Surgical or Medical Treatment (ST2OMP)

This study will test the hypothesis that metabolic bariatric surgery will be more effective at providing durable glycemic control and reduce co-morbidities than intensive medical therapy in youth with type 2 diabetes.

Youth-onset type 2 diabetes (T2D) leads to early dependence on exogenous insulin and progression of T2D co-morbidities, including dyslipidemia, hypertension, non-alcoholic fatty liver disease and diabetic kidney disease. The pathophysiology of T2D in youth differs considerably from adults and current treatment approaches are in-adequate for youth. Thus, exploration of innovative approaches to reduce co-morbidities is critical. Metabolic bariatric surgery (MBS) significantly improves multiple outcomes in adults with T2D. Initial small, uncontrolled studies of Roux-en-Y gastric bypass also suggest beneficial effects in youth with T2D, but definitive studies and understanding of mechanisms in youth-onset T2D are lacking, especially with the now more common form of MBS, vertical sleeve gastrectomy (VSG). We will test the hypothesis that VSG will be more effective in reducing glycemia and comorbidities than the best currently available medical treatment: advanced medical therapy (AMT), via pancreatic, enterohepatic and/or metabolic changes. To test this hypothesis, 90 adolescents with T2D will be studied to compare the effects of VSG vs. AMT on glycemic control and T2D-associated comorbidities, as well as underlying mechanisms.

Open label prospective clinical trial. Primary comparison is medical (n=45) vs surgical (n=45) groups. Patients with obesity and no diabetes (n=10) are a comparator group.

Vertical Sleeve Gastrectomy and Advanced Medical Therapy that could include metformin, GLP-1 agonist, SGLT-2 inhibitor, or basal insulin for youth with type 2 diabetes

Advanced Medical Therapy that could include metformin, GLP-1 agonist, SGLT-2 inhibitor, or basal insulin for youth with type 2 diabetes

Oral disposition index= Insulin secretion [insulinogenic index] * insulin sensitivity [1/fasting insulin]

Inclusion Criteria for the medical or surgical type 2 diabetes groups Age 13-19.9 years of age at time of signing the consent Type 2 diabetes by the American Diabetes Association criteria Negative diabetes-associated antibodies Exclusion Criteria for the medical or surgical type 2 diabetes groups Known type 1 diabetes, maturity onset diabetes of the young (MODY), or secondary diabetes Any chronic oral steroids use within 60 days of enrollment Current pancreatotoxic drugs Chronic kidney or liver disease (except NAFLD or DKD) Pregnancy, breast-feeding or intension of becoming pregnant Prior bariatric surgery History of malignancy Current participation in another clinical trial that may affect study outcomes Other conditions, that in the determination of the study investigator, may interfere with study participation Inclusion Criteria for the Obese control group Age 13-19.9 years of age at time of signing the consent Clinical indication to receive bariatric surgery Exclusion Criteria for the obese control group Known diabetes Any chronic oral steroids use within 60 days of enrollment Current pancreatotoxic drugs Chronic kidney or liver disease (except NAFLD or DKD) Pregnancy, breast-feeding or intension of becoming pregnant Prior bariatric surgery History of malignancy Current participation in another clinical trial that may affect study outcomes Other conditions, that in the determination of the study investigator, may interfere with study participation

The PI's will also report a of summary results information (including adverse events) after completion of the study. All data from the study including any negative findings will be published in peer reviewed manuscripts.

Shah AS, Helmrath MA, Inge TH, Xanthakos SA, Kelsey MM, Jenkins T, Trout AT, Browne L, Nadeau KJ. Study protocol: a prospective controlled clinical trial to assess surgical or medical treatment for paediatric type 2 diabetes (ST2OMP). BMJ Open. 2021 Aug 13;11(8):e047766. doi: 10.1136/bmjopen-2020-047766.