The DREAM trial

Abstract

It seems noteworthy and not just coincidence that the extent of hazard reduction for diabetes in individuals at risk in the rosiglitazone group of the DREAM trial1DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial InvestigatorsEffect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial.Lancet. 2006; 368: 1096-1105Summary Full Text Full Text PDF PubMed Scopus (1536) Google Scholar is almost identical to that seen in two large studies of diabetes prevention by lifestyle change.2Tuomilehto J Lindström J Eriksson JG et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.N Engl J Med. 2001; 344: 1343-1350Crossref PubMed Scopus (8202) Google Scholar, 3Knowler WC Barrett-Connor E Fowler SE et al.Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403Crossref PubMed Scopus (14207) Google Scholar The risk of overt type 2 diabetes (or death) within 3 years was reduced by 60% in DREAM, compared with 58% for diabetes in the Finnish Diabetes Prevention Study (DPS)2Tuomilehto J Lindström J Eriksson JG et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.N Engl J Med. 2001; 344: 1343-1350Crossref PubMed Scopus (8202) Google Scholar and the Diabetes Prevention Program (DPP).3Knowler WC Barrett-Connor E Fowler SE et al.Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403Crossref PubMed Scopus (14207) Google Scholar This similarity in outcome suggests that the same subset of individuals with dysglycaemia is responsive to either intense lifestyle change or rosiglitazone. If so, the effects of lifestyle changes or of rosiglitazone on diabetes risk would be mediated by the same mechanism, and genes regulated by peroxisome-proliferator-activated receptor γ (PPARγ) would be the common target. In the Finnish DPS, responders and non-responders to lifestyle changes could be predicted on the basis of patterns of inflammatory immune mediators at baseline.4Esposito K Ciotola M Merante D Giugliano D Rosiglitazone cools down inflammation in the metabolic syndrome.Arterioscler Thromb Vasc Biol. 2006; 26: 1413-1414Crossref PubMed Scopus (10) Google Scholar Indeed, both lifestyle changes and rosiglitazone have profound dampening effects on systemic inflammation,4Esposito K Ciotola M Merante D Giugliano D Rosiglitazone cools down inflammation in the metabolic syndrome.Arterioscler Thromb Vasc Biol. 2006; 26: 1413-1414Crossref PubMed Scopus (10) Google Scholar, 5Herder C Peltonen M Koenig W et al.Systemic immune mediators and lifestyle changes in the prevention of type 2 diabetes: results from the Finnish Diabetes Prevention Study.Diabetes. 2006; 55: 2340-2346Crossref PubMed Scopus (88) Google Scholar and this could be the common mechanism in diabetes prevention. Immunological post-hoc analyses of baseline variables versus outcome in participants in the DREAM trial would be highly desirable, particularly since metabolic variables did not show an association with outcome in the rosiglitazone group in this study. We thank Nanette Schloot and Volker Burkart, members of the Lifestyle and Health Study Group, for their contribution. We declare that we have no conflict of interest. The DREAM trial – Authors' replyThe main aim of the DREAM trial was to determine whether the interventions prevent diabetes, and not to determine their effect on cardiovascular outcomes. Indeed the very low rate of cardiovascular outcomes seen means that there was low power to detect any difference between groups, and that the observed differences in the cardiovascular composite outcome probably occurred by chance. We agree with Steven Nissen that only a large trial involving high-risk patients can reliably answer this question. Full-Text PDF