Glucose Counterregulation in Long Standing Type 1 Diabetes

Not Applicable

Completed

• Conditions: Hypoglycemia Unawareness; Healthy; Type 1 Diabetes
• Interventions: Device: RT-CGM

• Registration Number: NCT01474889
• Lead Sponsor: University of Pennsylvania

Brief 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2011-10
• Study First Submitted: 2011-11-15
• Study First Submitted QC: 2011-11-15
• Study First Posted: 2011-11-18
• Primary Completion: 2016-05
• Study Completion: 2021-03-05
• Results First Submitted: 2022-12-14
• Status Verified: 2023-08
• Results First Submitted QC: 2023-08-09
• Last Update Submitted: 2023-08-09
• Results First Posted: 2023-08-31
• Last Update Posted: 2023-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hypoglycemia Unaware T1 Diabetes RT-CGM	RT-CGM	This arm is the intervention group. It consists of participants with type 1 diabetes complicated by hypoglycemia unawareness. Patients wore an RT-CGM for 18 months. We studied glucose production and symptom generation during insulin-induced hypoglycemia (metabolic testing) by subjecting this intervention group to a pair of metabolic clamps (hypoglycemic and euglycemic) at baseline, at 6 months and at 18 months to determine if hypoglycemia avoidance can reverse unawareness. Please note: Arms are not assigned to the two control groups (non-diabetics and T1Ds with intact awareness) in ct.gov as they are 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.

Primary Outcome Measures

Name	Time	Method
Endogenous Glucose Production	6 months	Measure of hepatic glucose output during final hour of hypoglycemic clamp.; Outcome Measures are not assigned to the control groups in ct.gov as they were only used as a baseline for clinical significance. Neither group wore a CGM nor were they analyzed at 6-month and 18-month time-points.

Secondary Outcome Measures

Name	Time	Method
Autonomic Symptom Response to Hypoglycemia	18 months	Response measure during hypoglycemic clamp using an Autonomic Symptom Questionnaire.; The autonomic symptom response is calculated during the final hour of the Hypoglycemic clamp as the sum of scores ranging from 0 (none) to 5 (severe) for each of the following symptoms: anxiety, palpitations, sweating, tremor, hunger, and tingling. This results in a minimum of 0 or a maximum of 30 score with the higher score a better outcome. The scale title is Autonomic Symptom Response to hypoglycemia.
Endogenous Glucose Production	18 months	Measure of hepatic glucose output during final hour of hypoglycemic clamp

Trial Locations

Locations (3)

Clinical and Translational Research Center, Hospital of University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Rodebaugh Diabetes Center, University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pennsylvania - Institute for Diabetes, Obesity and Metabolism; 🇺🇸 Philadelphia, Pennsylvania, United States