Glucose Counterregulation in Long Standing Type 1 Diabetes
Condition: Hypoglycemia Unawareness; Type 1 Diabetes; Healthy
MeSH terms: Unconsciousness; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
Study type: Interventional

Summary: 
      Enrollment for this study is complete.

      This study is designed to determine if use of a real-time continuous glucose monitor (RT-CGM)
      can reverse defective Glucose counter regulation and hypoglycemia unawareness in long
      standing type 1 diabetes.
    

Detailed description: 
      The present protocol is designed to determine whether strict hypoglycemia avoidance by
      real-time continuous glucose monitoring (RT-CGM), can restore endogenous glucose production
      in response to hypoglycemia in patients with long standing disease. Twelve subjects with long
      standing type 1 diabetes complicated by hypoglycemia unawareness underwent assessment of the
      endogenous glucose production response to insulin-induced hypoglycemia using paired
      hyperinsulinemic euglycemic and hypoglycemic clamps with stable glucose isotope infusions
      before and at 6 and 18 months following initiation of RT-CGM. The primary analysis will be
      change in the endogenous glucose production response from before to 6 months following
      initiation of RT-CGM, and a secondary analysis will consider the persistence of any change at
      18 months. The clinical significance of any determined changes in the endogenous glucose
      production response to insulin-induced hypoglycemia will be determined by comparison to
      responses obtained using paired hyperinsulinemic euglycemic and hypoglycemic clamps on one
      occasion in a matched control group of 12 subjects with long-standing type 1 diabetes but no
      hypoglycemia unawareness (GROUP 2) and in a matched control group of 12 nondiabetic subjects
      (GROUP 3).

      Arms are not assigned to these two control groups in ct.gov as they were only used as a
      baseline for clinical significance. Neither group wore a CGM nor are they analyzed at 6-month
      and 18-month time-points. This said, for control group clarification, inclusion and exclusion
      criteria for each group is included in ct.gov

      Hypoglycemia is a major barrier to the achievement of adequate glycemic control for most
      patients with insulin-dependent diabetes. Type 1 diabetic patients with absolute insulin
      deficiency (C-peptide negative) are at greatest risk for experiencing severe hypoglycemic
      events because the near total destruction of insulin producing islet β-cells produces an
      associated defect in glucagon secretion from neighboring α-cells. Such patients then depend
      on the sympathoadrenal system as a final defense against hypoglycemia, but unfortunately,
      recurrent episodes of hypoglycemia blunt sympathoadrenal activation and produce a syndrome of
      hypoglycemia unawareness that is associated with a twenty-fold increased risk of
      life-threatening hypoglycemia. Without intact islet or sympathoadrenal (especially
      epinephrine) responses to hypoglycemia, these patients cannot increase endogenous (primarily
      hepatic) glucose production to prevent or correct low blood glucose.
    

Intervention name(s): RT-CGM
Intervention type(s): Device
Intervention description(s): Each device is approximately the size of a pager and transmits with a subcutaneously placed sensor consisting of a 21 - 26 gauge needle 5 - 12 mm in length. Sensors are placed using sterile precautions and changed every 3 - 7 days depending on the manufacturers' instructions. All devices are approved as adjunctive tools to blood glucose monitoring that will be continued at least 4 times daily, before each meal and at bedtime.
Other intervention name(s): DexCom SEVEN PLUS, Guardian R-T, or FreeStyle Navigator.
Intervention model: Single Group Assignment
Intervention model description: Hypoglycemia Unaware T1 Diabetics & 2 Control Groups. Non-Diabetics & T1Ds With Intact Awareness.
Masking: None (Open Label)
Primary purpose: Other
Keywords: Hypoglycemia, Unawareness, RT-CGM, Type 1 Diabetes