Counter-Regulatory Impairment and the Effect of Microvascular Insulin Transfer in Type 1 Diabetes Mellitus

Diabetes Mellitus, Type 1 Clinical Trial

— BPK003  

Official title:

Counter-regulatory Impairment and the Effect of Microvascular Insulin Transfer in Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00943787
• Other study ID #: 12252
• Status: Completed
• Phase: N/A
• First received: June 24, 2009
• Last updated: August 26, 2014
• Start date: January 2006
• Est. completion date: May 2009

Study information

• Verified date: August 2014
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The researchers plan to test the following hypothesis:

A good level of glucose control in Type 1 Diabetes Mellitus (T1DM) is dependent on two levels of feedback from the body:

1. the transport of insulin through small blood vessels: suggesting that hypoglycemia leads to increased insulin sensitivity which then causes recurrent hypoglycemia;

2. the endocrine level, defined as insulin-glucose interaction and hormonal counter-regulation.

The researchers plan to investigate the relationships between hypoglycemia, insulin transport, and counter-regulation. This study will ultimately lead to a better understanding of risk for recurrent hypoglycemia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participated in and satisfied all of the inclusion criteria of NCT00315939

• 18 years of age or older

• Have Type 1 Diabetes Mellitus defined by American Diabetes Association criteria or judgment of physician

• Since our major goal is the investigation of hypoglycemia, we will preferentially recruit patients with a history of severe hypoglycemia/moderate hypoglycemia anticipating that approximately (~) half of the recruited subjects will have had two or more severe or moderate hypoglycemia episodes in the past 12 months

Exclusion Criteria:

• Age < 18

• Pregnancy

• Use of oral steroids

• Hematocrit < 36% (females); < 38% (males)

• Symptomatic heart disease (e.g., history of myocardial infarction, history of coronary bypass or stenting procedure, angina, episode of chest pain of cardiac etiology with documented EKG changes, positive stress test or catheterization with coronary blockages > 50%)

• History of an ischemic cerebrovascular event

• Active substance abuse

• Psychosis

• Mental retardation

• Severe depression

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Procedure:
• Hyperinsulinemic, euglycemic and hypoglycemic clamp
At 21:30h, an overnight insulin infusion was titrated to control the subjects' BG overnight between 100 and 150mg/dL by blood sampling for plasma glucose via a YSI analyzer every 30min and adjusting the rate of insulin infusion as needed. At the beginning of the clamp, the overnight insulin was replaced by an insulin infusion via a Harvard pump given as a 20mU/kg priming over a 10-min period, followed by a constant rate delivery of 1mU/kg/min until the end of the clamp. Blood was sampled for plasma glucose, and glucose was clamped at basal levels for the euglycemic control period of 150min via a variable-rate infusion of 20% dextrose. Then the glucose concentration was lowered at a rate of 1mg/dL/min to a minimum of 50mg/dL, where it was held constant for 30min. Finally, the glucose concentration was increased at a rate of 1mg/dL/min to 90mg/dL, where it was held for an additional 30min. Blood was sampled for epinephrine during euglycemia, hypoglycemia, and recovery.

Locations

Country	Name	City	State
United States	University of Virginia Health System - Behavioral Medicine Center	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

References & Publications (1)

Pitsillides AN, Anderson SM, Kovatchev B. Hypoglycemia risk and glucose variability indices derived from routine self-monitoring of blood glucose are related to laboratory measures of insulin sensitivity and epinephrine counterregulation. Diabetes Technol Ther. 2011 Jan;13(1):11-7. doi: 10.1089/dia.2010.0103. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Epinephrine Response (LBGI Groups)	Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL.; Low blood glucose index (LBGI) is a metric to calculate the risk for hypoglycemia based on frequency and extent of past events based on SMBG readings. In studies, the LBGI typically accounted for 40-55% of the variance of future significant hypoglycemia in the subsequent 3-6 months. The LBGI has established risk categories: Low Risk, LBGI < 2.5; Moderate Risk, 2.5 < LBGI < 5; and High Risk, LBGI > 5, indicating an over 10-fold increase in future severe hypoglycemia from the lowest to the highest risk category.	285 min (time of clamp)	No
Secondary	Maximum Epinephrine Response (ADRR Groups)	Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL.; Average Daily Risk Range (ADRR) is associated with glycemic variability and risk of both hyper- and hypoglycemia.; Low Risk, ADRR < 20; Moderate Risk, 20 < ADRR < 40; and High Risk,ADRR > 40.	285 min (time of clamp)	No