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Lessons Learned from Glycemia Control Studies

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Abstract

Hyperglycemia occurs in patients with diabetes and in nondiabetic patients during acute illness. Epidemiologic and observational studies have demonstrated that hyperglycemia is associated with significant adverse outcomes. Nevertheless, studies evaluating the benefits of normalizing glycemia have produced inconsistent results. For instance, intensive control of hyperglycemia had been shown to provide microvascular benefit in type 1 and type 2 diabetic patients, but its macrovascular benefits had only been clearly demonstrated in type 1 diabetic patients. Moreover, although initial studies in critically ill patients showed decreased morbidity and mortality with tight glycemic control, subsequent studies yielded conflicting results. A series of recent studies provide further insight and show that intensive glycemic control in type 2 diabetic patients does provide macrovascular benefit but is associated with increased risk of hypoglycemia. In the critically ill patient, tight glycemic control could be detrimental; thus, a less aggressive glycemic target of 140 to 180 mg/dL is preferred.

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References

Papers of particular interest, published recently, have been highlighted as follows: • Of importance, •• Of major importance

  1. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) [no authors listed]. Lancet 1998, 352:837–853.

  2. World Health Organization: Diabetes. Available at http://www.who.int/mediacentre/factsheets/fs312/en/index.html. Accessed January 2010.

  3. Centers for Disease Control and Prevention: National diabetes fact sheet: general information and national estimates on diabetes in the United States. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2007. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf.

  4. Barr EL, Zimmet PZ, Welborn TA, et al.: Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation 2007, 116:151–157.

    Article  CAS  PubMed  Google Scholar 

  5. Krolewski AS, Warram JH, Valsania P, et al.: Evolving natural history of coronary artery disease in diabetes mellitus.. Am J Med 1991, 90(Suppl 2A):56S–61S.

    Google Scholar 

  6. Fox CS, Coady S, Sorlie PD, et al.: Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study. Circulation 2007, 115:1544–1550.

    Article  PubMed  Google Scholar 

  7. Moss SE, Klein R, Klein BE: Cause-specific mortality in a population-based study of diabetes. Am J Public Health 1991, 81:1158–1162.

    Article  CAS  PubMed  Google Scholar 

  8. Bagshaw SM, Egi M, George C, et al.: Early blood glucose control and mortality in critically ill patients in Australia. Crit Care Med 2009, 37:463–470.

    Article  CAS  PubMed  Google Scholar 

  9. Selvin E, Marinopoulos S, Berkenblit G, et al.: Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med 2004, 141:421–431.

    CAS  PubMed  Google Scholar 

  10. Clement S, Braithwaite SS, Magee MF, et al.: Management of diabetes and hyperglycemia in hospitals. Diabetes Care 2004, 27:553–591.

    Article  PubMed  Google Scholar 

  11. 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.

    Article  PubMed  Google Scholar 

  12. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group [no authors listed]. N Engl J Med 1993, 329:977–986.

  13. • Duckworth W, Abraira C, Moritz T, et al.: Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009, 360:129–139. This was an RCT of veterans with type 2 diabetes that confirmed microvascular benefit of tight glycemic control but showed no macrovascular benefit.

    Article  CAS  PubMed  Google Scholar 

  14. • Effects of intensive glucose lowering in type 2 diabetes. The Action to Control Cardiovascular Risk in Diabetes Study Group [no authors listed]. N Engl J Med 2008, 358:2545–2559. This was one of three recent RCTs. It showed no benefit of tight glycemic control and associated increased mortality.

    Google Scholar 

  15. • Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. The ADVANCE Collaborative Group [no authors listed]. N Engl J Med 2008, 358:2560–2572. One of three major recent RCTs looking at the effect of intensive glycemic control on macrovascular disease and mortality. It showed no benefit of tight glycemic control.

  16. • Intensive versus conventional glucose control in critically ill patients. The NICE-SUGAR Study Investigators [no authors listed]. N Engl J Med 2009, 360:1283–1297. This study was a large RCT that randomized tight control versus conventional therapy in critically ill patients and found no mortality benefit from tight control.

  17. Kannel WB, McGee DL: Diabetes and cardiovascular risk factors: the Framingham study. Circulation 1979, 59:8–13.

    CAS  PubMed  Google Scholar 

  18. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group [no authors listed]. N Engl J Med 2005, 353:2643–2653.

  19. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group [no authors listed]. Lancet 1998, 352:854–865.

  20. •• Holman RR, Paul SK, Bethel MA, et al.: 10-Year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008, 359:1577–1589. This study showed macrovascular benefit of intensive glycemic control became apparent after extended follow-up of the UKPDS participants.

    Article  CAS  PubMed  Google Scholar 

  21. • Turnbull FM, Abraira C, Anderson R, et al.: Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 2009, 52:2288–2298. This paper is a meta-analysis of the most recent RCTs (ACCORD, ADVANCE, VADT, and UKPDS 80) showing macrovascular benefit of intensive glycemic control.

    Article  CAS  PubMed  Google Scholar 

  22. Ray KK, Seshasai SR, Wijesuriya S, et al.: Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet 2009, 373:1765–1772.

    Article  CAS  PubMed  Google Scholar 

  23. Mannucci E, Monami M, Lamanna C, et al.: Prevention of cardiovascular disease through glycemic control in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis 2009, 19:604–612.

    Article  CAS  PubMed  Google Scholar 

  24. •• Reaven PD, Moritz TE, Schwenke DC, et al.: Intensive glucose-lowering therapy reduces cardiovascular disease events in Veterans Affairs Diabetes Trial participants with lower calcified coronary atherosclerosis. Diabetes 2009, 58:2642–2648. This study showed extent of atherosclerosis may predict cardiovascular benefit from intensive glycemic control.

    Article  CAS  PubMed  Google Scholar 

  25. Levetan CS, Passaro M, Jablonski K, et al.: Unrecognized diabetes among hospitalized patients. Diabetes Care 1998, 21:246–249.

    Article  CAS  PubMed  Google Scholar 

  26. Umpierrez GE, Isaacs SD, Bazargan N, et al.: Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002, 87:978–982.

    Article  CAS  PubMed  Google Scholar 

  27. Malmberg K: Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ 1997, 314:1512–1515.

    CAS  PubMed  Google Scholar 

  28. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A: Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999, 67:352–360.

    Article  CAS  PubMed  Google Scholar 

  29. Furnary AP, Gao G, Grunkemeier GL, et al.: Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003, 125:1007–1021.

    Article  CAS  PubMed  Google Scholar 

  30. Garber AJ, Moghissi ES, Bransome ED Jr, et al.: American College of Endocrinology position statement on inpatient diabetes and metabolic control. Endocr Pract 2004, 10(Suppl 2):4–9.

    PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. Brunkhorst FM, Engel C, Bloos F, et al.: Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008, 358:125–139.

    Article  CAS  PubMed  Google Scholar 

  33. Van den Berghe G, Wilmer A, Hermans G, et al.: Intensive insulin therapy in the medical ICU. N Engl J Med 2006, 354:449–461.

    Article  PubMed  Google Scholar 

  34. Van den Berghe G, Mesotten D, Vanhorebeek I: Intensive insulin therapy in the intensive care unit. CMAJ 2009, 180:799–800.

    PubMed  Google Scholar 

  35. • Griesdale DE, de Souza RJ, van Dam RM, et al.: Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ 2009, 180:821–827. This study was a very comprehensive meta-analysis of studies of glycemic control in critically ill patients. It suggested mortality benefit of tight control in surgical, but not in medical, intensive care units.

    PubMed  Google Scholar 

  36. •• Moghissi ES, Korytkowski MT, DiNardo M, et al.: American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract 2009, 15:353–369. This is the most current recommendations for inpatient management of hyperglycemia by AACE and ADA. It also provides the evidence to support the recommendations.

    Article  PubMed  Google Scholar 

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  1. Department of Medicine, Division of Endocrinology and Metabolism, University of Virginia Health System, Box 801406, Charlottesville, VA, 22908, USA

    Ayotunde O. Dokun

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Dokun, A.O. Lessons Learned from Glycemia Control Studies. Curr Diab Rep 10, 133–138 (2010). https://doi.org/10.1007/s11892-010-0094-6

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