NEW ORLEANS – For adolescents and children with type 2 diabetes, there aren’t a lot of therapeutic options other than insulin and metformin. And the situation isn’t likely to change without extraordinary collaboration, Kristen J. Nadeau, MD, research director of the department of pediatric endocrinology at Children’s Hospital Colorado, Colorado Springs, said at the annual scientific sessions of the American Diabetes Association.
“Type 2 diabetes in youth appears to differ not only from pediatric type 1 diabetes, but also from adult type 2 diabetes, and current treatment options are limited,” Dr. Nadeau said. The estimated number of type 2 diabetes cases in the United States per year stands at 1,469,000 cases (12.3 per 100) in adults, compared with 5,100 (0.5 per 100) in youth. In adults there is a slight male predominance, whereas in kids girls are almost twice as likely as boys to be affected. Moreover, beta cell function declines faster in youth with type 2 diabetes.
Dr. Kristen J. Nadeau
The majority of insulins used by adults with type 2 diabetes are also approved for use in children and adolescents, but the only non-insulin medication approved for youth is metformin. According to Dr. Nadeau, 11 clinical safety and efficacy studies and 3 pharmacokinetic studies are ongoing for four DPP-4 inhibitors, two GLP-1 analogs, three SGLT2 inhibitors, colesevelam, bromocriptine, and insulins. A total of 5,000 youth are needed to complete current and planned trials, which “would require 100% participation from every child diagnosed in the next year, which is not feasible,” she said.
The required safety and efficacy studies are too difficult “because of the combination of unique challenges of the target population, study design concerns, and a lack of collaboration between agencies,” Dr. Nadeau said during a session that focused on the conclusions of the American Diabetes Association’s consensus conference on youth with type 2 diabetes, which took place on Oct. 20, 2015 in Alexandria, Va.
The consensus report was published online in Diabetes Care, and addresses the current status of type 2 diabetes in youth, the challenges of treatment, and priorities for research. Dr. Nadeau co-chaired the effort along with Dr. Philip Zeitler, section head of pediatric endocrinology at Children’s Hospital Colorado and medical director of the Children’s Hospital Colorado Clinical and Translational Research Center, Denver. Collaborators included the American Academy of Pediatrics, the International Society for Pediatric and Adolescent Diabetes, and the Pediatric Endocrine Society.
One example of the research challenges is evident in data from the Today trial, which found that only about 39% of kids with type 2 diabetes live with both parents (J Clin Endocrinol Metab. 2011 Jan; 96[1]:159-67). “Whenever you have only one parent in the home, there are difficulties with transportation by definition, so it’s a lot harder for these kids to participate in studies,” Dr. Nadeau said. “In addition, only 17% of their parents had a college or advanced education and 41% had a household income of less than $25,000 per year.”
The social environment is critical, she continued, because the lifestyle factors associated with type 2 diabetes often result in poor outcomes. “It’s very hard to make lifestyle changes if there is a socioeconomic challenge,” she said. “We can’t make change without understanding the community and culture that these youth live in. It’s also critical that we have participation of minorities and other research participants with diverse backgrounds in order for [clinical] trials to be effective for the population that this disease is affecting.”
Another issue keeping drug trials of youth with type 2 diabetes from being completed is the entry criteria. Some studies require youth to be drug naive and have a hemoglobin A1c greater than 7%. “This is difficult, because many youth that are referred to our diabetes center already come in on metformin, leaving only about 7% of subjects available for this criteria,” Dr. Nadeau explained. Another common study entry criterion is being on metformin and having a hemoglobin A1c of about 7%, “so basically being a metformin failure,” she said. “This is difficult to meet because metformin is relatively effective in the early stages of diabetes.”
“We need clear strategies for research, prevention, and treatment. Clarifying unique pathophysiology, complications, and psychosocial impact will enable industry, academia, funding agencies, advocacy groups, and regulators to collectively evaluate the best approaches to research, treatment, and prevention,” Dr. Nadeau said.
The consensus conference participants recommended the following objectives: clarify the biology of type 2 diabetes in youth, obtain new pediatric information on drugs, encourage the use of appropriate medications, and inform clinical decision-making. “We have a desperate need to understand the actions of drugs in type 2 diabetes youth,” Dr. Nadeau said. “Our current approach is not working. Potential solutions include considering efficacy outcomes besides A1c, potentially looking at improvement in insulin sensitivity, preservation of beta-cell function, trying to prevent the A1c increase instead of looking for an A1c reduction, and trying to extrapolate from effects in adults, if we can understand enough to do that.”
The conference participants also called for infrastructure changes, such as creating a resource for patients with type 2 diabetes in the model of the Type 1 Diabetes Exchange. “We need to have collaborations internationally,” she said. “We also need support for teams and clinical groups to work together to be able to accomplish these collaboratively.”
Dr. Nadeau reported having no financial disclosures.