Translational Research for the Prevention and Control of Diabetes and Obesity (R18)
Several large, controlled clinical trials have established "gold standard" approaches for treating type 1 and type 2 diabetes, and for preventing or delaying type 2 diabetes in individuals at high risk for developing the disorder. Research is needed to translate the results of these trials into widespread practice. Studies to develop effective, sustainable, and costeffective methods to prevent and treat diabetes and obesity in clinical health care practice and other realworld settings are appropriate targets for translational research.
The Diabetes Control and Complications Trial (DCCT), for type 1 diabetes, and the United Kingdom Prospective Diabetes Study (UKDPS), for type 2 diabetes, established the importance of intensive glycemic control in dramatically reducing the devastating complications of diabetes.
Unfortunately, the therapies proven to delay or prevent complications in these studies have not been widely incorporated into general health care practice. Prevention and treatment of long-term micro-and macrovascular complications remain a critical problem in the management of type 1 and type 2 diabetes mellitus. In the United States, diabetes is the leading cause of new blindness in working- age adults, of new cases of end-stage renal disease, and of nontraumatic lower leg amputations. In addition, cardiovascular complications are now the leading cause of diabetes-related morbidity and mortality, particularly among women and the elderly. In adults with diabetes, the risk of cardiovascular disease (CVD) is 2-to 4-fold greater than in nondiabetics. Comorbid conditions (hypertension, dyslipidemia, and smoking) combine with hyperglycemia to contribute to accelerated atherosclerosis. Clinical trial data have established the unequivocal benefit of rigorous control of glycemia and blood pressure in preventing both micro-and macrovascular complications of diabetes. Smoking cessation, aspirin therapy, and lipid control have also been shown to prevent morbidity. Despite clear-cut evidence of benefit, recently available data demonstrate that patients with diabetes are not achieving recommended levels of glycemic, blood pressure, or lipid control, or adherence to other accepted treatment guidelines.
The difficulties inherent in achieving good glucose control and preventing diabetes complications make prevention a compelling strategy. This is particularly true for type 2 diabetes, which is clearly linked to modifiable risk factors, e.g., overweight or obesity and a sedentary lifestyle. The Diabetes Prevention Program (DPP) tested strategies to prevent or delay the development of type 2 diabetes in individuals at high risk for its development by virtue of their having impaired glucose tolerance (IGT). The DPP demonstrated that intensified lifestyle or drug intervention in individuals with IGT prevented or delayed the onset of type 2 diabetes. Lifestyle intervention, leading to moderate weight loss and increased exercise, reduced diabetes incidence by 58% and the drug metformin by 31% compared with placebo. The effects were similar for men and women and for all racial and ethnic groups. Similar effects of lifestyle intervention were seen in another study conducted in Finland. Cost-effective strategies for promoting lifestyle modification leading to weight loss in these high-risk individuals, outside the setting of a controlled, clinical trial, need to be established. In addition, while behavioral treatment of obesity in adults leads to clinically significant weight loss, prevention of weight regain remains an elusive goal for many.
Overweight in childhood, the prevalence of which has more than doubled in the past 2 decades, is a major risk factor for type 2 diabetes. Indeed, the increase in overweight children has been linked to a rise in type 2 diabetes in the pediatric population. Family-based behavioral interventions have been shown to have a long-term impact on degree of overweight. However, cost-effective interventions in primary care and community-based settings are needed. …