There is evidence that the physiologic stress imposed by intermittent hypoxaemia1-3 and / or sleep fragmentation 4, 5 may be involved in the pathogenesis of insulin resistance via one or more of the following biological mechanisms:
a. Sympathetic Nervous System Activation
The sympathetic nervous system plays a central role in the regulation of glucose and fat metabolism, contributing to reduced insulin-mediated uptake of glucose into muscle, and increased lipolysis leading to increased insulin resistance. OSA has been shown to be associated with increased sympathetic activity.
|Potential Mechanisms Linking Sleep Apnoea
and Glucose Metabolism6
b. Hypothalamic-Pituitary-Adrenal Dysfunction
The Hypothalamic-Pituitary-Adrenal (HPA) axis regulates the secretion of cortisol and other glucocorticoids, which influence glucose metabolism. Cortisol inhibits pancreatic insulin secretion and increases insulin resistance. Intermittent hypoxaemia and sleep fragmentation may lead to activation of the HPA axis and increased cortisol levels.
c. Systemic Inflammation
Patients with OSA are known to produce higher levels of inflammatory cytokines (tumour necrosis factor-a, interleukin-6 and C-reactive protein) largely due to the effects of intermittent hypoxaemia (independent of obesity). These inflammatory markers have been associated with the development of diabetes.
Adipose tissue hormones (leptin, adiponectin and resistin) have been implicated in the regulation of glucose metabolism. Leptin and adiponectin are thought to influence insulin resistance and both these hormones have been shown to be higher in patients with sleep apnea.
1 Larsen JJ, et al., The effect of altitude hypoxia on glucose homeostasis in men. J Physiol. 1997; 504:241-249
2 Braun B., et al. Women at altitude: short-term exposure to hypoxia and/or alpha(1)-adrenergic blockade reduces insulin sensitivity. J Appl Physiol 2001;91:623-631
3 Oltmanns K, et al. Hypoxia Causes Glucose Intolerance in Humans. Am J Respir Crit Care Med 2004; 169:1231-1237
4 Spiegel K., et al. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999 354:1435-1439
5 Gottlieb D., et al. Association of Sleep Time With Diabetes Mellitus and Impaired Glucose Tolerance. Arch Intern Med. 2005;165:863-867
6. Paul. Scientific session presentation. Sleep- disordered breathing and type 2 diabetes, 2008 ADA scientific sessions. San Fran, CA June 7, 2008