Role of Glucagon In Glucose Control in Cystic Fibrosis Related Diabetes

Role of Glucagon in Glucose Control in Cystic Fibrosis Related Diabetes

This project is designed to begin to characterize the abnormalities of glucagon secretion in subjects with cystic fibrosis related diabetes along the spectrum of glucose tolerance. Cystic fibrosis patients with normal glucose tolerance as well as cystic fibrosis related diabetes as well as control subjects will undergo an oral glucose tolerance test, mixed meal tolerance test, and one step hypoglycemic clamp. Cystic fibrosis patients will then return 12 months later to undergo repeat mixed meal tolerance test and hypoglycemic clamp test.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Cystic Fibrosis Related Diabetes
• Intervention / Treatment: Other: Oral Glucose Tolerance Test; Other: Mixed Meal Tolerance Test; Other: Hypoglycemic Clamp

Detailed Description

This project is designed to begin to characterize the abnormalities of glucagon secretion in subjects with cystic fibrosis related diabetes along the spectrum of glucose tolerance. This will be a descriptive, cross-sectional and longitudinal cohort study in a sample of children and young adults with CF and a continuum of glucose tolerance compared to healthy age-matched controls.

Cystic fibrosis patients with normal glucose tolerance as well as cystic fibrosis related diabetes as well as control subjects will be admitted to the research unit on three separate occasions to undergo an oral glucose tolerance test, mixed meal tolerance test, and one step hypoglycemic clamp. Cystic fibrosis patients will then return 12 months later to undergo repeat mixed meal tolerance test and hypoglycemic clamp test.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale New Haven Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of CF by clinical or genetic determination
• Normal glucose tolerance or CFRD
• Subjects routinely taking systemic or inhaled glucocorticoids on stable regimen are eligible

Exclusion Criteria:

• Subjects with active pulmonary infection requiring supplemental doses of corticosteroids
• Use of any oral diabetes medications
• Subjects who are pregnant/lactating
• Subjects with poor compliance with pancreatic enzyme replacement therapy

Control Subjects:

Approximately 10 control subjects who are matched for age, gender, are expected to be enrolled in the study. Non-CF subjects must be >12 years old, in good health and not taking any medications or have any medical problems the doctor feels would prevent the subject from completing the study and have BMI between 15-85% for age and gender. Control subjects whose fasting blood glucose is found to be >110 mg/dL will not be continued in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CF with Normal Glucose Tolerance; Individuals with CF without cystic fibrosis related diabetes	Other: Oral Glucose Tolerance Test; Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling. Patients will drink 1.75 gm/kg glucose (Glucola) to a maximum of 75 gm. Venous samples for glucose and c-peptide will be drawn from the IV at 0, 30, 60, 90 and 120 minutes. Subjects will be instructed to eat at least 75 gm carbohydrates daily in the week prior to this test.; Other: Mixed Meal Tolerance Test; Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling. Subjects will consume 6 kcal/kg (6 ml/kg) Boost High Protein Nutritional Energy Drink (Mead-Johnson) over five minutes to a maximum of 360 ml. Venous samples for glucose, glucagon, GLP-1, GIP, and c-peptide will be drawn at -10, 0, 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes.; Other: Hypoglycemic Clamp; All subjects with CF and adult (but not pediatric) controls will undergo one-step hypoglycemic clamp. Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling and a second IV for infusion of insulin and dextrose.
Experimental: Cystic Fibrosis Related Diabetes; Individuals with cystic fibrosis and cystic fibrosis related diabetes	Other: Oral Glucose Tolerance Test; Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling. Patients will drink 1.75 gm/kg glucose (Glucola) to a maximum of 75 gm. Venous samples for glucose and c-peptide will be drawn from the IV at 0, 30, 60, 90 and 120 minutes. Subjects will be instructed to eat at least 75 gm carbohydrates daily in the week prior to this test.; Other: Mixed Meal Tolerance Test; Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling. Subjects will consume 6 kcal/kg (6 ml/kg) Boost High Protein Nutritional Energy Drink (Mead-Johnson) over five minutes to a maximum of 360 ml. Venous samples for glucose, glucagon, GLP-1, GIP, and c-peptide will be drawn at -10, 0, 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes.; Other: Hypoglycemic Clamp; All subjects with CF and adult (but not pediatric) controls will undergo one-step hypoglycemic clamp. Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling and a second IV for infusion of insulin and dextrose.
Active Comparator: Control; Age matched control subjects	Other: Oral Glucose Tolerance Test; Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling. Patients will drink 1.75 gm/kg glucose (Glucola) to a maximum of 75 gm. Venous samples for glucose and c-peptide will be drawn from the IV at 0, 30, 60, 90 and 120 minutes. Subjects will be instructed to eat at least 75 gm carbohydrates daily in the week prior to this test.; Other: Mixed Meal Tolerance Test; Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling. Subjects will consume 6 kcal/kg (6 ml/kg) Boost High Protein Nutritional Energy Drink (Mead-Johnson) over five minutes to a maximum of 360 ml. Venous samples for glucose, glucagon, GLP-1, GIP, and c-peptide will be drawn at -10, 0, 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes.; Other: Hypoglycemic Clamp; All subjects with CF and adult (but not pediatric) controls will undergo one-step hypoglycemic clamp. Subjects will be instructed to fast after midnight the night prior to the study. Subjects will be admitted to the research unit on the morning of the test for placement of blood-drawing IV for frequent sampling and a second IV for infusion of insulin and dextrose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucagon levels	Glucagon levels in response to to a mixed meal stimulus	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-peptide levels	C-peptide levels during oral glucose tolerance test and mixed meal tolerance test	baseline
C-peptide levels	C-peptide levels during oral glucose tolerance test and mixed meal tolerance test	12 months
Epinephrine levels	Epinephrine and norepinephrine levels during hypoglycemic clamp	baseline
Epinephrine levels	Epinephrine and norepinephrine levels during hypoglycemic clamp	12 months
Norepinephrine levels	norepinephrine levels during hypoglycemic clamp	baseline
Norepinephrine levels	norepinephrine levels during hypoglycemic clamp	12 months
Hypoglycemia unawareness scores	Hypoglycemia unawareness scores in subjects during hypoglycemic clamps as measured by the Clarke Hypoglycemia Awareness survey	Baseline
Hypoglycemia unawareness scores	Hypoglycemia unawareness scores in subjects during hypoglycemic clamps as measured by the Clarke Hypoglycemia Awareness survey	12 months
GLP-1 and GIP levels	GLP-1 and GIP levels in response to mixed meal stimulus	Baseline
GLP-1 and GIP levels	GLP-1 and GIP levels in response to mixed meal stimulus	12 months
Glucagon levels	Glucagon levels in response to to a mixed meal stimulus and difference from baseline	12 months

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Bracha Goldsweig, MD, Yale University

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): June 22, 2017
• Study Completion (Actual): June 22, 2017

Study Registration Dates

• First Submitted: January 22, 2015
• First Submitted That Met QC Criteria: March 19, 2015
• First Posted (Estimate): March 25, 2015

Study Record Updates

• Last Update Posted (Actual): June 26, 2020
• Last Update Submitted That Met QC Criteria: June 24, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Respiratory Tract Diseases; Lung Diseases; Endocrine System Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Diabetes Mellitus; Cystic Fibrosis; Physiological Effects of Drugs; Hypoglycemic Agents
• Other Study ID Numbers: 1409014580