Insulin Sensitivity, Impaired Counterregulation, and Glucose Variability (BPK005)

This protocol will investigate physiological parameters including insulin sensitivity and counterregulatory function using a mixed meal test and induced hypoglycemia in subjects with type I diabetes.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: Mixed meal and insulin challenge

Detailed Description

The principal idea of the proposed research is: in order to be successful, closed-loop control of glucose in diabetes must adapt to individual physiologic characteristics and to the behavioral profile of each person. We propose to build a system that will use observers of patients' behavior and metabolic state and control modules that are responsible for insulin delivery and hypoglycemia prevention. In this phase of the project, we will investigate relationships of insulin sensitivity and impaired counterregulation with blood glucose variability, aiming to develop algorithmic physiology observers, which will track specific parameters of glucose variability and recurrent hypoglycemia as markers of change in a person's insulin sensitivity and counterregulatory ability.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia, Center for Diabetes Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type I diabetes mellitus (TIDM) (as defined by the American Diabetes Association criteria or judgment of a physician) for at least two years prior to the enrollment in the study.
• Use of an insulin pump to treat their diabetes for at least six months prior to the study.
• Ability to use a bolus calculator function with the current insulin pump with pre-defined parameters for glucose goal, carbohydrate ratio, and insulin sensitivity factor.
• Age 21 - 64 years. Adults age 65 and over are likely to have medical exclusions for the follow-up Phase 2 study, which involves induced hypoglycemia.
• Completed Phase 1 of the Institutional Review Board (IRB) #14956 "Development of a Behavioral Observer for Type 1 Diabetes Mellitus"
• Willingness to use lispro (Humalog) insulin two days prior to and during inpatient admission.
• Willingness to perform Self-Monitoring Blood Glucose (SMBG) 4 times per day at times before meals and bedtime.
• Demonstration of proper mental status and cognition for completion of the study.

Exclusion Criteria:

• Pregnancy
• Psychiatric disorders that would interfere with study tasks (e.g. mental retardation, substance abuse)
• History of a systemic deep tissue infection with methicillin-resistant staph aureus or Candida albicans
• Known bleeding diathesis or dyscrasia
• Active enrollment in another clinical trial
• Medical condition that would make operating an insulin pump difficult (e.g. blindness, severe arthritis, extensive scar tissue at sites where devices are inserted).
• Anemia (hematocrit <36% [females], <38% [males]),
• Allergy or adverse reaction to lispro (Humalog) insulin
• Conditions which may increase the risk of induced hypoglycemia such as symptomatic heart disease, congestive heart failure, history of a cerebrovascular event, atrial fibrillation, renal insufficiency (creatinine >1.5) or uncontrolled hypertension (resting blood pressure >140/90).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Insulin Sensitivity; Single arm. Each subject will consume a mixed meal beverage along with insulin administration in order to calculate insulin sensitivity.

Dietary supplement: Mixed meal and insulin challenge; The subject will undergo a mixed meal and insulin challenge as follows: an insulin bolus will be administered and a mixed meal nutrition drink will be consumed over 1-5 minutes. The mixed meal nutrition drink will be selected for that individual to be most likely to raise the glucose levels by 100mg/dl and then return to baseline within a four-hour time period. The nutrition drink will selected from the following types of product lines: Boost products (Nestle Nutrition), Ensure products (Abbott Nutrition), Carnation Instant Breakfast (Nestle Nutrition) or Glucerna (Abbott Nutrition).The pre-meal insulin bolus will be calculated to bring the subject to ~100mg/dl at 1100.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Sensitivity	Measure insulin sensitivity following a mixed meal across admissions. Insulin sensitivity was measured based on the minimal model of glucose kinetics using plasma glucose and insulin obtained frequently (approximately every 5-15 minutes) in response to mixed meal challenge.	24 hours

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: September 21, 2011
• First Posted (Estimate): September 23, 2011

Study Record Updates

• Last Update Posted (Estimate): December 6, 2016
• Last Update Submitted That Met QC Criteria: October 24, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Type 1 Diabetes Mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 15131; R01DK085623 (U.S. NIH Grant/Contract)