Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Effect of wine on carotid atherosclerosis in type 2 diabetes: a 2-year randomized controlled trial

Abstract

Background/Objectives

The progression of carotid-plaque volume in patients with type 2 diabetes is common. Previous observational studies showed an association between moderate alcohol and reduced risk of coronary disease. We examined whether consuming moderate wine affects the progression of carotid atherosclerosis.

Subjects/Methods

In the CASCADE (CArdiovaSCulAr Diabetes and Ethanol), a 2-year randomized controlled trial, we randomized abstainers with type 2 diabetes were to drink 150 ml of either red wine, white wine, or water, provided for 2 years. In addition, groups were guided to maintain a Mediterranean diet. We followed 2-year changes in carotid total plaque volume (carotid-TPV) and carotid vessel wall volume (carotid-VWV), using three-dimensional ultrasound.

Results

Carotid images were available from 174 of the 224 CASCADE participants (67% men; age = 59 yr; HbA1C = 6.8%). Forty-five percent had detectable plaque at baseline. After 2 years, no significant progression in carotid-TPV was observed (water, −1.4 (17.0) mm3, CI (−2.7, 5.5), white-wine, −1.2 (16.9) mm3, CI (−3.8, 6.2), red wine, −1.3 (17.6) mm3, CI (−3.4, 6.0; p = 0.9 between groups)). In post hoc analysis, we divided the 78 participants with detectable baseline carotid plaque into tertiles. Those with the higher baseline plaque burden, whom were assigned to drink wine, reduced their plaque volume significantly after 2 years, as compared to baseline.

Two-year reductions in Apo(B)/Apo(A) ratio(s) were independently associated with regression in carotid-TPV (β = 0.4; p < 0.001). Two-year decreases in systolic blood pressure were independently associated with regression in carotid-VWV (β = 0.2; p = 0.005).

Conclusions

No progression in carotid-TPV was observed. In subgroup analyses, those with the greatest plaque burden assigned to drink wine may have had a small regression of plaque burden

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and hemostatic factors. Br Med J. 1999;319:1523–8.

    Article  CAS  Google Scholar 

  2. Stampfer MJ, Colditz GA, Willett WC, Speizer FE, Hennekens CH. A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. N Engl J Med. 1988;319:267–73.

    Article  CAS  Google Scholar 

  3. Koppes LL, Dekker JM, Hendriks HF, Bouter LM, Heine RJ. Meta-analysis of the relationship between alcohol consumption and coronary heart disease and mortality in type 2 diabetic patients. Diabetologia. 2006;49:648–52.

    Article  CAS  Google Scholar 

  4. Solomon CG, Hu FB, Stampfer MJ, Colditz GA, Speizer FE, Rimm EB, et al. Moderate alcohol consumption and risk of coronary heart disease among women with type 2 diabetes mellitus. Circulation. 2000;102:494–9.

    Article  CAS  Google Scholar 

  5. Juonala M, Viikari JS, Kähönen M, Laitinen T, Taittonen L, Loo BM, et al. Alcohol consumption is directly associated with carotid intima–media thickness in Finnish young adults: The Cardiovascular Risk in Young Finns Study. Atherosclerosis. 2009;204:e93–8.

    Article  CAS  Google Scholar 

  6. Costanzo S, Di Castelnuovo A, Donati MB, Iacoviello L, de Gaetano G. Alcohol consumption and mortality in patients with cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2010;55:1339–47.

    Article  Google Scholar 

  7. Liu W, Redmond EM, Morrow D, Cullen JP. Differential effects of daily-moderate versus weekend-binge alcohol consumption on atherosclerotic plaque development in mice. Atherosclerosis. 2011;219:448–54. https://doi.org/10.1016/j.atherosclerosis.2011.08.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kohsaka S, Jin Z, Rundek T, Homma S, Sacco RL, Di Tullio MR. Alcohol consumption and atherosclerotic burden in the proximal thoracic aorta. Atherosclerosis. 2011;219:794–8.

    Article  CAS  Google Scholar 

  9. Mallett C, House AA, Spence JD, Fenster A, Parraga G. Longitudinal ultrasound evaluation of carotid atherosclerosis in one, two and three dimensions. Ultrasound Med Biol. 2009;35:367–75.

    Article  Google Scholar 

  10. Wagenknecht LE, Zaccaro D, Espeland MA, Karter AJ, O’Leary DH, Haffner SM. Diabetes and progression of carotid atherosclerosis the insulin resistance atherosclerosis study. Arterioscler Thromb Vasc Biol. 2003;23:1035–4.

    Article  CAS  Google Scholar 

  11. Makris GC, Lavida A, Griffin M, Geroulakos G, Nicolaides AN. Three-dimensional ultrasound imaging for the evaluation of carotid atherosclerosis. Atherosclerosis. 2011;219:377–83.

    Article  CAS  Google Scholar 

  12. Inaba Y, Chen JA, Bergmann SR. Carotid plaque, compared with carotid intima-media thickness, more accurately predicts coronary artery disease events: a meta-analysis. Atherosclerosis. 2012;220:128–33.

    Article  CAS  Google Scholar 

  13. Wannarong T, Parraga G, Buchanan D, Fenster A, House AA, Hackam DG, et al. Progression of carotid plaque volume predicts cardiovascular events. Stroke. 2013;44:1859–65.

    Article  Google Scholar 

  14. Spence JD, Parraga G. Three-dimensional ultrasound of carotid plaque. Neuroimaging Clin N Am. 2016;26:69–80. https://doi.org/10.1016/j.nic.2015.09.006

    Article  PubMed  Google Scholar 

  15. Shai I, Spence JD, Schwarzfuchs D, Henkin Y, Parraga G, Rudich A, Fenster A, et al. Dietary intervention to reverse carotid atherosclerosis. Circulation. 2010;121:1200–8.

    Article  Google Scholar 

  16. Chiu B, Egger M, Spence JD, Parraga G, Fenster A. Quantification of carotid vessel wall and plaque thickness change using 3D ultrasound images. Med Phys. 2008;35:3691–710.

    Article  Google Scholar 

  17. Shai I, Wainstein J, Harman-Boehm I, Raz I, Fraser D, Rudich A, et al. Glycemic effects of moderate alcohol intake among patients with type 2 diabetes. Diabetes Care. 2007;30:3011–6.

    Article  CAS  Google Scholar 

  18. 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;163:569–79.

    Article  Google Scholar 

  19. Shai I, Rosner BA, Shahar DR, Vardi H, Azrad AB, Kanfi A, et al. Dietary evaluation and attenuation of relative risk: multiple comparisons between blood and urinary biomarkers, food frequency, and 24-hour recall questionnaires: the DEARR study. J Nutr. 2005;135:573–9.

    Article  CAS  Google Scholar 

  20. Golan R, Schwarzfuchs D, Stampfer MJ, Shai I. Halo effect of a weight-loss trial on spouses: the DIRECT-Spouse study. Public Health Nutr. 2010;13:544–9.

    Article  Google Scholar 

  21. Egger M, Spence JD, Fenster A, Parraga G. Validation of 3D ultrasound vessel wall volume: an imaging phenotype of carotid atherosclerosis. Ultrasound Med Biol. 2007;33:905–14.

    Article  Google Scholar 

  22. Krasinski A, Chiu B, Spence JD, Fenster A, Parraga G. Three dimensional ultrasound quantification of intensive statin treatment of carotid atherosclerosis. Ultrasound Med Biol. 2009;35:1763–72.

    Article  Google Scholar 

  23. Ainsworth CD, Blake CC, Tamayo A, Beletsky V, Fenster A, Spence JD. 3D ultrasound measurement of change in carotid plaque volume: a tool for rapid evaluation of new therapies. Stroke. 2005;36:1904–9.

    Article  Google Scholar 

  24. Baraona E, Abittan CS, Dohmen K, Moretti M, Pozzato G, Chayes ZW, et al. Gender differences in pharmacokinetics of alcohol. Alcohol: Clin Exp Res. 2001;25:502–7.

    Article  CAS  Google Scholar 

  25. Tatsumi Y, Morimoto A, Asayama K, Sonoda N, Miyamatsu N, Ohno Y, Miyamoto Y, Izawa S, Ohkubo T Association between alcohol consumption and incidence of impaired insulin secretion and insulin resistance in Japanese: the Saku study. Diabetes Res Clin Pract. 2017. pii: S0168-8227;31228-7. https://doi.org/10.1016/j.diabres.2017.10.021.

    Article  CAS  Google Scholar 

  26. Kim JY, Lee DY, Lee YJ, Park KJ, Kim KH, Kim JW. et l. Chronic alcohol consumption potentiates the development of diabetes through pancreatic β-cell dysfunction. World J Biol Chem. 2015;6:1–15. http://doi.org/10.4331/wjbc.v6.i1.1

    Article  Google Scholar 

  27. OECD (2011), Health at a Glance 2011: OECD Indicators, OECD Publishing. https://doi.org/10.1787/health_glance-2011-en

  28. Maiorino MI, Bellastella G, Petrizzo M, Gicchino M, Caputo M, Giugliano D, et al. Effect of a Mediterranean diet on endothelial progenitor cells and carotid intima-media thickness in type 2 diabetes: follow-up of a randomized trial. Eur J Prev Cardiol. 2017;24:399–408.

    Article  Google Scholar 

  29. Gardener H, Wright CB, Cabral D, Scarmeas N, Gu Y, Cheung K, et al. Mediterranean diet and carotid atherosclerosis in the Northern Manhattan Study. Atherosclerosis. 2014;234:303–10.

    Article  CAS  Google Scholar 

  30. Murie-Fernandez M, Irimia P, Toledo E, Martínez-Vila E, Buil-Cosiales P, Serrano-Martínez M, et al. Carotid intima-media thickness changes with Mediterranean diet: a randomized trial (PREDIMED-Navarra). Atherosclerosis. 2011;219:158–62.

    Article  CAS  Google Scholar 

  31. Sala-Vila A, Romero-Mamani ES, Gilabert R, Núñez I, de la Torre R, Corella D, et al. Changes in ultrasound-assessed carotid intima-media thickness and plaque with a Mediterranean diet. Arterioscler Thromb Vasc Biol. 2014;34:439–45.

    Article  CAS  Google Scholar 

  32. Zanchetti A, Crepaldi G, Bond MG, Gallus GV, Veglia F, Ventura A, et al. Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima–media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study. J Hypertens. 2001;19:79–88.

    Article  CAS  Google Scholar 

  33. Su TC, Jeng JS, Chien KL, Sung FC, Hsu HC, Lee YT. Hypertension status is the major determinant of carotid atherosclerosis: a community-based study in Taiwan. Stroke. 2001;32:2265–71.

    Article  CAS  Google Scholar 

  34. Herder M, Johnsen SH, Arntzen KA, Mathiesen EB. Risk factors for progression of carotid intima-media thickness and total plaque area: a 13-year follow-up study: the Tromsø Study. Stroke. 2012;43:1818–23.

    Article  Google Scholar 

  35. Briasoulis A, Agarwal V, Messerli FH. Alcohol consumption and the risk of hypertension in men and women: a systematic review and meta-analysis. J Clin Hypertens. 2012;14:792–8.

    Article  Google Scholar 

  36. Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, et al. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003;289:2083–93.

    PubMed  Google Scholar 

  37. Chiva-Blanch G, Urpi-Sarda M, Ros E, Arranz S, Valderas-Martínez P, Casas R, et al. Dealcoholized red wine decreases systolic and diastolic blood pressure and increases plasma nitric oxide: short communication. Circ Res. 2012;111:1065–1068v.

    Article  CAS  Google Scholar 

  38. Gepner Y, Henkin Y, Schwarzfuchs D, Golan R, Durst R, Shelef I, et al. Differential effect of initiating moderate red wine consumption on 24-h blood pressure by alcohol dehydrogenase genotypes: randomized trial in type 2 diabetes. Am J Hypertens. 2016;29:476–83. https://doi.org/10.1093/ajh/hpv126

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge the participants of CASCADE for their valuable collaboration. We honor Harel Segal and Osnat Tangi-Rosental; we thank Dr. Tatiana Shuster, Sagit Saadon, Malka Kaminsky, Yasmin Asuly, Roman Tsirkin, David Shushan, Tamara Lipovetzky-Yasky, Maya Rovner, Ortal Chadad 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, Tzvika Tzur from Nuclear Research Center Negev; Canadian 3DUS team Aaron Fenster, Christiane Mallett, David Tessier, Andrew Wheatley, Christine Piechowicz, Sandra Halko, Shayna McKay, Shi Sherebrin, and Maria DiCiccco for their important contributions.

Funding

This study was funded by the European Foundation for the Study of Diabetes, which had no role in the design, analysis, or writing of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rachel Golan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Golan, R., Shai, I., Gepner, Y. et al. Effect of wine on carotid atherosclerosis in type 2 diabetes: a 2-year randomized controlled trial. Eur J Clin Nutr 72, 871–878 (2018). https://doi.org/10.1038/s41430-018-0091-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-018-0091-4

Search

Quick links