Glucose Counterregulation in Long Standing Type 1 Diabetes

Inclusion criteria

• . Male and female subjects aged 25 to 70 years
• . Able to provide written informed consent and to comply with the protocol procedures
• . Clinical history compatible with type 1 diabetes with disease onset \< 40 years of age OR onset ≥ 40 years and documented islet autoimmunity
• . Insulin-dependent for \> 10 years
• . Absent C-peptide (\< 0.3 ng/mL).
• . 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 under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least 3 clinical evaluations during the previous 12 months.)
• . Hypoglycemia unawareness manifested by a Clarke score of 4 or more AND at least one of the following:
• . At least one episode of severe hypoglycemia in the past 12 months defined as an event with symptoms or signs compatible with hypoglycemia in which the subject was unable to treat him/herself and which was associated with either a blood glucose level \< 54 mg/dl \[3.0 mmol/L\] or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration; OR documented \> 5% time spent in the hypoglycemic range (glucose \< 60 mg/dl) by 72-hour blinded CGM.

Exclusion criteria