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Editor's Message  |   May 2011
Diabetes—It's the Basics That Count
Author Notes
  • Dr Spellman is a professor and associate dean for research. He serves as the director of the Center for Diabetes and Metabolic Disorders, Department of Internal Medicine, Division of Endocrinology at Texas Tech University Health Sciences Center. 
  • Address correspondence to Craig W. Spellman, DO, PhD, Department of Internal Medicine, Division of Endocrinology, Texas Tech University Health Science Center, 701 W Fifth St, Odessa, TX 79763-4206.E-mail: craig.spellman@ttuhsc.edu 
Article Information
Endocrinology / Diabetes
Editor's Message   |   May 2011
Diabetes—It's the Basics That Count
The Journal of the American Osteopathic Association, May 2011, Vol. 111, Sii-S2. doi:
The Journal of the American Osteopathic Association, May 2011, Vol. 111, Sii-S2. doi:
The new numbers are in for 2011 (Table). The data from the National Diabetes Statistics Clearinghouse about the increasing incidence and prevalence of type 2 diabetes mellitus (T2DM) unfortunately demonstrate that all the forecasts from previous years are proving to be accurate.1,2 There are now nearly 26 million people with T2DM; an estimated 19 million cases have been diagnosed, and an estimated 7 million cases are undiagnosed. These estimates are based on fasting glucose levels and glycated hemoglobin (HbA1c) diagnostic criteria. In 2010 alone, 2 million people developed T2DM. The numbers are even more staggering when we consider that most people with a diagnosis of T2DM previously had prediabetes, and HbA1c values indicate that 35% of people aged 20 years or older and 50% of those aged 65 years or older have prediabetes. These statistics translate into almost 80 million people with prediabetes; with a conversion rate from prediabetes to T2DM at 6.8% per year, the consequences are obvious. 
Table.
Adults in the United States With Diagnosed or Undiagnosed Diabetes, 2010

Group

Persons With Diabetes, No. (%)
Age, y
□ ≥ 20 25.6 million (11.3)
□ ≥ 6510.9 million (26.9)
Sex
□ Men*13.0 million (11.8)
□ Women* 12.6 million (10.8)
Race
□ Non-Hispanic whites* 15.7 million (10.2)
▪ Non-Hispanic blacks*4.9 million (18.7)
 Source: National Diabetes Information Clearinghouse Web site1
 *Aged 20 years or older.
Table.
Adults in the United States With Diagnosed or Undiagnosed Diabetes, 2010

Group

Persons With Diabetes, No. (%)
Age, y
□ ≥ 20 25.6 million (11.3)
□ ≥ 6510.9 million (26.9)
Sex
□ Men*13.0 million (11.8)
□ Women* 12.6 million (10.8)
Race
□ Non-Hispanic whites* 15.7 million (10.2)
▪ Non-Hispanic blacks*4.9 million (18.7)
 Source: National Diabetes Information Clearinghouse Web site1
 *Aged 20 years or older.
×
The complications of diabetes are well known. The 2011 National Diabetes Statistics report1 reaffirms previous information that 70% of people aged 65 years or older who died of coronary heart disease had T2DM. The risk of stroke was 2- to 4-fold higher in those with T2DM. Further, hypertension occurs in about of 70% of all patients with T2DM, and retinopathy develops in approximately 30% of those aged 40 years or older.1 Diabetes remains the leading cause of new cases of blindness and is the leading cause of renal failure. Most people with T2DM develop distal sensory neuropathy. The other grim statistics are that 60% of nontraumatic amputations occur in patients with diabetes, periodontal disease is increased about 3-fold, and infections often take a more serious course. We know that depression is common in diabetes, but here is a new statistic: depression itself is associated with a 60% increased risk of developing T2DM!1 
It is well established that morbidity and mortality as a result of T2DM can be delayed or prevented. This understanding has been demonstrated in several worldwide clinical trials based on control of fuel metabolism with diet and exercise, as well as the use of oral antidiabetic medications.3-7 Although effective antidiabetic therapies are available, many patients are reluctant to use them. Factors impeding adherence to a regimen include the number of medications needed, dosing frequency, cost, lack of education about the use of the product, lack of confidence in the medication's benefits, and fears about weight gain and hypoglycemia.8-11 
The fears of weight gain and hypoglycemia are well based. Pooled data from the systematic review by Bolen et al12 showed that thiazolidinediones and second-generation sulfonylureas caused weight gain of approximately 3 kg. Weight gains in persons using glinides were similar to those in persons using sulfonylureas. Further, thiazolidinediones and sulfonylureas used in combination with metformin consistently increased body weight by 1 to 5 kg. Metformin alone was weight neutral.12 The recent meta-analysis by Phung et al13 revealed that the incidence of hypoglycemia varied from 0 to 38% in people taking oral antidiabetic agents. Specifically, and depending on the protocol, the incidence of hypoglycemia was approximately 15% in patients taking a sulfonylurea, and the range was from 6% to 38%. Glinides and sulfonylureas were similar, each with an incidence of hypoglycemia of about 16%. Hypoglycemia ranged from 0 to 4% in those taking a thiazolidinedione and metformin. 
Given that monotherapy and combination therapy are not durable, are associated with adverse effects, and have a limited capacity to reduce the HbA1c level, a strong argument can be made for introducing the new “incretin-based” drugs to achieve glycemic control. The article by Gavin et al14 in this supplement discusses the role and safety of the new glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 inhibitors in the management of T2DM. The importance of these drugs is realized when we note that the effects of GLP-1 account for as much as 60% of postprandial insulin secretion in healthy individuals.15 
As important as it is to develop safe new medications for managing diabetes, patient participation in the management of their disease is just as important. The finest protocols and the best medicines have no impact if the patient fails to implement the physician's treatment plan. The following article by Gavin et al14 also outlines what constitutes a contemporary diabetes visit and contains some excellent clinical pearls. Do you know that HbA1c goals are now health status based? Do you know all the components of a complete diabetes visit? Do you know why it is important to focus on early, comprehensive interventions for the management of diabetes? This last question, on early comprehensive interventions for diabetes, ties together the 2 major themes of this supplement: (1) early diagnosis coupled with establishment of effective physician visits and (2) initiation of therapy that facilitates patient adherence by minimizing weight gain and hypoglycemia. The rationale for emphasizing comprehensive management of diabetes in the early years is an unexpected benefit. Specifically, there is a marked reduction in end-organ complications, even if the patient does not continue to maintain tight control of his or her diabetes over time. This phenomenon is termed the legacy effect. 
The legacy effect was observed in the follow-up studies of the original Diabetes Control and Complications Trial (DCCT)16 and the United Kingdom Perspective Diabetes Study (UKPDS).17 In the DCCT, patients aged 13 to 39 years with type 1 diabetes were assigned to practice either tight or conventional glycemic control for about 5 years. The average HbA1c level attained in the intensive therapy group was 7.4%, whereas the HbA1c level in the standard treatment group was 9.1%. We are all familiar with the DCCT results, which demonstrated reductions in neuropathy, nephropathy, and retinopathy. Subsequently, however, 93% of the participants in the original DCCT were merely observed for an additional 17 years in the DCCT–Epidemiology of Diabetes Interventions and Complications follow-up study.18 Over time, the average HbA1c level among all the participants drifted to an average of about 8%. It was found that those participants who achieved tight glucose control in the original DCCT had a 42% decrease in all events related to cardiovascular disease and a 57% decrease in nonfatal myocardial infarctions, stroke, and death almost 20 years later.19 It was concluded that early aggressive control of type 1 diabetes reduced the future development of macrovascular disease. 
The UKPDS20 provided additional data to support the concept of the legacy effect with early, aggressive treatment of people with T2DM. In the UKPDS, differences between the intensive treatment goals and the conventional treatment goals were maintained for only 1 year. Ten years later, however, the patients who had been treated with an intensive antidiabetic regimen showed a decrease of approximately 25% in microvascular disease and of 15% in myocardial infarctions.20 Let me reemphasize that these benefits were seen in patients with T2DM 10 years later, even though tight control was maintained for only the first year of the study. 
The legacy effect suggests that early aggressive management of diabetes decreases the risk of developing macrovascular disease. As such, the stage is set for Gavin et al14 to stress the screening guidelines and the new diagnostic criteria for diabetes. They review the goals for glycemic targets, present check lists, and outline the logistics of the office visit for a patient with diabetes. Lastly, initiation and advancement of therapy are discussed, along with performance indicators. They conclude with the importance of patient participation by reflecting on the role of obesity as the major controllable risk factor for the development of diabetes. 
 Financial Disclosures: Dr Spellman discloses that he is a member of the Lilly–Boehringer Ingelheim speakers' bureau.
 
 This supplement is supported by an independent educational grant from Merck & Co, Inc.
 
National Diabetes Statistics, 2011. National Diabetes Information Clearinghouse Web site. http://diabetes.niddk.nih.gov/dm/pubs/statistics/#fast. Published February 2011. Accessed May 20, 2011.
DeFronzo RA, Tripathy D, Schwenke DC, et al; for the ACT NOW Study. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011;364:1104-1115.
Klein S, Sheard NF, Pi-Sunyer X, et al. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies—a statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Diabetes Care. 2004;27(8):2067-2073.
Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.
Tuomilehto J, Lindsträm J, Eriksson JG, et al; for the Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344(18):1343-1350.
Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: the Da Qing IGT and diabetes study. Diabetes Care. 1997;20(4):537-544.
Harris R, Donahue K, Rathore SS, Frame P, Woolf SH, Lohr KN. Screening adults for type 2 diabetes: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003;138(3):215-229.
Lee WC, Balu S, Cobden D, Joshi AV, Pashos CL. Prevalence and economic consequences of medication adherence in diabetes: a systematic literature review. Manag Care Interface. 2006;19(Jul):31-41.
Odegard PS, Capoccia K. Medication taking and diabetes: a systematic review of the literature. Diabetes Educ. 2007;33(6):1014-1029.
Wild D, von Maltzahn R, Brohan E, Christensen T, Clausen P, Gonder-Frederick L. A critical review of the literature on fear of hypoglycemia in diabetes: implications for diabetes management and patient education. Patient Educ Couns. 2007;68(1):10-15.
Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes. 2008;57(12):3169-3176.
Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007;147(6):386-399.
Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain and hypoglycemia in type 2 diabetes. JAMA. 2010;303(14):1410-1418.
Gavin JR III, Freeman JS, Shubrook JH Jr, Lavernia F. Type 2 diabetes mellitus: practical approaches for primary care physicians. J Am Osteopath Assoc. 2011;111(5 suppl 4):S3-S12.
Perley MJ, Kipnis DM. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest. 1967;46(12):1954-1962.
The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986.
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-853.
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.
Albers JW, Herman WH, Pop-Busui R, 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):1090-1096.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-Year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577-1589.
Table.
Adults in the United States With Diagnosed or Undiagnosed Diabetes, 2010

Group

Persons With Diabetes, No. (%)
Age, y
□ ≥ 20 25.6 million (11.3)
□ ≥ 6510.9 million (26.9)
Sex
□ Men*13.0 million (11.8)
□ Women* 12.6 million (10.8)
Race
□ Non-Hispanic whites* 15.7 million (10.2)
▪ Non-Hispanic blacks*4.9 million (18.7)
 Source: National Diabetes Information Clearinghouse Web site1
 *Aged 20 years or older.
Table.
Adults in the United States With Diagnosed or Undiagnosed Diabetes, 2010

Group

Persons With Diabetes, No. (%)
Age, y
□ ≥ 20 25.6 million (11.3)
□ ≥ 6510.9 million (26.9)
Sex
□ Men*13.0 million (11.8)
□ Women* 12.6 million (10.8)
Race
□ Non-Hispanic whites* 15.7 million (10.2)
▪ Non-Hispanic blacks*4.9 million (18.7)
 Source: National Diabetes Information Clearinghouse Web site1
 *Aged 20 years or older.
×