Forty years of large-scale, multicenter clinical trials supported by the National Institutes of Health have had a profound impact on the treatment of diabetes, including establishing intensive glucose control as the worldwide standard of care for individuals with diabetes.
A key leader of those landmark studies visited Vanderbilt University Medical Center last week to share his insights on diabetes research and treatment and what he foresees for the future. The number of adults living with diabetes worldwide has surpassed 800 million, and the World Health Organization has called the escalating prevalence of Type 2 diabetes an epidemic.
“We’re fighting a losing battle, as far as I can tell, against the societally mediating risk factors for obesity — overnutrition and the fact that we all just sit,” said David Nathan, MD, founder and director of the Diabetes Center and Diabetes Research Center at Massachusetts General Hospital and professor of Medicine at Harvard Medical School. “We are out of balance, and the prevalence of obesity is devastating.”
In the past decade, there has been an explosion of glucagon-like peptide-1 (GLP-1) receptor agonist medications that mimic a hormone that helps regulate blood sugar and control appetite, making them a powerful tool for weight loss and managing Type 2 diabetes. Despite studies showing their favorable risk-benefit profile, the drugs’ long-term impact remains largely unknown, Nathan cautioned.
Nathan presented the Albert and Miriam Weinstein Lecture, held in honor of Albert Weinstein, MD, clinician-educator and former director of the Vanderbilt Eskind Diabetes Clinic, and his wife, Miriam.
He has long been a principal investigator for NIH-sponsored longitudinal studies including the Diabetes Control and Complications Trial (DCCT), the Epidemiology of Diabetes Interventions and Complications (EDIC) study, and the Diabetes Prevention Program (DPP).
One of Nathan’s early mentors and research collaborators was Oscar Crofford, MD, a key architect of the National Commission on Diabetes, for which he served as inaugural chair, as well as a driving force behind the establishment of diabetes research and training centers throughout the United States.
Crofford, the first full-time diabetes specialist to practice at Vanderbilt University Medical Center, established the Division of Diabetes at VUMC and helped bring the nation’s first federally supported diabetes research center to Vanderbilt in 1973.
Crofford also led the establishment and served as chair of the DCCT research group and along with Nathan and other DCCT investigators authored landmark research that revolutionized the treatment of Type 1 diabetes. Crofford’s daughter, Leslie Crofford, MD, Wilson Family Professor of Medicine, is a past director of VUMC’s Division of Rheumatology and Immunology.
“That smiling guy at the top there is Oscar Crofford, and he’s really the father of this study,” said Nathan, as he showed the audience a 1982 group photo of DCCT researchers. “He was just a spectacular leader. He got the study moving and never let us forget what our mission was.”
Participants in the DCCT volunteered to also participate in the follow-up EDIC study, with unprecedented loyalty across 40 years, Nathan said.
“We have followed this population for 95% of their diabetes and for 65% of their lifespan in this remarkable, purely NIH-sponsored study,” he said. “To this day we are following about 90% of the original participants, 40 years later.”
When the DCCT began recruiting in 1983, diabetes was the third leading cause of death in the United States, with most individuals with the disease dying by their late 40s. Because of findings from the DCCT, EDIC and other studies, intensive blood glucose control became the standard of care for individuals with Type 1 diabetes and for some individuals with Type 2 diabetes.
Early glycemic control was also shown to reduce the risk of developing serious complications such as cardiovascular disease and damage to the eyes and kidneys. Knowledge gained from these studies has helped people diagnosed with diabetes live longer, healthier lives.
“We can now tell people with Type 1 diabetes that they are not fated to have loss of vision, kidney damage, loss of limbs, early loss of life,” Nathan said. “In the DCCT, the lifespan of those participants in the intensive treatment group that started in 1983 is now the same as that of a nondiabetic.”
Nathan spoke of the need to further develop precision medicine to consider the differences within Type 2 diabetes to make treatments more effective. He also emphasized the importance of improving access to treatment.
In March, Nathan and other investigators working on the national Diabetes Prevention Program Outcomes Study, a long-term follow-up of the original DPP study, learned that the National Institutes of Health has halted funding for the project. This initiative, begun in 2002, was tracking more than 2,700 patients with prediabetes and diabetes. The most recent phase of the program focused on tracking the development of Alzheimer’s disease and other dementias among participants.
