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Editor's Message  |   July 2011
Optimizing Treatment for Patients With Diabetes Mellitus: Glycemic and Nonglycemic Effects
Author Notes
  • Address correspondence to Jay H. Shubrook, Jr, DO, Associate Professor of Family Medicine, Ohio University College of Osteopathic Medicine, Grosvenor Hall, Athens, OH 45701-2979.E-mail: shubrook@oucom.ohiou.edu 
Article Information
Endocrinology / Diabetes
Editor's Message   |   July 2011
Optimizing Treatment for Patients With Diabetes Mellitus: Glycemic and Nonglycemic Effects
The Journal of the American Osteopathic Association, July 2011, Vol. 111, Sii-S1. doi:
The Journal of the American Osteopathic Association, July 2011, Vol. 111, Sii-S1. doi:
Despite an array of medications available in the United States to treat patients with type 2 diabetes mellitus (T2DM), physicians still have not achieved optimal control of this disease. In the present supplement to JAOA—The Journal of the American Osteopathic Association, we look at 3 contributing factors to this phenomenon. Mark D. Baldwin, DO, addresses the topic of cardiovascular risk associated with diabetes mellitus. Steven H. Barag, DO, discusses the advantages of using insulin early in the treatment of patients with T2DM. Finally, Alan J. Garber, MD, PhD, explores incretin-based agents, including their unique nonglycemic benefits. 
Dr Baldwin provides evidence to support the claim that diabetes mellitus is a cardiovascular risk equivalent. Furthermore, he reviews the outcomes of the major intensive glucose-lowering trials that evaluated cardiovascular outcomes—the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial,1 the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial,2 and the Veterans Affairs Diabetes Trial (VADT).3 Dr Baldwin then balances these findings with the long-term outcomes from the epidemiologic follow-ups of the United Kingdom Prospective Diabetes Study (UKPDS)4 and the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.5 He reviews glucose-lowering effects, nonglycemic benefits, and risks of available agents and discusses how these agents contribute to cardiovascular risk modification. 
Dr Barag covers various aspects of the early introduction of insulin in T2DM management. He offers compelling evidence of the benefit of this approach. He also explores patient and physician barriers to insulin use, noting how a pro active physician can overcome these barriers. Finally, Dr Barag provides physicians with a number of treatment algorithms6-8 to initiate and proactively titrate insulin doses with the goal of achieving glycemic control quickly and safely. 
Dr Garber reviews the pathophysiologic mechanisms of the incretin system in the development of T2DM. He further examines how to achieve glucose control while maintaining or even advancing other metabolic benefits. He provides an overview of glucagon-like peptide-1, or GLP-1, receptor agonists, including their effects on glucose levels, weight, and blood pressure. Dr Garber also reviews data on dipeptidyl peptidase-4, or DPP-4, inhibitors, an oral class of agents that have effects on the incretin system. Incretin-based agents offer a novel pathophysiologic mechanism with which to address T2DM, and their nonglycemic benefits (eg, increasing β-cell proliferation and decreasing β-cell apoptosis, increasing central nervous system-mediated satiety, exerting neuroprotective effects)9,10 also appear to be clinically useful. 
Only approximately half of individuals with T2DM meet national glucose control standards.11 More importantly, the majority of people with T2DM are likely to die from cardiovascular disease as a complication of T2DM.12,13 We know that many traditional medications (metformin being an exception) have limited benefits for cardiovascular disease prevention.14 Therefore, to be successful, physicians may need to become less “glucose-centric.” With the various options of glucose-controlling agents available, physicians can consider the nonglycemic effects of these medications in an effort to truly individualize treatment plans. 
Evidence is building to support the idea that early aggressive intervention is most important in the treatment of patients with T2DM.6,15 In light of the progressive nature of T2DM, it is crucial to achieve and maintain glucose control early—rather than trying to chase this disease after the patient becomes glucotoxic and lipotoxic. After reading this JAOA supplement, physicians will gain new information to help them select agents to manage diabetes mellitus early and aggressively, resulting in not only successful glucose control but also the prevention of cardiovascular morbidity and mortality. 
 Financial Disclosures: None reported.
 
 This supplement is supported by an independent education grant from Novo Nordisk Inc.
 
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group; Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med.. (2008). ;358(24):2545-2559.
ADVANCE Collaborative Group; Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med.. (2008). ;358(24):2560-2572.
Duckworth WC, Abraira C, Moritz T, et al; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes.N Engl J Med.. (2009). ;360(2):129-139.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359 (15):1577-1589.
Nathan DM, Cleary PA, Backlund JY, et al, for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643-2653.
Nathan DM, Buse JB, Davidson MB, et al; American Diabetes Association; European Association for the Study of Diabetes. Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes [published online ahead of print October 22, 2008].Diabetologia.. (2009). ;52(1):17-30.
LaSalle JR. Empowering patients during insulin initiation: a real-world approach. J Am Osteopath Assoc.. (2010). ;110(2):69-78.
Meneghini L, Koenen C, Weng W, Selam JL. The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes-results of the randomized, controlled PREDICTIVE 303 study. Diabetes Obes Metab.. (2007). ;9(6):902-913.
Freeman JS. Role of the incretin pathway in the pathogenesis of type 2 diabetes. Cleve Clin J Med.. (2009). ;76(suppl 5):S12-S19.
Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131-2157.
Hoerger TJ, Segel JE, Gregg EW, Saaddine JB. Is glycemic control improving in U.S. adults [published online ahead of print October 12, 2007]?Diabetes Care.. (2008). ;31(1):81-86.
Franco OH, Steyerberg EW, Hu FB, et al. Associations of diabetes mellitus with total life expectancy and life expectancy with and without cardiovascular disease. Arch Intern Med.. (2007). ;167 (11):1145-1151.
Fox CS, Coady S, Sorlie PD, et al. Increasing cardiovascular disease burden due to diabetes mellitus: The Framingham Heart Study.Circulation. 2007;115 (12): 1544-1550.
Tzoulaki I, Molokhia M, Curcin V, et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ.. (2009). ;339:b4731 .
American Diabetes Association. Standards of medical care in diabetes-2011. Diabetes Care.. (2011). ;34(suppl 1):S11-S61.