Insulin Signaling in Skeletal Muscle

Study Overview
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Brief Summary
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The insulin sensitizing effects of metformin and pioglitazone in the skeletal muscle remain unknown. Our group aims to analyze molecular changes within the skeletal muscle of pre-diabetic patients through the use of a clinical trial in humans.

Official Title
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Effect of Metformin and Pioglitazone on Insulin Signaling in Skeletal Muscle

Conditions
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Insulin Sensitivity

Intervention / Treatment
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* Drug: Metformin
* Drug: Pioglitazone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-diabetes as defined by an oral glucose tolerance test 2-hour level between 140 and 200 mg/dL General Inclusion Criteria: Able to communicate meaningfully with the investigator and legally competent to provide informed written consent. Female subjects must be non-lactating, have a negative pregnancy test, and be on acceptable birth control. Exclusion Criteria: Oral glucose tolerance test <140 or >200mg/dL Treated with any of the following medications: Systemic glucocorticoids (more than 2 weeks), antineoplastic agents, transplant medications, fibrates, anti-retroviral medications, or thiazolidinediones within 6 months prior to screening Start or change of hormonal replacement therapy within 3 months prior to screening Short-acting insulin (more than15 units per day) in DMT2 subjects, indicating severe insulin deficiency within 6 months prior to screening History or presence of any of the following conditions: Clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG) Peripheral vascular disease (history of claudication) Clinically significant pulmonary disease. Current uncontrolled hypertension (systolic BP>160 mmHg, diastolic BP>100 mmHg) History or presence of malignancy other than basal cell or squamous cell skin cancer Autonomic neuropathy Clinically significant hematologic disease Any of the following abnormal laboratory values: Hematocrit < 35 vol% Serum creatinine > 1.6 mg/dl AST, ALT or Alkaline phosphatase > 2.5 times the upper limit of normal PT, PTT outside the normal reference range TSH outside the normal reference range Triglycerides > 400 mg/dl Platelet count < 50,000 Current or history of drug abuse or alcohol abuse Blood donation within 2 months prior to screening Engage in exercise with moderate to hard intensity for greater than 1 hour per day for 5 or more days per week. Diagnosed with Type 1 diabetes

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br> | Drug: Metformin<br>* oral, 850 mg twice daily<br>|
| Experimental: Pioglitazone<br> | Drug: Pioglitazone<br>* oral, 45 mg daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* oral, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteomic | Changes in global protein abundance levels | 3 months | 
| Proteomic 2 | Changes in global protein phosphorylation levels | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epigenomic | Change in global DNA percent methylation | 3 months |