Hybrid Closed Loop Insulin Delivery System in Hypoglycemia

Prior treatment

• Presence of a seizure disorder not related to prior severe hypoglycemia.
• Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment.
• Use of any investigational agents within 4 weeks of enrollment.

Other illness

• Uncontrolled hypertension: systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg.
• Active cardiovascular disease
• Untreated hypothyroidism, Addison's disease, or Celiac disease.
• Any medical condition that, in the opinion of the PI, will interfere with the safe completion of the study

Lab values

• HbA1c ≥ 10%.
• Abnormal kidney function: eGFR \< 60 ml/min/1.73 m2.
• Anemia: baseline hemoglobin concentration \< 11 g/dl in women and \< 12 g/dl in men.

Other

• BMI ≥ 30 kg/m2.
• Insulin requirement of ≥ 1.0 units/kg•day.
• Untreated proliferative diabetic retinopathy.
• Abnormal liver function: persistent elevation of liver function tests \> 1.5 times the upper limit of normal.
• Use of glucocorticoids greater than 5 mg of prednisone daily, or an equivalent physiologic dose of hydrocortisone.
• For female participants of child-bearing potential: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of study participation. Oral contraceptives, intra-uterine devices, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.

• Male and female subjects age 25 to 70 years.
• Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol.
• Clinical history compatible with type 1 diabetes with disease onset \< 40 years of age and insulin dependent for \> 10 years.
• Absent C-peptide (\< 0.3 ng/ml).
• Involvement in intensive diabetes management defined as the use of basal-bolus insulin analog delivery by multi-dose injection (MDI) or continuous subcutaneous insulin infusion (CSII) together with self-monitoring of blood glucose values more than 3 times daily with or without continuous glucose monitoring (CGM) under the direction of an endocrinologist, diabetologist, or diabetes nurse practitioner 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 1 of the following: HYPO score greater than or equal to the 90th percentile (1047); OR marked glycemic lability defined by a glycemic lability index (LI) score greater than or equal to the 90th percentile (433 mmol/l2/h•wk-1); OR a composite of a HYPO score greater than or equal to the 75th percentile (423) and a LI greater than or equal to the 75th percentile (329) (Senior et al., 2015).
• Documented \> 5% time spent in the hypoglycemic range (glucose \< 60 mg/dl) by 7 day real- time or blinded CGM; at least one episode of hypoglycemic during the 7 days must occur overnight.