The Effect of Exercise on Hepatic Glucose Metabolism

Study Overview
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Brief Summary
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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 exercise training will increase the amount of glucose from an oral load that is taken up by the liver in subjects with DM. Hypothesis 2: Increases in hepatic insulin sensitivity as a result of exercise will cause reductions in EGP during the fasted state, and will improve the suppression of EGP seen in response to hyperinsulinemia.

Official Title
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The Effect of Exercise on Hepatic Glucose Metabolism in Type 2 Diabetes Mellitus

Conditions
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Obesity, Type 2 Diabetes

Intervention / Treatment
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* Behavioral: Aerobic exercise


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic Exercise<br>12 weeks of aerobic exercise | Behavioral: Aerobic exercise<br>* 12 weeks of aerobic exercise with weight maintenance<br>|
| No Intervention: Control<br>12 weeks with no change in diet or exercise habits (weight maintenance). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Splanchnic glucose uptake | 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. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endogenous glucose production | Increases in hepatic insulin sensitivity as a result of lifestyle intervention will cause reduced EGP during the fasted state, and in response to hyperinsulinemia. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Type 2 diabetes, Liver