Physiological Links Between Sleep Apnea & Diabetes

The physiological stress imposed by sleep apnea may be involved in the pathogenesis of insulin resistance and type 2 diabetes via several complex and interrelated pathways.1 Two primary characteristics of sleep apnea likely to have the strongest influence on abnormal glucose metabolism are sleep fragmentation and recurring intermittent hypoxia.

Sleep Fragmentation and Sleep Deprivation

Quality and quantity of sleep have been shown to affect glucose metabolism. Sleep fragmentation is an inevitable consequence of sleep apnea, as the body responds to the imbalance of oxygen and carbon dioxide in the blood by increasing sympathetic activity, which in turn leads to microarousals throughout the sleep period. In addition to sleep fragmentation, sleep apnea patients generally experience reduced total sleep time, which has been shown to result in impaired glucose tolerance.

Sleep fragmentation exerts effects on:

  • The sympathetic nervous system, responsible for the stress response
    Activation of the sympathetic system causes a release of catecholamines, which lead to an increase in heart rate, blood pressure and gluconeogenesis. Sleep apnea has been shown to be associated with increased sympathetic activity.
  • The somatotropic axis, the major hormonal system regulating growth
    Sleep apnea has been shown to result in down-regulation of IGF-1, which has been linked with development of type 2 diabetes.
  • The hypothalamic-pituitary-adrenal (HPA) axis, part of the neuroendocrine system that controls the physiological response to stress
    Increased activity of the HPA axis results in increased levels of catecholamines and cortisol. Prolonged exposure to elevated levels of cortisol leads to hyperglycemia. Increased cortisol levels have been reported in patients with sleep apnea.

Recurring Intermittent Hypoxia

Like sleep fragmentation, intermittent hypoxia affects multiple physiological pathways, including:

  • The sympathetic nervous system
    As described above, catecholamine release, a consequence of sympathetic activation, leads to elevated blood glucose.
  • Systemic inflammation
    Hypoxia results in increased levels of inflammatory cytokines, including IL-6, TNF-alpha and C-reactive protein, which have been implicated in the pathogenesis of insulin resistance and type 2 diabetes and in increased risk of atherosclerosis and cardiovascular events.
  • Adipokine regulation
    Hypoxia is associated with increased levels of adipose hormones leptin and adiponectin, which regulate metabolic processes and affect glucose regulation.
  • Oxidative stress
    Cycles of hypoxia/reoxygenation lead to increased reactive oxygen species and oxidative stress, which contribute to the development of insulin resistance and diabetes.

In addition to alterations to physiological pathways, the daytime somnolescence that frequently occurs as a result of sleep apnea can negatively influence the patient’s efforts to manage their type 2 diabetes by reducing cognitive function and motivation to exercise and follow dietary restrictions.

Read more about the cardiovascular implications of sleep apnea and type 2 diabetes.

For reviews, see Tasali E, et al. CHEST 2008;133:496-506 and Punjabi NM and Polotsky VY. J Appl Physiol 2005;99:1998-2007