Normal Versus Dual Wave Insulin Bolus for High-protein Food

Study Overview
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Brief Summary
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Patients receive a standardized high-protein test meal at breakfast time. Insulin is given as bolus (normal or dual-wave (normal plus square) and basal rate using an insulin pump. The 3h post-meal glucose excursions will be recorded by self-blood glucose measurements (SMBG) (every 1 hour) and continuous glucose monitoring system (CGMS). The intervention is taking part under in-patient clinical conditions.

Detailed Description
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The dual-wave bolus delivers an immediate normal pre-meal insulin bolus followed by square-wave bolus that is evenly delivered over several hours as programmed by the patient. The aim of this study is to compare post-prandial glycaemic excursions following a high-protein meal after administration of insulin by normal vs dual-wave bolus. During this prospective, cross-over, repeated measures study, pediatric patients with type 1 diabetes, treated with insulin pump therapy will be evaluated using the self-blood glucose measurements following standardized high-protein meal and two types of boluses (normal or dual-wave). The required insulin dose will be calculated based on patient's insulin-exchange ratio. A high-protein meal will be given on two subsequent breakfasts and comparisons will be made between normal and dual-wave insulin bolus delivery. Prolonged post-prandial glycaemic excursions will be identified using the CGMS.

Official Title
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The Optimal Type of Bolus Following a High-protein Meal in Type 1 Diabetic Children Treated With Insulin Pumps

Conditions
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Type 1 Diabetes

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


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 patients must be willing to wear a glucose sensor for two days insulin requirement more than 0,5 units/kg/day Exclusion Criteria: concomitant dietary restrictions (e.g. celiac disease or food allergy) diabetes related complications (e.g. nephropathy) 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal/ Dual-wave<br>On the first study day, pre-breakfast insulin was given as a normal bolus 15 minutes before a standardized high-protein meal. On the second day, pre-breakfast insulin was given as a dual-wave bolus before the same high-protein meal. The carbo-insulin and 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 aspart<br>* A kind of study bolus insulin will be insulin aspart if participant used insulin aspart 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®;Drug: insulin glulisine<br>* A kind of study bolus insulin will be insulin glulisine if participant used insulin glulisine before entering the trial<br>* Other names: Apidra®;|
| Experimental: Dual-wave/Normal<br>On the first study day, pre-breakfast insulin was given as a dual-wave bolus 15 minutes before a standardized high-protein meal. On the second day, pre-breakfast insulin was given as a normal bolus before the same high-protein meal. The carbo-insulin and 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 aspart<br>* A kind of study bolus insulin will be insulin aspart if participant used insulin aspart 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®;Drug: insulin glulisine<br>* A kind of study bolus insulin will be insulin glulisine if participant used insulin glulisine before entering the trial<br>* Other names: Apidra®;|

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) | 60 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose | 120 minutes after the meal | 
| Postprandial glycemia | Post-prandial blood glucose excursions measured by self monitoring of blood glucose | 180 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 | 3-hour study period | 
| Glucose Area Under the Curve (AUC) | measurements based on CGMS | 3-hour study period | 
| Mean amplitude of glycemic excursion | measurements based on CGMS | 3-hour study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dual-wave bolus, square bolus, normal bolus, standard bolus, high-protein meal, prandial insulin requirement