Effect of Alcohol Consumption on Diabetes Mellitus

Key Summary Points Best evidence suggests that moderate alcohol consumption is associated with a reduced incidence of diabetes mellitus. Some evidence suggests that heavy alcohol use may be associated with an increased incidence of diabetes mellitus. There is no evidence of an acute effect of moderate alcohol ingestion on glycemic control. The effect of alcohol use on diabetes self-care behaviors has not been well studied. Limited evidence suggests that ingestion of alcohol while using a sulfonylurea or thiazolidinedione does not result in an adverse event. Strong evidence shows that moderate alcohol consumption is associated with a decreased incidence of coronary heart disease in persons with diabetes. Evidence is insufficient to establish the effect of alcohol consumption on noncardiac complications in persons with diabetes. Diabetes mellitus is one of the most common chronic diseases in the United States, affecting 7.8% of adults 20 years of age or older (1). The microvascular and macrovascular complications of diabetes make it the 6th leading cause of death and a leading cause of blindness in the United States (2). Successful long-term control of hyperglycemia decreases the risk for diabetic complications (3). Although a family history of diabetes is an established risk factor for type 2 diabetes, lifestyle factors also play an important role in its cause (4). For example, the incidence of diabetes has been associated with physical inactivity and obesity, both of which can be modified to decrease the risk for diabetes (5). Alcohol consumption is also prevalent in the United States: An estimated 109 million Americans 12 years of age or older currently drink alcohol (6). Practicing physicians are thus likely to encounter patients who use alcohol in addition to having or being at risk for diabetes. Yet, physicians are poorly informed about how their patients' alcohol use affects risk for or management of diabetes. We performed a systematic review of the medical literature to assess the effects of alcohol consumption on 5 aspects of the epidemiology and treatment of diabetes: incidence, glycemic control, adherence to therapy and self-care behaviors, medication-associated complications, and disease complications. Methods Search Strategies We searched the MEDLINE database for reports published from 1966 to the third week of August 2003 by using a search strategy developed in collaboration with a medical librarian. The search was limited to English-language studies of persons 19 years of age or older. We conducted separate searches for the Medical Subject Headings diabetes mellitus, hypoglycemic agents, and receptors, angiotensin/antagonists & inhibitors, combined with each of the following Medical Subject Headings: ethanol, alcoholism, alcoholic beverages, alcohol-related disorders, or alcohol drinking. In addition, we manually searched the reference lists of retrieved articles and relevant reviews. Study Collection Two reviewers independently assessed each MEDLINE citation by using predefined inclusion and exclusion criteria. To be included, a study had to be an experimental, cohort, or casecontrol study; include persons who had been administered or were current users of alcohol; include persons who had not been administered or were not users of alcohol; and have a relevant primary outcome. For analyses of the incidence of diabetes, the outcome was diabetes. For glycemic control, outcomes were glucose and hemoglobin A1c levels. For self-management behaviors, outcomes were adherence to therapy, home glucose monitoring, diet, and exercise. For medication complications, outcomes were drug levels or adverse drug events. For diabetic complications, outcomes were acute complications, including diabetic ketoacidosis, hyperosmolar coma, infection, and amputation; chronic microvascular complications, including retinopathy, peripheral neuropathy, nephropathy, and erectile dysfunction; and chronic macrovascular complications, including coronary heart disease, cerebral vascular disease, and peripheral vascular disease. Experimental studies in which alcohol was administered to healthy volunteers were considered beyond the scope of this review and were excluded. We used SPSS software, version 10.1 (SPSS, Inc., Chicago, Illinois) to calculate agreement coefficients. Ratings between reviewers had 95% agreement ( = 0.75). Reviewer disagreements were resolved by discussion after review of the citation and the review protocol. Assessment of Study Quality Two reviewers independently rated the quality of each study by using the criteria of the U.S. Preventive Services Task Force for determining internal validity (7). For cohort studies, these criteria include consideration of and adjustment for potential confounders, maintenance of comparable groups, a low rate of and nondifferential loss to follow-up, use of valid measurements, use of clearly defined interventions, and consideration of important outcomes. For experimental trials, these specifications also include adequate randomization and intention-to-treat analysis. On the basis of these criteria, we assigned each study one of the following ratings: good (study meets all criteria well), fair (study does not meet at least 1 criterion but has no limitations that could invalidate its results), or poor (study does not meet at least 1 criterion and has important limitations). Studies that were found to be of poor quality were excluded. Ratings between reviewers had 89% agreement ( = 0.76). Reviewer disagreements were resolved by consensus after review of the article and the review protocol. Data Extraction From each included study, 2 investigators abstracted data on the study sample, study duration, alcohol dose or definition of alcohol exposure, definition and method of measuring outcome, confounders for which the investigators controlled, and measure of association. To aid in comparing results across studies, we converted the measures of alcohol consumption to a single scale whenever possible, in which one drink was equivalent to 12.6 g of ethanol. This conversion was based on the U.S. Department of Agriculture definition of a standard drink (8). Role of the Funding Source The funding source had no role in the collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Data Synthesis Search Results We identified 974 studies. Of these, 942 were excluded because they did not meet the predefined selection criteria (Figure). Of the 32 included studies, 27 were studies of type 2 diabetes only (8-34), 2 were studies of both type 1 and type 2 diabetes (35, 36), and 3 did not specify the type of diabetes (37-39). No included study assessed the effects of alcohol consumption on diabetes self-care behaviors or on diabetic complications other than coronary heart disease and retinopathy. Figure. Study selection Association of Alcohol Consumption and Diabetes Incidence Eighteen prospective cohort studies assessed the association between alcohol consumption and the incidence of diabetes (Appendix Table). Alcohol consumption was categorized in numerous ways, including times per week, grams per week or per day, drinks or units per week, and milliliters or ounces per day. The method by which diabetes was measured also varied, in part because of the change in American Diabetes Association criteria for the diagnosis of diabetes in 1997 (40). Six studies used oral glucose tolerance tests (10, 13, 14, 17, 18, 21), 11 used fasting glucose levels (10, 13, 14, 16-21, 24, 25), and one used random glucose levels (16). Seven studies used self-report of diabetes (8, 9, 11, 15, 22, 23) or use of hypoglycemic medication (12) as the only measure of diabetes incidence. In 2 studies, the outcome included impaired fasting glucose and diabetes (19, 20), and in one study, the outcome was worsening glucose tolerance (progression from normal glucose tolerance to impaired glucose tolerance or diabetes, or progression from impaired glucose tolerance to diabetes) (17). All studies were rated fair. A limitation of many studies was that a standard screening test was not used to diagnose diabetes (8, 9, 11, 12, 15, 22, 23). Another common limitation was that alcohol intake was assessed at baseline only (9-11, 13, 14, 16-19, 21, 22, 25). Several studies dichotomized alcohol consumption and did not distinguish moderate from heavy alcohol use (11, 13, 20, 24). In addition, many studies failed to control for important confounders, including waist-to-hip ratio, family history of diabetes, and race. Six studies used both an objective measure of diabetes incidence and a nondichotomous categorical measure of alcohol consumption (10, 16, 17, 19, 21, 25). Five of these studies (10, 16, 19, 21, 25) and 3 additional studies (12, 22, 23) found a U-shaped relationship between alcohol consumption and incidence of diabetes, with moderate drinkers having the lowest risk for diabetes and nondrinkers and heavy drinkers having a higher risk. Compared with nondrinkers, persons who consumed approximately one to 3 drinks daily had a 33% to 56% reduction in the risk for diabetes. Compared with moderate drinkers, persons who consumed more than 3 drinks daily had up to a 43% greater risk for diabetes; however, this difference was statistically significant in only 2 studies (19, 25). The study that assessed impaired glucose tolerance and diabetes found no association between alcohol use and worsening glucose tolerance (17). Three studies found an inverse relationship between alcohol consumption and diabetes incidence, with moderate drinkers having a 43% to 46% reduction in risk for diabetes compared with nondrinkers (8, 9, 15). In each of these studies, the prevalence of heavy drinking was low (1% to 3%), and power may have thus been insufficient to detect a relationship between heavy alcohol use and diabetes. The quantity of alcohol associated with the lowest risk for diabetes in these studies ran