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

NCT ID: NCT01786941

Last Updated: 2015-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2013-12-31

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.

Conditions

Branched-chain Amino Acid Metabolism; Insulin Sensitivity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Lean Group

Healthy Controls - no intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Pre-Diabetes Group

Pre-Diabetes Group will undergo a 6-mo Aerobic and Resistance combined exercise training intervention

Group Type: OTHER

Pre-Diabetes Group - 6-mo Aerobic and Resistance combined exercise training

Intervention Type: OTHER

Gastric Bypass Group

Non-diabetic patients intending to undergo Gastric Bypass surgery

Group Type: OTHER

GBP Group - Non-diabetics intending to undergo Gastric Bypass surgery

Intervention Type: OTHER

Interventions

Pre-Diabetes Group - 6-mo Aerobic and Resistance combined exercise training

Intervention Type: OTHER

GBP Group - Non-diabetics intending to undergo Gastric Bypass surgery

Intervention Type: OTHER

Eligibility Criteria

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)

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William E. Kraus, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

References

Glynn EL, Piner LW, Huffman KM, Slentz CA, Elliot-Penry L, AbouAssi H, White PJ, Bain JR, Muehlbauer MJ, Ilkayeva OR, Stevens RD, Porter Starr KN, Bales CW, Volpi E, Brosnan MJ, Trimmer JK, Rolph TP, Newgard CB, Kraus WE. Impact of combined resistance and aerobic exercise training on branched-chain amino acid turnover, glycine metabolism and insulin sensitivity in overweight humans. Diabetologia. 2015 Oct;58(10):2324-35. doi: 10.1007/s00125-015-3705-6. Epub 2015 Aug 9.

Reference Type: DERIVED

PMID: 26254576 (View on PubMed)

Other Identifiers

Pro00034434

Identifier Type: -

Identifier Source: org_study_id