Effect of Splitting Mealtime Insulin Doses After Mixed Meals High in Fat and Protein
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 4

Summary: 
      The current management of type 1 diabetes mellitus (T1DM) depends on the use of intensive
      insulin therapy - either by insulin pump therapy or multiple daily injection (MDI) therapy -
      and the use of carbohydrate counting to determine the mealtime bolus insulin dose according
      the carbohydrate contents of each meal or snack. However, several studies reported that the
      fat and protein contents of the meals can also affect the postprandial blood glucose levels
      and result in delayed postprandial hyperglycemia especially after high fat and protein meals.

      There is no widely accepted regimen to calculate insulin required for the fat and protein
      contents of meals especially for patients using multiple daily injection regimen. This study
      aims to find a better method to cover the increased insulin requirements following mixed fat
      and protein meals. The study will compare the effect of splitting mealtime bolus insulin
      doses into pre-meal and post-meal portions to the standard regimen which involve giving bolus
      dose depending on carbohydrate content only with additional correction doses 2 to 3 hours
      after the meal to compensate for the postprandial hyperglycemia induced by fat and protein
      content of the meals.
    

Detailed description: 
      The study will include children and adolescents aged 6 - 18 years, diagnosed with T1DM for at
      least 1 year, using multiple daily injection regimen and carbohydrate counting. The study
      participants will be admitted at the pediatric department, Sohag University Hospital for 1
      week to adjust insulin doses. adjustments will be made to basal doses, insulin to
      carbohydrate ratio (ICR), insulin sensitivity factor (ISF) if required.

      The study participants will have three test lunch meals on 3 consecutive days consumed at the
      pediatric department, Sohag university hospital at 12 PM. The test meals will consist of two
      slices of a deep pan pizza base topped with tomato sauce, mozzarella full fat soft cheese,
      and minced beef. (weight: 150 g, carb. 40 g, fat: 15 g, protein: 20 g, total calories 360
      kcal). The meal will be consumed within 20 minutes.

      Blood glucose level before the meal should be between 80 to 150 mg/dl. Correction doses can
      be given 3 hours before the test if needed to bring the blood glucose level to the desired
      target range before the test meals.

      The participant will be assigned to use each one of the following interventions on a separate
      day in a random sequence.

        -  Intervention A: the participant will have a mealtime bolus dose of fast-acting insulin
           10 minutes before the meal representing 100% of the dose calculated according to the
           carbohydrate content of the meal and the individual insulin to carbohydrate ratio (ICR).
           If hyperglycemia (blood glucose level >180 mg/dl) developed after 3 hours, the
           participant will receive an additional correction dose of fast-acting insulin calculated
           according to the individual insulin sensitivity factor (ISF).

        -  Intervention B: the bolus insulin dose for the meal will be calculated according to the
           carbohydrate content of the meal and the individual insulin to carbohydrate ratio (ICR)
           and additional 30% of the calculated dose will added to cover the fat and protein
           content of the meal. This total dose will be divided into 2 portions. A premeal portion
           (60% of the total dose) will be given 10 minutes before the meal. The remaining 40% of
           the total dose will be given 30 minutes after the premeal dose. Both doses will be given
           as fast-acting insulin.

        -  Intervention C: the bolus insulin dose for the meal will be calculated according to the
           carbohydrate content of the meal and the individual insulin to carbohydrate ratio (ICR)
           and additional 30% of the calculated dose will added to cover the fat and protein
           content of the meal. This total dose will be divided into 2 portions. A premeal portion
           (60% of the total dose) will be given 10 minutes before the meal as fast-acting insulin.
           The remaining 40% of the total dose will be given 30 minutes after the premeal dose as
           regular insulin.

      Types of insulin: insulin lispro (Humalog 100 IU/mL) as fast-acting insulin and regular
      insulin (Humulin R) as regular insulin (Eli Lilly and Company, Indianapolis, IN, USA).
      Insulin doses will be calculated, splitted, approximated to the nearest 0.5 unit and given
      using Humapen Luxura half- unit increments insulin pens.

      Capillary blood glucose level will be measured by a calibrated finger-prick blood glucose
      meter before the meals and every hour for the next 6 hours after the test meals. Moreover,
      venous blood glucose and serum cholesterol and triglycerides levels will be measured 3 hours
      after the test meals.
    

Intervention name(s): : Insulin, lispro and regular insulin
Intervention type(s): Drug
Intervention description(s): A: the participant will have a mealtime bolus dose of fast-acting insulin 10 minutes before the meal representing 100% of the dose calculated according to the carbohydrate content of the meal and the individual insulin to carbohydrate ratio
B: the bolus insulin dose for the meal will be calculated according to the carbohydrate content of the meal and the individual insulin to carbohydrate ratio and additional 30% of the calculated dose will added to cover the fat and protein content of the meal. This total dose will be divided into 2 portions. A premeal portion (60%) will be given 10 minutes before the meal and (40%) will be given 30 minutes after the premeal dose. Both doses will be given as fast-acting insulin.
C: the same as intervention B but the 40% of the total dose will be given as regular insulin.
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment