Bet Cell Therapy in Diabetes Type 1

Inclusion Criteria:

Group A:

Patients with loss of long-term function after intraportal implantation (- Patients with type 1 insulin-dependent diabetes who received two intraportal implantations > 12 months ago.

• Random C-peptide between 0.09 and 0.5 ng/dl (glycemia between 100 and 200 mg/dl)
• Cooperative and reliable patient giving informed consent by signature

Group B:

Patients that are candidates for islet cell transplantation - age 18-65 years, male or female, Caucasian or not; only subjects < 50 yrs will be allocated to the rituximab treatment arm

• body weight < 100 kg; patients with a bodyweight of < 80kg, will receive priority
• patients with a BMI ≤ 27 kg/m2 will receive priority
• Type 1 insulin-dependent diabetes
• C-peptide < 0.07 nmol/l (< 0.2 µg/l) 6 min. after glucagon IV (1mg) (glycemia > 180 mg/dl)
• Intensive insulin therapy for more than two years, patients with insulin pump during at least 2 months before inclusion will receive priority

• Patients should have at least one of the following chronic complications of diabetes:

  • albuminuria 30-1000mg/ 24hrs on 3 separate determinations (>1 month) outside an episode of illness, despite intake of ACE inhibitors; mean systolic blood pressure should be under 130 mmHg and mean diastolic blood pressure under 85 mmHg, when measured at home with ambulatory BP monitoring
  • moderate or severe non-proliferative or proliferative retinopathy
  • hypoglycemic unawareness
• Cooperative and reliable patient giving informed consent by signature

Exclusion Criteria:

• Women of reproductive age

  • Smoker
  • EBV antibody negativity
  • HIV 1 & 2 antibody positivity
  • CMV IgM positivity
  • Hepatitis B infection
  • GFR < 45 ml/min/1.72 m2
  • Albuminuria ≥ 1000 mg/24 hrs
  • History of thrombosis or pulmonary embolism
  • History of malignancy, tuberculosis or chronic viral hepatitis
  • History of any other serious illness which could be relevant for the protocol
  • Presence of clinical significant HLA antibodies
  • Blood donation within one month prior to screening
  • Symptoms and/or signs of infection, particularly (present or past) endocarditis, osteomyelitis
  • Any history of hepatic or neoplastic disease
  • Any history of renal disease (except diabetes)
  • Abnormal liver function tests and/or NMR of liver
  • Hemoglobinopathy
  • History of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risks to the patient
  • Use of illicit drugs or overconsumption of alcohol (> 3 IU/day) or history of drug or alcohol abuse
  • Being legally incapacitated, having significant emotional problems at the time of the study, or having a history of a psychiatric disorder that may be exacerbated by the transplantation procedure or interfere with compliance during follow-up
  • Having received antidepressant medications during the last 6 months
  • Participating in another pharmacological study