Comparing Treatments for Type 2 Diabetes in Severely Obese Adolescents

The incidence of type 2 diabetes has increased substantially in the pediatric population over the past few decades, and youth-onset type 2 disease now represents a substantial percentage of new cases of pediatric diabetes in the United States. “Sadly, many teens with type 2 diabetes experience disease progression and require insulin injections early after their initial diagnosis,” explains Thomas H. Inge, MD, PhD. “This progression is about five times faster than what we see in adults. There is a critical need to identify management approaches that may lead to significant and durable glycemic control in adolescents, including metabolic and bariatric surgery.”

Recently, two major clinical studies sponsored by the NIH have provided important insights on adolescents and youths with type 2 diabetes. The first trial, the Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY), investigated therapies directed designed to achieve durable glycemic control in pediatric type 2 diabetes and found that nearly 50% of youths with type 2 diabetes progressed to a need for insulin injections after a median of only 11 months. In addition, the prevalence of hypertension, LDL cholesterol, and albuminuria were much higher over 4 years follow-up of TODAY participants. The second study, Teen–Longitudinal Assessment of Bariatric Surgery (Teen-LABS), prospectively evaluated outcomes of adolescents who received bariatric surgery and observed significant improvements in weight, cardiometabolic health, and weight-related quality of life at 3 years after the procedure was performed.

 

A Comparative Analysis

A comparative analysis of outcomes of medical and surgical treatment was published in JAMA Pediatrics.  In this report, Dr. Inge and colleagues examined glycemic control and other health factors in the Teen-LABS and TODAY cohorts to compare medical and surgical interventions in severely obese adolescents with type 2 diabetes. In total, data were analyzed from 30 Teen-LABS participants and 63 TODAY patients. Results showed that adolescents with severe obesity and type 2 diabetes receiving medical treatment still experienced modest weight gain and disease progression and had no improvements in cardiovascular risk factors whereas the opposite was seen for the surgical management group. At 2 years follow-up, the average A1C concentrations increased from 6.4% to 7.8% in the TODAY cohort while A1C decreased from 6.8% to 5.5% in the Teen-LABS cohort (Table). “Moreover, when compared with baseline, BMI decreased by 29% in Teen-LABS patients but increased by about 4% in TODAY patients,” Dr. Inge says.

Most adolescents undergoing surgery experienced clinically significant weight reduction, remission of their diabetes, and improvements in cardiovascular risk factors and kidney dysfunction despite starting with a higher BMI. “Hypertension was seen in 45% of surgical patients at baseline, but this rate dropped to 20% at 2 years after surgery,” says Dr. Inge. “For those managed medically, hypertension rates nearly doubled at 2 years after treatment. Similar benefits were seen among surgery patients with regard to rates of dyslipidemia and kidney function when compared with medical management. These findings are especially important considering that the group receiving medical treatment did so in the context of a rigorous and well-staffed multicenter clinical trial.”

Click here for video summary of this study.

 

Important Caveats

Data from the comparative analysis suggest that surgery provides superior treatment of adolescent type 2 diabetes and its comorbidities, according to Dr. Inge. “At the same time, this patient population is susceptible to major surgical complications,” he says. “Relatively little is known about the long-term effects of surgery relative to medical therapy, indicating a critical need for additional research.”

Prior studies have shown that for adults with type 2 diabetes surgery offers significant benefits when compared with medical therapy. “The striking differences in metabolic and comorbidity outcomes between these treatments definitively shows that surgeries causing weight and resulting in metabolic improvements. This kind of evidence strongly supports the use of surgical treatment for adolescents with severe obesity and type 2 diabetes,” Dr. Inge says. “Future work should focus on longer-term assessments of health outcomes, use of surgery for diabetes in patients with even lower BMI thresholds, and further exploration of long-term effects, including diabetes relapse rates, nutritional concerns, cardiovascular endpoints, and mortality reduction.”