Clinical Context

The negative health effects of alcohol consumption, particularly in regard to heavy alcohol intake and addiction, are well understood. However, the deleterious effects of heavy alcohol consumption are counterbalanced by the potential health benefits of light to moderate alcohol intake. A systematic review and meta-analysis by Ronksley and colleagues, which was published in the February 22, 2011, issue of the BMJ, analyzed the potential cardiovascular benefits associated with drinking alcoholic beverages.^[1]

A total of 84 studies were included in the meta-analysis. Alcohol consumption was associated with lower risks for incident coronary heart disease and coronary heart disease mortality, with the greatest impact noted at 1 to 2 alcoholic beverages per day. However, alcohol consumption did not significantly affect the risk for stroke or stroke mortality. The overall pooled adjusted risk for cardiovascular disease mortality in comparing alcohol drinkers vs abstainers was 0.75 (95% confidence interval, 0.70-0.80).

Routine consumption of moderate levels of alcohol has been demonstrated to provide a cardiovascular benefit for patients with type 2 diabetes in cohort studies, but there are few prospective clinical trials of alcohol consumption among adults with diabetes. The current study by Shai and colleagues uses a randomized design to address this issue.

Study Synopsis and Perspective

A glass of wine with dinner can improve lipid and glycemic control profiles in patients with type 2 diabetes mellitus, suggests a small but prospective randomized trial^[2].

Findings from the Cardiovascular Diabetes and Ethanol trial (CASCADE)^[3], which included 224 patients from two centers in Israel with controlled diabetes, showed that those who consumed 150 mL/day of red wine plus a Mediterranean diet had significantly higher levels of high-density lipoprotein cholesterol (HDL-C)and apolipoprotein(a)₁ after 2 years compared with those who drank equal amounts of mineral water plus the healthy diet (the primary outcomes).

In addition, the group randomized to white wine intake had significantly decreased fasting plasma glucose levels vs the mineral-water group. Both wine groups also had significantly improved triglyceride levels.

Principal investigator Dr Iris Shai (Ben-Gurion University of the Negev, Beer Sheva, Israel) told heartwire from Medscape via email that long-term, large-scale multicenter trials are now needed to follow morbidity and mortality incidence rates.

"But for now, the results suggest modest beneficial effects of initiating moderate wine consumption, and red wine in particular" for this patient group, said Shai. However, "these benefits should be weighed against potential risks when translated into clinical practice."

The findings were published online October 13, 2015, in the Annals of Internal Medicine.

"Controversial" Research

"The risk/benefit balance of moderate alcohol consumption in persons with diabetes is controversial," write the investigators. They add that if wine does convey benefit, the question of which color is better has not been thoroughly examined.

As reported by heartwire , Shai presented results of an initial, 3-month feasibility trial at the 2007 European Association for the Study of Diabetes annual meeting.^[4] The team examined 109 "teetotaler diabetics" and found that initiating moderate consumption of red wine significantly decreased fasting plasma glucose levels compared with the participants who continued to abstain from alcohol.

For CASCADE, the researchers sought to assess both the long-term effects and safety of alcohol intake in patients with diabetes, while also examining whether type of wine mattered.

The participants, considered "mostly abstaining" from alcohol at baseline, were enrolled starting in November 2009 and were randomly assigned to consume a 5-oz serving (150 mL) of provided red wine (n=73), white wine (n=68), or mineral water (n=83) every night for 2 years.

"Compliance with alcohol intake was tightly monitored, with patients returning their empty wine bottles and receiving their new supplies," reported Shai.

Exclusion criteria for the study population included intake of more than one alcoholic drink per week at baseline or a personal or family history of myocardial infarction, stroke, or addiction.

All participants underwent several tests, including continuous monitoring of changes in blood pressure, heart rate, and blood glucose levels, "and follow-up for the dynamic of atherosclerosis and fat by ultrasound and MRI [magnetic resonance imaging] tests," Shai noted. "Genetic analysis of alcohol dehydrogenase [ADH]" was also conducted and electronic questionnaires were filled out.

Ethanol's Role

At the end of 2 years, the red-wine group significantly increased their HDL-C levels by 0.05 mmol/L (2.0 mg/dL) (P<0.001) vs the water group and increased their apolipoprotein(a)₁ level by 0.03 g/L (P=0.05). The red-wine group also decreased total cholesterol/HDL-C ratio by 0.27 (P=0.04).

There were no significant differences in lipid changes between the white-wine and water groups. However, the white-wine group did significantly decrease their fasting plasma glucose level by 1.0 mmol/L vs the water group (P=0.004) -- a result that was not found in the red-wine group.

Secondary outcomes included triglyceride levels, which were significantly more favorable for both the red-wine group (-0.1 mmol/L [-12.0 mg/dL], P=0.02) and the white-wine group (-0.09 mmol/L [-7.9 mg/dL], P=0.004) vs the water group.

Carriers of the ADH1B*1 allele ("slow ethanol metabolizers") in the combined wine groups had significant improvements in glycemic control vs those who carried ADH1B*2 homozygotes ("fast ethanol metabolizers"). This included lower fasting plasma glucose (P=0.01) and glycated hemoglobin (HbA_1c) levels (P=0.02).

The ADH1B variants "may assist in identifying patients with [diabetes] for whom moderate wine consumption may be clinically beneficial," write the researchers.

There were no significant changes in blood pressure, liver function, adiposity, drug treatment, or adverse events/symptoms in any of the groups. However, both wine groups saw significantly improved sleep quality vs the water group (P=0.04).

Shai noted that the investigators had hypothesized that "because of the ethanol component," the wine groups would have similar cardiometabolic effects on all measures. So the between-group differences actually found were surprising.

"The provided wines were nearly equal in alcohol and caloric content, but the red wine had sevenfold higher levels of total phenols and four- to 13-fold higher levels of the specific resveratrol group compounds than the white wine," she said.

"The genetic interactions suggest that ethanol plays an important role in glucose metabolism, while red wine's effects additionally involve nonalcoholic constituents."

"An Option for Improving Risk"

"There hasn't been much randomized controlled trial evidence on the effects of alcohol done in this way," Dr William Yancy (Duke University Department of Medicine, Durham, NC) told heartwire .

However, he noted that the current study "just looked at interim or surrogate markers" and not actual outcomes, such as mortality. "I think it provides some interesting information for us to think about, but I don't know if it'll change our clinical recommendations."

In other words, "it's important to keep in mind while we do other research, although it'll be hard to do that kind of long-term research with the end points that you need. Until then, we'll use observational studies to try to answer the issues."

Yancy said that past observational studies have shown that moderate alcohol intake is associated with a lower risk for mortality. "So it's reasonable to say, 'if you're drinking in moderation, keep doing it.' Just like the data show that drinking excessively is not good -- and that message doesn't go away," he said.

"The biggest question we have is: do we advise people to initiate drinking if they don't already drink? This study speaks to that and gives some evidence that alcohol in moderation could be started and you'd see some improvement in their risks."

He added that seeing benefits from both types of wine, albeit with some differences, was interesting. "Red wine benefited HDL cholesterol and the white wine benefited blood sugar control. So it seems like either one could be an option for improving a patient's risk."

The study was funded by a grant from the European Foundation for the Study of Diabetes. Shai, the study coauthors, and Yancy have disclosed no relevant financial relationships.

Clinical Implications

• A previous meta-analysis by Ronksley and colleagues found that moderate alcohol consumption is associated with reductions in incident coronary heart disease and coronary heart disease mortality, but not stroke or stroke mortality.
• The current study by Shai and colleagues demonstrates that moderate, regular wine consumption appears to be safe among adults with type 2 diabetes. Consumption of wine was associated with modest improvements in the lipid profile (red wine) and glucose metabolism (white wine).
• Implications for the Healthcare Team: Patients with type 2 diabetes may have widely variable beliefs and practices when it comes to alcohol consumption. The current study provides reassurance that moderate alcohol consumption should not be harmful for these patients, but it does not dramatically improve the cardiovascular risk profile either.

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