Obesity has epidemic proportions in Western societies and, because of
its significant association with morbidity and mortality, is a major
public health issue. Excessive daytime sleepiness (EDS) and fatigue
(tiredness without increased sleep propensity)-which have been
associated with obesity-have a significant impact on individual
wellbeing and public safety. In this article, we review data that
challenge the belief that sleep apnea and sleep disruption per se are
the primary determinants of obesity-related daytime sleepiness and
fatigue. Specifically, it appears that obesity per se is associated with
objective and subjective daytime sleepiness compared to normal-weight
controls regardless of sleep apnea and sleep loss. Indeed, obese
patients without sleep apnea are sleepier compared to nonobese controls
whereas within the morbidly obese, those who have high sleep efficiency
at night are sleepier than those who have low sleep efficiency. In
addition, in recent studies based on large random samples of the general
population, the primary determinants of subjective EDS were depression
and metabolic disturbances, that is, obesity/diabetes, and not sleep
apnea or objective sleep disruption. Furthermore, sleepiness and fatigue
are very prevalent in conditions associated with insulin resistance, for
instance, the polycystic ovary syndrome (PCOS), independently of sleep
apnea or obesity, or in conditions of insufficient physical activity. On
the basis of these data, we propose that obesity-related objective
daytime sleepiness and fatigue are associated primarily with metabolic
and psychological factors and less with sleep apnea and sleep disruption
per se. Furthermore, we suggest that objective sleepiness is primarily
related to metabolic factors, whereas fatigue appears to be related to
psychological distress. Finally, based on data from studies in normal
controls and patients with sleep disorders, we propose that the
interaction of the hypothalamic-pituitary-adrenal (HPA) axis and
proinflammatory cytokines determines the level of sleep/arousal within
the 24-h cycle, that is, “hypercortisolemia” plus hypercytokinemia
is associated with low sleep efficiency and fatigue, whereas
“eucortisolemia” or “hypocortisolemia” plus hypercytokinemia is
associated with high sleep efficiency and objective sleepiness
