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 (HbA_1c) 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 HbA_1c 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. 

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 HbA_1c 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 HbA_1c 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 HbA_1c level attained in the intensive therapy group was 7.4%, whereas the HbA_1c 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 HbA_1c 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.