Surgical or Medical Treatment

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Surgical or Medical Treatment for Pediatric Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2, Pediatric Obesity, Bariatric Surgery Candidate

Intervention / Treatment
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* Procedure: Advanced Medical Therapy and Bariatric Surgery
* Drug: Advanced Medical Therapy
* Procedure: Bariatric Surgery


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Medical Therapy and Bariatric Surgery in Youth with Type 2 Diabetes<br>Youth with type 2 diabetes undergoing bariatric surgery, n=45 | Procedure: Advanced Medical Therapy and Bariatric Surgery<br>* 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<br>|
| Active Comparator: Medical Therapy in Youth with Type 2 Diabetesin Youth with Type 2 Diabetes<br>Youth with type 2 diabetes receiving medical management, n=45 | Drug: Advanced Medical Therapy<br>* Advanced Medical Therapy that could include metformin, GLP-1 agonist, SGLT-2 inhibitor, or basal insulin for youth with type 2 diabetes<br>|
| Active Comparator: Bariatric Surgery in Youth with Obesity<br>Youth with no obesity undergoing bariatric surgery, n=10 | Procedure: Bariatric Surgery<br>* Vertical Sleeve Gastrectomy for youth without type 2 diabetes<br>* Other names: Vertical Sleeve Gastrectomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Control | Hemoglobin A1c of <6.5% | At one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Control | Hemoglobin A1c <6.5% at 2 years | At two years | 
| Glycemic Variability | Time In Range by Continuous Glucose Monitoring | At one year | 
| Beta Cell Function | Oral disposition index= Insulin secretion [insulinogenic index] * insulin sensitivity [1/fasting insulin] | at 1 and 2 years | 
| Alpha cell function | Glucagon area under the curve from mixed meal tolerance testing | at 1 and 2 years | 
| Incretin Response | GLP-1 area under the curve from mixed meal tolerance testing | at 1 and 2 years | 
| Fatty Liver Disease | Hepatic Fat (<5% )by Magnetic Resonance imaging | at 1 and 2 years | 
| Dyslipidemia | LDL <130mg/dL | at 1 and 2 years | 
| Hypertension | Blood pressure <130/80 mmHg | at 1 and 2 years | 
| Diabetic Kidney Disease | Urinary albumin excretion <30μg/mg | At 1 and 2 years |