The Effect of Exercise on Hepatic Glucose Metabolism
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.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
|Official Title:||The Effect of Exercise on Hepatic Glucose Metabolism in Type 2 Diabetes Mellitus|
- Splanchnic glucose uptake [ Time Frame: 3 years ]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.
- Endogenous glucose production [ Time Frame: 3 years ]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
|Study Start Date:||February 2013|
|Study Completion Date:||September 2016|
|Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
Experimental: Aerobic Exercise
12 weeks of aerobic exercise
Behavioral: Aerobic exercise
12 weeks of aerobic exercise with weight maintenance
No Intervention: Control
12 weeks with no change in diet or exercise habits (weight maintenance).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01783275
|United States, Tennessee|
|Vanderbilt University Medical Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Jason Winnick, PhD||Vanderbilt University Medical Center|
|Study Chair:||Naji Abumrad, MD||Vanderbilt University Medical Center|