Rationale: Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity. Objectives: To examine whether sleep apnea and nocturnal hypoxemia predict the severity of insulin resistance, systemic inflammation, and steatohepatitis in severely obese individuals presenting for bariatric surgery. Methods: We performed sleep studies and measured fasting blood glucose, serum insulin, C-reactive protein, and liver enzymes in 90 consecutive severely obese individuals, 75 women and 15 men, without concomitant diabetes mellitus or preexistent diagnosis of sleep apnea or liver disease. Liver biopsies (n 5 20) were obtained during bariatric surgery. Measurements and Main Results: Obstructive sleep apnea with a respiratory disturbance index greater than 5 events/hour was diagnosed in 81.1% of patients. The median respiratory disturbance index was 15 6 29 events/hour and the median oxygen desaturation during apneic events was 4.6 6 1.8%. All patients exhibited high serum levels of C-reactive protein, regardless of the severity of apnea, whereas liver enzymes were normal. Oxygen desaturation greater than 4.6% was associated with a 1.5-fold increase in insulin resistance, according to the homeostasis model assessment index. Histopathology data suggested that significant nocturnal desaturation might predispose to hepatic inflammation, hepatocyte ballooning, and liver fibrosis. Fasting blood glucose levels and steatosis scores were not affected by nocturnal hypoxia. There was no relationship between the respiratory disturbance index and insulin resistance or liver histopathology. Conclusions: Hypoxic stress of sleep apnea may be implicated in the development of insulin resistance and steatohepatitis in severe obesity.Keywords: hypoxemia; fatty liver disease; metabolic syndrome; sleepdisordered breathing; liver injury Obstructive sleep apnea (OSA) is a complex disorder consisting of upper airway obstruction, chronic intermittent hypoxia (CIH), and sleep fragmentation (1). Epidemiologic studies have demonstrated that OSA is associated with insulin resistance and glucose intolerance, independent of obesity (2-4). Clinical investigations have also shown that OSA results in low-grade systemic inflammation (5, 6). Both insulin resistance and systemic inflammation may contribute to the increased cardiovascular risk in patients with OSA (7-9). Insulin resistance, systemic inflammation, and OSA are particularly prevalent in patients with severe obesity defined as a body mass index (BMI) exceeding 40 kg/m 2 (2, 10-12). While obesity causes systemic inflammation, insulin resistance, and sleep apnea (12-15), sleep apnea may further exacerbate the inflammatory and metabolic disturbances (2, 3, 6). Nevertheless, it is not known whether concomitant OSA is implicated in metabolic dysregulation and systemic inflammation in severe obesity.One of the consequences of obesity and insulin resistance is nonalcoholic fatty liver disease (N...

Abstract-Obstructive sleep apnea leads to chronic intermittent hypoxia (CIH) and is associated with atherosclerosis. We have previously shown that C57BL/6J mice exposed to CIH and a high-cholesterol diet develop dyslipidemia, atherosclerosis of the aorta, and upregulation of a hepatic enzyme of lipoprotein secretion, stearoyl coenzyme A desaturase 1 (SCD-1). We hypothesized that (1) SCD-1 deficiency will prevent dyslipidemia and atherosclerosis during CIH; and (2) human OSA is associated with dyslipidemia and upregulation of hepatic SCD. C57BL/6J mice were exposed to CIH or normoxia for 10 weeks while being treated with either SCD-1 or control antisense oligonucleotides.Obese human subjects underwent sleep study and bariatric surgery with intraoperative liver biopsy. In mice, hypoxia increased hepatic SCD-1 and plasma very-low-density lipoprotein cholesterol levels and induced atherosclerosis lesions in the ascending aorta (the cross-section area of 156514Ϯ57408 m 2 ), and descending aorta (7.0Ϯ1.2% of the total aortic surface). In mice exposed to CIH and treated with SCD-1 antisense oligonucleotides, dyslipidemia and atherosclerosis in the ascending aorta were abolished, whereas lesions in the descending aorta showed 56% reduction. None of the mice exposed to normoxia developed atherosclerosis. In human subjects, hepatic SCD mRNA levels correlated with the degree of nocturnal hypoxemia (rϭ0.68, Pϭ0.001). Patients exhibiting oxyhemoglobin desaturations at night showed higher plasma triglyceride and low-density lipoprotein cholesterol levels, compared to subjects without hypoxemia. In conclusion, CIH is associated with dyslipidemia and overexpression of hepatic SCD in both humans and mice alike; SCD-1 deficiency attenuates CIH-induced dyslipidemia and atherosclerosis in mice. Key Words: atherosclerosis Ⅲ hypercholesterolemia Ⅲ hypoxia Ⅲ lipoproteins Ⅲ obstructive sleep apnea O bstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) during sleep. 1 OSA occurs in 9% of women and 24% of men in the United States, but the prevalence exceeds 30% to 50% in the obese population. 2,3 OSA poses significant cardiovascular risk, which has been attributed to the high prevalence of atherosclerosis in patients with OSA. 4 -6 OSA is associated with dyslipidemia, lipid peroxidation, and vascular inflammation, all of which induce atherosclerosis. 7-10 Recent studies have shown independent associations between the hypoxic stress of OSA and increased carotid artery intima-media thickness 11,12 that is reversed by treatment with continuous positive airway pressure. 13 Our group has previously explored relationships between CIH and atherosclerosis using a mouse model of CIH that mimics the oxygen profile in patients with severe OSA. 14,15 We have shown that CIH induces atherosclerosis in C57BL/6J mice on a high-cholesterol diet. 16 We have also found that the development of atherosclerosis during CIH was associated with increases in lipoprotein secretion, plasma very-low-density lipoprotein VLDL levels, an...

Performing a brief warm-up exercise before a major or minor laparoscopic procedure significantly improved the intraoperative performance of residents irrespective of the difficulty of the case.

Background The effect of bariatric surgery on health care utilization and costs among individuals with type 2 diabetes remains unclear. Objective To examine healthcare utilization and costs in an insured cohort of individuals with type 2 diabetes after bariatric surgery. Research Design Cohort study derived from administrative data from 2002–2008 from 7 Blue Cross Blue Shield Plans. Subjects 7,806 individuals with type 2 diabetes who had bariatric surgery Measures Cost (inpatient, outpatient, pharmacy, other) and utilization (number of inpatient days, outpatient visits, specialist visits). Results Compared to pre-surgical costs, the ratio of hospital costs (excluding the initial surgery), among beneficiaries who had any hospital costs, was higher in years 2 through 6 of the post-surgery period and increased over time [post 1: OR = 0.58 (95% CI: 0.50, 0.67); post 6: OR = 3.43 (95% CI: 2.60, 4.53)]. In comparison to the pre-surgical period, the odds of having any healthcare costs was lower in the post-surgery period and remained relatively flat over time. Among those with hospitalizations, the adjusted ratio of inpatient days was higher after surgery [post 1: OR = 1.05 (95% CI: 0.94, 1.16); post 6: OR = 2.77 (95% CI: 1.57, 4.90)]. Among those with primary care visits, the adjusted odds ratio was lower after surgery [post 1: OR = 0.80 (95% CI: 0.78, 0.82); post 6: OR = 0.66 (95% CI: 0.57, 0.76)]. Conclusion In the six years following surgery, individuals with type 2 diabetes did not have lower healthcare costs than before surgery.