Insulin Requirement for Pure-protein Meal in Children With Type 1 Diabetes on Insulin Pumps.

Study Overview
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Brief Summary
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This is a randomized, cross-over study. The aim of this study is to compare the post-prandial glycaemic variability after pure protein meal following with an administration of square-wave bolus of meal-insulin or without any meal-insulin bolus on the other day. Prolonged post-prandial glycaemic variability will be identified using the self-monitoring of blood glucose (10-point curve) and CGMS.

Detailed Description
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The square-wave bolus (for meals rich in fat and/or protein) is evenly delivered over several hours as programmed by the patient. The required insulin dose will be calculated based on patient's insulin-exchange ratio. Pure protein meal will be given 3 hours after a first breakfast. To provide the minimal impact of the previous breakfast, all patients will receive up to 120 kcal of carbohydrates and <100 kcal from protein and fat for the first breakfast (without any extended bolus) Patients receive a standardized pure protein meal at a second breakfast time. Meal insulin will be given as a square bolus or no meal -insulin will be given at all. The 5h post-meal glucose excursions will be recorded by self-blood glucose measurements (SMBG) (every 30 minutes) and continuous glucose monitoring system (CGMS). The intervention is taking part under in-patient clinical conditions.

Official Title
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Insulin Requirement for Pure- Protein Meal in Children With Type 1 Diabetes Treated With Continuous Subcutaneous Insulin Infusion - a Cross-over, Randomized Trial.

Conditions
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Diabetes type1

Intervention / Treatment
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* Drug: Insulin glulisine
* Drug: Insulin aspart
* Drug: Insulin lispro


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: duration of type 1 diabetes longer than 12 months insulin pump therapy longer than 3 months written informed consent by patients and parents insulin requirement more than 0,5 units/kg/day Exclusion Criteria: diabetes related complications (e.g. nephropathy) chronic kidney diseases any disease judged by the investigator to affect the trial withdrawal of consent to participate in the study

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: group A<br>On the first study day, insulin bolus was not given before a standardized pure protein meal. On the second day, pre-breakfast insulin was given as a square-wave bolus before the same standardized pure protein meal. The fat-protein-insulin ratio on both study days were identical to the patient's ratio when entering trial. Kind of study bolus insulin will be a rapid-acting insulin analog same as previously used by the participant (before entering the trial) - insulin aspart, insulin lispro or insulin glulisine | Drug: Insulin glulisine<br>* A kind of study bolus insulin will be insulin aspart if participant used insulin aspart before entering the trial<br>* Other names: Apidra®;Drug: Insulin aspart<br>* A kind of study bolus insulin will be insulin lispro if participant used insulin lispro before entering the trial<br>* Other names: NovoRapid®;Drug: Insulin lispro<br>* A kind of study bolus insulin will be insulin lispro if participant used insulin lispro before entering the trial<br>* Other names: Humalog®;|
| Active Comparator: group B<br>On the first study day, pre-breakfast insulin was given as a square-wave bolus before a standardized pure protein meal. On the second day, insulin bolus was not given before the same standardized pure protein meal. The fat-protein-insulin ratio on both study days were identical to the patient's ratio when entering trial. Kind of study bolus insulin will be a rapid-acting insulin analog same as previously used by the participant (before entering the trial) - insulin aspart, insulin lispro or insulin glulisine | Drug: Insulin glulisine<br>* A kind of study bolus insulin will be insulin aspart if participant used insulin aspart before entering the trial<br>* Other names: Apidra®;Drug: Insulin aspart<br>* A kind of study bolus insulin will be insulin lispro if participant used insulin lispro before entering the trial<br>* Other names: NovoRapid®;Drug: Insulin lispro<br>* A kind of study bolus insulin will be insulin lispro if participant used insulin lispro before entering the trial<br>* Other names: Humalog®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 30 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 60 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 90 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 120 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 150 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 180 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 210 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 240 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 270 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 300 minutes after the meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemia episodes | Hypoglycemia defined as a plasma glucose concentration below 65 mg/dl with or without symptoms | 5-hour study period | 
| Glucose Area Under the Curve (AUC) | Measurements based on CGMS | 5-hour study period | 
| Mean amplitude of glycemic excursion | measurements based on SMBG | 5-hour study period | 
| The difference between the maximum and baseline glucose level | Post-prandial blood glucose excursions measured by self monitoring of blood glucose (SMBG) | 5-hour study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes type 1, insulin pump, prandial insulin requirement, pure protein meal, high protein meal, square bolus, square-wave bolus, insulin bolus, dietary protein