leptin and Blood-Coagulation-Disorders

There is a very high prevalence of OSA in obese individuals and a high prevalence of obesity in patients with OSA. The pathophysiology of OSA is intimately linked to obesity. Anatomic and functional considerations of the pharyngeal airway, the CNS, central obesity, and leptin likely interact in the development of OSA in obese individuals. OSA may itself predispose individuals to worsening obesity because of sleep deprivation, daytime somnolence, and disrupted metabolism. The diagnosis of OSA requires the clinician's awareness of its potential to cause a spectrum of acute and chronic neurocognitive, psychiatric, and nonspecific symptoms in patients who may be unaware that their sleep is disturbed. Symptoms and examination findings help predict which obese individuals have OSA, and polysomnography is the gold standard by which to make the diagnosis and assess the effects of treatment. Numerous disease states are associated with both OSA and obesity, and it is becoming clear that the relationships are mediated by complex interrelated mechanisms. Common diseases and disease mechanisms in OSA and obesity suggest that conditions related to obesity may be better managed if patients, particularly those who are morbidly obese, are evaluated and treated for previously undiagnosed OSA. OSA is cured in only specific cases with craniofacial or upper airway surgery, and the general application of UVP is not efficacious. OSA also can be cured with sufficient lifestyle-mediated or surgical weight loss; however, in the absence of long-term weight maintenance, OSA returns with weight gain. Although not curative, nasal CPAP is the initial treatment of choice for most patients because of its noninvasive approach and technical efficacy. It is limited, however, by patient acceptance and long-term compliance. Advances in mask comfort and use of humidified air should increase its acceptance. Future management strategies include newer generations of positive airway devices that automatically titrate pressures (which are not yet recommended by expert organizations) and multidisciplinary approaches to managing the care of patients with OSA.

Topics: Blood Coagulation Disorders; Cardiovascular Diseases; Drug Therapy; Genetic Predisposition to Disease; Humans; Inflammation; Leptin; Life Style; Obesity; Sleep Apnea, Obstructive; Surgical Procedures, Operative

Abnormalities in coagulation and haemostasis represent a well-known link between obesity and thrombosis (both arterial and venous). Several studies have shown that obese patients have higher plasma concentrations of all pro-thrombotic factors (fibrinogen, vonWillebrand factor (vWF), and factor VII), as compared to non-obese controls, with a positive association with central fat. Similarly, plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) have been shown to be higher in obese patients as compared to non-obese controls and to be directly correlated with visceral fat. Furthermore, obesity is characterized by higher plasma concentrations of anti-thrombotic factors, such as tissue-type plasminogen activator (t-PA) and protein C, as compared to non-obese controls, the increase in these factors being likely to represent a protective response partly counteracting the increase in pro-thrombotic factors. The issue of whether adipose tissue contributes directly to plasma PAI-1, its products stimulating other cells to produce PAI-1, or whether it primarily contributes indirectly has not yet been resolved. It has been proposed that the secretion of interleukin-6 (IL-6) by adipose tissue, combined with the actions of adipose tissue-expressed TNF-alpha in obesity, could underlie the association of insulin resistance with endothelial dysfunction, coagulopathy, and coronary heart disease. The role of leptin in impairing haemostasis and promoting thrombosis has been recently reported. Finally, some hormonal abnormalities (androgen, F, catecholamines) associated with the accumulation of body fat may contribute to the impairment of coagulative pathway in obesity. As to intervention strategies, dietary (i.e., low-fat high-fiber diet) and lifestyle (i.e., physical activity) measures have been demonstrated to be effective in improving the obesity-associated pro-thrombotic risk profile.

Topics: Adipose Tissue; Blood Coagulation Disorders; Endocrine Glands; Fibrinolysis; Hemostasis; Humans; Insulin Resistance; Leptin; Obesity; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Thrombosis

Topics: Adolescent; Blood Coagulation Disorders; Craniopharyngioma; Humans; Hypopituitarism; Leptin; Liver Cirrhosis; Male; Non-alcoholic Fatty Liver Disease; Obesity; Pituitary Neoplasms

Topics: Adipocytes; Adiponectin; Animals; Blood Coagulation Disorders; Complement Factor D; Diabetes Mellitus, Type 2; Hormones, Ectopic; Humans; Hyperlipidemias; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Obesity; Proteins; Resistin; Serine Endopeptidases; Triglycerides; Tumor Necrosis Factor-alpha