Inclusion Criteria:

• Type 1 diabetes mellitus diagnosed > 5 years previously
• Body mass index less than or equal to 26
• 18 to 65 years of age
• Compliance with an optimized diabetic management plan as assessed by an Emory University endocrinologist
• Checking and recording blood sugars at least 3 times per day
• Intensive insulin therapy (injecting insulin at least 3 times a day or using an insulin pump)
• Severe hypoglycemia and/or hyperglycemia. Severe hypoglycemia is defined by: episodes requiring assistance by others and/or hypoglycemic unawareness (the inability to recognize blood glucose < 54 mg/dL). Severe hyperglycemia is defined by: two episodes of ketoacidosis requiring hospitalization within the past year.

Exclusion Criteria:

• Renal dysfunction
• Severe co-existing cardiac disease, characterized by any one of these conditions: recent myocardial infarction (within past six months); angiographic evidence of non-correctable coronary artery disease; or evidence of ischemia on a dobutamine stress echocardiogram.
• Current bacterial or fungal infection
• Macroproteinuria
• Baseline hemoglobin < 11.4 gm/dL in women; < 12.9 gm/dL in men.
• Hyperlipidemia
• Positive tests for human immunodeficiency virus (HIV), or hepatitis B or C
• Negative antibody test for varicella zoster virus (subjects may be reconsidered if they receive the vaccination and convert to a positive antibody)
• History of malignancy (except squamous or basal cell skin carcinoma)
• Previous/concurrent organ transplantation
• Presence of HLA panel reactive antibodies > 20%
• Active peptic ulcer disease
• Evidence of gallbladder disease including cholecystitis and cholelithiasis
• Evidence of liver disease including hepatic neoplasm, portal hypertension, or persistently abnormal liver function tests.
• Persistent coagulopathy or current use of anticoagulants (not including aspirin)
• Sickle cell anemia
• Positive pregnancy test, intent for future pregnancy, failure to follow effective contraceptive measures, or presently breastfeeding
• Active alcohol or substance abuse. This includes smoking (must be abstinent for six months). Active alcohol abuse should be considered using the current National Institute on Alcohol Abuse and Alcoholism (NIAAA) definitions.
• Psychiatric disorder making the subject not a suitable candidate for transplantation
• Current use of systemic steroid medications
• Evidence of insulin resistance (insulin requirement > 1.2 units/kg/day)
• Inability to provide informed consent
• Any condition or any circumstance that makes it unsafe to undergo an islet transplant