Medical hypotheses; 2011 Nov;77(5):930-4. PMID: 21899957
Department of Physiology and Sleep Laboratory, School of Medicine, P.J. Safarik University, Kosice, Slovakia. firstname.lastname@example.org
AbstractDespite a large body of epidemiologic and clinical evidence suggesting that sleep disordered breathing is an independent risk factor for development of type 2 diabetes (T2DM), the underlying pathogenesis of altered glucose metabolism in sleep apnea remains to be unraveled. While previous studies have proposed some causal pathways linking sleep apnea with T2DM through increased insulin resistance and deterioration in insulin sensitivity, there has been a particular lack of research into sleep apnea-related alterations in pancreatic beta-cell function. Drawing upon our previous observation that sleep apnea is independently associated with an increased basal pancreatic beta-cell function in adults with normal glucose metabolism, the idea presented here suggests that sleep apnea imposes an excessive demand for insulin secretion, which may lead to progressive pancreatic beta-cell failure in high-risk individuals. Specifically, we hypothesize that in addition to diabetogenic effects of acute hypoxic activation of the sympathetic nervous system, the chronic intermittent hypoxemia represses the expression of key genes regulating biosynthesis of pancreatic proinsulin convertases with a resultant progressive decrease in their catalytic activity. The long-term hypoxic damage to pancreatic beta-cells may thus contribute to progression of glucose dysregulation in persons with untreated sleep apnea over time. Strategies to prevent and decrease the high prevalence and associated morbidity of T2DM are critically needed. The ideas and hypotheses presented here address the unexplored pathophysiological mechanisms underlying the potential causal link between sleep apnea and T2DM. Future hypotheses-testing will seek to delineate the role of sleep apnea in the development of T2DM, probe the underlying molecular mechanisms for pancreatic beta-cell dysfunction in sleep apnea, and obtain information on clinical, epidemiologic, and other factors responsible for protecting individuals from alterations in insulin-glucose homeostasis. These results could further be utilized in testing genetic susceptibilities and various therapy modalities to prevent pancreatic beta-cell dysfunction and maintain normal glucose status in persons with sleep apnea in the long term.