David S. Ludwig

Study objectives: Sleep duration influences metabolic health, but the impact of daily sleep variation on next-day glycaemia in healthy individuals under real-world conditions is poorly understood. Materials and methods: We studied 206 adolescents (18 years) from the Copenhagen Prospective Studies on Asthma in Childhood 2000 cohort with 2245 person-days of overlapping accelerometer-derived sleep and continuous glucose monitoring recordings (median 13 days, IQR 9-13). Sleep duration was assessed using wrist-worn accelerometry, and glycemic concentration, variability, and risk indices were derived from continuous glucose monitoring during the accelerometer-defined waking period. Associations were examined using linear mixed-effects models adjusted for sociodemographic, behavioral, circadian, and cardiometabolic factors, with random effects of individuals across repeated days. Results: Each additional hour of sleep was associated with higher next-day glycaemic concentration (median β 0.39 mg/dL [0.15, 0.63], p = .002), lower variability (standard deviation (SD) mg/dL β −0.12 [−0.23, −0.01], p = .036), and reduced deviation risk (Average Daily Risk Range, indicating lower risk of extreme glucose excursions; β −0.27 [−0.43, −0.10], p = .002). Within-person deviations in sleep predicted next-day glycaemic concentration and deviation risk, whereas habitual between-person differences were more strongly associated with variability. Higher daytime glycaemic variability predicted shorter subsequent sleep (β −0.11 h [−0.18, −0.05], p < 0.001). The early-morning pre-wake glucose rise partly mediated the link between longer sleep and higher next-day median glucose (indirect effect 5.0%, p = 0.036). Conclusions: These findings indicate dynamic, bidirectional coupling between sleep and glucose regulation in free-living adolescents, with longer sleep associated with lower next-day glycemic variability and reduced risk of extreme glucose excursions. Statement of Significance Adolescence is a critical period for establishing lifelong sleep and metabolic health patterns, yet real-world links between nightly sleep and glucose regulation remain poorly defined. This study combines accelerometer-derived sleep with continuous glucose monitoring across repeated free-living days in 206 generally healthy adolescents. Wake-anchored analyses showed that longer sleep was associated with modestly higher next-day glycemic concentration, but lower glycemic variability and deviation risk, while greater daytime variability predicted shorter subsequent sleep. A pre-wake glucose rise partly mediated the association between sleep duration and next-day glycemia, suggesting that the transition from sleep to wake may be an important physiological window linking sleep with metabolic regulation.

“[A]s good a clinical trial as you can get” (Wilson 2020), “the most important study ever done to explain weight gain” (Nestle 2024), and “worse than worthless” (Khullar 2025). These sharply diverg...

A recent lawsuit against "hyper-palatable" ultra-processed foods has amplified controversies over its effects on obesity-related chronic disease. Addressing this public health crisis requires a new framework, centered on the metabolic effects of food.

Diet plays a crucial role in health, with low-carbohydrate diets often proposed to exert metabolic benefits. We aim to investigate metabolomic adaptations in 164 adults with overweight or obesity who were randomly assigned to high- (n = 54), moderate- (n = 53), or low-carbohydrate (n = 57) diets during a 20-week weight-loss maintenance phase of the Framingham State Food Study [(FS)2], a controlled, parallel feeding trial (ClinicalTrials.gov: NCT02068885). We measure fasting plasma metabolites by liquid chromatography-tandem mass spectrometry using samples from 147 participants who completed the study (n = 45, 48, and 54 in the high-, moderate-, and low-carbohydrate diet groups, respectively). Significant associations (False Discovery Rate<0.05) are identified between carbohydrate-to-fat ratio (CFR) and diet-induced changes in 148 of 479 metabolites at 20 weeks, with nearly all showing consistent trends at 10 and 20 weeks. Phosphatidylcholines plasmanyls/plasmalogens, phosphatidylethanolamines plasmanyls/plasmalogens, and sphingomyelins generally decrease with higher CFR, whereas lysophosphatidylcholines, lysophosphatidylethanolamines, and triglycerides generally increase. Our findings are largely reproducible in an independent feeding trial involving diets with similar CFR (Popular Diets Study, ClinicalTrials.gov: NCT00315354). Eleven triglyceride species (≤3 double bonds), linked to type 2 diabetes risk, increase with higher CFR. Our findings demonstrate metabolomic changes caused by varying CFR dietary patterns, offering potential insights into mechanisms that could guide targeted dietary intervention strategies.