Comparison of Meal-Time Dosing of Insulin in Cystic Fibrosis Related Diabetes

Study Overview
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Brief Summary
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The aim of this study is to assess the utility of CGMs to determine the optimal method to dose meal-time insulin. The investigators will examine glucose excursions in patients with CF who will dose meal-time rapid-acting insulin by carbohydrate counting versus fixed-dose rapid-acting insulin. The carbohydrate ratio and fixed doses will be determined by existing doses, total daily insulin doses, body weight, and insulin sensitivity along with predisposition to hypoglycemia. Bolus insulin dosing is an important part of CFRD management due to the high nutritional demands of these patients. If dosed incorrectly, this could lead to marked hyperglycemia and could worsen nutritional status due to urinary glucose losses. In this project, the investigators will perform a within-subjects' comparison of the 2 standard methods of meal-time rapid-acting insulin dosing.

Detailed Description
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Background and Introduction Cystic fibrosis-related diabetes (CFRD) is the most common extra-pulmonary comorbidity in patients with cystic fibrosis (CF). CFRD is also associated with an accelerated decline in pulmonary function, increased pulmonary exacerbations, and increased mortality. Continuous glucose monitoring (CGM) involves the use of a small disposable sensor sited in the subcutaneous interstitial fluid that makes frequent glucose measurements. There is data suggesting that the Medtronic iPro continuous glucose monitors (CGM) can predict hemoglobin a1c levels in patients with CFRD. The aim of this study is to assess the utility of CGMs to determine the optimal method to dose meal-time insulin. The investigators will examine glucose excursions in patients with CF who will dose meal-time rapid-acting insulin by carbohydrate counting versus fixed-dose rapid-acting insulin. The carbohydrate ratio and fixed doses will be determined by existing doses, total daily insulin doses, body weight, and insulin sensitivity along with predisposition to hypoglycemia. Bolus insulin dosing is an important part of CFRD management due to the high nutritional demands of these patients. If dosed incorrectly, this could lead to marked hyperglycemia and could worsen nutritional status due to urinary glucose losses. In this project, the investigators will perform a within-subjects' comparison of the 2 standard methods of meal-time rapid-acting insulin dosing. Hypothesis: Postprandial interstitial fluid glucose levels in participants who utilize carbohydrate counting to dose mealtime rapid-acting insulin will have improved control as defined as the area under the curve and time in target compared to participants who used fixed-dose mealtime insulin Participants who utilize carbohydrate counting will have fewer hypoglycemia events compared to participants who use fixed-dose meal-time insulin Specific Aims: To compare within-subject glucose excursions defined as the percentage of time in target glucose level, percentage of glucose in target, and peak postprandial glucose with fixed insulin dosing versus carbohydrate count based insulin dosing. To compare the frequency and duration of hypoglycemia (defined as the daily, weekly, and average duration of the event) between insulin delivery methods described above. To test the use of 'rule of 500' for carb counting estimation in patients with CFRD To compare the effect of two methods of rapid-acting insulin delivery on fasting glycemia

Official Title
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Comparison of Meal-Time Dosing of Rapid Acting Insulin Using Carbohydrate Counting vs. Fixed Doses Utilizing Continuous Glucose Monitoring In Patients With Cystic Fibrosis Related Diabetes

Conditions
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Cystic Fibrosis-related Diabetes

Intervention / Treatment
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* Drug: Insulin
* Device: Continuous glucose monitor (CGM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 age of years Diagnosis of cystic fibrosis related diabetes Using basal bolus insulin Cystic Fibrosis with Lung Transplantation Exclusion Criteria: Use of continuous glucose monitors Patient unable to check fingerstick blood sugars

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This study design involves a within-subjects comparison using a sequential cross over that occurs over a 2-week time frame. During the first seven days of wear, the participants will be asked to dose their mealtime rapid-acting insulin by fixed-dose, and the next seven days, participants will be asked to dose their mealtime rapid-acting insulin by carbohydrate counting. After the 14 days, participants will return their continuous glucose monitor (CGM) devices for analysis and interpretation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fixed Dosing, Followed by Carbohydrate Counting<br>Dosing of premeal insulin with fixed doses | Drug: Insulin<br>* Participants will be asked to dose insulin during the first week using fixed doses. During the second week of the study, participants will dose insulin based on carbohydrate counting. Blood sugar control will be compared between the 2 weeks to determine the outcomes of the study.<br>Device: Continuous glucose monitor (CGM)<br>* Participants will be required to wear a CGM to measure glucose trends<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in Target | Measurement of percentage of time in target of glucose level | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemia number | To determine the number of hypoglycemic events under 70 mg/dl | 2 weeks | 
| Hypoglycemia duration | To determine the duration of hypoglycemic events in minutes | 2 weeks |