Glycemic Targets and Prevention of Chronic Complications
Hyperglycemia is the main cause and critical initiating factor of chronic microvascular complications of diabetes and also a major contributor to the macrovascular complications. In diabetes care it is therefore essential to set appropriate glycemic targets (or target ranges) that guide the management of the disease in order to reduce the risk of long-term complications, while avoiding unnecessary burden or adverse events. In this chapter we discuss the role of hyperglycemia in inducing diabetes chronic complications and evidence from clinical trials proving the benefit of glycemic control in preventing or ameliorating the progression of micro- and macrovascular complications. We also review the recommendations of current clinical guidelines, including individualization of glycemic targets when treating patients with diabetes.
KeywordsGlycemic targets Microvascular complications Macrovascular complications Glycemic control Clinical trials Guidelines
- Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Eye Study Group and the Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Study Group. Persistent effects of intensive glycemic control on retinopathy in type 2 diabetes in the action to control cardiovascular risk in diabetes (ACCORD) follow-on study. Diabetes Care. 2016;39(7):1089–100.CrossRefGoogle Scholar
- Albers JW, Herman WH, Pop-Busui R, Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group, et al. Effect of prior intensive insulin treatment during the Diabetes Control and Complications Trial (DCCT) on peripheral neuropathy in type 1 diabetes during the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Diabetes Care. 2010;33(5):1090–6.PubMedPubMedCentralCrossRefGoogle Scholar
- American Diabetes Association. Glycemic targets. Diabetes Care. 2016;39(Suppl 1):S39–46.Google Scholar
- DCCT/EDIC Research Group. Effect of intensive diabetes treatment on albuminuria in type 1 diabetes: long-term follow-up of the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study. Lancet Diabetes Endocrinol. 2014;2(10):793–800.CrossRefGoogle Scholar
- Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular outcomes in type 1 diabetes: the DCCT/EDIC study 30-year follow-up. Diabetes Care. 2016;39(5):686–93.CrossRefGoogle Scholar
- Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group, Lachin JM, White NH, Hainsworth DP, et al. Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC. Diabetes. 2015;64(2):631–42.CrossRefGoogle Scholar
- FLAT-SUGAR Trial Investigators, Probstfield JL, Hirsch I, O’Brien K, et al. Design of FLAT-SUGAR: randomized trial of prandial insulin versus prandial GLP-1 receptor agonist together with basal insulin and metformin for high-risk type 2 diabetes. Diabetes Care. 2015;38(8):1558–66.CrossRefGoogle Scholar
- Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm – 2016 executive summary. Endocr Pract. 2016;22(1):84–113.PubMedPubMedCentralCrossRefGoogle Scholar
- Geiss LS, Herman WH, Smith PJ. Mortality among persons with non-insulin dependent diabetes. In: Harris MI, Cowie CC, Stern MP, Boyko EJ, Reiber GE, Bennett PH, editors. Diabetes in America. 2nd ed. Bethesda: National Institutes of Health; 1995. p. 233–58.Google Scholar
- International Diabetes Federation Clinical Guidelines Task Force. Global guideline for type 2 diabetes. 2012. http://www.idf.org/sites/default/files/IDF-Guideline-for-Type-2-Diabetes.pdf.
- Inzucchi SE, Bergenstal RM, Buse JB, American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):1364–79.PubMedPubMedCentralCrossRefGoogle Scholar
- Lingvay I, Manghi FP, García-Hernández P, DUAL V Investigators, et al. Effect of insulin glargine up-titration vs. insulin degludec/liraglutide on glycated hemoglobin levels in patients with uncontrolled type 2 diabetes: The DUAL V randomized clinical trial. JAMA. 2016;315(9):898–907.CrossRefGoogle Scholar
- Mosenzon O, Cahn A, Hirshberg B, et al. Cardiovascular outcomes by albumin creatinine ratio categories in the SAVOR trial. Diabetes. 2015;64(Suppl 1). https://ada.scientificposters.com/epsAbstractADA.cfm?id=2. Accessed 3 July 2016.
- Nathan DM, Cleary PA, Backlund JY, Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643–53.CrossRefGoogle Scholar
- Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28(2):103–17.PubMedCrossRefGoogle Scholar
- Reaven PD, Moritz TE, Schwenke DC, Veterans Affairs Diabetes Trial, et al. Intensive glucose-lowering therapy reduces cardiovascular disease events in Veterans Affairs Diabetes Trial participants with lower calcified coronary atherosclerosis. Diabetes. 2009;58(11):2642–8.PubMedPubMedCentralCrossRefGoogle Scholar
- Riddle MC, Ambrosius WT, Brillon DJ, Action to Control Cardiovascular Risk in Diabetes Investigators, et al. Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care. 2010;33(5):983–90.PubMedPubMedCentralCrossRefGoogle Scholar
- Rosenstock J, Guerci B, Hanefeld M, GetGoal Duo-2 Trial Investigators, et al. Prandial options to advance basal insulin glargine therapy: testing lixisenatide plus basal insulin versus insulin glulisine either as basal-plus or basal-bolus in type 2 diabetes: the GetGoal Duo-2 trial. Diabetes Care. 2016;39(8):1318–28.PubMedCrossRefGoogle Scholar
- Skyler JS, Bergenstal R, Bonow RO, American Diabetes Association, American College of Cardiology Foundation, American Heart Association, et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Diabetes Care. 2009;32(1):187–92.PubMedPubMedCentralCrossRefGoogle Scholar