Findings from OU Health Harold Hamm Diabetes Center Study Show Youth-Onset Type 2 Diabetes Results in Serious Complications by Young Adulthood

A clinical study conducted at OU Health Harold Hamm Diabetes Center on the University of Oklahoma Health Sciences Center campus 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 recently in the prestigious New England Journal of Medicine.

The TODAY study has demonstrated that youth-onset Type 2 diabetes is much more aggressive than Type 2 diabetes in adults. 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,” said OU Health pediatric endocrinologist and researcher Jeanie Tryggestad, M.D., who led the study at the OU Health Sciences Center for the past several years.

“Until recent years, children almost never got Type 2 diabetes; it has primarily been a disease of adults,” said Jacob E. “Jed” Friedman, Ph.D., director of OU Health Harold Hamm Diabetes Center. “Because one-third of U.S. children are now overweight, more and more young people are being diagnosed with Type 2 diabetes. The TODAY study shows that severe complications can develop from that diagnosis while patients are still in young adulthood.”

The TODAY and TODAY2 studies were conducted at the OU Health Sciences Center and 14 other centers in the United States. 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. Approximately 40% of study participants in Oklahoma were youth from tribal nations.

“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.

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.

Participants in TODAY2 were monitored annually for signs of diabetes complications, including heart disease, kidney disease, nerve complications, and other reported health events. Diabetic eye disease was also assessed during the study.

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 levels of fat in the blood
• Nearly 55% had kidney disease
• 32% had evidence of nerve disease
• 51% had eye disease

In addition, certain participants had a higher likelihood of developing 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.

Tryggestad, who is co-director of the OU Health Type 2 Diabetes Comprehensive Clinic in Youth, said the TODAY study findings reflect what she sees in her own patient population. “While Type 1 diabetes is still the most prevalent form of diabetes in children, Type 2 diabetes is increasing and now represents about 1 of every 3 new diagnoses,” she said. “Youth with Type 2 diabetes experience a more rapid failure of the beta cells than do adults with Type 2 diabetes. Beta cells make insulin in the pancreas; without them, the body cannot make enough insulin to meet the demands of insulin resistance, the underlying problem associated with Type 2 diabetes.”

Part of the role of the Type 2 Diabetes Comprehensive Clinic is to address the fact that Type 2 diabetes is not the same disease in children as it is in adults. Many families assume that Type 2 is the less aggressive form of diabetes in children and that complications will only occur later in life. The TODAY studies confirm that is not the case.

“Type 2 diabetes in youth is a serious disease from onset, and it needs to be treated much more aggressively,” Tryggestad said. “We decided to create the comprehensive clinic because there are so many facets to this disease. We want to ensure we are following standards of care and appropriate screening for microvascular issues and other potential complications. In addition to physicians, our interdisciplinary team includes diabetes educators, nurses, pharmacy support, as well as a psychologist because diabetes distress is very common in this age group.”

The TODAY study 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.