Exercise Training and Glucose Metabolism in Aging

Aging, Angiogenesis and Metabolic Responses to Aerobic Exercise

Diabetes and its associated complications affect more than 20 million Americans, and the prevalence of type 2 diabetes and impaired glucose tolerance rises dramatically with age such that 40% of Americans over age 60 are affected. In older adults, glucose metabolism may be affected by reduced skeletal muscle capillary supply, which limits insulin, glucose, and oxygen delivery to skeletal muscle. Reduced capillary supply to skeletal muscle is found in older individuals with impaired glucose tolerance and we hypothesize that this is due to reduced vascular growth factor expression, and chronic inflammation. Further, we hypothesize that reversal of a sedentary lifestyle through aerobic exercise training will increase insulin signaling and vascular growth factor expression, as well as decrease inflammation, to increase capillary supply to skeletal muscle, which contributes to improved glucose metabolism in older adults. This study will: 1) Determine the mechanisms underlying reduced skeletal muscle capillarization in older adults with impaired glucose tolerance; and 2) Determine the effect of aerobic exercise training-induced increases in skeletal muscle capillarization on glucose metabolism in older adults.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Impaired Glucose Tolerance (Prediabetes)
• Intervention / Treatment: Behavioral: Aerobic exercise training; Behavioral: Detraining (cessation of exercise)

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • VA Maryland Health Care System, Baltimore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 50-75 years
• Non-smoker >2 years
• Body mass index = 18-35 kg/m2

Exclusion Criteria:

• History of CAD or cerebrovascular disease that would preclude exercise
• Implantable defibrillator
• Active cancer
• Chronic pulmonary, thyroid, renal, liver, or hematological disease
• HIV positive or prone to malnutrition
• Sickle cell anemia
• Type 1 diabetes, or currently on medication to treat type 2 diabetes
• Poorly-controlled type 2 diabetes
• Poorly-controlled hypertension
• Taking medications including: beta-blockers, oral steroids, warfarin, certain statins, hormone replacement therapy (HRT), oral contraceptives (OCP), thiazolidinediones (TZD), or chronic steroids or nonsteroidal analgesics (NSAIDS) that may not be safely discontinued temporarily for specific procedures (i.e. for 72 hours prior)
• Allergic to lidocaine or heparin
• Recent weight change (>5kg in 3 months)
• Currently pregnant or nursing
• Physical impairment limiting exercise
• Dementia or unstable clinical depression

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; Older adults, normal glucose tolerance	Behavioral: Aerobic exercise training; 24 weeks of aerobic exercise training: 3 times per week, 60 minutes per session, at 70% of maximal aerobic capacity; Behavioral: Detraining (cessation of exercise); Cessation of exercise for 2 weeks
Experimental: Arm 2; Older adults, impaired glucose tolerance	Behavioral: Aerobic exercise training; 24 weeks of aerobic exercise training: 3 times per week, 60 minutes per session, at 70% of maximal aerobic capacity; Behavioral: Detraining (cessation of exercise); Cessation of exercise for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Glucose Utilization	Insulin-stimulated glucose uptake	baseline
Glucose Utilization (Pre/Post Intervention)	Insulin-stimulated glucose uptake	baseline, 24 weeks, 26 weeks
Baseline Skeletal Muscle Capillarization		baseline
Skeletal Muscle Capillarization (Pre/Post Intervention)		baseline, 24 weeks, 26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline 2-hour Postprandial Glucose		baseline
2-hr Post-prandial Plasma Glucose Level		baseline, 24 weeks, 26 weeks
Baseline Cardiorespiratory Fitness	maximal oxygen consumption	baseline
Cardiorespiratory Fitness	Maximal oxygen consumption	baseline, 24 weeks, 26 weeks
Body Composition (%Fat)		baseline, 24 weeks

Collaborators and Investigators

• Sponsor: US Department of Veterans Affairs
• Collaborators: University of Maryland; National Institutes of Health (NIH); National Institute on Aging (NIA)
• Investigators: Principal Investigator: Steven J. Prior, PhD, VA Maryland Health Care System, Baltimore

Publications and helpful links

General Publications

• Prior SJ, Goldberg AP, Ortmeyer HK, Chin ER, Chen D, Blumenthal JB, Ryan AS. Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining. Diabetes. 2015 Oct;64(10):3386-95. doi: 10.2337/db14-1771. Epub 2015 Jun 11.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: June 18, 2008
• First Submitted That Met QC Criteria: June 18, 2008
• First Posted (Estimate): June 19, 2008

Study Record Updates

• Last Update Posted (Estimate): April 6, 2015
• Last Update Submitted That Met QC Criteria: March 23, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Diabetes Mellitus, Type 2; Glucose Intolerance
• Other Study ID Numbers: CDA-2-039-08S; H-27940 (Other Identifier: IRB); 5P30AG028747-05 (U.S. NIH Grant/Contract)