Yftach Gepner, MPH (*); Rachel Golan, RD, PhD (*); Ilana Harman-Boehm, MD; Yaakov Henkin, MD; Dan Schwarzfuchs, MD; Ilan Shelef, MD; Ronen Durst, MD; Julia Kovsan, MSc; Arkady Bolotin, PhD; Eran Leitersdorf, MD; Shoshana Shpitzen, MA; Shai Balag, MD; Elad Shemesh, MD; Shula Witkow, RD, MPH; Osnat Tangi-Rosental, BA (†); Yoash Chassidim, PhD; Idit F. Liberty, MD; Benjamin Sarusi, MSc; Sivan Ben-Avraham, RD, MPH; Anders Helander, PhD; Uta Ceglarek, PhD; Michael Stumvoll, MD; Matthias Blüher, MD; Joachim Thiery, MD; Assaf Rudich, MD, PhD; Meir J. Stampfer, MD, DrPH; Iris Shai, RD, PhD
* Mr. Gepner and Dr. Golan contributed equally to this work.
This article was published online first at www.annals.org on 13 October 2015.
Acknowledgment: The authors thank the CASCADE participants for their consistent cooperation. They thank Harel Segal from Nuclear Research Center Negev; Dr. Lena Novak, Dr. Michael Friger, Dr. Arie Moran, Dr. Amos Katz, Noa Cohen, Michal Rein, Nitzan Bril, and Dana Serfaty from Ben-Gurion University of Negev; Dr. Tatiana Shuster, Sagit Saadon, Malka Kaminsky, Yasmin Asuly, Roman Tsirkin, and David Shushan from Soroka Medical Center; Eyal Goshen, Meir Aviv, Hassia Krakauer, Haim Strasler, Dr. Ziva Schwartz, Dr. Einat Sheiner, Dr. Dov Brickner, Dr. Rachel Marko, Esther Katorza, Ilanit Asulin, and Tzvika Tzur from Nuclear Research Center Negev; and Dr. Rosa M. Lamuela-Raventos, University of Barcelona.
Grant Support: By the European Foundation for the Study of Diabetes of the European Association for the Study of Diabetes.
Disclosures: The authors have no relationship with the companies that make products relevant to the manuscript. Drs. Shai and Bolotin had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Bluüher reports compensation as a board member of Novartis Pharmaceuticals, Boehringer Ingelheim, and Sanofi; compensation as a consultant for Novo Nordisk, Eli Lilly Pharmaceuticals, and AstraZeneca; and payment for lectures (including service on speakers bureaus) for Sanofi, Eli Lilly Pharmaceuticals, Novo Nordisk, Bayer HealthCare Pharmaceuticals, AstraZeneca, Novartis Pharmaceuticals, and Berlin-Chemie outside of the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1650.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement:Study protocol: Available from Dr. Shai (e-mail, email@example.com). Statistical code and data set: Not available.
Requests for Single Reprints: Iris Shai, RD, PhD, Department of Public Health, The S. Daniel Abraham International Center for Health and Nutrition, Ben-Gurion University of the Negev, PO Box 653, Beer Sheva, 8410501, Israel; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Golan, Bolotin, Rudich, and Shai; Mr. Gepner, Ms. Kovsan, Ms. Witkow, Ms. Tangi-Rosental, and Ms. Ben-Avraham: Department of Public Health, Ben-Gurion University of the Negev, PO Box 653, Beer Sheva, 8410501, Israel.
Drs. Harman-Boehm, Henkin, Shelef, Shemesh, Chassidim, and Liberty: Soroka Medical Center, Rager Boulevard, PO Box 151, Beer Sheva, 85025, Israel.
Dr. Schwarzfuchs and Mr. Sarusi: Nuclear Research Center Negev, 16th Beth Lethem Street, Dimona, 8477605, Israel.
Drs. Durst, Leitersdorf, Balag; and Ms. Spitzen: Hadassah Hebrew University Medical Center, Kiryat Hadassah, PO Box 12000, Jerusalem, 91120, Israel.
Dr. Helander: Department of Laboratory Medicine, H5, Division of Clinical Chemistry, CI:74, Karolinska Institute, Karolinska University Laboratory Hudding, Stockholm, SE-14186, Sweden.
Drs. Ceglarek, Stumvoll, Blüher, and Thiery: Department of Diagnostics, University of Leipzig, Paul List Street 13-15, 04103 Leipzig, Germany.
Dr. Stampfer: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard School of Public Health, 181 Longwood Avenue, Boston, MA 02115.
Author Contributions: Conception and design: Y. Gepner, I. Harman-Boehm, Y. Henkin, D. Schwarzfuchs, I. Shelef, R. Durst, E. Shemesh, S. Witkow, M. Stumvoll, A. Rudich, M.J. Stampfer, I. Shai.
Analysis and interpretation of the data: Y. Gepner, R. Golan, I. Harman-Boehm, I. Shelef, R. Durst, J. Kovsan, A. Bolotin, S. Shpitzen, E. Shemesh, Y. Chassidim, A. Helander, U. Ceglarek, M. Stumvoll, M. Bluüher, A. Rudich, M.J. Stampfer, I. Shai.
Drafting of the article: Y. Gepner, R. Golan, Y. Henkin, D. Schwarzfuchs, I. Shelef, R. Durst, J. Kovsan, A. Helander, U. Ceglarek, M. Stumvoll, A. Rudich, M.J. Stampfer, I. Shai.
Critical revision of the article for important intellectual content: Y. Gepner, I. Harman-Boehm, Y. Henkin, I. Shelef, R. Durst, J. Kovsan, E. Shemesh, A. Helander, M. Stumvoll, M. Bluüher, J. Thiery, A. Rudich, I. Shai.
Final approval of the article: Y. Gepner, R. Golan, I. Harman-Boehm, Y. Henkin, D. Schwarzfuchs, I. Shelef, R. Durst, J. Kovsan, A. Bolotin, E. Leitersdorf, E. Shemesh, I.F. Liberty, B. Sarusi, A. Helander, U. Ceglarek, M. Stumvoll, M. Bluüher, J. Thiery, A. Rudich, M.J. Stampfer, I. Shai.
Provision of study materials or patients: Y. Gepner, R. Golan, I. Harman-Boehm, Y. Henkin, D. Schwarzfuchs, R. Durst, S. Witkow, O. Tangi-Rosental, I.F. Liberty, I. Shai.
Statistical expertise: R. Golan, R. Durst, A. Bolotin.
Obtaining of funding: Y. Gepner, R. Durst, M. Stumvoll, I. Shai.
Administrative, technical, or logistic support: I. Shelef, J. Kovsan, E. Leitersdorf, S. Balag, E. Shemesh, O. Tangi-Rosental, B. Sarusi, M. Stumvoll.
Collection and assembly of data: Y. Gepner, R. Golan, Y. Henkin, D. Schwarzfuchs, I. Shelef, R. Durst, J. Kovsan, E. Shemesh, S. Witkow, O. Tangi-Rosental, I.F. Liberty, B. Sarusi, S. Ben-Avraham, M. Bluüher, A. Rudich, I. Shai.
Gepner Y, Golan R, Harman-Boehm I, Henkin Y, Schwarzfuchs D, Shelef I, et al. Effects of Initiating Moderate Alcohol Intake on Cardiometabolic Risk in Adults With Type 2 Diabetes: A 2-Year Randomized, Controlled Trial. Ann Intern Med. 2015;163:569-579. doi: 10.7326/M14-1650
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Published: Ann Intern Med. 2015;163(8):569-579.
Published at www.annals.org on 13 October 2015
Recommendations for moderate alcohol consumption remain controversial, particularly in type 2 diabetes mellitus (T2DM). Long-term randomized, controlled trials (RCTs) are lacking.
To assess cardiometabolic effects of initiating moderate alcohol intake in persons with T2DM and whether the type of wine matters.
2-year RCT (CASCADE [CArdiovaSCulAr Diabetes & Ethanol] trial). (ClinicalTrials.gov: NCT00784433)
Ben-Gurion University of the Negev–Soroka Medical Center and Nuclear Research Center Negev, Israel.
Alcohol-abstaining adults with well-controlled T2DM.
Patients were randomly assigned to 150 mL of mineral water, white wine, or red wine with dinner for 2 years. Wines and mineral water were provided. All groups followed a Mediterranean diet without caloric restriction.
Primary outcomes were lipid and glycemic control profiles. Genetic measurements were done, and patients were followed for blood pressure, liver biomarkers, medication use, symptoms, and quality of life.
Of the 224 patients who were randomly assigned, 94% had follow-up data at 1 year and 87% at 2 years. In addition to the changes in the water group (Mediterranean diet only), red wine significantly increased high-density lipoprotein cholesterol (HDL-C) level by 0.05 mmol/L (2.0 mg/dL) (95% CI, 0.04 to 0.06 mmol/L [1.6 to 2.2 mg/dL]; P < 0.001) and apolipoprotein(a)1 level by 0.03 g/L (CI, 0.01 to 0.06 g/L; P = 0.05) and decreased the total cholesterol–HDL-C ratio by 0.27 (CI, −0.52 to −0.01; P = 0.039). Only slow ethanol metabolizers (alcohol dehydrogenase alleles [ADH1B*1] carriers) significantly benefited from the effect of both wines on glycemic control (fasting plasma glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c) compared with fast ethanol metabolizers (persons homozygous for ADH1B*2).
Across the 3 groups, no material differences were identified in blood pressure, adiposity, liver function, drug therapy, symptoms, or quality of life, except that sleep quality improved in both wine groups compared with the water group (P = 0.040). Overall, compared with the changes in the water group, red wine further reduced the number of components of the metabolic syndrome by 0.34 (CI, −0.68 to −0.001; P = 0.049).
Participants were not blinded to treatment allocation.
This long-term RCT suggests that initiating moderate wine intake, especially red wine, among well-controlled diabetics as part of a healthy diet is apparently safe and modestly decreases cardiometabolic risk. The genetic interactions suggest that ethanol plays an important role in glucose metabolism, and red wine's effects also involve nonalcoholic constituents.
European Foundation for the Study of Diabetes.
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Cardiology, Endocrine and Metabolism, Diabetes, Dyslipidemia, Tobacco, Alcohol, and Other Substance Abuse.
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