Exercise Snacks and Glutamine to Improve Glucose Control in Adolescents With Type 1 Diabetes
Condition: Diabetes Mellitus, Type 1; Autoimmune Diseases; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Immune System Diseases; Metabolic Diseases
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases
Study type: Interventional

Summary: 
      This project will assess the feasibility and efficacy of the use of exercise and dietary
      supplementation with a non essential amino acid - glutamine - a component of most protein
      supplements, on the regulation of plasma glucose homeostasis in a clinical setting of
      children with type 1 diabetes (T1D). The study specifically targets patients in puberty as
      this period is associated with a physiological decline in insulin sensitivity, the latter
      often associated with poor control. Although physical exercise has long been known to exert
      beneficial effects on metabolism, lack of time is the most common reason perceived as
      preventing the performance of exercise in both healthy and diabetic subjects. In earlier
      studies, the investigators showed that oral supplementation with glutamine, a non essential
      amino acid given prior to exercise decreases overnight post-exercise blood glucose in
      adolescents with T1D. Hence, the objective of the current study is to investigate if a novel
      way of exercising, such as performing 6 short bouts of just 1 min each of intense exercise
      ('exercise snacks') 30 min before meals, with or without glutamine, improves glycemic control
      in adolescents with T1D. Designing innovative ways to improve diabetes control in adolescents
      is highly desirable. The specific aim of the project is to determine whether the sustained
      use of the proposed exercise snacks with or without glutamine results in diminished glycemic
      variability and/or improved glucose control
    

Detailed description: 
      This protocol will help determine whether 'exercise snacks', alone or in combination with
      dietary glutamine improves diabetes control in adolescents with type 1 diabetes.

      All subjects for group A and B will have a full physical exam including Tanner staging as
      well as waist circumference measurement. A HbA1c, will be obtained as well as fasting
      triglycerides. A continuous glucose monitor (CGM IPro®, Medtronic Minimed, or a DexCom ^4)
      will be worn blindly for 6 days and data downloaded. Subjects will then be randomized to 2
      study groups of 12 patients each:

      (A) an 'exercise group', in which subjects will perform daily 'exercise snacks' within 30 min
      before breakfast, lunch, and/or dinner or bedtime snack, along with a placebo drink which
      will be given before breakfast and dinner (twice daily); (B) an 'exercise + glutamine group',
      in which subjects will receive a glutamine drink (0.25 g/kg per dose) before breakfast and
      dinner (twice daily), and perform 'exercise snacks' before each meal.

      Randomization to the exercise + placebo or the exercise + glutamine group or no exercise+ no
      glutamine supplements will be stratified according to HbA1c range (eg, 7.0-7.4%; 7.5-8.0 %;
      8.4-9.0%;9.5-10%), so as to ensure the comparability of groups.

      The placebo and glutamine drink will be prepared at home using measured doses of glutamine or
      placebo powder to be mixed in a calorie-free, flavored soft drink tailored to the child's
      individual taste. Patients, families and investigators will be blinded as to the contents of
      the supplement. Exercise snacks will be designed to be feasible using 6 min worth of simple
      resistance activities (SRA's) designed by the exercise physiology consultants, Drs. Churilla
      and Hawley. They may spread them throughout the day if needed. These will consist of
      activities such as alternating half-squats, calf raises, brief gluteal contractions and knee
      raises by using stretching bands. The tension of bands may be adjusted as needed during the
      study. A short video has been created showing the participants how to conduct these exercises
      and these will be updated periodically in order to keep their interest and compliance. An
      accelerometer will not be used given the short nature of these bouts of exercise. These will
      be completed 30 min before breakfast, lunch and dinner.

      Patients of group A +B will keep a record of their dietary intake and physical activity for 2
      days while CGM is placed (one weekday+ one weekend day) at baseline, during the first week
      after study initiation and at 1,and 3 months during the study. If the family has a smart
      phone, a free application will be installed which is "My diet diary calorie count " for
      better assessment of total caloric intake during this study. Otherwise, a log book would be
      used. Dietary records will be examined to ensure that potential improvement in glucose
      control is not due to alterations in dietary intake, such as inadvertently switching to a
      diet composed of foods with a lower glycemic index. Compliance will be monitored by weekly
      contact with the study subjects either via phone call or text messaging or via MyNemours.
      Each participant will also be given a script with the following questions based on the group
      assignment:

        -  How many times have you drank your glutamine before meals during the last week?

        -  How many times have you performed exercise snacks before meals during the last week? In
           addition, subjects will be asked to check their blood glucose before meals, at bedtime
           and twice a week around midnight. They will be also asked to record their pulse rate
           three times weekly at bedtime. A spread sheet will be also provided to each patient for
           daily documentation of exercise performance and glutamine consumption or text us the
           results. The number of blood glucose measured per day prior and during the study will be
           recorded to determine if the compliance with BG checking has increased during the study.

      CGM will be placed during the first week after the study initiation, then at one month visit
      after the enrollment, for 6 days, then all baseline studies, including CGM, HbA1c and
      triglycerides will be repeated at 3 months. Every patient will undergo a body composition
      analysis using a dual X-ray absorptiometry (DEXA) at the beginning and the end of the study
      to express the changes in insulin sensitivity both per kg as well as per kg of fat free mass
      (FFM).Total insulin dosing will be carefully recorded as units/kg/day during the study.
    

Intervention name(s): Glutamine vs. Placebo; Exercise
Intervention type(s): Drug; Behavioral
Intervention description(s): oral supplementation with either glutamine or placebo twice daily for 3 months; short bouts of exercise ('exercise snacks') 3 times daily for 3 months
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Continuous Glucose Monitoring; Children; Exercise; Glycated hemoglobin; Adolescents; Insulin sensitivity; Glutamine