Islet Transplantation in Patients With "Brittle" Type I Diabetes

Inclusion Criteria:

- Male and female patients 18 to 70 years of age.

- Subjects who are able to provide written informed consent and to comply with the
procedures of the study protocol.

- Clinical history compatible with T1D with onset of disease at < 40 years of age,
insulin-dependence for ≥ 5 years at the time of enrollment, and a sum of patient age
and insulin dependent diabetes duration of ≥ 28.

- Absent stimulated c-peptide (<0.3ng/mL) in response to a mixed meal tolerance test
(MMTT; Boost® 6 mL/kg body weight to a maximum of 360 mL; another product with
equivalent caloric and nutrient content may be substituted for Boost) measured at 60
and 90 min after the start of consumption.

- Involvement in intensive diabetes management defined as self monitoring of glucose
values no less than a mean of three times each day averaged over each week and by the
administration of three or more insulin injections each day or insulin pump therapy.
Such management must be under the direction of an endocrinologist, diabetologist, or
diabetes specialist with at least 3 clinical evaluations during the 12 months prior to
study enrollment.

- At least one episode of severe hypoglycemia in the 12 months prior to study
enrollment.

- Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more OR a HYPO
score greater than or equal to the 90th percentile (1047) during the screening period
and within the last 6 months; OR marked glycemic lability characterized by wide swings
in blood glucose despite optimal diabetes therapy and defined by an LI score greater
than or equal to the 90th percentile (433 mmol/L2/h -wk1) during the screening period
and within the last 6 months prior to randomization; OR a composite of a Clarke score
of 4 or more and a HYPO score greater than or equal to the 75th percentile (423) and a
LI greater than or equal to the 75th percentile (329) during the screening period and
within the last 6 months.

Exclusion Criteria:

- Body mass index (BMI) >30 kg/m2 or patient weight <50kg.

- Insulin requirement >1.0 IU/kg/day or <15 U/day.

- HbAlc>10%.

- Untreated proliferative diabetic retinopathy.

- Blood Pressure: SBP >160 mmHg or DBP >100 mmHg.

- Measured glomerular filtration rate <80 mL/min/1.73m2 (using iohexol or calculated
using the subject's measured serum creatinine and the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI equation) or based on 24-hrs urine collection.
Strict vegetarians (vegans) with a calculated GFR <70 mL/min/1.73m2 are excluded. The
absolute (raw) GFR value will be used for subjects with body surface areas >1.73 m2.

- Presence or history of macroalbuminuria (>300 mg/g creatinine).

- Presence or history of panel-reactive anti-HLA antibodies above 30% or
history/presence of donor specific anti-HLA antibodies in order to avoid unacceptable
antigen(s) (Campbell PM 2007).

- For female subjects: Positive pregnancy test, presently breast-feeding, or
unwillingness to use effective contraceptive measures for the duration of the study
and 4 months after discontinuation. For male subjects: intent to procreate during the
duration of the study or within 4 months after discontinuation or unwillingness to use
effective measures of contraception. Oral contraceptives, Norplant®, Depo-Provera®,
and barrier devices with spermicide are acceptable contraceptive methods; condoms used
alone are not acceptable.

- Presence or history of active infection including hepatitis B, hepatitis C, HIV, or
tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded
even in the absence of clinical evidence of active infection.

- Known active alcohol or substance abuse.

- Severe co-existing cardiac disease

- Known hypercoagulative state.

- Symptomatic cholecystolithiasis.

- Acute or chronic pancreatitis.

Other protocol related inclusion/exclusion criteria may apply.