Sleep Disorders and Glucose Metabolism: What's the Connection?

©FXQuandro/Shutterstock.com

Twenty to 30 per cent of middle-aged Americans report sleeping less than 6 hours per night. The brevity is ascribed to voluntary and employment-related restrictions as well as to common sleep disorders such as insomnia and obstructive sleep apnea syndrome (OSA). The latter contribute to impaired sleep in more than 30% of adults.

Recently sleep has been causally related to regulation of glucose homeostasis and appetite control and sleep impairment is implicated in the rising prevalence of obesity and type 2 diabetes (T2DM). This brief overview highlights evidence for possible mechanisms underlying the impact of common sleep disorders on development of glucose intolerance, insulin resistance, and pancreatic endocrine dysfunction.   

Mechanisms of Sleep Disorders and Glucose Metabolism

► Sleep duration has shortened from >8 hours in the 1960s to ~ 6.5 hours per night in 2012; the result is that many people are chronically sleep deprived^1,2

► Abnormal sleep has been linked to obesity, metabolic syndrome, T2DM, and impaired appetite control

► Sleep quality and quantity may have important effects on whole body metabolism

► The most prevalent sleep disturbances include short sleep duration, shift work disorder, and obstructive sleep apnea (OSA)

Short Sleep Duration: Next page →

Short Sleep Duration

► Most epidemiologic studies consider 7-8 hours per night normal, with short sleep duration considered to be <5 hours to <7 hours per night

► Short sleep duration is an independent risk factor for weight gain and abdominal fat accumulation:
   o May increase appetite and total daily caloric intake, especially of foods high in fat and carbohydrates

► Suggested mechanisms:
   o Increased ghrelin (increases food intake) and decreased leptin (decreases food intake)
   o HPA axis dysfunction, sympathetic activation and elevated cortisol levels may lead to:
      -Elevated pro-inflammatory cytokines
      -Lower circulating testosterone, lower TSH levels, impaired pulsatility of growth hormone secretion
      -Changes in adipokines secreted from adipose tissue

Circadian Rhythm Disruption: Next page →

Circadian Rhythm Disruption: Shift Work

► Irregular sleep, shift work, and travel across time zones can disrupt circadian rhythm

► May cause misalignment between the master hypothalamic clock in the suprachiasmatic nucleus (SCN) and pacemakers in peripheral tissues like the liver, adipose tissue, and muscle

► Suggested mechanism:
   o SCN helps control synthesis and release of glucocorticoids in peripheral tissues through direct sympathetic innervation from adrenals
   o Central and peripheral pacemaker misalignment interferes with cortisol rhythm; leads to decreased leptin levels, increased FFA levels and pro-inflammatory cytokines, causing insulin resistance and pancreatic ß-cell dysfunction
   o Melatonin may help resynchronize pacemakers and improve glucose homeostasis

Obstructive Sleep Apnea: Next page →

Obstructive Sleep Apnea (OSA)

► OSA is an independent risk factor for CVD and is linked to dyslipidemia, insulin resistance, glucose intolerance, T2DM, nonalcoholic fatty liver disease

► Intermittent hypoxia and sleep fragmentation are key aspects of OSA

► Sleep fragmentation:
   o Arousals during apneic periods can cause partial or full awakenings and sleep fragmentation which may lead to sympathetic activation
   o Decrease in slow wave sleep duration may affect satiety perception, leading to weight gain
   o Increased metabolic activity during REM sleep is lost when time spent in REM sleep is reduced

Intermittent Hypoxia: Next page →

Intermittent Hypoxia

► Intermittent hypoxia (IH) in OSA may lead to sympathetic activation during sleep; effects on:
   o Liver: IH may cause OSA-related hepatic injury through:
      -Decreased activity of hepatic antioxidant enzymes
      -Increased hepatic glucose production, hepatic nitric oxide metabolites, lipid biosynthesis, inflammation, oxidative stress, and HIF-1α activity (a regulator of cellular response to hypoxia which has been implicated in cancer, inflammation)
   o Skeletal muscle: Decreased glucose metabolism, abnormal glucose-transporter-type 4 (GLUT4) activity
   o Adipocytes: Decreased lipoprotein clearance, and increased lipolysis, FFA release, HIF-1α activity, inflammation
   o Pancreas: Increased ß-cell death, proliferation; decreased insulin content, secretion

Take-home Points: Next page →

Take-home Points

► The most prevalent sleep disturbances include short sleep duration, shift work, and obstructive sleep apnea (OSA)

► The most likely mediators of metabolic dysregulation in sleep disorders include:

   o HPA axis activation and increased circulating cortisol

   o Misalignment between central and peripheral circadian pacemakers

   o Abnormal adipokine release from adipose tissues and increased lipolysis

   o Intermittent hypoxia-induced sympathetic nervous system activation

   o Generation of reactive oxygen species and activation of inflammatory pathways leading to whole-body inflammation