Most children who are obese and have type 2 diabetes do not achieve adequate control of their blood glucose levels with conventional therapy, according a major study reported at the recent 72nd Scientific Sessions of the American Diabetes Association.
Health officials are concerned about the rising incidence of type 2 diabetes in children, which is becoming increasingly common among children and teenagers because of the upswing in obesity rates among young people. Of particular concern is the finding that poor control of the disease is alarmingly frequent among minority children, noted Griffin Rodgers, MD, Director of the National Institute of Diabetes and Digestive and Kidney Diseases, who said that the institute is funding studies to better understand how to manage diabetes in children.
One major investigation is the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, a large longitudinal study of children with the disorder. In the study, 699 children (aged 10 to 17 years and with a body mass index [BMI] at or above the 85th percentile) with type 2 diabetes were given diet and lifestyle counseling and prescribed metformin with the goal of achieving and maintaining a hemoglobin A1c level of less than 8.0%. (HbA1c is a measure of long-term blood glucose control.) Participants were then randomly assigned to 3 groups: 1 group continued to receive metformin alone, a second group received rosiglitazone as well as metformin, and a third group received metformin and also had family-based weight-loss counseling that included in-person visits for the first 2 years and quarterly medical contact thereafter.
“Nearly half of youth with type 2 diabetes maintain long-term control, irrespective of treatment,” said the study’s principal investigator, Phil Zeitler, MD, PhD, of the department of pediatrics at the University of Colorado, but “metformin monotherapy is inadequate for half of youth with type 2 diabetes.” He noted that addition of a second agent will be needed early in the treatment course for children who do not experience adequate blood glucose control with metformin alone. In the study, about 61% of those receiving both metformin and rosiglitazone achieved adequate blood glucose control; however, the US Food and Drug Administration has now restricted use of rosiglitazone in the United States because of potential safety concerns, so some other agent will be required.
Another disappointment was that although the children who received metformin and lifestyle counseling did lose some weight, they did not experience improved glycemic control. Most worrisome was a high failure rate for minority children.
One of the TODAY study’s major objectives was understanding the characteristics associated with treatment success or failure. Among the 699 children in the study, there were 172 who maintained glycemic control (as measured by an HbA1c level of less than 8.0% for at least 48 months). Those who did not maintain glycemic control “were more obese, with higher A1c and lower IGI [insulinogenic index, an indicator of how well insulin-producing beta cells respond to an increase in glucose] at baseline,” said Kenneth Copeland, MD, of the department of pediatrics of the University of Oklahoma Health Sciences Center. Copeland pointed out that multivariate analysis indicated that higher levels of baseline HbA1c were associated with failed treatment. As the study progressed, failed diabetes treatment was predicted by high HbA1c levels, low insulin secretion levels that continually declined with time, and higher BMI that increased during the study. “Baseline A1c is the best predictor of failure (regardless of therapy), even within the nondiabetic range,” said Copeland. “During treatment, a rapidly rising A1c, even within the normal range, is associated with failure and may suggest the need to intensify treatment early.”
Because obese children typically grow up to be obese adults who tend to have significant complications from diabetes, understanding how best to treat obese diabetic children is of paramount importance. The TODAY study’s finding that obese children and teens with diabetes do not achieve adequate blood glucose control with conventional treatment highlights the importance of very aggressive monitoring and a readiness to escalate treatment when needed in such patients.