More aggressive type 2 diabetes in adolescents; early treatment unlikely to slow progression

ORLANDO, Florida – Adolescents with prediabetes or newly diagnosed type 2 diabetes have a much more aggressive disease than adults with similar glycemic profiles, and early treatment with insulin and metformin does not significantly slow down its progression.

"Indirect evidence suggests that the disease in young people is more aggressive than in adults … There has never been a single study that has fused youth and adults using sophisticated methods to examine this. " Steven E. Kahn, MB, ChB, Professor of Medicine and President Leonard L. Wright and Marjorie C. Wright at the VA Puget Sound Health System / University of Washington, said at a press briefing. "That's exactly what the RISE study … did."

Kahn and RISE Consortium researchers recruited 91 adolescents aged 10 to 19 (mean age 14.2, 71% girls, 28.8% white, 21.2% black, 37.9% female). 39 Hispanic, 3% Asian and 9.1% kg / m²) and 355 adults (average age 52.7 years, 51.5% female, 46.8% white, 27.3% black, 19.2% Hispanic, 5.1% female). Asians, 1.1% mixed origins, 0.6% of others, average BMI of 35.1 kg / m²). Participants had impaired glucose tolerance (80.3% of adolescents, 70.7% of adults) or a type 2 diabetes duration of less than 6 months. Adolescents and adults had similar glucose profiles; 66 teenagers and no adults were prescribed metformin.

In separate studies, adult and pediatric participants who were not prescribed metformin experienced a hyperglycemic clamp and oral glucose tolerance tests to assess insulin sensitivity, C responses and -peptide and insulin and insulin concentrations. The researchers compared baseline data between the two age groups.

In both studies, researchers found that insulin sensitivity was about 50% lower in adolescents compared to adults, Kahn said. Younger participants demonstrated hyper-responsive beta-cell function and reduced insulin clearance.

"Young people have higher beta cell responses than adults, and these differences, we believe, can provide for the first time a true explanation for the more aggressive evolution of the disease among youth who struggle not only with glucose problems. but also with complications observed in adults, at a much younger age. "

In a study of the entire adolescent cohort (n = 91), the researchers randomized participants to receive 12 months of metformin or 3 months of insulin glargine followed by 9 months metformin; After 12 months, the drugs were stopped for a three month elimination period. A hyperglycemic forceps was used to assess beta cell function at baseline and at 12 months and 15 months (the end of the elimination period).

At 6 months, HbA1c was transiently reduced from baseline in both groups, but it was not maintained at 12 months. At 12 and 15 months, beta cell function was significantly worse than at baseline.

"Despite early interventions in youth with impaired glucose tolerance or recent diagnosis of type 2 diabetes, beta-cell dysfunction progressed and was worse than baseline, showing no evidence of impact. early treatment " Kristen J. Nadeau, MD, MS, associate professor in pediatrics-endocrinology at the University of Colorado Anschutz Medical Campus, said at the briefing. "These results contrast with those published in adults who showed improved beta cell function with both metformin and with insulin for diabetes prevention and treatment. insulin are currently the only FDA-approved therapies for young people with type 2 diabetes, we need to better understand these young people, why their diabetes is more aggressive and how we can better treat them.

Nadeau and Kahn both pointed out that the results do not indicate that doctors should stop these drugs in adolescents.

"Obviously, we need to look at alternative therapies in this context, but the biggest message is that this epidemic of childhood obesity has real implications and that these kids have problems," he said. John buzzard, MD, PhD, Director of the Diabetes Center, Director of the Institute of Translational Sciences and Clinics of North Carolina, and Associate Dean of Clinical Research at the University of North Carolina School of Medicine at Chapel Hill , who led the press briefing. "If we can not treat them with insulin and metformin … to get their HbA1c levels in a reasonable range for 80 years, they're going to have problems with complications. 39 moral imperative to do something about the epidemic of obesity, to restrict the marketing of food patently unreasonable to children. "

Studies and comments have been published in Diabetic treatments at the same time as the presentation at the scientific sessions of the American Diabetes Association. – by Jill Rollet

References:

The RISE (Restoring Insulin Secretion) study on baseline data in young people and adults and the results of the pediatric drug study. Presented at: 78th Scientific Sessions of the American Diabetes Association; June 22-26, 2018; Orlando, Florida.

JB nozzle, et al. Diabetic treatments. 2018; doi: 10.2337 / dci18-0025.

RISE Consortium. Diabetic treatments. 2018; doi: 10.2337 / dc18-0243.

RISE Consortium. Diabetic treatments. 2018; doi: 10.2337 / dc18-0244.

RISE Consortium. Diabetic treatments. 2018; doi: 10.2337 / dc18-0787.

Disclosures Buse reports that it receives research support or is advisor to Adocia, AstraZeneca, Boehringer Ingelheim, Dexcom, Elclyx Therapeutics, Eli Lilly, Intarcia, Johnson & Johnson, Lexicon, Metavention, NovaTarg, Novo Nordisk, Sanofi, Senseonics, Theracos and vTv. Therapeutics, and holds stock options in Mellitus Health and PhaseBio Pharmaceuticals. Kahn reports that he is a paid consultant for Novo Nordisk. Nadeau does not communicate any relevant financial information. Please consult the studies for the relevant financial disclosures of all other authors.