Persistent daytime sleepiness causes individuals to have an increased likelihood of accidents. A study by the US National Transportation Safety Board (NTSB) found that the most probable cause of fatal truck accidents was sleepiness-related fatigue [41]. In another study by the NTSB [42], 58 % of the heavy-truck accidents were fatigue related and 18 % of the drivers admitted having fallen asleep at the wheel. The NTSB also reported sleepiness- and fatigue-related motor coach [43, 44] and railroad [45] accidents. New York State police estimated that 30 % of all fatal crashes along the New York throughway occurred because the driver fell asleep at the wheel. Approximately 1 million crashes annually (one-sixth of all crashes) are thought to be produced by driver inattention or lapses [46, 47]. Sleep deprivation and fatigue make such lapses more likely to occur. Truck drivers are especially susceptible to fatigue-related crashes [41, 42, 48–51]. Many truckers drive during the night while they are the sleepiest. Truckers may also have a high prevalence of sleep apnea [52]. The US Department of Transportation estimated that 200,000 automobile accidents each year may be related to sleepiness. Nearly one-third of all trucking accidents that are fatal to the driver are related to sleepiness and fatigue [53]. A general population study done by Hays et al. [54] involving 3962 elderly individuals reported an increased mortality risk of 1.73 in those with EDS, defined by napping most of the time. The presence of sleep disorders (see section “Primary Sleep Disorders Associated with EDS” later in this chapter) increases the risk of crashes. Individuals with untreated insomnia, sleep apnea, or narcolepsy and shift workers—all of whom may suffer from excessive sleepiness—have more automobile crashes than other drivers [55].

A telephone survey [56] of a random sample of New York State licensed drivers by the State University of New York found that 54.6 % of the drivers had driven while drowsy within the past year, 1.9 % had crashed while drowsy, and 2.8 % had crashed when they fell asleep. Young male drivers are especially susceptible to crashes caused by falling asleep, as documented in a study in North Carolina [57] in 1990, 1991, and 1992 (e.g., in 55 % of the 4333 crashes, the drivers were predominantly male and 25 years of age or younger). Surveys in Europe also noted an association between crashes and long-distance automobile and truck driving [50, 58–61]. A 1991 Gallup organization [62] national survey found that individuals with chronic insomnia reported 2.5 times as many fatigue-related automobile accidents as did those without insomnia. The same 1991 Gallup survey found serious morbidity associated with untreated sleep complaints, as well as impaired ability to concentrate and accomplish daily tasks, and impaired memory and interpersonal discourse. In a 1999 Gallup Poll [63], 52 % of all adults surveyed said that, in the past year, they had driven a car or other vehicle while feeling drowsy, 31 % of adults admitted dozing off while at the wheel of a car or other vehicle, and 4 % reported having had an automobile accident because of tiredness during driving. A number of national and international catastrophes [10] involving industrial operations, nuclear power plants, and all modes of transportation have been related to sleepiness and fatigue, including the Exxon Valdez oil spill in Alaska; the nuclear disaster at Chernobyl in the former Soviet Union; the near-nuclear disaster at 3-Mile Island in Pennsylvania; the gas leak disaster in Bhopal, India, resulting in 25,000 deaths; and the Challenger space shuttle disaster in 1987.

The prevalence of obesity in adults in the United States was 15 % in 1970 and increased to 31 % in 2001 [65]. In children, the figures for obesity were 5 % in 1970 and went up to 15 % in 2001. In the Zurich study [66], 496 Swiss adults followed for 13 years showed a body mass index (BMI) of 21.8 at age 27 that increased to 23.3 at the age of 40, with concurrent decrease in sleep duration from 7.7 to 7.3 h in women and 7.1 to 6.9 h in men. This longitudinal study confirms the cross-sectional studies in adults [67] and children [68]. In the Wisconsin sleep cohort study [69] (a population-based longitudinal study) using 1024 volunteers, short sleep was associated with reduced leptin and elevated ghrelin contributing to increased appetite, causing increased BMI. Several other more recent studies using various approaches have also documented the association of obesity or weight gain with short sleep duration [29, 30, 70–72]. In the study by Altman et al. [72], sleep duration of less than five hours was associated with an additional BMI point of 2.7 and this strong association was not accounted for perceived insufficient sleep. A large-scale prospective study found that the incidence of obesity at one-year follow-up was higher among Japanese men sleeping five hours or less compared with those sleeping seven hours [28].

Elevated evening cortisol levels, reduced glucose tolerance, and altered growth hormone secretion after experimental acute sleep restriction by Spiegel et al. [73, 74] suggest that participation of the hypothalamic–pituitary axis may contribute toward obesity after sleep deprivation by leading to increased hunger and appetite. There is epidemiologic evidence of reduced sleep duration associated with reduced leptin (a hormone in adipocytes stimulating the satiety center in the hypothalamus), increased ghrelin (an appetite stimulant gastric peptide), and increased BMI [75, 76]. Spiegel et al. [73] in studies using sleep restriction (4 h per night for 6 nights) and sleep extension (12 h per night for 6 nights) experiments in healthy young adults found increased evening cortisol, increased sympathetic activation, decreased thyrotropin activity, and reduced glucose tolerance in the sleep-restricted group. Rogers et al. [77] found similar elevation of evening cortisol levels following chronic sleep restriction. In recurrent partial sleep restriction studies in young adults, the following endocrine and metabolic alterations have been documented [78]: (1) decreased glucose tolerance and insulin sensitivity and (2) decreased levels of the anorexigenic hormone leptin and increased levels of the orexigenic peptide ghrelin. A combination of these findings caused increased hunger and appetite leading to weight gain. Because of these changes, short sleep duration is a risk factor for diabetes and obesity.

Several epidemiologic studies have shown an association between sleep duration and type 2 diabetes mellitus [79]. Ayas et al. [80] found an association between long sleep duration (>9 h) and diabetes mellitus. Yaggi et al. [81] reported an association between diabetes and both short (<5 h) and long (>8 h) sleep duration. Several other reviews [82–85] including some recent studies [29, 30, 32, 83, 86–90] supported a link between sleep duration, particularly short sleep duration and diabetes mellitus. Buxton and Marcelli [29] used the 2004–2005 National Health Interview Survey (NHIS), and Shankar et al. [30] used the 2008 Behavioral Risk Factor Surveillance System (BRFSS) to find a positive correlation between short sleep duration and diabetes. Hancox and Landhuis [90] from a study conducted in New Zealand found an association between short sleep duration and prediabetes as well as an association between HgA1C and sleep duration.

Epidemiologic studies by Kripke et al. [91, 92] and Hublin et al. [93] showed increased mortality in short sleepers (also in relatively long sleepers). There is a U-shaped association between sleep duration (both long and short) and mortality [27, 38, 94–96]. The earliest study was by Hammond in 1964 [97]. Another significant early study by Kripke et al. [91, 92] in 1979 found that the chances of death from coronary artery disease, cancer, or stroke are greater for adults who sleep less than 4 h or more than 9 h when compared to those who sleep an average of 7½–8 h. The latest studies by Kripke et al. in 2002 [98] confirmed the earlier observations and documented an increased mortality in those sleeping less than 7 h and those sleeping more than 7½ h. Other factors, such as sleeping medication, may have confounded these issues. In more recent studies, Gallicchio and Kalesan [95] conducted meta-analysis using 23 studies from 2007 to 2009 and Cappuccio et al. [27] using 16 studies from 1993 to 2009 a relationship between sleep duration (both long and short) and all-cause mortality emerged. There is, however, insufficient evidence to make a definite conclusion about sleep duration and mortality. The underlying etiologic factors remain to be determined. One possibility is a common pathway of increased risk of cardiometabolic disease [24].

Several studies documented abnormal physiologic changes after sleep restriction as follows: reduced glucose tolerance [73], increased blood pressure [99], sympathetic activation [100], reduced leptin levels [101], and increased inflammatory markers (e.g., an increased C-reactive protein, an inflammatory myocardial risk after sleep loss) [102].

Limited studies in the literature suggest the following responses following sleep restriction: (1) decreased antibody production following influenza vaccination in the first 10 days [103]; (2) decreased febrile response to endotoxin (Escherichia coli) challenge [104]; and (3) increased inflammatory cytokines [105] (e.g., interleukin-6 and tumor necrosis factor-α), which may lead to insulin resistance, cardiovascular disease, and osteoporosis.

Studies by Mallon et al. [106] in 2002 addressed the question of sleep duration and cardiovascular disease. They did not find increased risk of cardiovascular disease-related mortality associated with sleep duration, but found an association between difficulty falling asleep and coronary arterial disease mortality. However, several other more recent studies found a relationship between increased risk of cardiovascular disease and sleep duration [29, 72, 99, 107–109]. In a 12-year prospective study covering 20,432 men and women with no prior history of cardiovascular disease investigators from the Netherlands [108] observed that short sleepers (≤6 h) had higher risk of cardiovascular disease than those sleeping 7–8 h. These findings agree with the observations made by Altman et al. [72], Buxton and Marcelli [29], Cappuccio et al. [109].

Kripke et al. [98] and Newman et al. [107] in their studies concluded that daytime sleepiness and reduced sleep duration predict mortality and cardiovascular disease in older adults. What is the mechanism of increased cardiovascular risk after chronic sleep deprivation? This is not exactly known but may be related to increased C-reactive protein, an inflammatory marker found after sleep loss. In many of the sleep restriction experiments in humans, however, an added stress may have acted as a confounding factor, and therefore, some of the conclusions about sleep restriction regarding mortality, cardiovascular disease, diabetes mellitus, and endocrine changes may have been somewhat flawed.