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Increased waist circumference (WC) and related anthropometric indices have been shown to be, independently of body weight and body mass index (BMI), associated with adverse metabolic traits in many populations. It is unknown, however, whether WC also predicts adverse metabolic traits in severely obese subjects displaying a BMI greater than 35 kg/m. To address this question, we analyzed a dataset including 838 severely obese patients (597 women, BMI 44.6 ± 6.2 kg/m; 241 men, BMI 44.3 ± 5.7 kg/m). Body weight, height, WC, hip circumference, and blood pressure were measured in all subjects along with the following metabolic blood markers: fasting glucose, insulin, glycolized hemoglobin levels, triglycerides, total cholesterol, low- and high-density cholesterol, and uric acid. Multivariate regression analyses indicated that WC as well as related anthropometric indices, in particular those accounting for subjects' height, were associated with many metabolic variables independently of body weight and BMI. In general, height-adjusted WC indices were more closely associated with metabolic traits in women than in men. Collectively, our findings suggest that body fat distribution also plays an important role in determining metabolic traits in severely obese subjects and that WC represents a valuable marker of abdominal/visceral obesity in this population. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown a reduction of elevated androgen levels in premenopausal women after marked weight loss induced by bariatric surgery. In this study, we aimed to assess whether circulating androgen levels also decline after bariatric surgery in women displaying normal values preoperatively as well as in postmenopausal women. Methods: In 36 severely obese women (six postmenopausal), levels of total testosterone, dehydroepiandresterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) were assessed before and at ~1 year after gastric bypass. Free and bioavailable testosterone levels as well as the free androgen index were calculated by established formulas. Results: After the surgery, women had lost on average 43.1 ± 1.8 kg. Independently of the pre/postmenopausal state, women showed a marked reduction in all testosterone-related androgen markers and DHEA-S levels, while SHBG levels markedly increased (all P < 0.001). Respective changes were found in both women with and without preoperatively elevated levels. Changes after the surgery in testosterone-related markers as well as in SHBG levels but not in DHEA-S levels were correlated with changes in insulin levels independently of body weight changes. Conclusions: Data show a marked reduction of androgen levels in severely obese women after a surgically induced weight loss, which is independent from the menopausal state and preoperative levels. The mechanisms and consequences of these hormonal changes induced by bariatric surgery should be addressed in further studies. [ABSTRACT FROM AUTHOR]

Severely obese subjects have been found to show a high prevalence of distinct nutritional deficiencies even without any bariatric intervention but the underlying reasons remain obscure. We tested the hypothesis that gastric Helicobacter pylori infection is associated with increased nutritional deficiency rates. Taking advantage of our large database, we identified 404 patients who had undergone a gastroscopy-as a standard diagnostic assessment before bariatric surgery-along with a histological examination of gastric mucosal biopsies with concurrent nutritional blood measurements. Eighty-five (21 %) of the obese patients included in the study displayed a gastric H. pylori infection. Sex distribution, age and body mass index did not differ between H. pylori+ and H. pylori− patients ( P > 0.29). Referring to nutritional markers, neither serum levels of total protein, albumin, calcium, phosphate, magnesium, ferritin, zinc, copper, vitamin B, folate and 25-OH vitamin D nor respective deficiency rates differed between the H. pylori+ and H. pylori− patients group (all P > 0.13). Overall, 49.5 % of the bariatric candidates displayed at least one nutritional deficiency. Our data confirm previous reports on high prevalences of nutritional deficiencies in severely obese subjects. However, they do not provide evidence for a contributing role of gastric H. pylori infection to these nutritional alterations. [ABSTRACT FROM AUTHOR]

While LRYGB has become a cornerstone in the surgical treatment of morbidly obese patients, concomitant cholecystectomy during LRYGB remains a matter of debate. The aim of this meta-analysis was to estimate the rate and morbidity of subsequent cholecystectomy after laparoscopic Roux-en-Y gastric bypass (LRYGB) in obese patients. A meta-analysis was performed analyzing the rate and morbidity of subsequent cholecystectomy in patients who underwent LRYGB without concomitant cholecystectomy. Thirteen studies met the inclusion criteria. The rate of subsequent cholecystectomy was 6.8 % (95 % CI, 5.0-8.7 %) based on 6,048 obese patients who underwent LRYGB without concomitant cholecystectomy. The rate of subsequent cholecystectomy due to biliary colic or gallbladder dyskinesia was 5.3 %; due to cholecystitis, 1.0 %; choledocholithiasis, 0.2 %; and biliary pancreatitis, 0.2 %. The mortality after subsequent cholecystectomy was 0 % (95 % CI, 0-0.1 %). The surgery-related complication rate after subsequent cholecystectomy was 1.8 % (95 % CI, 0.7-3.4 %) resulting in a risk of 0.1 % (95 % CI, 0.03-0.3 %) to suffer from a cholecystectomy-related complication in patients undergoing LRYGB without concomitant cholecystectomy. A prophylactic concomitant cholecystectomy during LRYGB should be avoided in patients without cholelithiasis and exclusively be performed in patients with symptomatic biliary disease. [ABSTRACT FROM AUTHOR]

Background: Exercise performance and pulmonary function are often impaired in severely obese subjects. Bariatric surgery represents the most effective therapy for severe obesity, but data on changes in exercise performance after massive weight loss induced by bariatric surgery have rarely been assessed so far. Methods: Exercise performance was obtained by bicycle spiroergometry in 18 severely obese patients before and at least 1 year after bariatric surgery. Additionally, pulmonary function was assessed by spirometry. Results: BMI was reduced from 46.3 ± 1.6 to 33.5 ± 1.4 kg/m after surgery. Pulmonary function (forced expiratory volume within 1 s; inspiratory vital capacity) improved after weight loss (both p ≤ 0.01). At peak exercise, heart rate (HR) peak, absolute oxygen uptake (VO) peak, and load peak did not differ between both assessments (all p > 0.25). However, relative (related to actual body weight) VO peak and workload peak were higher after than before surgery (both p ≤ 0.005), while gross efficiency peak and ventilatory equivalent peak remained unchanged (both p > 0.30). At anaerobic threshold (AT), patients showed lower HR AT and absolute VO AT after than before surgery (both p < 0.05), while absolute workload AT did not differ ( p = 0.58). In turn, relative VO AT did not change ( p = 0.30), whereas relative workload AT was higher after surgery ( p = 0.04). Also, ventilatory efficiency AT and gross efficiency AT tended to be improved (both p = 0.08). Before surgery, the patients performed 27.0 % of VO peak above their AT, while this fraction increased to 35.3 % ( p = 0.006). Conclusions: Results indicated differential changes in exercise performance, with the relative but not the absolute peak performance being improved after massive weight loss. Interestingly, anaerobic exercise tolerance was markedly improved after surgery. [ABSTRACT FROM AUTHOR]

Background: Many obese subjects suffer from an increased hedonic drive to consume palatable foods, i.e., hedonic hunger, and often show unfavorable dietary habits. Here, we investigated changes in the hedonic hunger and dietary habits after Roux-en-Y gastric bypass (RYGB) surgery. Methods: Forty-four severely obese patients were examined before and on average 15.9 ± 0.9 months after RYGB surgery with the Power of Food Scale (PFS), a questionnaire that reliably measures an individual's motivation to consume highly palatable foods but not actual consumptive behavior. Dietary habits were assessed by a food frequency questionnaire. Results: After the RYGB procedure, patients showed markedly lower aggregated PFS scores and sub-domain scores related to generally available, physically present, as well as tasted foods than before the surgery (all P < 0.001). Changes in dietary habits after the surgery were characterized by a more frequent consumption of poultry, fish, eggs, and cooked vegetables ( P < 0.008) and a less frequent consumption of chocolate ( P < 0.048), cakes/biscuits/cookies ( P = 0.09), and fruit juice/soft drinks ( P = 0.08). Conclusions: Data show a marked reduction of the hedonic drive to consume palatable food and beneficial changes in dietary habits characterized by an increased intake of protein-rich foods and vegetables and a reduced consumption of sugar-containing snacks and beverages after RYGB surgery. Based on these findings, it can be speculated that the reduction of the hedonic drive to consume palatable foods induced by RYGB surgery helps severely obese patients to establish healthier dietary habits. [ABSTRACT FROM AUTHOR]

Background Sleep loss has been shown to reduce secretory activity of the pituitary-gonadal axis in men, but the determinants of this effect are unknown. Objective To discriminate the effects of sleep duration and sleep timing on serum concentrations of luteinizing hormone ( LH), testosterone ( T) and prolactin ( PRL). Methods Fifteen young, healthy men (27·1 ± 1·3 years; BMI, 22·9 ± 0·3 kg/m2) were examined in a condition of sleep time restriction to 4 h (bedtime, 02:45 -07:00 h) for two consecutive nights and in a control condition of 8 h regular sleep (bedtime, 22:45-07:00 h). After the second night, serum concentrations of LH, T and PRL were monitored over a 15-h period. In addition, these hormones were measured in serum samples obtained in a further experiment in eight healthy men (24·5 ± 1·1 years; BMI, 23·7 ± 0·6 kg/m2) in the morning after one night of total sleep deprivation, of 4·5 h sleep (bedtime, 22:30-03:30 h), and of regular 7 h sleep (bedtime, 22:30-06:00 h). Results Serum LH, T and PRL concentrations showed characteristic diurnal variations across the 15-h period without any differences between the 4- and 8-h sleep conditions. However, total sleep deprivation and 4·5 h of sleep restricted to the first night-half markedly decreased morning T and PRL concentrations (both P ≤ 0·05). Conclusion Collectively, our data suggest that the effect of sleep restriction on pituitary-gonadal secretory activity may be modulated by sleep timing. While sleep loss in the early part of the night does not affect T and PRL, early awakening and wakefulness during the second part of the night reduces morning circulating T and PRL concentrations. [ABSTRACT FROM AUTHOR]

Proximal Roux-en Y gastric bypass (RYGB) representing the most frequently performed bariatric procedure yields a weight loss failure rate of around 20 %. In order to reduce failure rates, we established a novel distal RYGB variant characterized by a very long alimentary (Roux) limb and a short common channel. Up to 5 years, follow-up data (complication rates, weight loss, nutritional/metabolic changes) of the first 355 patients (mean ± SD preoperative age, 41.4 ± 10.8 years; BMI, 48.5 ± 11.5 kg/m) who underwent the novel Distal Very Long Roux-en Y Gastric Bypass (DVLRYGB) were analysed. Overall follow-up rate was 98.9 %, mean follow-up time 1.6 ± 1.4 years. Limb lengths were as follows: common channel 76 ± 7 cm, biliopancreatic limb 79 ± 14 cm, and alimentary (Roux) limb 604 ± 99 cm. The operation was performed laparoscopically in 95.2 % of the cases. Thirty-day mortality was zero; major and minor complication rate was 4.5 % and 10.4 %, respectively. Average excess weight loss (EWL) was >74 % 3, 4, and 5 years after the operation and failure rate defined by an EWL < 50 % remained < 6 %. Annually blood measurements revealed a relatively low incidence rate of severe nutritional deficiencies, but mild anaemia and hypoproteinemia were frequently observed. Laparoscopic revision with a proximalization of the lower anastomosis was required in 4 (1.1 %) patients. Data indicate that our DVLRYGB leads to excellent weight loss results. Furthermore, within the setting of a structured multidisciplinary follow-up program, the incidence of severe malnutrition states was relatively low. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to evaluate whether serum C-reactive protein (CRP) is a useful predictor of early post-operative complications, particularly of intestinal leaks after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Methods: The present study was a retrospective analysis of a prospectively maintained database with 809 patients who underwent LRYGB from 2002 until 2011. For 410 of these patients, at least one CRP measurement within the first seven post-operative days was available. The diagnostic value was determined by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results: Forty-nine of 410 patients (12.0 %; 95 % confidence intervals [95 % CI], 9.2-15.5 %) developed surgery-related complications. Leaks occurred in 17 patients (4.1 %; 95 % CI, 2.6-6.5 %) at a median of 5 days after surgery. CRP levels 2 days after surgery showed the highest diagnostic value for post-operative complications (AUC, 0.74; 95 % CI, 0.60-0.89). Sensitivity was 0.53 (95 % CI, 0.31-0.74) and specificity was 0.91 (95 % CI, 0.79-0.96) on day 2 (cutoff level, 229 mg/l). The sensitivity for intestinal leaks was 1.00 (95 % CI, 0.51-1.00). Conclusion: CRP on post-operative day 2 is a valuable predictor of post-operative complications, in particular intestinal leaks. Radiological imaging studies for intestinal leaks could be restricted to patients with CRP values exceeding 229 mg/l. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to evaluate the risks and benefits of concurrent prophylactic cholecystectomy (CPC) during laparoscopic Roux-en-Y gastric bypass (LRYGB). Methods: From December 2000 to November 2006, CPC during LRYGB was only performed in the presence of gallbladder pathology ( n = 140). Beginning in December 2006, CPC was performed during all LRYGB procedures ( n = 134). Exclusion criteria were open bypass procedure, previous bariatric surgery other than gastric banding, and previous cholecystectomy (CCE) or necessary concurrent CCE due to gallbladder pathology. Results: During a median follow-up of 3.1 years, 26 (18.6%; 95% CI, 12.9-25.9%) of 140 patients without CPC subsequently required a CCE, leading to a gallbladder disease-free survival rate at 5 years of 77.4% (95% CI, 67.3-87.6%). Multivariate analysis identified a distal LRYGB and excess weight loss of >75% at 2 years to be significant risk factors for the development of biliary complications while a preoperative BMI > 50 m/kg was protective. In the second series, prophylactic CCE was not associated with prolonged hospitalization or operative time. The postoperative complications were not related to the CPC. Conclusions: The present data indicate that a substantial number of patients develop gallbladder complications after LRYGB. Furthermore, CPC can safely be performed during LRYGB. Based on these findings, CPC should be considered a reasonable approach in severely obese patients undergoing LRYGB. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic evidence indicates that chronic sleep curtailment increases risk of developing obesity, but the mechanisms behind this relation are largely unknown. Objective: We examined the influence of a single night of total sleep deprivation on morning energy expenditures and food intakes in healthy humans. Design: According to a balanced crossover design, we examined 14 normal-weight male subjects on 2 occasions during a regular 24-h sleep-wake cycle (including 8 h of nocturnal sleep) and a 24-h period of continuous wakefulness. On the morning after regular sleep and total sleep deprivation, resting and postprandial energy expenditures were assessed by indirect calorimetry, and the free-choice food intake from an opulent buffet was tested in the late afternoon at the end of the experiment. Circulating concentrations of ghrelin, leptin, norepinephrine, cortisol, thyreotropin, glucose, and insulin were repeatedly measured over the entire 24-h session. Results: In comparison with normal sleep, resting and postprandial energy expenditures assessed on the subsequent morning were significantly reduced after sleep deprivation by ≈5% and 20%, respectively (P < 0.05 and P < 0.0001). Nocturnal wakefulness increased morning plasma ghrelin concentrations (P < 0.02) and nocturnal and daytime circulating concentrations of thyreotropin, cortisol, and norepinephrine (P < 0.05) as well as morning postprandial plasma glucose concentrations (P < 0.05). Changes in food intakes were variable, and no differences between wake and sleep conditions were detected. Conclusion: Our findings show that one night of sleep deprivation acutely reduces energy expenditure in healthy men, which suggests that sleep contributes to the acute regulation of daytime energy expenditure in humans. [ABSTRACT FROM AUTHOR]

Undetected nocturnal hypoglycaemia frequently occurs in patients with diabetes, having a negative influence on well-being, counterregulation against and awareness of subsequent hypoglycaemia, and even causing sudden death in some cases most likely by inducing cardiac arrhythmia. Sleep markedly weakens the neuroendocrine defence mechanism against hypoglycaemia by shifting the glycaemic threshold for counterregulatory activation to lower levels. While hypoglycaemia triggers awakening in healthy subjects, patients with type 1 diabetes frequently fail to awake in the presence of low plasma glucose levels. Little is known about the frequency of and responses to nocturnal hypoglycaemia in patients with type 2 diabetes. Unfortunately, effective strategies to prevent or even safely detect nocturnal hypoglycaemia are still lacking. Taken together, hypoglycaemia occurring during sleep presents a major, often neglected problem in the management of diabetic patients. Different aspects of this phenomenon such as responses to and consequences of nocturnal hypoglycaemia as well as strategies for its prevention are highlighted in this review. [ABSTRACT FROM AUTHOR]

Abstract: The objective of the study was to evaluate the accuracy of established prediction equations that calculate resting energy expenditure (REE) in obese women. This was a cross-sectional study. In 273 mildly to severely obese women (age, 41.7 ± 13.2 years; body mass index, 42.8 ± 7.0 kg/m2), REE was measured by indirect calorimetry (mREE), along with fat mass (FM) and fat-free mass (FFM) by bioelectrical impedance analysis. Eleven established equations were used to predict REE (pREE), with 9 equations basing on the anthropometric parameters body weight and height and 2 equations including body composition parameters (FM, FFM). All equations provided pREE values that significantly correlated with mREE (r > 0.66, P < .001), although 8 equations systematically underestimated mREE (P < .05). Of note, even the best equation was not able to accurately predict mREE with a deviation of less than ±10% in more than 70% of the tested women. Furthermore, equations using body composition data were not superior in predicting REE as compared with equations exclusively including anthropometric variables. Multiple linear regression analyses revealed 2 new equations—one including body weight and age and another including FM, FFM, and age—that explained 56.9% and 57.2%, respectively, of variance in mREE. However, when these 2 new equations were applied to an independent sample of 33 obese women, they also provided an accurate prediction (±10%) of mREE in only 56.7% and 60.6%, respectively, of the women. Data show that an accurate prediction of REE is not feasible using established equations in obese women. Equations that include body composition parameters as assessed by bioelectrical impedance analysis do not increase the accuracy of prediction. Based on our results, we conclude that calculating REE by standard prediction equations does not represent a reliable alternative to indirect calorimetry for the assessment of REE in obese women. [Copyright &y& Elsevier]

Based on our findings, we concluded that the extent of weight loss-associated QTc interval shortening largely depends on the applied heart rate correction equation and appears to be overestimated when the most popular Bazett's equation is used. Based on their meta-analysis of seven studies, the authors report on a heart rate-corrected QT (QTc) interval length shortening of - 33.6 ms, 95%CI [- 49.8 to - 17.4 ms] after bariatric surgery. [Extracted from the article]

Background: Compelling evidence indicates that central nervous insulin enhances learning and memory and in particular benefits hippocampus-dependent (i.e., declarative) memory. Intranasal administration of insulin provides an effective way of delivering the compound to the central nervous system, bypassing the blood-brain barrier and avoiding systemic side effects. Methods: Here we review a series of recent studies on the effects of intranasally administered insulin on memory functions in humans. In accordance with the beneficial effects of intravenously administered insulin on hippocampus-dependent declarative memory observed in hyperinsulinemic-euglycemic clamp studies, intranasal insulin administration similarly improves this type of memory, but in the absence of adverse peripheral side effects. Result andConclusion: Considering that cerebrospinal fluid insulin levels are reduced in patients suffering from Alzheimer’s disease, these results may be of considerable relevance for future clinical applications of insulin in the treatment of memory disorders. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

There is compelling evidence that intranasal administration of regular human insulin (RH-I) improves memory in humans. Owing to the reduced tendency of its molecules to form hexamers, the rapid-acting insulin analog insulin aspart (ASP-I) is more rapidly absorbed than RH-I after subcutaneous administration. Since after intranasal insulin administration, ASP-I may also be expected to access the brain, we examined whether intranasal ASP-I has stronger beneficial effects on declarative memory than RH-I in humans. Acute (40 IU) and long-term (4 × 40 IU/day over 8 weeks) effects of intranasally administered ASP-I, RH-I, and placebo on declarative memory (word lists) were assessed in 36 healthy men in a between-subject design. Plasma insulin and glucose levels were not affected. After 8 weeks of treatment, however, word list recall was improved compared to placebo in both the ASP-I (p<0.01) and the RH-I groups (p<0.05). ASP-I-treated subjects performed even better than those of the RH-I-treated group (p<0.05). Our results indicate that insulin-induced memory improvement can be enhanced by using ASP-I. This finding may be especially relevant for a potential clinical administration of intranasal insulin in the treatment of memory disorders like Alzheimer's disease.Neuropsychopharmacology (2007) 32, 239–243. doi:10.1038/sj.npp.1301193; published online 16 August 2006 [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is known to be upregulated by hypoxia in vitro. However, in vivo data about VEGF regulation in chronic hypoxic diseases are conflicting. We investigated the effects of hypoxia on plasma VEGF concentration in healthy subjects. To control known confounders, such as insulin, glucose concentrations, or exercise, hypoxic effects on VEGF were studied during experimentally clamping glucose concentrations at rest. In a double-blind crossover study design, we induced hypoxia for 30 min by decreasing oxygen saturation to 75% (vs. normoxic control) in 14 healthy men. Plasma VEGF concentration was determined at baseline, immediately after hypoxia had ended, and after a further 150 min. Levels of its soluble (s)Flt-1 receptor were assessed at baseline and at the end of the clamp. In parallel, catecholamine and cortisol levels were monitored. To investigate potential effects of glucose administration on the release of VEGF, we performed a third session, reducing glucose infusion for 30 min while serum insulin was held stable thereby inducing hypoglycemia. Hypoxia decreased VEGF levels compared with the normoxic control (P < 0.05). VEGF concentrations increased during hypoglycemia (P < 0.02) but were comparable to the normoglycemic control at the end of the clamp (P > 0.80). sFlt-1 receptor concentration remained unchanged during hypoxia and hypoglycemia compared with control (both P > 0.4). Epinephrine concentration (P < 0.01) increased upon hypoxia, whereas norepinephrine and cortisol did not change. Contrary to in vitro studies, in healthy humans hypoxia decreases plasma VEGF concentration, suggesting that systemic VEGF concentration may be differently regulated than the expression on cellular basis. [ABSTRACT FROM AUTHOR]