Impact of Meal Timing on Glycemic Profile in Latino Adolescents With Obesity

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.