Mechanisms of Skeletal Muscle Insulin Resistance in Older Adults

NCT02971098 | Completed DMC

• 1 other identifier: 84354
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The over-65 population is not only increasing at an alarming rate, but because six out of 10 will be managing more than one chronic condition by 2030, they will make up a much greater proportion of hospitalizations than ever before. Hospitalizations for disease, injury, and/or surgery in this group are likely to impair physical mobility and, therefore, the older adults capacity to be physically active both during hospitalization and beyond. The resulting sedentary lifestyle is likely to be accepted as the "new normal", ultimately increasing the risk of skeletal muscle and metabolic dysfunction (e.g. impaired glucose disposal, insulin resistance). These devastating outcomes are neither inevitable nor necessary if prevented with an appropriate mechanism-based intervention. A novel mechanism that may contribute to physical inactivity-induced insulin resistance is accumulation of inflammation and ceramide within skeletal muscle. Of interest, increased skeletal muscle inflammation and ceramide has been tied to various metabolic disturbances such as diabetes and insulin resistance. However, it is currently unknown if skeletal muscle inflammation and ceramide are a key mechanism associated with insulin resistance due to physical inactivity in older adults.

Conditions

Reduced Physical Activity

Outcome Measures

Primary Outcomes (1)

• Steady state glucose infusion rate

  Glucose infusion rate will be determined by a hyperinsulinemic-euglycemic clamp

  percent change from baseline at 14 days

Secondary Outcomes (1)

• lean mass

  percent change from baseline at 14 days

Study Arms (1)

Reduced activity

EXPERIMENTAL

participants will undergo a reduced physical activity period (75% step reduction) for two weeks.

Procedure: Reduced activity

Interventions

Reduced activity PROCEDURE

Participants will reduced their physical activity level to approximately 2000 steps or 75% of their normal activity levels.

Reduced activity

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 60-85 yrs
• Ability to sign informed consent
• Free-living, prior to admission

You may not qualify if:

• Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
• History of kidney disease or failure
• Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes, hypercholesterolemia \> 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal and pedal arteries)
• Risk of deep vein thrombosis (DVT) including family history of thrombophilia, DVT, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb\>18 g/dL) or thrombocytosis (platelets\>400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocysteinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombin III
• Use of anticoagulant therapy (e.g., Coumadin, heparin)
• Elevated systolic pressure \>150 or a diastolic blood pressure \> 100
• Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
• Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
• Currently on a weight-loss diet or body mass index \> 30 kg/m2
• Recent anabolic or corticosteroids use (within 3 months)
• History of stroke with motor disability
• A recent history (\<12 months) of GI bleed
• Exercise training (\>2 session of moderate to high intensity aerobic or resistance exercise/week)
• History of liver disease
• History of respiratory disease (acute upper respiratory infection, history of chronic lung disease)

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Study Officials

• Micah J Drummond, PhD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D.

Model Details: 2 weeks of physical inactivity

Study Record Dates

• First Submitted: November 15, 2016
• First Posted: November 22, 2016
• Study Start: September 1, 2016
• Primary Completion: December 17, 2019
• Study Completion: December 17, 2019
• Last Updated: June 22, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)