Impact of Meal Timing on Glycemic Profile in Latino Adolescents With Obesity
Condition: Pediatric Obesity; Meal Timing
MeSH terms: Obesity; Pediatric Obesity
Study type: Interventional

Summary: 
      In adolescents, conventional obesity treatment comprehensively addresses nutritional,
      activity, and behavioral topics. Due to limited resources in historically marginalized
      communities, implementation of nutrition-based interventions that require easy access to
      fresh food and ability to change the home environment is difficult, which may exacerbate
      health disparities. It is critical to find nutrition strategies and recommendations that are
      impactful, sustainable, and cost effective across all communities. There is growing interest
      in time-based interventions focusing on "when" food is consumed rather than on prescribed
      macronutrient composition. Time-restricted eating (TRE) is a type of meal-timing which
      involves fasting for at least 14-hours per day and eating over a 10-hour eating window
      initiated in the morning, mid-day, or afternoon. TRE recommendations are simple in merely
      dictating when eating occurs and thus may represent a more straightforward approach for
      adolescents than other caloric restriction regimens relying on numeracy (kilocalories and
      macronutrients) and goal setting. In adults, early-day TRE has been shown to reduce body
      weight, fasting glucose, and insulin resistance. By contrast, restricting food intake to the
      evening has produced mostly null results or even worsened post prandial glucose levels and
      β-cell responsiveness. To date, there has been no trial comparing early vs. late TRE on
      glycemic profiles in adolescents, and it is unclear how meal-timing impacts glycemic profiles
      in youth. The optimal timing of food intake for adolescents may be very different than adults
      due to increasing sex steroids and growth hormone levels overnight which may contribute to
      increased insulin resistance in the early morning. The proposed proof-of-concept study
      addresses this question by measuring metabolic response to a test meal consumed in the
      morning, afternoon, and evening among 30 adolescents with obesity using a within participant
      design. These findings will provide the needed research base for the refinement of TRE
      interventions in adolescence.
    

Detailed description: 
      The prevalence of type 2 diabetes in adolescents is steadily increasing, specifically among
      Latino youth. Unfortunately, there is a lack of effective preventative treatments available
      to delay the progression to type 2 diabetes in youth living with obesity and pre-diabetes.
      Specifically, it is challenging for many adolescents to maintain adherence to multicomponent
      interventions resulting in high attrition which then decreases efficacy. There is growing
      interest in time-based interventions focusing on "when" food is consumed rather than on
      prescribed macronutrient composition. In the adult population there has been increasing
      evidence that time-restricted eating (TRE), which consists of limiting daily food intake to
      an 8 to 10-hour period or less may improve insulin sensitivity and β-cell responsiveness.
      However the results of TRE in adults appear to depend on when eating occurs. Early TRE (last
      eating event prior to 16:00) has been shown to reduce body weight, fasting glucose and
      insulin, and insulin resistance. However, restricting food intake to the evening produced
      mostly null results or worsened post prandial glucose level. One possible explanation is that
      consuming food early in the day synchronizes the central and peripheral circadian clocks
      involved in energy expenditure and fat oxidation and minimizes glycemic excursions and
      endogenous glucose production via enhanced insulin secretion. It has been proposed that the
      enhanced insulin secretion may be secondary to corresponding diurnal variations in the
      release of incretin hormones such as glucagon, glucagon-like-peptide-1 (GLP-1),
      glucose-dependent insulinotropic polypeptide (GIP), and pancreatic peptide (PP).

      Because of its simplicity, TRE may represent a more feasible approach for adolescents than
      other caloric restriction regimens. Our team recently conducted the first study examining the
      feasibility of TRE in adolescents with obesity. In this study, fifty adolescents were
      randomized to a self-selected 8-hour TRE compared to a prolonged eating window. TRE was found
      to be feasible, safe, and acceptable but there was no difference in glycemic profiles or
      weight loss between groups. These null findings may be due to the late eating window that was
      selected. To date, there have been no trial comparing early vs. late TRE on glycemic profiles
      in adolescents and it is unclear how meal-timing impacts glycemic profiles in youth. It
      remains unknown how the timing of meal consumption directly effects glycemic profiles and
      cardiometabolic endpoints in this age group. Thus, to address this question, in our
      proof-of-concept study, the investigators aim to measure glycemic and metabolic responses to
      a test meal (controlled for macronutrient profile and caloric amount) at various meal-timings
      (early vs. afternoon vs. late) in thirty Latino adolescents (ages 13-19 years), with obesity,
      without diabetes. All participants will consume three standard test meals administered in
      random order at different times of day over a two-week period: (1) Early: test meal consumed
      at 8 AM; (2) Afternoon: 12 PM; (3) Late: 4 PM. Test meals will be consumed on different days
      at least three days apart after a minimum of a 16-hour fasting period. A continuous glucose
      monitor (CGM) will be placed on the participant for the duration of the 2-week period. The
      primary endpoints will be frequently sampled glucose, insulin, and c-peptide area under the
      curve (AUC) collected after consumption of a standard test meal, insulinogenic index (IGI:
      change in insulin/change in glucose over the first 30 min after the load), and glucose
      variability as captured by percent time in range on CGM. The investigators hypothesize that
      adolescents with obesity will have reduced AUC and IGI following the later meals compared to
      the early meal. The investigators will test these hypotheses with the following aims:

      Aim 1: Identify how timing of meal consumption after a prolonged 16-h fast affects glucose
      and insulin response in Latino adolescents with obesity. The investigators will measure
      insulin secretion, clearance rates, and sensitivity assessed with a) 3-h frequent sampling of
      glucose, insulin, and c-peptide post meal, b) calculated insulinogenic index, and c) percent
      time in range measured by CGM. The investigators expect that meal consumption at 12 and 4 PM
      will be associated with lower post prandial glucose excursions, decreased AUC and IGI, and
      increased percent time in range compared to that same meal consumed at 8 AM.

      Aim 2: Examine the association between timing of meal consumption and incretin and pancreatic
      hormones in Latino adolescents with obesity. The investigators will collect frequent sampling
      of glucagon, total GLP-1, GIP, and PP concentrations post-meal to explore how diurnal
      variation in these hormones impact insulin sensitivity. The investigators expect that meal
      consumption at 12 and 4 PM will in greater change in incretin and pancreatic hormones
      concentrations compared to that same meals consumed at 8 AM.

      Future Direction: The data collected during this pilot will inform the design of a randomized
      clinical trial to test the feasibility, safety, and efficacy of early vs. late TRE in
      adolescents with obesity to reduce glycemic and insulin response for the prevention of type 2
      diabetes.
    

Intervention name(s): Meal-timing
Intervention type(s): Other
Intervention description(s): We propose a cross-over, proof-of-concept study to measure glycemic and metabolic responses to a test meal (controlled for macronutrient profile and caloric amount) administered at various times of the day (early vs. afternoon vs. late) in thirty Latino adolescents (ages 13-19 years), with obesity, without diabetes, to determine how timing of eating impacts glycemic response to the test meal after a 16-h fasting period. All participants will consume three standard test meals administered in random order at different times of day over two-weeks: (1) Early: test meal consumed at 8 AM; (2) Afternoon: test meal consumed at 12 PM; (3) Late: test meal consumed at 4 PM. A continuous glucose monitor (CGM) will be placed on the participant for the duration of the 2-week period. Baseline and post-meal samples will be assayed for glucose, insulin, c-peptide, GLP-1, GIP, PP at times -10, -5, 0, 10, 20, 30, 45, 60, 90, 120, 150 and 180 minutes after glucose.
Intervention model: Single Group Assignment
Intervention model description: proof-of-concept study to measure glycemic and metabolic responses to a test meal (controlled for macronutrient profile and caloric amount) administered at various times of the day (early vs. afternoon vs. late) in thirty Latino adolescents. All participants will consume three standard test meals administered in random order at different times of day over two-weeks: (1) Early: test meal consumed at 8 AM; (2) Afternoon: test meal consumed at 12 PM; (3) Late: test meal consumed at 4 PM. A continuous glucose monitor (CGM) will be placed on the participant for the duration of the 2-week period. Baseline and post-meal samples will be assayed for glucose, insulin, c-peptide, GLP-1, GIP, PP at times -10, -5, 0, 10, 20, 30, 45, 60, 90, 120, 150 and 180 minutes after glucose. The primary endpoints will be glucose, insulin, and C-peptide area under the curve, insulinogenic index, and glucose variability as captured by percent time in range on CGM following the test meal.
Masking: None (Open Label)
Primary purpose: Other