The Effect of Exercise on Hepatic Glucose Metabolism

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Jason Winnick, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01783275
First received: July 19, 2012
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

It is known that obesity and/or physical inactivity greatly increase a person's risk of developing heart disease and other serious health problems. This is partly because diabetes is associated with inflammation, oxidative stress, and insulin resistance. Diabetes is also associated with high levels of triglycerides in the blood and tissues such as the liver (known as fatty liver or steatosis). This elevation of fat in the liver is known to cause liver insulin resistance and impair the function of the liver and this impairment contributes to the development of diabetes.

Studies have shown that both aerobic exercise and weight loss have beneficial results on insulin resistance. However, the cause of this benefit remains unclear. We know that both aerobic exercise and/or weight loss can improve how muscle responds to insulin. However, it is also known that aerobic exercise and/or weight loss lowers liver fat content, thereby making it possible that the liver's response to insulin is also improved by weight loss and/or exercise training. An improved responsiveness of the liver to insulin could lower blood sugar levels after a meal and it could also lower morning blood sugar levels. However, very little is known about how exercise and/or weight loss improves liver function in people with type 2 diabetes.

Hypothesis 1: Improved hepatic insulin sensitivity, as a result of either exercise training or weight loss, will increase the amount of glucose from an oral load that is taken up by the liver in subjects with DM. We also hypothesize that the amount of glucose taken up by the liver will be increased even further in response to exercise training plus weight loss compared to either treatment alone.

Hypothesis 2: Increases in hepatic insulin sensitivity as a result of exercise with weight loss will cause reductions in EGP during the fasted state, and will improve the suppression of EGP seen in response to hyperinsulinemia.


Condition Intervention
Obesity
Type 2 Diabetes
Behavioral: Aerobic exercise
Behavioral: Weight loss

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: The Effect of Exercise on Hepatic Glucose Metabolism in Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Splanchnic glucose uptake [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Improved hepatic insulin sensitivity, as a result of lifestyle intervention, will increase the amount of glucose from an oral load that is taken up by the liver in subjects with DM.


Secondary Outcome Measures:
  • Endogenous glucose production [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Increases in hepatic insulin sensitivity as a result of lifestyle intervention will cause reduced EGP during the fasted state, and in response to hyperinsulinemia. This reduction will be accounted for by reductions in glycogenolysis


Estimated Enrollment: 68
Study Start Date: February 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aerobic Exercise
12 weeks of aerobic exercise
Behavioral: Aerobic exercise
12 weeks of aerobic exercise with weight maintenance
Experimental: Weight Loss
12 weeks of low calorie diet to achieve 7-10% weight loss
Behavioral: Weight loss
12 weeks of caloric restriction to achieve 7-10% weight loss
Experimental: Aerobic Exercise with weight loss
12 weeks of aerobic exercise with reduced caloric intake to achieve 7 - 10% weight loss
Behavioral: Aerobic exercise
12 weeks of aerobic exercise with weight maintenance
Behavioral: Weight loss
12 weeks of caloric restriction to achieve 7-10% weight loss
No Intervention: Control
12 weeks with no change in diet or exercise habits (weight maintenance).

  Eligibility

Ages Eligible for Study:   40 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 40-60 yrs of age
  • sedentary lifestyle
  • stable weight
  • BMI 30 - 40kg/m2
  • Hgb A1c <8.5
  • Type 2 diabetes

Exclusion Criteria:

  • Use of insulin
  • Use of TZDs
  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: NCT01783275

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Jason Winnick, PhD Vanderbilt University
Study Chair: Naji Abumrad, MD Vanderbilt University
  More Information

No publications provided

Responsible Party: Jason Winnick, Principal Investigator, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01783275     History of Changes
Other Study ID Numbers: 121031, DK093799
Study First Received: July 19, 2012
Last Updated: January 31, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Obesity
Type 2 diabetes
Liver

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Obesity
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on August 18, 2014