Exercise Snacks and Glutamine to Improve Glucose Control in Adolescents With Type 1 Diabetes

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

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.

Diabetes Mellitus, Type 1, Autoimmune Diseases, Diabetes Mellitus, Endocrine System Diseases, Glucose Metabolism Disorders, Immune System Diseases, Metabolic Diseases

Continuous Glucose Monitoring, Children, Exercise, Glycated hemoglobin, Adolescents, Insulin sensitivity, Glutamine

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);

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

MAGE describes the average amplitude of glycemic variations measured using continuous glucose monitoring (CGM)

Change in insulin sensitivity score, determined using SEARCH ISS model published equation: logeIS = 4.64725 - 0.02032 × (waist, cm) - 0.09779 × (HbA1c, %) - 0.00235 × (Triglycerides, mg/dL). The range of ISS scores is between 1-15. Higher scores imply a better insulin sensistivity.

Inclusion Criteria: Type 1 diabetes for >12 months Age between 13 and 19 years Males and females at Tanner stage 4 and 5 All insulin programs, including intermediate,short acting insulin, Lantus, Detemir and short acting insulin or insulin pump therapy. Weight of 40 kilograms or higher. Hemoglobin A1C between 7%-10% and total daily insulin dose at least 0.9 unit/kg/day. BMI between 10 centile to less than 95 percentiles. Patients on stable thyroid replacement therapy will be allowed to participate. Exclusion Criteria Celiac disease. Cystic Fibrosis Chronic steroid therapy Chronic medications that may interfere with glucose metabolism or liver function. History of mental retardation Presence of diabetic complications Being pregnant or having positive pregnancy test at any time during the study. Presence of significant anemia (hemoglobin less than11 g/dL) Presence of intercurrent infection Subjects involved in an active exercise program or in an organized sport team

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