Kimberly Steele

Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity.

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 = 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 +/- 29 events/hour and the median oxygen desaturation during apneic events was 4.6 +/- 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.

Dyslipidemia and Atherosclerosis Induced by Chronic Intermittent Hypoxia Are Attenuated by Deficiency of Stearoyl Coenzyme A Desaturase

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 156514±57408 &mgr;m2), and descending aorta (7.0±1.2% 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 (r=0.68, P=0.001). 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.

The Effect of Restrictive Bariatric Surgery on Urinary Stone Risk Factors

OBJECTIVES Malabsorptive bariatric procedures such as Roux-en-Y gastric bypass (RYGB) place patients at risk for developing kidney stones. Stone risk factors after purely restrictive procedures such as gastric banding and sleeve gastrectomy are not well characterized. Therefore, we performed a study to examine urinary risk factors of patients who underwent restrictive gastric surgery for bariatric indications. METHODS A total of 18 patients were enrolled in the study; 14 underwent gastric banding and 4 underwent sleeve gastrectomy. All subjects collected 24-hour urine specimens; at least 6 months had elapsed between surgery and urine collection. Standard stone risk parameters were assessed, and comparisons were made with a group of normal adult nonstone-formers, routine stone-formers, and RYGB bariatric surgery subjects. RESULTS Urinary oxalate excretion of the restrictive cohort was significantly less than the RYGB cohort (35.4 vs. 60.7 mg/d; P <.001) and not significantly different from that of the normal subjects (32.9 mg/d; P = .798) and routine stone-formers (37.2 mg/d; P = .997). There were no other significant differences in urinary parameters. CONCLUSIONS Restrictive bariatric surgery does not appear to be associated with an increased risk for kidney stone disease. In particular, urinary oxalate levels were significantly less than those of RYGB subjects and not significantly different from routine stone-formers and nonstone-forming controls.

Warm-up on a simulator improves residents' performance in laparoscopic surgery: a randomized trial.

Introduction and hypothesisOur aim was to assess the impact of immediate preoperative laparoscopic warm-up using a simulator on intraoperative laparoscopic performance by gynecologic residents.MethodsEligible laparoscopic cases performed for benign, gynecologic indications were randomized to be performed with or without immediate preoperative warm-up. Residents randomized to warm-up performed a brief set of standardized exercises on a laparoscopic trainer immediately before surgery. Intraoperative performance was scored using previously validated global rating scales. Assessment was made immediately after surgery by attending faculty who were blinded to the warm-up randomization.ResultsWe randomized 237 residents to 47 minor laparoscopic cases (adnexal/ tubal surgery) and 44 to major laparoscopic cases (hysterectomy). Overall, attendings rated upper-level resident performances (postgraduate year [PGY-3, 4]) significantly higher on global rating scales than lower-level resident performances (PGY-1, 2). Residents who performed warm-up exercises prior to surgery were rated significantly higher on all subscales within each global rating scale, irrespective of the difficulty of the surgery. Most residents felt that performing warm-up exercises helped their intraoperative performances.ConclusionPerforming 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.

Impact of bariatric surgery on health care utilization and costs among patients with diabetes

Background:The effect of bariatric surgery on health care utilization and costs among individuals with type 2 diabetes remains unclear. Objective:To examine health care 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 to 2008 from 7 Blue Cross Blue Shield Plans. Participants:Seven thousand eight hundred six individuals with type 2 diabetes who had bariatric surgery. Measures:Cost (inpatient, outpatient, pharmacy, and others) and utilization (number of inpatient days, outpatient visits, specialist visits). Results:Compared with presurgical 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 postsurgery period and increased over time [post 1: odds ratio (OR)=0.58; 95% confidence interval (CI), 0.50–0.67; post 6: OR=3.43; 95% CI, 2.60–4.53]. In comparison with the presurgical period, the odds of having any health care costs was lower in the postsurgery 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 OR 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). Conclusions:In the 6 years after surgery, individuals with type 2 diabetes did not have lower health care costs than before surgery.

Effects of meal composition on postprandial incretin, glucose and insulin responses after surgical and medical weight loss

Meal tolerance tests are frequently used to study dynamic incretin and insulin responses in the postprandial state; however, the optimal meal that is best tolerated and suited for hormonal response following surgical and medical weight loss has yet to be determined.

Proxy measures of vitamin D status – season and latitude – correlate with adverse outcomes after bariatric surgery in the Nationwide Inpatient Sample, 2001–2010: a retrospective cohort study

To investigate the association between adverse surgical outcomes following bariatric surgery and proxy measures of vitamin D (VitD) status (season and latitude) in the Nationwide Inpatient Sample (NIS).