Therefore, successfully identifying candidate serum biomarkers for NT1 would be a head start for accurate diagnosis and development of therapeutics for this disorder. Misdiagnosis of NT1 is also quite common, although it is not exceedingly rare. To date, no cure has been established for this life-threatening conditions. It is characterized by its association with cataplexy and abnormalities in rapid eye movement. Narcolepsy type 1 (NT1) is the most common type of narcolepsy known to be caused by 21 the loss of specific neurons responsible for producing peptide neurotransmitters (orexins/hypocretins) resulting in a sleep-wake cycle disorder. Understanding the common pathophysiological mechanisms of NA, DM and obesity could guide us in designing life-style modification programs, genetic consultations, and targeted therapies, such as immunotherapy, for obesity in NA.
Ongoing research on the use of orexin receptor (OXR) antagonists in sleep disorders has opened a window to the pathomechanisms of NA and the potentials for OXR modulation in eating disorders and obesity. GDM patients have lower serum orexin expression which is associated with increased fasting glucose and decreased fasting insulin. Gestational DM (GDM) is associated with obesity which is a potential outcome of narcolepsy. HLA genes that confer a risk for NA, such as DQB1*0602 are protective against T1DM, while catepsin gene (CTSH) mutations are a risk factor for both NA and T1DM. The main pathomechanisms relating type 1 DM (T1DM) to NA involve autoimmunity and inflammation. The anti-apoptotic effect of orexin on pancreatic beta-cells, increase in peripheral insulin sensitivity, and reduced lipolysis in the adipose tissue, together confer an increased risk for obesity and type 2 DM (T2DM) in NA patients. Orexin deficiency is associated with increased food intake and reduced basal metabolic rate (BMR) both leading to obesity.
Proposed mechanisms for this association are alterations in food intake, disruption of energy balance, glucose tolerance, and insulin sensitivity, as well as inflammation and genetic factors. NA is associated with an increased risk for metabolic disorders such as diabetes mellitus (DM). Narcolepsy (NA) is a primary sleep disorder characterized by loss of hypocretinergic/orexinergic neurons.
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