Hepatic Mitochondrial Function in Youth

University of Colorado, Denver20 enrolled

Overview

Assess the impact of bariatric surgery on hepatic energy metabolism and glucose and insulin dynamics in obese youth

A metabolic study that will be performed prior to and 12 months following bariatric surgery. The study will include 31-phosphorus magnetic resonance spectroscopy to measure phosphate concentrations in the liver; a 4 hour mixed meal tolerance test, an intravenous arginine test, Abdominal Magnetic Resonance Imaging (MRI) for visceral and hepatic fat, Magnetic Resonance (MR) Elastography of the liver, indirect calorimetry, body composition assessment with Bodpod, serum metabolomics and hepatic tissue mitochondrial measures from the time of surgery only.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Hepatic Steatosis Bariatric Surgery Candidate Adolescent Obesity Obesity

Eligibility

Sex: ALLMin age: 13 YearsMax age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Obese youth ages 13-20 years, scheduled for bariatric surgery at Children's Hospital Colorado 2. BMI 35-55 m2/kg 3. Maximal body circumference \<200 cm Exclusion Criteria: 1. Use of medications known to affect insulin sensitivity: oral glucocorticoids within 10; days, atypical antipsychotics, immunosuppressant agents, HIV medications. 2. Infectious hepatitis 3. Alcohol abuse 4. Mitochondrial disease 5. Type 2 diabetes 6. Medications that affect hepatic outcomes (e.g. PPAR-γ or PPAR-α, metformin) 7. Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study. 8. Severe illness requiring hospitalization within 60 days 9. Diabetes, defined as Hemoglobin A1C \> 6.4% 10. Anemia, defined as Hemoglobin \< 10 mg/dL 11. Diagnosed major psychiatric or developmental disorder limiting informed consent 12. Implanted metal devices that are not compatible with MRI

Locations (1)

University of Colorado Anshutz Medical Campus/Children's Hospital Colorado

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Change in Percentage of Liver Fat Per MRI

Percentage of liver fat at 1 year post-bariatric surgery minus percentage of liver fat prior to bariatric surgery. Liver fat measured with MRI and calculated via the Dixon method as the proton density hepatic fat. A negative value means a decrease in liver fat after bariatric surgery.

Time frame: Prior to bariatric surgery and 1 year post-bariatric surgery

Change in %Direct TG-Glycerol Appearance

Change in %TG-Glycerol appearance from a labeled glycerol drink via direct pathway. TCA substrate cycling assessed via change in fractional direct glycerol carbon contributions to newly synthesized triglycerides using a U-13C glycerol tracer drink. A higher direct percentage is beneficial, indicating decreased oxidative stress resulting from excess glycerol metabolism through the TCA cycle.

Time frame: Prior to bariatric surgery and 1 year post-bariatric surgery

Secondary Outcomes

Change in Insulin Sensitivity

Mixed meal tolerance test (MMTT): measured with SI. This is a measure of post-prandial (MMTT) insulin sensitivity as calculated with the Oral Minimal Model (OMM) using SAAM II Software. This software uses participant weight, glucose and insulin concentrations at various time points during the MMTT to calculate the participant insulin sensitivity. A positive Si value means an increase in insulin sensitivity.

Time frame: Prior to bariatric surgery and 1 year post-bariatric surgery

Change in Peak Glucose

Mixed meal tolerance test (MMTT): Peak glucose concentration (mg/dL) during 4 hour MMTT with 16 time points.

Time frame: Prior to bariatric surgery and 1 year post-bariatric surgery

Change in Minimum Glucose

Mixed meal tolerance test (MMTT): Minimum glucose concentration (mg/dL) during 4 hour MMTT with 16 time points.

Data from ClinicalTrials.gov

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