Effect of Metformin on Vascular and Mitochondrial Function in Type 1 Diabetes (MeT1)

Inclusion Criteria:

• Age 20-59 years of age,
• Type 1 diabetes based on antibody-positivity, rapid persistent conversion to insulin requirement after diagnosis, absent C-peptide, or DKA at diagnosis, or a clinical course consistent with T1D,
• HbA1c 6.0 - 9.5, and
• Willing and able to commit to two 6 week-long periods of blinded medication followed by hyperinsulinemic euglycemic clamp, vascular testing, and muscle biopsies.

Exclusion Criteria:

• Any comorbid condition associated with:

  • inflammation,
  • insulin Resistance, or

  • dyslipidemia including:

    1. cancer,
    2. heart failure,
    3. active or end stage liver disease,
    4. kidney disease, or
    5. rheumatological disease;
• Tobacco use;
• Pregnancy or women who are breastfeeding;
• Steroid use;
• Scheduled strenuous physical activity >3 days a week;
• Angina, known CAD, or any other cardiovascular or pulmonary disease;
• A history of COPD or asthma;
• Presence of systolic blood pressure >190 at rest or >250 with exercise, or diastolic pressure >95 at rest or >105 with exercise;
• Untreated thyroid disease;
• Proteinuria (urine protein >200 mg/dl) or a creatinine > 1.5 mg/dl (males) or 1.4 mg/dL (females), suggestive of severe renal disease;
• Severe Proliferative retinopathy;
• Niacin treatment;
• Administration of experimental agent for T1D within 30 days prior to screening;
• Recent (prior 6 months) or current metformin or thiazolidenedione use;
• Hypoglycemia unawareness or recurrent severe hypoglycemia (no symptoms of hypoglycemia with FSBS<40 and episodes of this severity >1 per week);
• Weight instability (weight change >5% in last 6 months);
• History of any organ transplant, including islet cell transplant;
• Current or prior infection with HIV, hepatitis B or hepatitis C or hepatic -insufficiency (AST or ALT > 2x the upper limits of normal);
• Any condition, medical or otherwise that would, in the opinion of the investigator, prevent complete participation in the study, or that would pose a significant hazard to the subject;
• History of substance abuse within the 12 months prior to screening.