Inclusion Criteria:

• Adults (males or females) in the age range 35 to 65 years.
• Diagnosis of type 1 diabetes mellitus (minimum duration of 5 years) in accordance with the American Diabetes Association's criteria. Patients should have been treated continuously with insulin since diagnosis (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2002)
• Patients with established brittle type I diabetes mellitus with a well- documented chronic history of severe metabolic instability who cannot achieve acceptable metabolic control without experiencing multiple episodes of severe hypoglycaemia, often with unawareness; or
• with degrees of hypoglycaemia, who cannot be adequately managed with intensive insulin therapy alone despite intensive diabetes management delivered by a qualified diabetes team for at least six months prior to enrollment.
• Patients should have an HbA1C >=7% and <=10% calculated as the average of the last four consecutive HbA1C readings during the 8-week baseline run-in period. The difference between the highest and lowest of the four HbA1C reading should be no more than 0.5%.
• Plasma C-peptide <0.2 ng/ml following a glucagon stimulation test (Scheen et al. 1996)
• If female, no childbearing capability (those who are more than 2 years postmenopausal or have undergone voluntary sterilisation can be considered for enrollment).
• Provision of written informed consent. Patients will be required to agree to comply with all tests and visits specified in the protocol, and they (and their partners/close contacts) will also be required to consent to long-term microbiological monitoring, which is an integral part of the study.

Exclusion Criteria:

• Type 2 diabetes, defined as age of onset >30 years and/or a history of treatment with oral hypoglycaemic medications and/or insulin resistance (defined as an insulin dose requirement >=1.2 U/kg/day).
• An average HbA1C <7% and >=10% during the 8-week baseline run-in period.
• Body mass index (BMI) >=30 kg/m2 or <=20 kg/m2.
• Active infection, with plasma C-reactive protein >=10 mg/L at baseline.
• Previous receipt of an organ, skin graft, or other tissue transplant from a human or animal donor.
• Treatment with immunosuppressive medications for another medical condition.
• Previous history of peritoneal disease or abnormal findings at baseline laparoscopy.
• Previous abdominal surgery, excluding uncomplicated appendectomy or cholecystectomy.
• History of pelvic inflammatory disease or endometriosis.
• Inability to tolerate oral medications or a history of significant malabsorption.
• HIV antibody and/or risk factors for HIV infection.
• Positive hepatitis C antibody, hepatitis B surface antigen, or hepatitis B core antibody.
• Kidney disease, defined as serum creatinine >130 μmol/L in men and >110 μmol/L in women and/or urinary albumin >300 mg/L and/or haematuria and/or active urinary sediment or casts.
• Diabetes microvascular complications defined as untreated, potentially vision-threatening proliferative or pre-proliferative retinopathy or maculopathy; painful peripheral neuropathy; autonomic neuropathy manifesting as postural hypotension; gastroparesis or diabetic enteropathy.

• Serious comorbid conditions that are likely to affect participation in the study, including:

  • Previous coronary heart disease manifesting as non-ST elevation myocardial infarction (NSTEMI), Q-wave infarction or unstable angina; coronary artery bypass graft (CABG); or percutaneous angioplasty.
  • Previous cerebrovascular disease manifesting as transient ischaemic attacks (TIAs) or stroke.
  • Peripheral vascular disease with foot ulcer and/or previous amputation
  • History of New York Heart Association (NYHA) class II, III or IV congestive heart failure (CHF) and/or chronic atrial fibrillation.
  • Chronic obstructive pulmonary disease (COPD) or asthma with previous hospitalisation for decompensation; a requirement for mechanical ventilation at any stage; or long-term treatment with oral corticosteroids.
  • Liver disease with abnormal liver function tests defined as serum bilirubin >=20 umol/L, and/or ALT >=100 U/L, and/or GGT >=100 U/L, and/or albumin <35 g/L.
  • Haematological disorders, including haemoglobin <=110 g/L or platelet count <80 x 109/L.
  • Peptic ulcer disease and/or history of previous gastrointestinal bleeding.
  • Malignancy other than basal cell carcinoma.
  • History of epilepsy.
  • Untreated hypothyroidism.
  • Known adrenal insufficiency.
• History of drug, substance or alcohol abuse.
• Current estrogen (e.g., cortisol) therapy.
• Any factor detected from psychometric evaluation at Visit 2 Pre-Tx during the screening period which may in the opinion of the Clinical Psychologist affect an individual's ability to fully participate in the study.
• Any other condition that, in the opinion of the Investigator, may interfere with adherence to the study protocol, including dementia, mental illness, or a history of non-adherence to appointments or treatments.