in a study using 23 healthy middle-aged men consuming 40 g of whisky with dinner daily for 17 days (vs. tap water for 17 days) (8). Insulin sensitivity index improvement correlated positively with the relative alcohol-induced increase in plasma adiponectin level in that study. Another study showed that consumption of 30 g of alcohol per day for an 8-week period had beneficial effects on insulin and triglyceride concentrations and insulin sensitivity in a group of 51 nondiabetic postmenopausal women (9).

Possible reasons for the variations in study outcome may be related to the outcome measurement analyzed, the duration of the intervention, the dose of alcohol used, and the group of subjects chosen. Additional randomized controlled trials are needed to further substantiate improved insulin sensitivity in moderate alcohol consumers.

Insulin sensitivity may be affected by moderate alcohol consumption through several mechanisms. Possible mechanisms include modulation of changes in the endocrine functioning of fat tissue, modulation of the inflammatory status of several organs, or modulation of metabolism.

Fat tissue has been appreciated more over the last several years as an organ that is actively involved in communication with other organs through endocrine and other mechanisms, for example, through the production of adipocytokines, such as adiponectin. Plasma adiponectin concentrations are significantly lower in subjects with obesity and type 2 diabetes. Also, low fasting plasma adiponectin concentrations are associated with high basal and low insulin-stimulated skeletal muscle insulin receptor tyrosine phosphorylation, which is one possible cause of decreased insulin sensitivity.

Epidemiologic studies have shown that moderate alcohol consumption is associated with increased adiponectin concentrations (10). Randomized control trials have shown that moderate alcohol consumption will increase plasma adiponectin levels by about 11% 8, 11. In these trials, increases in plasma adiponectin concentrations correlated with increased insulin sensitivity. Adiponectin is thought to improve insulin sensitivity by suppression of glucose production, or increased glucose uptake and fatty acid oxidation in muscle tissue. Possibly, other adipokines like leptin, resistin, and acylation-stimulating protein are also affected.

Alternatively, inflammation of adipose tissue may cause insulin resistance. Interestingly, there appears to be an association between moderate alcohol consumption and inflammatory status. C-reactive protein (CRP) is one of the inflammatory biomarkers, being a nonspecific acute-phase protein produced by the liver in response to tissue injury, infection, and inflammation. A mild CRP elevation within the normal, nonacute-phase range has recently emerged as a valuable marker of cardiovascular risk. Biomarkers for inflammation have been shown to be affected by moderate alcohol consumption both in epidemiologic studies as well as in randomized controlled trials. These include CRP 12, 13 and several others.

A final possible mechanism by which moderate alcohol consumption may affect insulin sensitivity is through a change in intermediary metabolism. Studies are now under way to investigate the effects of moderate alcohol consumption on glucose and fatty acid metabolism in plasma and muscle. These studies may use several genotypes of alcohol metabolizing enzymes generating differing levels of alcohol metabolites which may modulate insulin sensitivity.