DYNAMMO-T2DEX: Dynamics of Muscle Mitochondria in Type 2 Diabetes Exercise

Sponsor

Pennington Biomedical Research Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02977442

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Insulin promotes the clearance of sugars from the blood into skeletal muscle and fat cells for use as energy; it also promotes storage of excess nutrients as fat. Type 2 diabetes occurs when the cells of the body become resistant to the effects of insulin, and this causes high blood sugar and contributes to a build-up of fat in muscle, pancreas, liver, and the heart. Understanding how insulin resistance occurs will pave the way for new therapies aimed at preventing and treating type 2 diabetes.

Mitochondria are cellular structures that are responsible for turning nutrients from food, into the energy that our cells run on. As a result, mitochondria are known as "the powerhouse of the cell." Mitochondria are dynamic organelles that can move within a cell to the areas where they are needed, and can fuse together to form large, string-like, tubular networks or divide into small spherical structures. The name of this process is "mitochondrial dynamics" and the process keeps the cells healthy. However, when more food is consumed compared to the amount of energy burned, mitochondria may become overloaded and dysfunctional resulting in a leak of partially metabolized nutrients that can interfere with the ability of insulin to communicate within the cell. This may be a way for the cells to prevent further uptake of nutrients until the current supply has been exhausted. However, long term overload of the mitochondria may cause blood sugar levels to rise and lead to the development of type 2 diabetes.

This study will provide information about the relationship between mitochondrial dynamics, insulin resistance and type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Insulin Resistance, Diabetes	Behavioral: exercise	N/A

Detailed Description

The traditional view of mitochondria as isolated, spherical, energy producing organelles is undergoing a revolutionary transformation. Emerging data show that mitochondria form a dynamic networked reticulum that is regulated by cycles of fission and fusion. The discovery of a number of proteins that regulate these activities has led to important advances in understanding human disease. Data show that activation of dynamin related protein 1 (Drp1), a protein that controls mitochondrial fission, is reduced following exercise in prediabetes, and the decrease is linked to increased insulin sensitivity and fat oxidation. The proposed research will test the hypothesis that mitochondrial dynamics is a key mechanism of insulin resistance in type 2 diabetes. The experimental approach harnesses innovative molecular and cellular tools, interfaced with physiologically significant human studies to obtain meaningful data on insulin resistance, and has the potential to generate insights that will lead to new diabetes therapies for future generations.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Dynamics of Muscle Mitochondria in Type 2 Diabetes

Study Start Date :

Nov 1, 2016

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: exercise 12 week exercise program, 5 days/week, 60 min/day	Behavioral: exercise
No Intervention: standard of care 12 week standard of care recommendations

Arm

Intervention/Treatment

Experimental: exercise

12 week exercise program, 5 days/week, 60 min/day

Behavioral: exercise

No Intervention: standard of care

12 week standard of care recommendations

Outcome Measures

Primary Outcome Measures

Effects of exercise on mitochondrial dynamics [5 years]
Dynamics will be assessed from quantitative measures of dynamin-related protein-1.

Secondary Outcome Measures

Effects of exercise on mitochondrial function [5 years]
Function will be assessed from oxygen consumption.
Insulin sensitivity [5 years]
Insulin sensitivity will be assessed by euglycemic hyperinsulinemic clamp.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Type 2 Diabetes
Body Mass Index (BMI) between 25 and 40 kg
HbA1C < 8.5%
sedentary

Exclusion Criteria:

pharmacotherapy for diabetes
smoking

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pennington Biomedical Research Center	Baton Rouge	Louisiana	United States	70808

Sponsors and Collaborators

Pennington Biomedical Research Center

Investigators

Principal Investigator: John Kirwan, PhD, Pennington Biomedical Research Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

John Kirwan, Executive Director, Pennington Biomedical Research Center

ClinicalTrials.gov Identifier:

NCT02977442

Other Study ID Numbers:

15-1311 EX

First Posted:

Nov 30, 2016

Last Update Posted:

Apr 22, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by John Kirwan, Executive Director, Pennington Biomedical Research Center

Mitochondrial Dynamics

Insulin Resistance

Exercise and Diabetes

Additional relevant MeSH terms:

Diabetes Mellitus

Insulin Resistance

Study Results

No Results Posted as of Apr 22, 2022