Counter-Regulatory Impairment and the Effect of Microvascular Insulin Transfer in Type 1 Diabetes Mellitus (BPK003)

August 26, 2014 updated by: Boris Kovatchev, PhD, University of Virginia

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System - Behavioral Medicine Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: SMBG followed by clamp
One month of self-monitored blood glucose (SMBG) field data was used to calculate measures of glucose variability and risk of hypoglycemia, while the hyperinsulinemic, euglycemic and hypoglycemic clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Epinephrine Response (LBGI Groups)
Time Frame: 285 min (time of clamp)

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)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Epinephrine Response (ADRR Groups)
Time Frame: 285 min (time of clamp)

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Virginia

Investigators

  • Principal Investigator: Boris Kovatchev, Ph.D., University of Virginia Health Systems - Behavioral Medicine Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

May 1, 2009

Study Completion (Actual)

May 1, 2009

Study Registration Dates

First Submitted

June 24, 2009

First Submitted That Met QC Criteria

July 21, 2009

First Posted (Estimate)

July 22, 2009

Study Record Updates

Last Update Posted (Estimate)

September 8, 2014

Last Update Submitted That Met QC Criteria

August 26, 2014

Last Verified

August 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12252

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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