Long-term Function of Beta Cell Allografts in Non-uremic Type 1 Diabetic Patients

Inclusion Criteria: * 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: * Plasma creatinine \<2 mg/dl and albuminuria 30-1000 mg/ 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: * Smoker * EBV antibody negativity * HIV 1 \& 2 antibody positivity * CMV IgM positivity * Plasma creatinine ≥ 2 mg/dl and/or 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 HLA antibodies * Blood donation within one month prior to screening or during the study * Symptoms and/or signs of infection, particularly (present or past) endocarditis, osteomyelitis, past tuberculosis with requirement for therapy * 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 * Pregnancy or use of inadequate contraception by female patients of childbearing potential * Use of illicit drugs or overconsumption of alcohol (\> 3 beers/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 psychiatric disorders * Having received antidepressant medications during the last 6 months * Having participated the last 12 months or participating in another clinical study