UC Berkeley

Two of the top killers of the human race are cardiovascular disease and type 2 diabetes. These diseases, which have shared etiology, collectively form the domain of cardiometabolic health. Multiple functions of cardiometabolic health are perturbed by impaired sleep, and conversely, restored by increased sleep quantity and/or improved sleep quality. That is, impairments in sleep are closely related to impairments in cardiometabolic health. This leads to the proposition that specific features of sleep act as biomarkers for specific features of cardiometabolic health. This thesis aims to determine the impact of sleep on three major domains of cardiometabolic health: 1) atherosclerosis (arterial plaque accumulation), 2) dyslipidemia (unhealthy blood lipids), and 3) hyperglycemia (high blood sugar). Accordingly, three key findings emerge that comprise the three chapters of this report. 1) The quality of human sleep, specifically the degree of fragmentation, raises inflammatory-related white blood cells, thereby conferring an increased risk for atherosclerosis. This was true of sleep fragmentation assessed across a week or a single night, which predicted increasingly higher CAC scores through a mediating association with increased neutrophils. 2) Unique features of an individual’s sleep (duration, efficiency, timing, regularity) predict aspects of triglyceride metabolism under fasting (homeostatic) and post-food intake (allostatic) conditions. First, later sleep timing predicts higher fasting triglycerides, emphasizing a unique relation with triglyceride homeostasis (not allostasis). Second, this homeostatic link is mediated by increased systemic inflammation (GlycA levels). Third, and conversely, declining sleep efficiency negatively impacts post-food lipid clearance, reflecting allostatic regulation. Fourth, these effects are replicated in a second independent cohort. 3) The coupling of NREM sleep spindles and slow oscillations the night prior is associated with improved next-day peripheral glucose control. Further, this sleep-associated glucose pathway may influence glycemic status through altered insulin sensitivity, rather than through altered pancreatic beta cell function. Moreover, these associations are replicated in an independent dataset of over 1900 adults. Of therapeutic significance, the coupling between slow oscillations and spindles was the most significant sleep predictor of next-day fasting glucose, even more so than traditional sleep markers, relevant to the possibility of an EEG index of hyperglycemia. Collectively, beyond these scientific insights, these results support a sleep–cardiometabolic homeostasis framework, such that unique features of sleep act as biomarkers for unique aspects of cardiometabolic health. Importantly, these findings help reinform public health sleep-related guidelines to reduce the mortality and economic burden of cardiometabolic disease globally.