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

NCT00943787 | Completed Results

• 1 other identifier: 12252
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief 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. 1.the transport of insulin through small blood vessels: suggesting that hypoglycemia leads to increased insulin sensitivity which then causes recurrent hypoglycemia;
2. 2.the endocrine level, defined as insulin-glucose interaction and hormonal counter-regulation.

Conditions

Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (1)

• Maximum Epinephrine Response (ADRR Groups)

  285 min (time of clamp)

Study Arms (1)

SMBG followed by clamp

OTHER

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

Interventions

Hyperinsulinemic, euglycemic and hypoglycemic clamp PROCEDURE

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.

SMBG followed by clamp

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia Health System - Behavioral Medicine Center

Charlottesville, Virginia, 22908, United States

Location

Related Publications (2)

• 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.

  PMID: 21175266 BACKGROUND

• Chan A, Barrett EJ, Anderson SM, Kovatchev BP, Breton MD. Muscle microvascular recruitment predicts insulin sensitivity in middle-aged patients with type 1 diabetes mellitus. Diabetologia. 2012 Mar;55(3):729-36. doi: 10.1007/s00125-011-2402-3. Epub 2011 Dec 14.

  PMID: 22167126 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Mary Oliveri
• Organization: University of Virginia

mc7m@virginia.edu

434-982-0602

Study Officials

• Boris Kovatchev, Ph.D.

  University of Virginia Health Systems - Behavioral Medicine Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 24, 2009
• First Posted: July 22, 2009
• Study Start: January 1, 2006
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: September 8, 2014
• Results First Posted: September 8, 2014

Record last verified: 2014-08

Locations

US (1)