MeT1Effect of Metformin on Vascular and Mitochondrial Function in Type 1 Diabetes

Fecha de inicio: 1 de junio de 2011

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: cancer, heart failure, active or end stage liver disease, kidney disease, or 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.