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.

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Key information

Conditions

Diabetes Mellitus, Type 1 Autoimmune Diseases Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Virginia Health System - Behavioral Medicine Center

Charlottesville, Virginia, 22908, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Primary outcomes

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.

Secondary outcomes

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.

Sponsors and collaborators

Lead sponsor

University of Virginia

Other

Registry information

Acronym: BPK003

Important dates

Study start: 2006
Primary completion: 2009
Study completion: 2009
First posted: Jul 22, 2009
Registry last updated: Sep 8, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed