Regulation of Branched-chain Amino Acid Metabolism in Pre-Diabetes

Not Applicable

Completed

Interventions: Other: Pre-Diabetes Group - 6-mo Aerobic and Resistance combined exercise training
Other: GBP Group - Non-diabetics intending to undergo Gastric Bypass surgery

Brief Summary: Elevated circulating levels of certain amino acids (the building blocks of protein) are strongly associated with insulin resistance. This study will investigate the metabolism of these amino acids in individuals with normal glucose metabolism compared to overweight or obese pre-diabetic individuals. The purpose of this study is to determine how elevated levels of the branched-chain amino acids may contribute to the development of insulin resistance and ultimately diabetes. An additional purpose is to determine whether exercise or gastric bypass (GBP) surgery intervention can correct aberrations in branched-chain amino acid metabolism as insulin sensitivity improves. This information will be used to further our understanding of the development of insulin resistance and type 2 diabetes in at-risk populations and potentially improve clinical treatment of such conditions.

Recruitment & Eligibility

Inclusion Criteria

Age:
- Lean and Overweight Pre-diabetic (PD) groups: 40-65 years
- Obese Gastric Bypass (GBP) patients: 30-65 years
Body Mass Index (BMI) within desired range for group:
- Lean group: 18.0 - 24.9
- Overweight PD group: 25.0 - 35.4
- GBP group: 35.0 - 50.0
Fasting Plasma Glucose level within desired range for group:
- Lean: < 99 mg/dL
- PD: > 105 - < 126 mg/dL
- GBP: > 99
Oral Glucose Tolerance Test, 2-hour Plasma Glucose results within desired range:
- Lean: < 139 mg/dL
- PD: 140-199 mg/dL
Low density (LDL) cholesterol: < 190 mg/dL
Triglycerides: < 600 mg/dL
Resting blood pressure: <160/90 mmHg
Inactive: Exercise < two days/week (GBP and PD only);
Peak oxygen use: > 14.0 - < 40.0 ml/kg/min (PD only)
Medications: Stable use of all medications for > three months
Body Weight < 495 lbs

Exclusion Criteria

Smoker: Tobacco use within the last 12 months
Dieting or intending to diet (excluding intention for gastric bypass procedure in GBP group)- Not weight stable for > six months or weight loss exceeding five pounds in last six months
Use of potential confounding medications, e.g. Niacin containing drugs
History of diabetes, heart disease or taking medication for those conditions
History of hypertension (high blood pressure) not controlled with medication
Pregnant or intending to become pregnant
Unwillingness to participate in study visits, submit to skeletal muscle biopsies and all other study testing or continuously participate in the exercise training intervention program for six months if in overweight PD group
Orthopedic limitations, musculoskeletal disease and/or injury
Allergic to xylocaine
Inability to give blood continuously through an intravenous catheter
Unwillingness to exercise at least three times per week at the Duke Center for Living during staff supervised times (PD only)
Exercise compliance less than 85% in any 6 week period (missing > 3 exercise sessions in a 6 week period)

Arm && Interventions

Group	Intervention	Description
Pre-Diabetes Group	Pre-Diabetes Group - 6-mo Aerobic and Resistance combined exercise training	Pre-Diabetes Group will undergo a 6-mo Aerobic and Resistance combined exercise training intervention
Gastric Bypass Group	GBP Group - Non-diabetics intending to undergo Gastric Bypass surgery	Non-diabetic patients intending to undergo Gastric Bypass surgery

Primary Outcome Measures

Name	Time	Method
Changes in Branched-chain Amino Acid Metabolism in Pre-Diabetes at Baseline and post-intervention	Baseline and pre- and post-intervention: 1) Lean Group-Baseline measures only; 2)Pre-Diabetic group - Baseline and 6-months post exercise intervention; 3) GBP group - Baseline and 3-months post Gastric Bypass Surgery	1. Lean Healthy Controls - Baseline only 2. Pre-Diabetic Group - Baseline and 6-months post the Aerobic and Resistance combined exercise training intervention 3. Gastric Bypass Group - Baseline and 3-months post Gastric Bypass surgery

Secondary Outcome Measures

Name	Time	Method
Changes in Insulin Sensitivity at Baseline and post-intervention	Baseline and pre- and post-intervention: 1) Lean Group-Baseline measures only; 2)Pre-Diabetic group - Baseline and 6-months post exercise intervention; 3) GBP group - Baseline and 3-months post Gastric Bypass Surgery	1. Lean Healthy Controls - Baseline only 2. Pre-Diabetic Group - Baseline and 6-months post the Aerobic and Resistance combined exercise training intervention 3. Gastric Bypass Group - Baseline and 3-months post Gastric Bypass surgery

Locations (1): Duke University Medical Center
🇺🇸
Durham, North Carolina, United States