Role of Glucagon In Glucose Control in Cystic Fibrosis Related Diabetes

Early Phase 1CompletedNCT02398383

Yale University7 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Cystic Fibrosis Cystic Fibrosis Related Diabetes

Interventions

Oral Glucose Tolerance TestOTHER

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.

Mixed Meal Tolerance TestOTHER

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.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Yale New Haven Hospital

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

Glucagon levels

Glucagon levels in response to to a mixed meal stimulus

Time frame: baseline

Secondary Outcomes

C-peptide levels

C-peptide levels during oral glucose tolerance test and mixed meal tolerance test

Time frame: baseline

C-peptide levels

C-peptide levels during oral glucose tolerance test and mixed meal tolerance test

Time frame: 12 months

Epinephrine levels

Epinephrine and norepinephrine levels during hypoglycemic clamp

Time frame: baseline

Epinephrine levels

Epinephrine and norepinephrine levels during hypoglycemic clamp

Time frame: 12 months

Norepinephrine levels

norepinephrine levels during hypoglycemic clamp

Time frame: baseline

Norepinephrine levels

norepinephrine levels during hypoglycemic clamp

Time frame: 12 months

Hypoglycemia unawareness scores

Hypoglycemia unawareness scores in subjects during hypoglycemic clamps as measured by the Clarke Hypoglycemia Awareness survey

Time frame: Baseline

Hypoglycemia unawareness scores

Data from ClinicalTrials.gov

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