Background Previous studies have suggested that blockade ofthe reninangiotensin system may prevent diabetes in peoplewith cardiovascular disease or hypertension.
Methods In a double-blind, randomized clinical trial with a2-by-2 factorial design, we randomly assigned 5269 participantswithout cardiovascular disease but with impaired fasting glucoselevels (after an 8-hour fast) or impaired glucose toleranceto receive ramipril (up to 15 mg per day) or placebo (and rosiglitazoneor placebo) and followed them for a median of 3 years. We studiedthe effects of ramipril on the development of diabetes or death,whichever came first (the primary outcome), and on secondaryoutcomes, including regression to normoglycemia.
Results The incidence of the primary outcome did not differsignificantly between the ramipril group (18.1%) and the placebogroup (19.5%; hazard ratio for the ramipril group, 0.91; 95%confidence interval [CI], 0.81 to 1.03; P=0.15). Participantsreceiving ramipril were more likely to have regression to normoglycemiathan those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07to 1.27; P=0.001). At the end of the study, the median fastingplasma glucose level was not significantly lower in the ramiprilgroup (102.7 mg per deciliter [5.70 mmol per liter]) than inthe placebo group (103.4 mg per deciliter [5.74 mmol per liter],P=0.07), though plasma glucose levels 2 hours after an oralglucose load were significantly lower in the ramipril group(135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg perdeciliter [7.80 mmol per liter], P=0.01).
Conclusions Among persons with impaired fasting glucose levelsor impaired glucose tolerance, the use of ramipril for 3 yearsdoes not significantly reduce the incidence of diabetes or deathbut does significantly increase regression to normoglycemia.(ClinicalTrials.gov number, NCT00095654
[ClinicalTrials.gov]
.)
Source Information
The members of the Writing Committee (Jackie Bosch, M.Sc., Salim Yusuf, D.Phil., Hertzel C. Gerstein, M.D., Janice Pogue, M.Sc., Patrick Sheridan, M.Sc., McMaster University, Hamilton; Gilles Dagenais, M.D., Laval University Heart and Lung Institute, Quebec; Jean Louis Chiasson, M.D., Research CentreCentre Hospitalier de l'Université de MontrealHôtel-Dieu, Montreal all in Canada; Rafael Diaz, M.D., Instituto Cardiovascular de Rosario, Rosario, Argentina; Alvaro Avezum, Ph.D., Dante Pazzanese Institute of Cardiology, São Paulo, Brazil; Fernando Lanas, M.D., Universidad de la Frontera, Temuco, Chile; Jeffrey Probstfield, M.D., Fred Hutchinson Cancer Research Center, Seattle; George Fodor, Ph.D., University of Ottawa Heart Institute, Ottawa; and Rury R. Holman, F.R.C.P., Oxford Centre for Diabetes, Endocrinology, and Metabolism, Oxford, United Kingdom) of the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial assume responsibility for the overall content and integrity of the article. This article was published at www.nejm.org on September 15, 2006.
Address reprint requests to the DREAM Project Office, Population Health Research Institute, 2nd Fl., McMaster Clinic, 237 Barton St. E, Hamilton, ON L8L 2X2, Canada, or to dream{at}cardio.on.ca.
Freel, E M, Tsorlalis, I K, Lewsey, J D, Latini, R, Maggioni, A P, Solomon, S, Pitt, B, Connell, J M C, McMurray, J J V
(2009). Aldosterone status associated with insulin resistance in patients with heart failure--data from the ALOFT study. Heart
95: 1920-1924
[Abstract][Full Text]
Postma, M. J., de Zeeuw, D.
(2009). The economic benefits of preventing end-stage renal disease in patients with type 2 diabetes mellitus. Nephrol Dial Transplant
24: 2975-2983
[Full Text]
Klapholz, M.
(2009). {beta}-Blocker Use for the Stages of Heart Failure. Mayo Clin Proc.
84: 718-729
[Abstract][Full Text]
Lonn, E. M., Gerstein, H. C., Sheridan, P., Smith, S., Diaz, R., Mohan, V., Bosch, J., Yusuf, S., Dagenais, G. R., DREAM (Diabetes REduction Assessment with ramipril,
(2009). Effect of Ramipril and of Rosiglitazone on Carotid Intima-Media Thickness in People With Impaired Glucose Tolerance or Impaired Fasting Glucose STARR (STudy of Atherosclerosis with Ramipril and Rosiglitazone).. J Am Coll Cardiol
53: 2028-2035
[Abstract][Full Text]
Verdecchia, P., Angeli, F., Cavallini, C., Gattobigio, R., Gentile, G., Staessen, J. A., Reboldi, G.
(2009). Blood pressure reduction and renin-angiotensin system inhibition for prevention of congestive heart failure: a meta-analysis. Eur Heart J
30: 679-688
[Abstract][Full Text]
Kohlstedt, K., Gershome, C., Trouvain, C., Hofmann, W.-K., Fichtlscherer, S., Fleming, I.
(2009). Angiotensin-Converting Enzyme (ACE) Inhibitors Modulate Cellular Retinol-Binding Protein 1 and Adiponectin Expression in Adipocytes via the ACE-Dependent Signaling Cascade. Mol. Pharmacol.
75: 685-692
[Abstract][Full Text]
Cooper-DeHoff, R. M., Pacanowski, M. A., Pepine, C. J.
(2009). Cardiovascular therapies and associated glucose homeostasis: implications across the dysglycemia continuum.. J Am Coll Cardiol
53: S28-S34
[Abstract][Full Text]
Muniyappa, R., Hall, G., Kolodziej, T. L, Karne, R. J, Crandon, S. K, Quon, M. J
(2008). Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension. Am. J. Clin. Nutr.
88: 1685-1696
[Abstract][Full Text]
Cornier, M.-A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., Eckel, R. H.
(2008). The Metabolic Syndrome. Endocr. Rev.
29: 777-822
[Abstract][Full Text]
Friedman, A., Marrero, D., Ma, Y., Ackermann, R., Narayan, K.M. V., Barrett-Connor, E., Watson, K., Knowler, W. C., Horton, E. S., for the Diabetes Prevention Program Research Group,
(2008). Value of Urinary Albumin-to-Creatinine Ratio as a Predictor of Type 2 Diabetes in Pre-Diabetic Individuals. Diabetes Care
31: 2344-2348
[Abstract][Full Text]
Yusuf, S., Diener, H.-C., Sacco, R. L., Cotton, D., Ounpuu, S., Lawton, W. A., Palesch, Y., Martin, R. H., Albers, G. W., Bath, P., Bornstein, N., Chan, B. P.L., Chen, S.-T., Cunha, L., Dahlof, B., De Keyser, J., Donnan, G. A., Estol, C., Gorelick, P., Gu, V., Hermansson, K., Hilbrich, L., Kaste, M., Lu, C., Machnig, T., Pais, P., Roberts, R., Skvortsova, V., Teal, P., Toni, D., VanderMaelen, C., Voigt, T., Weber, M., Yoon, B.-W., the PRoFESS Study Group,
(2008). Telmisartan to Prevent Recurrent Stroke and Cardiovascular Events. NEJM
359: 1225-1237
[Abstract][Full Text]
McDonald, S. D., Yusuf, S., Sheridan, P., Anand, S. S., Gerstein, H. C., for the DREAM Trial Investigators,
(2008). Dysglycemia and a History of Reproductive Risk Factors. Diabetes Care
31: 1635-1638
[Abstract][Full Text]
Blaha, M. J., Bansal, S., Rouf, R., Golden, S. H., Blumenthal, R. S., DeFilippis, A. P.
(2008). A Practical 'ABCDE' Approach to the Metabolic Syndrome. Mayo Clin Proc.
83: 932-943
[Abstract][Full Text]
Bloomgarden, Z. T.
(2008). Approaches to Treatment of Pre-Diabetes and Obesity and Promising New Approaches to Type 2 Diabetes. Diabetes Care
31: 1461-1466
[Full Text]
Balzer, J., Rassaf, T., Heiss, C., Kleinbongard, P., Lauer, T., Merx, M., Heussen, N., Gross, H. B., Keen, C. L., Schroeter, H., Kelm, M.
(2008). Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial.. J Am Coll Cardiol
51: 2141-2149
[Abstract][Full Text]
Norris, S. L., Kansagara, D., Bougatsos, C., Fu, R.
(2008). Screening Adults for Type 2 Diabetes: A Review of the Evidence for the U.S. Preventive Services Task Force. ANN INTERN MED
148: 855-868
[Abstract][Full Text]
Werner, C. M., Bohm, M.
(2008). Review: The therapeutic role of RAS blockade in chronic heart failure. Ther Adv Cardiovasc Dis
2: 167-177
[Abstract]
Solski, L. V., Longyhore, D. S.
(2008). Prevention of type 2 diabetes mellitus with angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm
65: 935-940
[Abstract][Full Text]
Schocken, D. D., Benjamin, E. J., Fonarow, G. C., Krumholz, H. M., Levy, D., Mensah, G. A., Narula, J., Shor, E. S., Young, J. B., Hong, Y.
(2008). Prevention of Heart Failure: A Scientific Statement From the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group. Circulation
117: 2544-2565
[Abstract][Full Text]
Gupta, A. K., Dahlof, B., Dobson, J., Sever, P. S., Wedel, H., Poulter, N.R., on behalf of the Anglo-Scandinavian Cardiac Outcom,
(2008). Determinants of New-Onset Diabetes Among 19,257 Hypertensive Patients Randomized in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm and the Relative Influence of Antihypertensive Medication. Diabetes Care
31: 982-988
[Abstract][Full Text]
The DREAM Trial Investigators,
(2008). Effects of Ramipril and Rosiglitazone on Cardiovascular and Renal Outcomes in People With Impaired Glucose Tolerance or Impaired Fasting Glucose: Results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial. Diabetes Care
31: 1007-1014
[Abstract][Full Text]
Bonnet, F., Patel, S., Laville, M., Balkau, B., Favuzzi, A., Monti, L. D., Lalic, N., Walker, M., on behalf of the European Group for the Study of I,
(2008). Influence of the ACE Gene Insertion/Deletion Polymorphism on Insulin Sensitivity and Impaired Glucose Tolerance in Healthy Subjects. Diabetes Care
31: 789-794
[Abstract][Full Text]
McGuire, D. K, Winterfield, J. R, Rytlewski, J. A, Ferrannini, E.
(2008). Blocking the renin-angiotensin-aldosterone system to prevent diabetes mellitus. Diabetes and Vascular Disease Research
5: 59-66
[Abstract]
Black, H. R., Davis, B., Barzilay, J., Nwachuku, C., Baimbridge, C., Marginean, H., Wright, J. T. Jr., Basile, J., Wong, N. D., Whelton, P., Dart, R. A., Thadani, U.
(2008). Metabolic and Clinical Outcomes in Nondiabetic Individuals With the Metabolic Syndrome Assigned to Chlorthalidone, Amlodipine, or Lisinopril as Initial Treatment for Hypertension: A report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) . Diabetes Care
31: 353-360
[Abstract][Full Text]
Wright, J. T. Jr, Harris-Haywood, S., Pressel, S., Barzilay, J., Baimbridge, C., Bareis, C. J., Basile, J. N., Black, H. R., Dart, R., Gupta, A. K., Hamilton, B. P., Einhorn, P. T., Haywood, L. J., Jafri, S. Z. A., Louis, G. T., Whelton, P. K., Scott, C. L., Simmons, D. L., Stanford, C., Davis, B. R.
(2008). Clinical Outcomes by Race in Hypertensive Patients With and Without the Metabolic Syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med
168: 207-217
[Abstract][Full Text]
Fernandez, M., Triplitt, C., Wajcberg, E., Sriwijilkamol, A. A., Musi, N., Cusi, K., DeFronzo, R., Cersosimo, E.
(2008). Addition of Pioglitazone and Ramipril to Intensive Insulin Therapy in Type 2 Diabetic Patients Improves Vascular Dysfunction by Different Mechanisms. Diabetes Care
31: 121-127
[Abstract][Full Text]
Salley, K. E. S., Wickham, E. P., Cheang, K. I., Essah, P. A., Karjane, N. W., Nestler, J. E.
(2007). POSITION STATEMENT: Glucose Intolerance in Polycystic Ovary Syndrome A Position Statement of the Androgen Excess Society. J. Clin. Endocrinol. Metab.
92: 4546-4556
[Abstract][Full Text]
Clerk, L. H., Vincent, M. A., Barrett, E. J., Lankford, M. F., Lindner, J. R.
(2007). Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiogensin-converting enzyme inhibition. Am. J. Physiol. Endocrinol. Metab.
293: E1804-E1809
[Abstract][Full Text]
Schlechte, J. A.
(2007). Update in Endocrinology. ANN INTERN MED
147: 563-572
[Full Text]
Greenstone, C. L.
(2007). Clinician's Corner: Type 2 Diabetes: A Disease of Epidemic Proportion That Is Largely Preventable But How?. AMERICAN JOURNAL OF LIFESTYLE MEDICINE
1: 335-338
[Abstract]
Miner, M.
(2007). Patient Education: Preventing Progression of Type 2 Diabetes: The Reflex to Use Pharmacological Therapy. AMERICAN JOURNAL OF LIFESTYLE MEDICINE
1: 358-359
[Abstract]
Marre, M., Leye, A.
(2007). Effects of perindopril in hypertensive patients with or without type 2 diabetes mellitus, and with altered insulin sensitivity. Diabetes and Vascular Disease Research
4: 163-173
[Abstract]
Gupta, M., Verma, S., Mancini, G B J.
(2007). ACE inhibitors: back to prime time?. Heart
93: 1015-1016
[Abstract][Full Text]
Muniyappa, R., Montagnani, M., Koh, K. K., Quon, M. J.
(2007). Cardiovascular Actions of Insulin. Endocr. Rev.
28: 463-491
[Abstract][Full Text]
Bloomgarden, Z. T.
(2007). Insulin Resistance, Dyslipidemia, and Cardiovascular Disease. Diabetes Care
30: 2164-2170
[Full Text]
Harrington, D. W., Munekata, M. T.
(2007). Update in General Internal Medicine. ANN INTERN MED
147: 104-116
[Full Text]
Wasko, M. C. M., Hubert, H. B., Lingala, V. B., Elliott, J. R., Luggen, M. E., Fries, J. F., Ward, M. M.
(2007). Hydroxychloroquine and Risk of Diabetes in Patients With Rheumatoid Arthritis. JAMA
298: 187-193
[Abstract][Full Text]
Authors/Task Force Members:, , Mancia, G., De Backer, G., Dominiczak, A., Cifkova, R., Fagard, R., Germano, G., Grassi, G., Heagerty, A. M., Kjeldsen, S. E., Laurent, S., Narkiewicz, K., Ruilope, L., Rynkiewicz, A., Schmieder, R. E., Struijker Boudier, H. A.J., Zanchetti, A., ESC Committee for Practice Guidelines (CPG):, , Vahanian, A., Camm, J., De Caterina, R., Dean, V., Dickstein, K., Filippatos, G., Funck-Brentano, C., Hellemans, I., Kristensen, S. D., McGregor, K., Sechtem, U., Silber, S., Tendera, M., Widimsky, P., Zamorano, J. L., ESH Scientific Council:, , Kjeldsen, S. E., Erdine, S., Narkiewicz, K., Kiowski, W., Agabiti-Rosei, E., Ambrosioni, E., Cifkova, R., Dominiczak, A., Fagard, R., Heagerty, A. M., Laurent, S., Lindholm, L. H., Mancia, G., Manolis, A., Nilsson, P. M., Redon, J., Schmieder, R. E., Struijker-Boudier, H. A.J., Viigimaa, M., Document Reviewers:, , Filippatos, G., Adamopoulos, S., Agabiti-Rosei, E., Ambrosioni, E., Bertomeu, V., Clement, D., Erdine, S., Farsang, C., Gaita, D., Kiowski, W., Lip, G., Mallion, J.-M., Manolis, A. J., Nilsson, P. M., O'Brien, E., Ponikowski, P., Redon, J., Ruschitzka, F., Tamargo, J., van Zwieten, P., Viigimaa, M., Waeber, B., Williams, B., Zamorano, J. L.
(2007). 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J
0: ehm236v1-75
[Full Text]
Marx, N.
(2007). Rosiglitazone and cardiovascular disease: a cardiologist's perspective. Diabetes and Vascular Disease Research
4: 80-81
Bloomgarden, Z. T.
(2007). Nonalcoholic Fatty Liver Disease and Insulin Resistance in Youth. Diabetes Care
30: 1663-1669
[Abstract][Full Text]
Authors/Task Force Members, , Ryden, L., Standl, E., Bartnik, M., Berghe, G. V. d., Betteridge, J., de Boer, M.-J., Cosentino, F., Jonsson, B., Laakso, M., Malmberg, K., Priori, S., Ostergren, J., Tuomilehto, J., Thrainsdottir, I., Other Contributors, , Vanhorebeek, I., Stramba-Badiale, M., Lindgren, P., Qiao, Q., ESC Committee for Practice Guidelines (CPG), , Priori, S. G., Blanc, J.-J., Budaj, A., Camm, J., Dean, V., Deckers, J., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J., Zamorano, J. L., Document Reviewers, , Deckers, J. W., Bertrand, M., Charbonnel, B., Erdmann, E., Ferrannini, E., Flyvbjerg, A., Gohlke, H., Juanatey, J. R. G., Graham, I., Monteiro, P. F., Parhofer, K., Pyorala, K., Raz, I., Schernthaner, G., Volpe, M., Wood, D.
(2007). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: full text: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J Suppl
9: C3-C74
[Full Text]
Buchanan, T. A.
(2007). (How) Can We Prevent Type 2 Diabetes?. Diabetes
56: 1502-1507
[Full Text]
Montori, V. M, Isley, W. L, Guyatt, G. H
(2007). Waking up from the DREAM of preventing diabetes with drugs. BMJ
334: 882-884
[Full Text]
Sattar, N., McConnachie, A., Ford, I., Gaw, A., Cleland, S. J., Forouhi, N. G., McFarlane, P., Shepherd, J., Cobbe, S., Packard, C.
(2007). Serial Metabolic Measurements and Conversion to Type 2 Diabetes in the West of Scotland Coronary Prevention Study: Specific Elevations in Alanine Aminotransferase and Triglycerides Suggest Hepatic Fat Accumulation as a Potential Contributing Factor. Diabetes
56: 984-991
[Abstract][Full Text]
Rathmann, W., Kostev, K., Haastert, B., Parashar, A., Varma, A., Garg, R., Gandhi, G. Y., Montori, V. M., Kahn, S. E., Viberti, G., the ADOPT Steering Committee,
(2007). Glycemic Durability of Monotherapy for Diabetes. NEJM
356: 1378-1380
[Full Text]
Nathan, D. M., Berkwits, M.
(2007). Trials That Matter: Rosiglitazone, Ramipril, and the Prevention of Type 2 Diabetes. ANN INTERN MED
146: 461-463
[Full Text]
Bailey, C. J
(2007). Treating insulin resistance: future prospects. Diabetes and Vascular Disease Research
4: 20-31
[Abstract]
Crutchlow, M. F., Bloom, R. D.
(2007). Transplant-Associated Hyperglycemia: A New Look at an Old Problem. CJASN
2: 343-355
[Abstract][Full Text]
Bangalore, S., Messerli, F. H., Potter, B. J., LeLorier, J., Epstein, B. J., Cooper-DeHoff, R. M., Bosch, J., Yusuf, S., Gerstein, H.
(2007). Effect of Ramipril on the Incidence of Diabetes. NEJM
356: 522-524
[Full Text]
Gerstein, H. C.
(2007). Point: If It Is Important to Prevent Type 2 Diabetes, It Is Important to Consider All Proven Therapies Within a Comprehensive Approach. Diabetes Care
30: 432-434
[Full Text]
Tuomilehto, J.
(2007). Counterpoint: Evidence-Based Prevention of Type 2 Diabetes: The Power of Lifestyle Management. Diabetes Care
30: 435-438
[Full Text]
Lindsay, A.
(2007). JournalScan. Heart
93: 277-278
[Full Text]
Brown, J. D., Plutzky, J.
(2007). Peroxisome Proliferator Activated Receptors as Transcriptional Nodal Points and Therapeutic Targets. Circulation
115: 518-533
[Abstract][Full Text]
Pignone, M.
(2007). Rosiglitazone Reduced the Incidence of Diabetes in Patients With Impaired Glucose Tolerance. Clin. Diabetes
25: 23-24
[Full Text]
Fonseca, V. A., Kahn, S. E.
(2006). Of Hopes and DREAMS: The Quest to Prevent Type 2 Diabetes. J. Clin. Endocrinol. Metab.
91: 4762-4763
[Full Text]
Goldfarb, B.
(2006). DREAM Results: Drug Delays Diabetes. DOC News
3: 1-19
[Full Text]
Inzucchi, S. E.
(2006). Diabetes Prevention. DOC News
3: 3-19
[Full Text]
(2006). ACE Inhibition for Preventing Diabetes: Still Just a DREAM. Journal Watch Cardiology
2006: 1-1
[Full Text]
Tonks, A.
(2006). What's new in the other general journals. BMJ
333: 835-836
[Full Text]
Ingelfinger, J. R., Solomon, C. G.
(2006). Angiotensin-Converting-Enzyme Inhibitors for Impaired Glucose Tolerance -- Is There Still Hope?. NEJM
355: 1608-1610
[Full Text]
(2006). Rosiglitazone, but Not Ramipril, Prevents Progression to Diabetes in Patients at Risk. JWatch General
2006: 1-1
[Full Text]
Conlon, D.
(2006). DREAM -- a diabetes prevention study. British Journal of Diabetes & Vascular Disease
6: 230-233
[Abstract]