Mechanisms of Insufficient Sleep Contributing to Metabolic Disease Risk and Impact from Weekend Recovery Sleep

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PROJECT SUMMARY/ABSRACT Obesity is epidemic and ~50% of the United States population has diabetes or prediabetes. Furthermore, death rates from all causes are ~1.5 times greater for individuals with versus without diagnosed diabetes and the economic cost of diabetes in the US was $245 billion in 2012. Thus, diabetes and associated metabolic diseases represent major public health and economic burdens. Short nightly sleep duration and untreated sleep disorders are now recognized as risk factors for metabolic diseases with more than 50% of Americans sleeping less than the recommended 7 hours/night, and sleep and wakefulness disorders impacting 50 to 70 million Americans. However, the biochemical mechanisms by which sleep loss contributes to metabolic disease are largely unknown, impeding the development of novel and effective countermeasures that target the negative metabolic consequences of sleep loss. Furthermore, it is unknown if the common and self-selected countermeasure of weekend recovery sleep attenuates the negative metabolic consequences of sleep loss. As such, I propose to identify the influence of insufficient sleep on mechanisms underlying metabolic dysregulation and determine the impact of “weekend recovery” sleep on these mechanisms. The proposed project will utilize metabolomics to analyze plasma samples from an ongoing in-laboratory study investigating insulin sensitivity and energy balance during insufficient sleep followed by weekend recovery sleep. Guided by my preliminary research efforts, I will use targeted and untargeted metabolomics approaches to identify metabolites and metabolic pathways impacted by insufficient sleep and weekend recovery sleep. Additionally, the untargeted discovery approach may identify potential “biomarkers” that change with sleep loss and “weekend recovery” sleep. My proposed findings will help inform future validation and sleep countermeasure investigations including testing at risk populations (i.e. obesity, pre-diabetes, shift-workers). This proposed F32-award is responsive to a key goal of the 2011 NIH Sleep Disorders Research Plan to “enable sleep and circadian research training to inform science in cross-cutting domains, accelerate the pace of discovery, and the translation of enhanced therapies from bench to bedside to community”, and is designed to advance my training in sleep and circadian physiology and metabolomics to strengthen my potential for a successful NIH Career Development K-award.