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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boris Kovatchev, PhD, University of Virginia
ClinicalTrials.gov Identifier:
NCT00943787
First received: June 24, 2009
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
Diabetes Mellitus, Type 1
Procedure: Hyperinsulinemic, euglycemic and hypoglycemic clamp

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Counter-regulatory Impairment and the Effect of Microvascular Insulin Transfer in Type 1 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Maximum Epinephrine Response (LBGI Groups) [ Time Frame: 285 min (time of clamp) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Maximum Epinephrine Response (ADRR Groups) [ Time Frame: 285 min (time of clamp) ] [ Designated as safety issue: No ]

    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.



Enrollment: 41
Study Start Date: January 2006
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00943787

Locations
United States, Virginia
University of Virginia Health System - Behavioral Medicine Center
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Boris Kovatchev, Ph.D. University of Virginia Health Systems - Behavioral Medicine Center
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boris Kovatchev, PhD, Professor, University of Virginia
ClinicalTrials.gov Identifier: NCT00943787     History of Changes
Other Study ID Numbers: 12252
Study First Received: June 24, 2009
Results First Received: August 8, 2014
Last Updated: August 26, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Hypoglycemic Agents
Insulin
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014