American Heart Journal
Volume 155, Issue 1 , Pages 26.e1-26.e13 , January 2008

Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: The ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention)

  • The ORIGIN Trial Investigators

      Affiliations

    • Corresponding Author InformationReprint requests: Hertzel C. Gerstein, ORIGIN Project Office, Population Health Research Institute, 237 Barton Street East, 2nd Floor, Hamilton, Ontario, Canada L8L 2X2.

Received 4 July 2007 ,Accepted 21 September 2007.

References 

  1. Bartnik M, Ryden L, Ferrari R, et al. The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on diabetes and the heart. Eur Heart J. 2004;25:1880–1890
  2. Lotufo PA, Gaziano JM, Chae CU, et al. Diabetes and all-cause and coronary heart disease mortality among US male physicians. Arch Intern Med. 2001;161:242–247
  3. Hu FB, Stampfer MJ, Solomon CG, et al. The impact of diabetes mellitus on mortality from all causes and coronary heart disease in women: 20 years of follow-up. Arch Intern Med. 2001;161:1717–1723
  4. Santaguida PL, Balion C, Hunt D, et al. Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose. Evid Rep Technol Assess (Summ). 2005;1–11
  5. Brunner EJ, Shipley MJ, Witte DR, et al. Relation between blood glucose and coronary mortality over 33 years in the Whitehall Study. Diabetes Care. 2006;29:26–31
  6. Meigs JB, Nathan DM, D'Agostino RB, et al. Fasting and postchallenge glycemia and cardiovascular disease risk: the Framingham Offspring Study. Diabetes Care. 2002;25:1845–1850
  7. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes epidemiology: collaborative analysis of diagnostic criteria in Europe. [see comments] Lancet. 1999;354:617–621
  8. Lawes CM, Parag V, Bennett DA, et al. Blood glucose and risk of cardiovascular disease in the Asia Pacific region. Diabetes Care. 2004;27:2836–2842
  9. Yan SF, Yan SD, Herold K, et al. Receptor for advanced glycation end products and the cardiovascular complications of diabetes and beyond: lessons from AGEing. Endocrinol Metab Clin North Am 2006; 35:511-24, viii.
  10. Schwartz EA, Reaven PD. Molecular and signaling mechanisms of atherosclerosis in insulin resistance. Endocrinol Metab Clin North Am 2006; 35:525-49, viii.
  11. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–820
  12. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction. Eur J Clin Invest. 2002;32(Suppl 3):14–23
  13. Lewis GF, Carpentier A, Adeli K, et al. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev. 2002;23:201–229
  14. Dubois M, Kerr-Conte J, Gmyr V, et al. Non-esterified fatty acids are deleterious for human pancreatic islet function at physiological glucose concentration. Diabetologia. 2004;47:463–469
  15. Oliver MF, Opie LH. Effects of glucose and fatty acids on myocardial ischaemia and arrhythmias. Lancet. 1994;343:155–158
  16. Oliver MF. Sudden cardiac death: the lost fatty acid hypothesis. QJM. 2006;99:701–709
  17. Boden G, She P, Mozzoli M, et al. Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver. Diabetes. 2005;54:3458–3465
  18. Pilz S, Scharnagl H, Tiran B, et al. Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease. J Clin Endocrinol Metab. 2006;91:2542–2547
  19. Dandona P, Aljada A, Mohanty P. The anti-inflammatory and potential anti-atherogenic effect of insulin: a new paradigm. Diabetologia. 2002;45:924–930
  20. Chaudhuri A, Janicke D, Wilson MF, et al. Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction. Circulation. 2004;109:849–854
  21. Vehkavaara S, Makimattila S, Schlenzka A, et al. Insulin therapy improves endothelial function in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2000;20:545–550
  22. Vehkavaara S, Yki-Jarvinen H. 3.5 years of insulin therapy with insulin glargine improves in vivo endothelial function in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2004;24:325–330
  23. Taskinen MR, Kuusi T, Helve E, et al. Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin-dependent diabetes. Arteriosclerosis. 1988;8:168–177
  24. Gerstein HC, Yale JF, Harris SB, et al. A randomized trial of adding insulin glargine vs. avoidance of insulin in people with type 2 diabetes on either no oral glucose-lowering agents or submaximal doses of metformin and/or sulphonylureas. The Canadian INSIGHT (Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment) Study. Diabet Med. 2006;23:736–742
  25. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359–1367
  26. Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. BMJ. 1997;314:1512–1515
  27. Malmberg K, Ryden L, Wedel H, et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J. 2005;26:650–661
  28. Pittas AG, Siegel RD, Lau J. Insulin therapy for critically ill hospitalized patients: a meta-analysis of randomized controlled trials. Arch Intern Med. 2004;164:2005–2011
  29. Gerstein HC, Rosenstock J. Insulin therapy in people who have dysglycemia and type 2 diabetes mellitus: can it offer both cardiovascular protection and beta-cell preservation?. Endocrinol Metab Clin North Am. 2005;34:137–154
  30. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353:2643–2653
  31. Calder PC. n-3 Fatty acids and cardiovascular disease: evidence explained and mechanisms explored. Clin Sci (Lond). 2004;107:1–11
  32. Lopez-Garcia E, Schulze MB, Manson JE, et al. Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women. J Nutr. 2004;134:1806–1811
  33. Hu FB, Cho E, Rexrode KM, et al. Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Circulation. 2003;107:1852–1857
  34. Mozaffarian D, Ascherio A, Hu FB, et al. Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men. Circulation. 2005;111:157–164
  35. GISSI-Prevenzione Investigators . Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet. 1999;354:447–455
  36. Bucher HC, Hengstler P, Schindler C, et al. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2002;112:298–304
  37. Burr ML, Ashfield-Watt PA, Dunstan FD, et al. Lack of benefit of dietary advice to men with angina: results of a controlled trial. Eur J Clin Nutr. 2003;57:193–200
  38. Hooper L, Thompson RL, Harrison RA, et al. Omega 3 fatty acids for prevention and treatment of cardiovascular disease. Cochrane Database Syst Rev. 2004;CD003177
  39. Buse JB, Rosenstock J. Prevention of cardiovascular outcomes in type 2 diabetes mellitus: trials on the horizon. Endocrinol Metab Clin North Am. 2005;34:221–235

 NCT00069784@clinicaltrials.gov.

PII: S0002-8703(07)00772-7

doi: 10.1016/j.ahj.2007.09.009

American Heart Journal
Volume 155, Issue 1 , Pages 26.e1-26.e13 , January 2008