OR34-05 Second Phase Insulin Secretion Varies By Time Of Day And Body Mass Index
Authors: Naaman Sandra , Sintetas Stephanie , Van Cauter Eve , Hanlon Erin C 
Published: October 2023

Disclosure: S. Naaman: None. S. Sintetas: None. E. Van Cauter: None. E.C. Hanlon: None.

Diurnal variation in insulin secretion (ISR) is documented in healthy adults with and without obesity. However, in previous studies, the caloric content of meals varied across the day or the analysis focused solely on morning versus evening differences. It remains unclear if dietary intake timing is associated with metabolic response differences to the same dietary challenge if presented across a full day in individuals categorized as lean (L), with overweight (OW) or obesity (OB). Thus, we examined ISR following consumption of identical meals, equally spaced across the day, in a lab setting with controlled sleep and energy expenditure. Our study included 74 individuals; 41 lean (19 women), 14 overweight (4 women), and 19 obese (14 women). Obstructive sleep apnea (OSA), a known confounder of glucose metabolism, was an exclusion criterion. Mean age between groups was similar (L, 25.2 ± 5.3yrs vs OW, 27.0 ± 6.6yrs vs OB, 32.2 ± 7.6yrs). BMI was 38 ± 5.9 kg/m2 in the OB, 27 ± 1.2 kg/m2 in the OW, vs 22 ± 1.8 kg/m2 in the L groups, respectively (p &lt; 0.0001). We collected blood samples continuously at regular intervals over a 24hr period in which participants ate isocaloric identical high carbohydrate meals (20% fat, 68% carbohydrate, 12% protein) at 0900, 1400, and 1900; each meal was 33% of total caloric intake. Serum C-peptide was measured using high-sensitivity chemiluminescence assays (Immulite). ISR was derived from plasma C-peptide levels by mathematical deconvolution using a two-compartment model for C-peptide clearance. Each profile was expressed as a percentage of individual 24hr mean ISR to examine the profile wave shape independently of individual differences in mean ISR. We examined 2 phases of ISR following meal ingestion; 1st phase (AUC, 0 - 1.5hrs) and 2nd phase (AUC, 1.5hrs - 3.5hrs). The profiles were analyzed with ANOVA for repeated measures with participants as a random factor and mealtime, group (L, OW, OB), and interaction “mealtime by group” as fixed effects. Despite 3 equally spaced identical meals, significant differences emerged. Irrespective of BMI, 1st phase relative ISR was similar across breakfast, lunch and dinner. Second phase relative ISR, however, revealed significant time of day effects; with midday eliciting the highest relative ISR for all groups (p = 0.0002). Significant time x group effects emerged in the 2nd phase such that relative ISR varied across the day, differently for each group (p &lt; 0.0001). Specifically, 2nd phase relative ISR was lowest following dinner in those with obesity. This is the first study to compare 24hr profiles of ISR in healthy individuals at multiple BMI ranges, without OSA, in an experimental setting of 3 equally spaced identical meals. These findings imply that the midday meal elicits the highest ISRs, irrespective of BMI. Further, BMI impacts ISR across the day in response to identical meals. These findings have implications for obesity management.

Presentation: Sunday, June 18, 2023