Biobehavioral Mechanisms of Glucose Variability

NCT01835964 | Completed Results

• 1 other identifier: 16723
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate how blood sugar changes in response to insulin and what the body does to counter-act low blood sugar in people with Type 1 Diabetes Mellitus. Insulin sensitivity is the term used to describe blood sugar changes within the body in response to insulin. Greater understanding of insulin sensitivity, particularly how the body responds to low blood sugar, will help us to better predict how blood sugar levels will change. All subjects will receive a liquid mixed-meal and will have their blood sugar response monitored in order to study insulin sensitivity. All subjects will receive additional insulin injections that are given to cause a low blood sugar in order to understand how the body responds to a low blood sugar. All subjects will be closely monitored during the time the insulin is given, by frequent checks of blood sugar and constant medical and nursing supervision. Details of the visits, tests and procedures are described below. During this study, the study team will ask that subjects to use their own insulin pump and own glucometer. Subjects will need to use the same glucometer for the entire study. Subjects will be provided 1 box of strips. Subjects will be required to use lispro (Humalog) insulin 2-3 days before your inpatient admission which will be provided free of charge.

Conditions

Diabetes Mellitus, Type 1

Keywords

Glucose Variability (GV); Continuous Glucose Monitor (CGM); Average Daily Risk Range (ADRR); Self Monitoring Blood Glucose (SMBG)

Outcome Measures

Primary Outcomes (1)

• Change Between Pre and Post Challenge Glucose Variability

  Glucose variability in the days leading to and following the challenge was assessed by computing Low Blood Glucose Index (LBGI) on daily self-monitoring of BG (SMBG) readings. Low LBGI values correspond to lower glucose variability associated with hypoglycemic risk. LBGI values lie between 0 and 100

  3 days

Study Arms (1)

Glucose Variability Observation

EXPERIMENTAL

The study procedures will start after CGM device training \& practice using the blinded CGM for 2 days and will continue over the course of \~33 days. The study team will collect data about diabetes management including blood glucose data from fingerstick and CGM values along with insulin pump records throughout the 4 week observation period. Insulin sensitivity will be evaluated at home with predetermined meals' carbohydrate count. At the mid-study point glucose variability will be simulated in clinic with a metabolic challenge (liquid mixed meal) followed 4 hours later by the induction of hypoglycemia with an intravenous insulin injection. Insulin sensitivity, as well as glucagon and epinephrine counterregulatory responses will be evaluated to be related to overall Glucose Variability.

Procedure: Glucose Variability Observation

Interventions

Glucose Variability Observation PROCEDURE

On the morning of \~Day 17 for a metabolic challenge involving a standardized liquid mixed meal intended to raise the blood glucose approximately 150 mg/dl, followed four hours later by the induction of hypoglycemia with intravenous insulin administration with goal glucose of 55 mg/dl. After carbohydrate rescue, the subject will receive a meal and will be monitored until glucose is stable above 80 mg/dl.

Glucose Variability Observation

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of type 1 diabetes mellitus for ≥2 years. For an individual to be enrolled at least one criterion from each list must be met.
• Criteria for documented hyperglycemia (at least 1 must be met):
• Fasting Blood Glucose (BG) ≥126 mg/dL
• h Oral Glucose Tolerance Test (OGTT) ≥200 mg/dL
• Hemoglobin (HbA1c) ≥6.5%
• BG ≥200 mg/dL with symptoms
• History of hyperglycemia consistent with diabetes
• Criteria for requiring insulin at diagnosis (1 must be met):
• required insulin at diagnosis and continually thereafter
• no insulin at diagnosis but upon investigator review likely needed insulin (significant hyperglycemia that did not respond to oral agents) and insulin eventually required and used continually
• no insulin at diagnosis but continued hyperglycemia, positive islet cell antibodies - consistent with latent autoimmune diabetes in adults (LADA) and insulin eventually required and used continually
• Use of an insulin pump for at least six months prior to the study.
• Using a bolus calculator with pre-defined parameters for carbohydrate ratio(s), and insulin sensitivity factor(s).
• Signed informed consent.
• Age ≥21 and \<65 years old.

You may not qualify if:

• Uncontrolled arterial hypertension (resting blood pressure \>160/100 mm Hg).
• Impaired hepatic function measured as alanine aminotransferase or aspartate aminotransferase ≥3 times the upper reference limit.
• Impaired renal function: glomerular filtration rate (calc GFR) of \<60 ml/min/1.73 m2.
• Diabetic ketoacidosis in the past 6 months
• Conditions which may increase the risk of induced hypoglycemia such as:
• uncontrolled coronary artery disease
• stable or unstable angina
• episode of chest pain of cardiac etiology with documented Electrocardiography changes or positive troponin levels
• positive stress test
• catheterization with coronary blockages \>50%
• congestive heart failure
• significant cardiac arrhythmia
• history of a cerebrovascular event
• seizure disorder
• syncope

Sponsors & Collaborators

• University of Virginia: lead
• DexCom, Inc.: collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22904, United States

Location

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: Marc Breton, PhD
• Organization: University of Virginia

mb6nt@virginia.edu

434-982-6484

Study Officials

• Marc Breton, PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: April 11, 2013
• First Posted: April 19, 2013
• Study Start: April 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: February 1, 2014
• Last Updated: July 7, 2023
• Results First Posted: July 7, 2023

Record last verified: 2022-08

Locations

US (1)