A clinical study at the University of Oklahoma Health Sciences Center has found that people with Type 2 diabetes diagnosed during youth — as young as 10 years old — have a high risk of developing complications at early ages and have a greater chance of multiple complications within 15 years after diagnosis. The findings are the culmination of a first-of-its-kind trial funded largely by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health.
Within 15 years of a Type 2 diabetes diagnosis, 60% of participants had at least one diabetes-related complication, and nearly a third of participants had two or more complications, according to results of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) follow-up study, called TODAY2. The findings were published in the New England Journal of Medicine.
“Until recent years, children almost never got Type 2 diabetes; it has primarily been a disease of adults. Because one-third of U.S. children are now overweight, more and more young people are being diagnosed with Type 2 diabetes,” said Jacob E. “Jed” Friedman, Ph.D., director of OU Health Harold Hamm Diabetes Center. “This study shows that severe complications can develop from that diagnosis while patients are still in young adulthood. We previously called Type 2 diabetes ‘adult-onset diabetes,’ but that definition no longer fits the disorder.”
TODAY2 involved 500 original participants from the TODAY study, which began in 2004. TODAY was the first major comparative effectiveness trial for the treatment of Type 2 diabetes in youth. At the time of enrollment, participants were between the ages of 10-17, had been diagnosed with Type 2 diabetes for fewer than two years, and were overweight or had obesity. The average age of participants after the TODAY2 follow-up was 26 years.
The study compared three treatments for managing blood glucose: metformin alone, metformin plus rosiglitazone, and metformin plus an intensive lifestyle intervention. Metformin is the only oral medication approved by the U.S. Food and Drug Administration to treat Type 2 diabetes in youth.
Participants in TODAY2 were monitored annually for signs of diabetes complications, including heart disease, kidney disease, diabetic foot complications, and to report other health events. Diabetic eye disease was assessed once during the study, at the seven-year study visit.
Overall, researchers saw a steady decline in blood glucose control over 15 years. In addition:
- 67% of participants had high blood pressure
- Nearly 52% had dyslipidemia, or high fat levels in the blood
- Nearly 55% had kidney disease
- 32% had evidence of nerve disease
- 51% had eye disease.
Rates did not differ based on the original TODAY study treatment group assignment.
In addition, certain participants had a higher likelihood to develop multiple complications over time, with 28% developing two or more over the follow-up period. Participants who belonged to a minority racial or ethnic group, or who had high blood glucose, high blood pressure, and dyslipidemia were at higher risk for developing a complication.
The TODAY study’s diverse cohort is representative of the U.S. youth diagnosed with Type 2 diabetes. Study participants had regular, intensive diabetes management through the study at no cost during the original TODAY trial, which researchers note may have actually lowered the rate of complications.
The TODAY and TODAY2 studies were conducted at the OU Health Sciences Center and 14 other centers in the United States. The George Washington University, Washington, D.C., served as the data coordinating center. The OU Health Sciences Center, the largest of the 15 clinical sites in the trial, also partnered with many tribal nations and communities, including the Absentee Shawnee Tribe, the Cherokee Nation, the Choctaw Nation of Oklahoma, and the Oklahoma City Area Office of the Indian Health Service.
“The TODAY study offered unique scientific opportunities and has led to important scientific discoveries. Equally important is the study’s leadership vision for promoting tribal engagement and treating its tribal partners with the respect and dignity that tribal nations are deserving of,” said Sohail Khan, MBBS, MPH, CIP, Director of Health Research at the Cherokee Nation.
During the initial years of TODAY in Oklahoma, the study was led Kenneth Copeland, M.D., now Professor Emeritus in the Section of Diabetes and Endocrinology, Department of Pediatrics, of the OU College of Medicine. Following his leadership, the study has been directed by two other faculty members in the section, Associate Professor Jeanie Tryggestad, M.D., and Section Chief Steven Chernausek, M.D.
“The TODAY study has demonstrated that youth-onset Type 2 diabetes is much more aggressive than Type 2 diabetes in adults,” said Tryggestad, who serves as the study’s local principal investigator. “Youth experience multiple complications very early in their disease process. This demonstrates the need to aggressively treat youth-onset Type 2 diabetes as well as continue to strive for better treatment to prevent the disease progression.”
This work was completed with funding from NIDDK/NIH grant numbers U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01-DK61254; the National Center for Research Resources General Clinical Research Centers Program; and the NCRR Clinical and Translational Science Award Program.
TODAY received additional support from Becton, Dickinson and Company; Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; LifeScan, Inc.; Pfizer; and Sanofi Aventis.