Youth-Onset Type 2 Diabetes Better After Bariatric Surgery

Kristin Jenkins

March 12, 2018

In severely obese teens with type 2 diabetes, bariatric surgery provides significantly better weight reduction, diabetes remission, and improvement of cardiovascular risk factors than did medical therapies, according to researchers.

A secondary analysis of data from two large cohort studies makes a case for considering a surgical solution to youth-onset type 2 diabetes, even though the surgical benefits do come with the caveat of a higher risk for complications, say Thomas H Inge, MD, PhD, Department of Pediatric Surgery, Children's Hospital Colorado, Aurora, and colleagues.

In a subgroup of 30 patients from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study, there was a 95% improvement in type 2 diabetes with hemoglobin A1c (HbA1c) concentration less than 6.5% at the 2-year follow-up.

This is not only "greater than expected" but better than what has been observed in adults after similar operations and similar weight loss, the study authors say in their paper, published March 12 in JAMA Pediatrics.

Of the 30 patients, 24 underwent Roux-en-Y gastric bypass and 6 had vertical sleeve gastrectomy; overall, HbA1c values fell from 6.8% to 5.5%, and body mass index (BMI) fell 29% from baseline. Blood pressure, dyslipidemia, and kidney function also improved significantly.

By comparison, a subgroup of 63 participants from the Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY) study, treated with medical therapies, experienced weight gain, diabetes progression, and no improvement in cardiovascular risk factors.

"These individuals experienced progressive worsening of glycemic control, hypertension, dyslipidemia, and abnormal renal function," the investigators note. HbA1c concentration increased from 6.4% to 7.8%, with a median time to failure of 11.5 months. BMI increased by 3.7% from baseline.

"These data, combined with the effects of type 2 diabetes on mortality being greatest for those who received diagnoses at a young age, suggest that surgical therapy should be considered earlier rather than later for those who are diagnosed with youth-onset type 2 diabetes," say Inge and colleagues.

The findings also "support the need for a well-designed, prospective controlled study to define the role of surgery for adolescents with type 2 diabetes, including health and surgical outcomes," they stress.

Indications for Bariatric Surgery in Teens Based on Studies in Adults

The indications for bariatric surgery in adolescents include type 2 diabetes among those with a BMI of 35 or greater, but this guidance has been based on studies in adults, the investigators point out.

The secondary analyses of Teen-LABS and TODAY were carried out between July 6, 2015, and June 24, 2017, and included data collected at baseline and at 6-month, 1-year, and 2-year study visits from both cohorts.

Teen-LABS originally enrolled 242 adolescents aged 13 to 18 years with a mean baseline BMI of 54 between March 1, 2007, and December 31, 2011. The TODAY study enrolled 699 patients aged 10 to 17 years with a mean BMI of 41 between May 1, 2004, and December 31, 2009. The TODAY participants were randomly assigned to metformin, metformin plus lifestyle counseling, or metformin plus rosiglitazone.

Of the subgroup examined in this new analysis, 20 of the 30 Teen-LABS patients (45%) had high blood pressure at baseline, and just 5 (20%) still had elevated blood pressure at 2 years.

In contrast, in the 63 patients in the TODAY subgroup, the number of patients with hypertension nearly doubled, from 13 (22%) at baseline to 23 (41%) after 2 years.

Similarly, the number of participants with dyslipidemia in the Teen-LABS subgroup decreased from 21 (72%) at baseline to 9 (24%) at 2 years. This included improvements in triglyceride and high-density lipoprotein cholesterol concentrations.

In the TODAY subgroup, however, the prevalence of dyslipidemia did not change appreciably, although the investigators say they observed a modest increase in triglyceride concentrations.

Bariatric Surgery Is Not Without Risks

Still, the benefits of bariatric surgery came with an increased risk for complications, the analysis shows. Seven Teen-LABS patients (23%) underwent subsequent surgery and/or hospital readmission for procedures such as cholecystectomy to remove gallstones. An additional five patients (17%) had complications unrelated to surgery.

In the TODAY subgroup, two patients (3%) had complications that required hospital admission: one for calf swelling and ankle edema and the other for knee pain and anemia.

"Clinical events that required surgical management were observed in one-fifth of surgical participants," the study authors say.

These new data suggest that "surgery provides superior treatment of adolescent type 2 diabetes and its comorbidities. However, this patient population is susceptible to major surgical complications.

"These types of events should be understood by physicians, teenagers, and families when considering the treatment options currently available for adolescents with type 2 diabetes."

And, the authors stress, little is known about the long-term effects of surgery compared with medical therapy, indicating a critical need for additional research. Such research should focus on longer-term assessments of health outcomes, including nutritional and other effects of surgery, recurrence of type 2 diabetes, cardiovascular end points, and mortality.

Funding for this study was received from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health (University of Cincinnati), the National Center for Research Resources General Clinical Research Centers Program (Washington University School of Medicine, Children's Hospital Los Angeles, University of Colorado Denver, Children's Hospital of Pittsburgh, Massachusetts General Hospital, Yale University, University of Oklahoma Health Sciences Center), the National Centre for Advancing Translational Science (Children's Hospital of Philadelphia, Yale University, Children's Hospital of Pittsburgh, Case Western Reserve University, Washington University in St Louis, Massachusetts General Hospital, University of Colorado Denver), and the National Center for Research Resources Clinical and Translational Science Awards (Cincinnati Children's Hospital Medical Center, Nationwide Children's Hospital, Texas Children's Hospital/Baylor College of Medicine, University of Pittsburgh, and the University of Alabama, Birmingham).  Inge reported a relationship with Standard Bariatrics. Study coauthor Lori M. Laffel, MD, reported relationships with AstraZeneca, Boehringer Ingelheim Pharmaceuticals Inc, Dexcom Inc, Eli Lilly and Company, Insulet, Johnson & Johnson, MannKind Corporation, Menarini, Diagnostics, Novo Nordisk Inc, Roche Diagnostics, and Sanofi US. Marsha D. Marcus, PhD, reported a relationship with Weight Watchers International Inc. Philip S. Zeitler, MD, PhD, reported relationships with Daichii-Sankyo, Merck, Janssen, Takeda, and Eli Lilly and Co. No other financial relationships were disclosed.

JAMA Pediatr. Published online on March 12, 2018. Abstract

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