Abstract
Epidemiological studies have repeatedly shown that insomnia disorder or symptoms of insomnia are prospectively associated with increased risks for developing a diverse range of medical conditions affecting multiple biological systems. Specifically, insomnia-related disease risks include cardiovascular diseases (Javaheri and Redline, 2017), metabolic diseases, such as type 2 diabetes and metabolic syndrome (Anothaisintawee et al., 2016; Lin et al., 2016), Alzheimer’s disease (Shi et al., 2018), pain (Afolalu et al., 2018), autoimmune diseases (Kok et al., 2016), and cancer (Shi et al., 2020). Insomnia is associated with changes in the regulation of immune, neuroendocrine, and metabolic systems among other physiological consequences, which are thought to mechanistically link insomnia with increased risk for these diseases. The exact pathophysiological mechanisms through which such physiological changes promote disease risk are now intensively studied for some conditions, such as type 2diabetes(Cedernaes et al., 2015; Depner et al., 2014), but less so for others, such as pain or autoimmune conditions (Haack et al., 2020; Zielinski et al., 2019). There is some evidence, however, suggesting that the physiological consequences are most pronounced in insomnia with objective short sleep duration, generally defined as less than 6 h of sleep per night (Vgontzas et al., 2013). For example, the risks of low-grade systemic inflammation, hypertension, or diabetes are greatest in individuals who have insomnia in combination with short sleep (Fernandez-Mendoza et al., 2017; Vgontzas et al., 2013), suggesting that this insomnia phenotype is a biologically more severe form of the disorder.
Fig. 1 depicts immune, neuroendocrine, and metabolic consequences associated with insomnia disorder and their potential role in mediating increased disease risk, which will be reviewed in the following. Autonomic consequences of insomnia (e.g., blood pressure, heart rate variability) will not be discussed here; the interested reader is referred to recent comprehensive reviews (Grimaldi et al., 2019; Nano et al., 2017).
