Clinical Trials at the NIDDK: A Translational Perspective

AADE program session
Thursday August 12, 2004
Reviewed by Aric Fader, PhD

Dr. Garfield reviewed some of the well-publicized demographics of patients suffering from diabetes in the United States, including the fact that an estimated 18 million patients have been diagnosed, as many as an additional 6 million individuals with diabetes remain undiagnosed, 41 million patients have prediabetes with impaired glucose tolerance (IGT) are already need treatment, and type 2 diabetes accounts for roughly 95% of the patient population. By the year 2050 the projected number of patients in the United States will have increased by120% from 1990, but the overall population of the country will only increase by 45% during that same time period. The working age population will only increase by 25%, but they will make up the population paying for all the medical costs. In 1990 no states had a population of greater than 20% obese, however, by 2002 more than half the states had reached that demographic, and three states had more than 25% of the population obese. Right now type 2 diabetes accounts for 25% of the monetary impact of healthcare costs in the United States, equating to $132 billion dollars per year. Diabetes causes 200,000 deaths per year, and decreases life expectancy of patients by 10-15 years.

The DCCT study assessed the progression of patients with type 1 diabetes in the United States, whereas the UPKDS study did the same for type 2 patients in the United Kingdom. Those studies measured the possibility of tight glucose control for preventing long-term complications. The DCCT published results in 1993 that reported intensive treatment of patients could result in normalizing hemoglobin A1C and reducing the incidence of diabetic retinopathy by 76%, diabetic neuropathy by 50%, and diabetic nephropathy by 60%. A follow-up study entitled EDIC was designed to monitor these patients over time and included 96% of the patient population. The A1C levels of the patients in the intensive treatment group of DCCT increased back to the baseline levels within 7 years of the initiation of the EDIC trial; however, the diabetic retinopathy incidence rate was still significantly lower in that group, demonstrating that 6 years of intensive treatment during DCCT helped those patients tremendously. Cardiovascular impact is still being tracked and will be published when that study is concluded. The results from the UKPDS revealed a 25% decrease in diabetic microvascular complications (DMC) and 32% decrease in mortality among the intensively treated type 2 patient group.

Other studies have helped alter treatment guidelines. The NHANES trial reported that among the 37% of type 2 patients in that study that were able to decrease A1C below 7%, 36% were able to decrease blood pressure below 130/80, and 52% had cholesterol below 200 mg/dL. A study by Molitch et al that was published in 2003 reported that intensive changes in lifestyle, such as exercise and weight loss, along with metformin 850 mg 2x/day delayed the onset of type 2 diabetes among IGT patients. Among the placebo group in that study 11% developed diabetes, along with 7.8% of the metformin group, but only 4.8 % of the group that received metformin and lifestyle changes did, equating to a 58% difference from the placebo group. The conclusions were that diabetes can be prevented for at least 3 years. That study will continue through 2009, reporting other results, such as prevention of CVD. Other ongoing studies include Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY), Studies to Treat or Prevent Type 2 Diabetes in Schools (STOPP-T2D) which is designed to measure the efficacy of lifestyle changes in school systems, and Action for Health in Diabetes (AHEAD), which is investigating the results of weight loss in obese type 2 patients over a period of twelve years.