Clinical Research Directory

Inclusion Criteria: * Type 1 diabetes mellitus for more than 5 years complicated by the following situations that persist despite intensive insulin management efforts: * At least one episode of severe hypoglycemia in the past 3 years defined as an event with symptoms compatible with hypoglycemia in which the subject required the assistance of another person, and which was associated with either a blood glucose level \<50 mg/dL (2.8 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration * Reduced awareness of hypoglycemia, defined by the absence of adequate autonomic symptoms at capillary glucose levels of \<54 mg/dL (3 mmol/l) as reported by the subject Exclusion Criteria: * Co-existing cardiac disease: myocardial infarction within the past 6 months, angiographic evidence of non-correctable coronary artery disease, ischemia on functional cardiac exam, heart failure * Active alcohol or substance abuse, including cigarette smoking (must be abstinent for six months) * Psychiatric disorder: schizophrenia, bipolar disorder, or major depression that is unstable on medication * History of non-adherence to prescribed regimens * Active infection including hepatitis C, hepatitis B, HIV * TB by history, current infection, or under treatment for suspected TB * History of malignancies except squamous or basal skin cancer * Family history of MEN2 or MCT * Stroke within the past 6 months * BMI \>27 kg/m2 * C-peptide response to glucagon stimulation, any C-peptide \>0.3 ng/mL * Inability to provide informed consent * Age less than 18 or greater than 75 years * Creatinine clearance \<80 mL/min/1.73 m2 by 24-hour urine collection * Serum creatinine consistently \>1.5 mg/dL * Macroalbuminuria \>300 mg/24h * Baseline Hb \<12 gm/dL in women, \<13 gm/dL in men * Baseline liver function tests outside normal range * Untreated proliferative retinopathy * Positive pregnancy test, intent for pregnancy, male's intent to procreate, unwilling to use effective contraception, breast feeding * Previous transplant or PRA reactivity \>80% * Insulin requirement \>0.7 IU/kg/day * HbA1c \>12% * Hyperlipidemia (fasting cholesterol \>130 mg/dL or fasting triglycerides \>200 mg/dL * Medical condition requiring chronic use of steroids * Use of Coumadin or other antiplatelet or anticoagulant therapy, or PT-INR \>1.5 * Factor V deficiency * Smoking tobacco * Addison's disease * Allergy to radiographic contrast material * Symptomatic cholecystolithiasis * Acute or chronic pancreatitis * Symptomatic peptic ulcer disease * Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could interfere with medication absorption * Treatment with antidiabetic medication other than insulin within 4 weeks of enrollment * Use of any study medication within 4 weeks of enrollment * Received live attenuated vaccine(s) within 2 months of enrollment * Any medical condition that, in the opinion of the investigator, might interfere with safe participation