High-resolution lifestyle profiling and metabolic subphenotypes of type 2 diabetes

Distinct metabolic susceptibilities (beta-cell dysfunction, insulin resistance (IR), and impaired incretin response) underlie type 2 diabetes (T2D). However, their relationships with habitual lifestyle behaviors are underexplored. This study integrated high-resolution lifestyle data from wearable devices, continuous glucose monitoring, and smartphone-based food logs with gold-standard physiological tests in 36 individuals at risk for T2D (ClinicalTrials.Gov; NCT03919877; 2019-04-18). Over 6400 timestamped records of diet, sleep, and physical activity were analyzed with in participants with measures of beta-cell function, tissue-specific IR (muscle, hepatic, adipose), and incretin response. We found that lifestyle timing and variability were strongly associated with metabolic subphenotypes: (1) eating timing was associated with muscle IR and incretin function; (2) irregular sleep correlated to IR and incretin function; and (3) Time-of-day effects of physical activity varied by subphenotype. These findings were validated in an independent cohort. Our results highlight novel physiological links between daily behaviors and metabolic risk, informing potential lifestyle modifications for T2D prevention.