Time Limited Eating in Adolescents With Type 2 Diabetes

Summary

Participation Requirements

Description

The implementation steps of the proposed RCT are as follows: The staff will introduce the study to all eligible participants either in person or virtually and consent interested families for the study. All participants and their families will receive training on the use and application of the CGM. A...

The implementation steps of the proposed RCT are as follows: The staff will introduce the study to all eligible participants either in person or virtually and consent interested families for the study. All participants and their families will receive training on the use and application of the CGM. All equipment will be distributed to the participants, who will download the CGM app onto their smartphone and set up an account with a pseudonym. All participants will wear the CGM for a 7-day period prior to being randomized. All participants and their families will receive standard nutritional counseling promoting low added sugar and carbohydrate intake (Healthy Eating through Reduction of Excess Sugar (HEROES) intervention R01 MD010358-A1) and will be randomized to one of two meal-timing schedules at week 0: (a) Control: 12-hour eating window; (b) TLE: 8-hour eating period (16 hours of daily fasting 5 days per week). Participants will be randomized 1:1 via stratified, blocked randomization to ensure the groups are balanced in terms of number of participants and the distribution of potential confounding variables including sex, age, and ethnicity. Block size will be blinded from the PI performing the study. During the eating window, participants will not be required to count calories or monitor food intake in any way. Participants will choose and pay for their own food during the intervention. All participants will record their eating window daily and submit it to the study staff via email. All participants will receive standard advice for physical activity, and screen and sleep time as per the American Academy of Pediatrics age appropriate recommendations. The study staff will conduct study assessments of participants at weeks -1, 0, 1, 4, 8, and 12. Based on institutional research restrictions, these visits will either be conducted in-person or virtually via a HIPAA compliant platform. The study staff will perform weekly phone encounters with the participants to assess barriers to adherence and review CGM data. The study staff will record any medication changes or health encounters that have occurred in the last 7 days. The PI and research team will complete and oversee data management and analysis. Intervention Components Dietary counseling low added sugar and carbohydrate (all participants): The dietary counseling is modeled after the Healthy Eating through Reduction of Excess Sugar (HEROES) intervention (NIH R01 MD010358-A1), which is currently used by Dr. Michael Goran's lab at CHLA as a method to reduce added sugar intake in diets of youth with fatty liver disease. The intervention consists of recommendations for low added sugars (approximately equal to 5% of daily energy for a teenager and roughly equivalent to the American Heart Association and World Health Organization recommendations for patients with T2D) and a moderate carbohydrate-restricted (<100 grams per day) daily diet. Added sugars consumed from juices are included in the recommended daily amount; however, sugars from whole fruit or sugar in regular unsweetened milk and dairy are not. No specific caloric restriction will be recommended, and participants will not be required to keep logs of daily consumption. They will be provided with culturally appropriate, general recommendations for low sugar and low carbohydrate food options to reference. Time-Limited Eating (TLE): This intervention arm will involve TLE, in which participants are instructed to only eat from 11 AM to 7 PM for 5 days per week and to consume food within their habitual eating period for the remaining 2 days per week. The investigators conducted a cross sectional analysis of a cohort of 100 adolescents with obesity and found that most total calories, carbohydrates, and added sugars were consumed between 11 AM and 7 PM (Vidmar AP, Raymond JK, Goran MI, 2020, Pediatr Obes, under review). Therefore, to align with the normal developmental eating patterns seen in adolescents, the investigators will implement an afternoon/evening-based TLE approach. Participants will be allowed to consume non-caloric beverages (water, tea, coffee) during the fasting period. No energy restriction will be used, but participants will be given the low added sugar/carbohydrate guidelines described above. All participants will be asked to record their eating windows daily. Control: The control arm will involve no mealtime restrictions. Participants will be instructed to consume food over a 12-hour or more eating window. No energy restriction will be used, but participants will be given the low added sugar and carbohydrate guidelines described above. All participants will be asked to record their eating windows daily and submit to the study staff. Exercise: No structured exercise intervention will be included. However, regular physical activity is encouraged, consistent with guidelines for T2D management in youth.71 Participants will complete the Physical Activity Questionnaire throughout the study period to monitor physical activity. Continuous Glucose Monitor: Participants will wear Dexcom G6 continuous glucose monitors (CGM, Dexcom, San Diego, CA, USA) continuously for 13 weeks (week -1 to week 12). All participants will be blinded to CGM for seven days prior to commencement of the dietary intervention for baseline data collection, and then randomized to either TLE or control. Participants and their family member will be educated on the use of the Dexcom G6 Mobile CGM system at the first visit. Participants will receive training on the system using prepared training materials. All initial sensor insertions will be performed at the clinic by participants and/or family member, under the supervision of the study team, using the automated sensor applicator. The sensor will be changed every 10 days. Diurnal glucose profiles derived from interstitial fluid readings performed every 5 minutes over back-to-back 10-day cycles for 91 days will be collected using the CGM device. The CGM data will be uploaded to the cloud platform, Clarity, into a research clinic group to be reviewed by the research team. The Dexcom app will be downloaded to the participants and family members' personal smart phone and an account will be created with a pseudonym of the subjects' choice. Measurements: The study team will conduct all assessments at week -1, 0, 4, 8 and 12. All data will be collected and stored in REDCap. Primary Outcomes Quantifying glycemic control: Using a CGM, the investigators will capture glucose readings every 5 minutes and obtain the percent time in range (TIR: defined as glucose levels from 70 mg/dL to 180 mg/dL72) for the 7 days prior to the intervention period compared to the last 7 days of the intervention period between groups. HbA1c will be measured using a DCA 2000 (Bayer Corporation, Elkhart, IN) and compared pre- and post- intervention between groups. Quantifying change in ?-cell function: To improve participant burden and decrease project cost, the modified MMTT will be utilized.83 Therefore, the investigators will evaluate the effect of TLE on changes in C-peptide and insulin levels measured after MMTT. The MMTT will be performed at weeks 0 and 12. The MMTT will occur after an overnight fast. Participants will be instructed to not take their Metformin for 48 hours prior to their MMTT. Following baseline sampling (0 min), a test meal (470 kcal, ?66% carbohydrate, 18% fat, and 16% protein) composed of one 8-fluid-ounce Boost nutrition supplement drink (Nestlé Health Science) and one Power Bar (Nestlé Nutrition) will be administered. The meal will be consumed within 10 min, with the bar consumed first and repeat sampling for C-peptide, glucose and insulin levels performed at 60-, 90- and 120- minutes post-meal. Baseline plasma C-peptide concentration divided by the baseline plasma glucose concentration will be calculated as a pragmatic marker of ?-cell function. Secondary Outcomes Quantification of total body fat percentage: Using a Hologic QDR 5400 densitometer (Hologic, Inc., Bedford, MA) DEXA scan, the investigators will measure TBF% change at 12 weeks compared to baseline. The results will be reported as fat mass (kg) and TBF%. Quantification of liver fat fraction: Change in visceral and liver fat will be measured by MRI-PDFF. Participants will undergo MRI screening examinations at baseline and 12 weeks using an advanced magnitude-based spoiled-gradient-echo MRI-PDFF estimation technique previously validated to measure hepatic steatosis in children.84-86 Participant's weight change: Height and weight will be assessed at all in-person visits with the study team for all participants. Height will be measured using a Quick Medical stadiometer, accurate to 0.1 cm (Quick Medical, Issaquah, WA). Weight will be measured on a self-calibrating Mobile Stand Digital Scale, accurate to 0.1 kg. Participants will wear minimal clothing during the height and weight measurements. BMI will be calculated as kilograms per meter squared from which zBMI and percent over the 95th percentile (%BMIp95) will be determined utilizing the CDC growth charts. Nutrient Data System Recall (NDSR) 24 Hour Dietary Recall: Twenty-four-hour dietary recalls will be conducted for all participants at 3 time points throughout the study. For the control group, one weekday and one weekend day will be collected. For the TLE group, one TLE day and one non-TLE day will be collected. One recall will be completed at each study visit, in-person, for the day prior to the visit and the second recall will be completed over the phone to ensure the recalls are capturing the 24-hour period prior to completion of the recall. Psychosocial and Behavioral Metrics of Disease: Participants will complete a battery of self-reported questionnaires, described below. Pediatric Quality of Life Scale (PedsQL): Quality of life will be measured utilizing the Pediatric Quality of Life Scale (PedsQL) which is a 10-item questionnaire designed to assess quality of life parameters for youth under 19 years of age. The PedsQL is a brief, standardized, generic assessment instrument that systematically assesses patients' and parents' perceptions of health-related quality of life (HRQOL) in pediatric patients. The PedsQL is based on a modular approach to measuring HRQOL and consists of a 15-item core measure of global HRQOL and eight supplemental modules assessing specific symptom or treatment domains. Patient Reported Outcomes Measurement Information System (PROMIS®): Physical Activity: The Physical Activity Questionnaire component of PROMIS® will be utilized to evaluate self-reported levels of physical activity in all study participants. PROMIS® pediatric instruments have been developed and validated to assess domains of health in children less than 18 years of age. Binge Eating Disorder Screener (BEDS): Given that adolescents with obesity and T2D are at high risk of binge-eating disorder (BED) symptoms; our goal is to screen participants at baseline to ensure appropriate referrals are made in a timely manner.

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