Effect of Age on Glucose and Lipid Metabolism

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by The University of Texas Health Science Center at San Antonio
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Nicolas Musi, MD, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:
NCT01737164
First received: November 26, 2012
Last updated: November 28, 2012
Last verified: November 2012
  Purpose

Aging is a major risk factor for the development of type 2 diabetes (T2DM). Approximately 50% of subjects aged ≥65 have diabetes or impaired glucose tolerance, a pre-diabetic state. Purpose: In the proposed study, the investigators will test the hypotheses that the decrease in fat oxidation that occurs in muscle from older human subjects is secondary to an age-mediated reduction in AMPK signaling, in vivo, and that upregulating AMPK signaling through exercise training will result in (and correlate with) increased fat oxidation, reduced intramyocellular lipids, and improved insulin action.


Condition Intervention
Glucose Metabolism Disorders
Lipid Metabolism Disorders
Metabolic Diseases
Behavioral: Aerobic Exercise

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Effect of Age on Glucose and Lipid Metabolism

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Effect of Age on Glucose and Lipid Metabolism [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Effect of Age on Glucose and Lipid Metabolism; Measurement of glucose and lipid metabolism will be done pre and post exercise in two groups (younger and older subjects)


Estimated Enrollment: 40
Study Start Date: September 2010
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aerobic Exercise - Older Subjects
Subjects aged 65 and higher will perform 16 weeks of moderate intensity exercise
Behavioral: Aerobic Exercise
Experimental: Aerobic Exercise - Young Subjects
Subjects 18-30 years old will perform 16 weeks of moderate intensity exercise
Behavioral: Aerobic Exercise

Detailed Description:

Aging is a major risk factor for the development of type 2 diabetes (T2DM). Approximately 50% of subjects aged ≥65 have diabetes or impaired glucose tolerance, a pre-diabetic state. Skeletal muscle is the main site of insulin-stimulated glucose disposal and aging is characterized by muscle insulin resistance. It has been suggested that the insulin resistance of aging results from an age-related accumulation of intramyocellular lipids which impair insulin action. However, the molecular basis for the accumulation of intramyocellular fat and insulin resistance in the elderly remains unknown. AMP-activated protein kinase (AMPK) is an energy-sensing enzyme whose activation results in increased fatty acid oxidation. Purpose: In the proposed study, we will test the hypotheses that the decrease in fat oxidation that occurs in muscle from older human subjects is secondary to an age-mediated reduction in AMPK signaling, in vivo, and that upregulating AMPK signaling through exercise training will result in (and correlate with) increased fat oxidation, reduced intramyocellular lipids, and improved insulin action. Using a primary human muscle cell culture system, also we will test that hypotheses that reduced AMPK signaling in old myotubes leads to lower fat oxidation (in vitro) and that chemical activation of AMPK in old myotubes to the same level as young muscle cells will restore insulin action and help prevent fat-induced insulin resistance. To test these hypotheses the following specific aims (objectives) are proposed:

Specific Aim 1) To determine whether reduced AMPK signaling in muscle from older subjects, in vivo, is associated with lower fat oxidation rates and insulin resistance, and whether physical activity improves glucose homeostasis in older subjects by upregulating AMPK signaling in muscle. We will test the hypotheses that (i) reductions in AMPK signaling in muscle from older subjects will be associated with (predict) lower fat oxidation rates and insulin resistance, in vivo; and (ii) training-induced increases in AMPK signaling in older subjects will be associated with (predict) increases in fat oxidation, reductions in intramyocellular lipids, and improvements in insulin action/sensitivity.

Specific Aim 2) To determine whether age-related declines in AMPK signaling are involved in the reductions in fat oxidation and insulin resistance that occur in aging. Using an in vitro primary muscle cell culture system, we will test the hypotheses that (i) reduced AMPK signaling in myotubes from older subjects leads to decreased mitochondrial fatty acid oxidation; and (ii) reduced AMPK signaling and fat oxidation in myotubes from older subjects will result in increased susceptibility to fat-induced insulin resistance.

Specific Aim 3) To examine whether the age-related reductions in fat oxidation and insulin sensitivity in old muscle cells can be reversed by upregulating AMPK signaling. We will test the hypothesis that chemical activation of AMPK in old myotubes (in vitro) to the same level as young muscle cells will restore insulin signaling and help prevent fat-induced insulin resistance.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. healthy, normally active, younger (18-30 y), normal glucose tolerant subjects, without a family history of T2DM (neither parent nor siblings), and BMI of 23-26 kg/m2.
  2. healthy, normally active, older (≥65 y), normal glucose tolerant subjects without a family history of T2DM, and BMI of 23-26 kg/m2.
  3. Women must be non-lactating. Female patients are eligible only if they have a negative pregnancy test throughout the study period (or postmenopausal). Postmenopausal women taking hormone replacement will be included if they have been on a stable dose for ≥6 months. In younger menstruating woman, all metabolic studies will be performed on the follicular phase of the menstrual cycle.
  4. Subjects must have the following laboratory values: Hematocrit ≥ 35%, serum creatinine ≤ 1.5 mg/dl, AST < 2 X upper limit of normal, ALT < 2 X upper limit of normal, alkaline phosphatase < 2 X upper limit of normal, normal urinalysis, and normal platelets, PT and PTT.

Exclusion Criteria:

  1. Subjects with diabetes or impaired glucose tolerance based on ADA criteria.
  2. Subjects taking drugs known to affect glucose and lipid homeostasis will be excluded.
  3. Patients with a history of heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the ECG), peripheral vascular disease, or pulmonary disease.
  4. Recent pulmonary embolus, poorly controlled blood pressure (systolic BP>170, diastolic BP>95), resting heart rate >100, electrolyte abnormalities, neuromuscular or musculoskeletal disease.
  5. Subjects who smoke.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01737164

Locations
United States, Texas
Texas Diabetes Insitute Recruiting
San Antonio, Texas, United States, 78207
Contact: Jennifer Todora, RN    210-358-7200      
Principal Investigator: Nicolas Musi, MD         
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
  More Information

No publications provided

Responsible Party: Nicolas Musi, MD, Professor, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT01737164     History of Changes
Other Study ID Numbers: HSC20100133H, 1R01DK089229-01
Study First Received: November 26, 2012
Last Updated: November 28, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center at San Antonio:
Glucose
Lipid
Metabolism
Non Diabetic
Healthy

Additional relevant MeSH terms:
Disease
Glucose Metabolism Disorders
Lipid Metabolism Disorders
Metabolic Diseases
Sphingolipidoses
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lipidoses
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Nervous System Diseases
Metabolism, Inborn Errors
Pathologic Processes

ClinicalTrials.gov processed this record on October 23, 2014