What is the Dose Response of Varying Meal Content of Fat on Postprandial Glycaemia in Children With T1DM?
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      Background: Based on international evidence, current management of people with T1DM on
      intensive insulin therapy (IIT) use algorithms based on the meal carbohydrate content (MCC)
      to calculate the prandial insulin dose. Typically, these calculations do not take into
      account the protein or fat content of the meal. There is a lack of clinical advice for
      optimal management of high protein/fat meals due to a paucity of evidence regarding the
      impact of protein/fat on glycaemic control.

      Objective: To determine the mean glucose excursion from fasting (measured by continuous
      glucose monitoring, CGMS) at each 30 minute interval over the 8 hour postprandial period for
      each test condition. Protein effects will be looked at in a separate parallel study in
      Australia.

      Hypothesis: The fat content of a meal will cause a dose-response change in the postprandial
      glucose concentration in children with T1DM.

      Research Design and Methods: Randomised cross-over study involving thirty patients. Inclusion
      criteria: T1DM >1 year, aged 8-18 years, with HbA1c <8% and BMI <91st centile, on intensive
      insulin therapy. Participants will be given a test meal on 6 consecutive nights in random
      order; 4 test meals varying in fat content, and one 20g carbohydrate test meal with zero fat
      given as control meal. A CGMS will be used to assess glucose responses at 5 minute intervals
      for 8 hours after test meal consumption. The relationship between the fat loads in the test
      meals and the mean change in postprandial glucose concentration will be analysed and
      described.

      Conclusions: This study will determine whether fat causes dose dependent response in glucose
      concentrations leading to refining the guidelines and possible adjustment of insulin doses
      for the fat content of a meal.
    

Detailed description: 
      1. Aims of the project To determine the postprandial glucose dose-response curves response
           to varying fat amounts by studying various parameters (glycaemic excursion, rate of
           glucose level increase, area under the curve, percent time in target glucose range,
           maximal glucose excursion, time to maximal glucose excursion and time until the glucose
           level returns to fasting concentration) provided by continuous glucose monitoring over a
           6 day study period with a view to provide data to calculate an accurate insulin dosing
           schedule to account for varying dietary fat ingestion.

           Objective 1 To define the impact of varying quantities (dose) of fat on the
           post-prandial glucose concentrations i.e. determine the relationship between the fat
           load in the test meals and the mean change in postprandial glucose concentrations.

           Objective 2 To compare the impact of the varying fat quantities in the test meals each
           with a control carbohydrate snack (20g) without extra insulin.

        2. Protocol Participants will be contacted daily for one week prior to the study to review
           their overnight and fasting glucose concentrations and if necessary, adjust their
           insulin doses. The study will be carried out during a week long period for each patient.
           Participants will be given test meals over 6 consecutive days in random order, with 5
           test meals varying in lipid content and one carbohydrate (20g) test meal as comparator.
           A continuous glucose monitoring system (CGMS) will be inserted on the day of the first
           test meal and will be removed at the completion of the sixth night.

           To define the impact of lipid on the post-prandial glucose concentration, participants
           will consume a standardised meal at 18:00hours and receive a standard insulin bolus by
           injection or pump (using standard wave bolus if on insulin pump) based on the meal
           carbohydrate content. At 22:00 hours the participants will consume a lipid test meal
           dose (varying fat content of 2.5, 12.5, 25, 37.5, 50g) or carbohydrate snack 20g. The
           calculations of the fat doses have been based on the Pankowska algorithm [3] which
           recommends additional insulin for every 100 kcal fat or protein. There will be
           randomised order of test meals.

           Test meals will be formulated to be palatable, consumed within 5 minutes and to contain
           negligible carbohydrate, protein and fibre. A dietician will design the test meals in
           conjunction with the co-investigator in detail to ensure ease of formulation and
           practical administration.

           The lipid dose in test meals will be tested for acceptability and palatability to ensure
           adherence to protocol. The order of the test meal types/carbohydrate snacks will be
           random (computer generated randomisation). The comparator 20g carbohydrate snack has
           been included to assess the participant's typical glucose response to 20g of
           carbohydrate. No insulin will be given for the lipid or carbohydrate snacks.
           Participants will fast until breakfast.

        3. Outcomes Glucose concentrations will be measured at the start of the test meal and at 5
           minute intervals over the 8 hour postprandial period. Therefore, the data will consist
           of repeated measurements on the same individual within test meal loads as well as the
           same individuals across test meal loads.

      The primary outcome of interest will be the Area Under the Curve (AUC) of glucose
      concentrations during the post prandial 8 hours. Linear regressions, within a generalised
      linear mixed model framework, will be used to test for a dose response in AUCs with
      increasing size of fat means.
    

Intervention name(s): Test drink
Intervention type(s): Other
Intervention description(s): The intervention is a drink taken 4 hours after the evening meal insulin injection, or 10PM, whichever is later. All drinks are 116-120g in weight and similar volume.
All drinks are served in a double blind fashion, apart from the 20g carbohydrate which is visibly different from other drinks in colour, texture and flavour.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Lipid; Carbohydrate counting; Adolescent; Continuous glucose monitoring; Insulin requirements