JMIR Publications

ABSTRACT

Background:

Cortisol is the body's primary glucocorticoid hormone and is deeply involved in metabolism, immune regulation, and stress response. Small shifts in hormonal release dynamics may serve as early indicators of metabolic dysfunction, yet standard measurement approaches often miss fast-changing, tissue-level details. Understanding how adipose tissue processes cortisol across different body mass index (BMI) categories may open new avenues for early metabolic risk stratification.

Objective:

This study aimed to characterize free cortisol release dynamics in men grouped by BMI (normal weight versus overweight) using continuous subcutaneous tissue sampling, sparse-recovery deconvolution, and Bayesian hidden-state estimation adapted for cortisol physiology.

Methods:

Subcutaneous free cortisol readings from 23 age-matched men were collected using the U-RHYTHM portable hormone sampler at 20-minute intervals over a 24-hour period (72 samples per participant). Participants were classified as normal weight (BMI 18.5-24.9 kg/m²) or overweight (BMI ≥25 kg/m²) following National Institutes of Health (NIH) cutoffs. A three-compartment pharmacokinetic model combined with a sparsity-promoting signal extraction pipeline was used to recover cortisol burst events from raw tissue data. A Bayesian hidden-state estimator, adapted from a cognitive-arousal tracking framework, then mapped cortisol dynamics onto an energy-mobilization index. Two-sample t-tests assessed group differences at an α = .05 significance level.

Results:

Signal extraction achieved high fidelity (R²=0.9875). Burst count, amplitude, and energy (ℓ0, ℓ1, ℓ2 norms) were statistically indistinguishable between groups across all time windows and meal periods (P>.05). However, cumulative cortisol exposure (area under the curve [AUC]) was significantly higher in normal-weight men over 24 hours (P=.009), during sleep (P=.020), and during waking hours (P=.036). Peak and trough tissue concentrations were significantly higher in normal-weight men (P=.016 and P=.003, respectively). The tissue clearance rate constant (θ4) was significantly elevated in overweight men (P=.040). After breakfast, normal-weight men exhibited significantly higher energy mobilization (P=.040) and a higher High Energy Index (P=.036).

Conclusions:

Cortisol burst frequency and magnitude are preserved regardless of weight status, indicating that hypothalamic-pituitary-adrenal (HPA) axis pulsatility is not altered by moderate overweight. Differences in cumulative cortisol exposure, peak and trough levels, and tissue clearance rates point to a peripheral, tissue-level mechanism rather than a central one. These findings suggest that adipose tissue cortisol dynamics particularly clearance kinetics and post-breakfast energy mobilization may serve as early biomarkers for metabolic risk screening. The Bayesian hidden-state framework originally developed for cognitive-arousal tracking translates effectively to cortisol physiology.