New Youth-onset Type 2 Diabetes Study Reveals Long-term Complications

A new Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study led by Phil Zeitler, MD, PhD, and a team of researchers on the long-term complications of type 2 diabetes is featured in the New England Journal of Medicine.

As a pediatric endocrinologist, Dr. Zeitler has been treating youth with type 2 diabetes for more than 20 years and is the chair of the TODAY2 study group. He serves as the medical director of the pediatric Clinical and Translational Research Center at Children’s Hospital Colorado and a professor of pediatrics at the University of Colorado School of Medicine.  

The study shows that not only is type 2 diabetes having an impact on youth and young adults at a young age, but it also shows that 60% of participants had some complication and the majority had two, three or more complications.

“It is really critical for governments, policymakers, and healthcare systems to be prepared for what this means in terms of healthcare usage; loss of productivity years; loss of life; impact on families; unemployment; as well direct costs – a lot of money will be spent on these kids through dialysis, medications, cardiac bypass and more,” Dr. Zeitler says.

Study identifies complications from type 2 diabetes on youth and young adults over a 15-year period

The first phase of this study focused on complications of youth-onset type 2 diabetes took place from 2004 - 2011; and phase two from 2011 - 2020. Both phases involved more than 550 participants from across the country. Overall, researchers saw a steady decline in blood glucose control in study participants over 15 years, which causes various complications:

• 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

Some groups face higher risk of type 2 diabetes complications

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.

“Youth-onset of type 2 diabetes is associated with an accumulation of diabetes-related complications such as eye disease, kidney disease, nerve disease and other co-morbidities like strokes, heart disease, amputations – and this is occurring at least as rapidly as in adults. Potentially more rapidly,” says Dr. Zeitler.

Additionally, some teens diagnosed with the disease, and who have lived with it for 10-12 years, have suffered strokes, kidney failure, heart attacks, toe and foot amputations—all while in their 20s.

Seeking best treatment approaches for type 2 diabetes

 The initial TODAY study was designed to look at the best treatment approaches: 1) metformin or 2) metformin plus rosiglitazone or 3) metformin plus a lifestyle intervention. Researchers followed the youth to determine the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. Glycemic control is a medical term referring to the optimal levels of blood sugar (glucose) in a person with diabetes mellitus.

“Even at that time [the study began in 2004], it was recognized that type 2 diabetes seemed to be more aggressive in kids,” Dr. Zeitler says. “Since they are going to live with it longer, we want good [glycemic] control as early as possible.” 

Type 2 diabetes guidelines are based on this landmark study

In 2012, the New England Journal of Medicine published the results of this initial study, which is considered a landmark in youth-onset type 2 diabetes. The guidelines that currently exist for the management of type 2 in youth are based on the results.

“The study was so foundational that it immediately translated into treatment recommendations,” says Ronald Sokol, MD, director of the Colorado Clinical and Translational Science Institute (CCTSI). The CCTSI’s pediatric Clinical Translational Research Center at Children’s Hospital Colorado was crucial to the operation of these two studies that lasted 15 years.

Researchers found that therapy with metformin alone was associated with durable glycemic control in only half of children and adolescents with type 2 diabetes. The addition of second pharmacologic agent, but not an intensive lifestyle intervention, was superior to metformin alone. Researchers found that it was very difficult for participants to change their lifestyles as many lived in very challenging home environments.

The next step is to put together a new cohort of younger children to understand who gets type 2 diabetes to develop targeted interventions. Zeitler says, “If we want to do any kind of prevention, we need to have a better idea of who is at risk.”