Insulin Signaling in Skeletal Muscle

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