Diabetes Mellitus, Type 2, Pediatric Obesity, Bariatric Surgery Candidate
Conditions
Brief summary
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
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.
Interventions
PROCEDUREAdvanced Medical Therapy and Bariatric Surgery
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
PROCEDUREBariatric Surgery
Vertical Sleeve Gastrectomy for youth without type 2 diabetes
Sponsors
Children's Hospital Medical Center, Cincinnati
Children's Hospital Colorado
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
13 Years to 19 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Control | At one year | Hemoglobin A1c of \<6.5% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Control | At two years | Hemoglobin A1c \<6.5% at 2 years |
| Glycemic Variability | At one year | Time In Range by Continuous Glucose Monitoring |
| Beta Cell Function | at 1 and 2 years | Oral disposition index= Insulin secretion \[insulinogenic index\] \* insulin sensitivity \[1/fasting insulin\] |
| Alpha cell function | at 1 and 2 years | Glucagon area under the curve from mixed meal tolerance testing |
| Incretin Response | at 1 and 2 years | GLP-1 area under the curve from mixed meal tolerance testing |
| Fatty Liver Disease | at 1 and 2 years | Hepatic Fat (\<5% )by Magnetic Resonance imaging |
| Dyslipidemia | at 1 and 2 years | LDL \<130mg/dL |
| Hypertension | at 1 and 2 years | Blood pressure \<130/80 mmHg |
| Diabetic Kidney Disease | At 1 and 2 years | Urinary albumin excretion \<30μg/mg |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAmy S Shah, MD MS
Cincinnati Childrens Hospital Medical Center
PRINCIPAL_INVESTIGATORKristen J Nadeau, MD MS
Children's Hospital Colorado
PRINCIPAL_INVESTIGATORMichael A Helmrath, MD MS
Children's Hospital Medical Center, Cincinnati
PRINCIPAL_INVESTIGATORThomas H Inge, MD PhD
Ann & Robert H Lurie Children's Hospital of Chicago
Outcome results
None listed