Comparison of metabolic risk factors between severely and very severely obese patients

Objective: A prospective clinical intervention study was performed to estimate the metabolic risk factors in patients with very severe obesity (VSO) vs. severe obesity (SO). Research Methods and Procedures: Two hundred twenty‐eight VSO (BMI ≥ 50 kg/m²) and 221 SO patients (BMI = 40 to 49.9 kg/m²) participated in the study (367 women and 82 men). Metabolic measurements included plasma lipids, glucose and insulin, hemoglobin A_1c, leptin, and sex hormones, as well as hepatic steatosis in a subgroup of patients. Subgroups of patients with non–insulin‐dependent diabetes and hyperlipidemia (HLP) were examined. Results: The most unexpected result of our study was that VSO men showed significantly better lipid profiles than SO men. Furthermore, 18% of VSO men had no metabolic aberrations, whereas all SO men did. The advantageous metabolic status of VSO men was associated with sex hormone changes that favor gynoid fat distribution. The beneficial metabolic situation with VSO seems to be sex specific for men. Discussion: This study shows that the metabolic situation in VSO is not more severe than in the less obese cohort. These findings distinctly differ from the positive associations that have previously been reported between BMI, lipids, and other metabolic indices among individuals whose BMI is <40 kg/m².     

Nonalcoholic fatty liver disease in severely obese adolescent and adult patients

Objectives:

Nonalcoholic fatty liver disease (NAFLD) is increasingly an indication for liver transplantation in adults. While severe obesity (SO, BMI ≥40 kg m^?2) in adults is long standing, it is recent in duration in adolescents. With adolescent obesity on the rise, NAFLD is becoming the most frequent liver disease in adolescents. The hypothesis that SO adolescents and adults have different severity of NAFLD because of longer duration of obesity in SO adults was tested.

Design and Methods:

Preoperative clinical data, NAFLD activity and NASH (Nonalcoholic steatohepatitis) scores from intraoperative liver biopsies were extracted from a prospective database of consecutively operated SO adolescents and adults (n = 24 each). Fasting preoperative serum inflammatory mediators were evaluated by ELISA.

Results:

Other than age, baseline BMI, ethnicity and gender distribution, the incidence and extent of dyslipidemia, hypertension, and metabolic syndrome were comparable between groups. Histologic scores for steatosis and inflammation were similar. Adolescents have significantly higher NASH incidence, hepatocyte injury scores and fibrosis. This was associated with higher serum C‐reactive protein and sCD14 levels.

Conclusion:

For comparable BMI and metabolic profile, SO adolescents have more advanced liver damage, more severe systemic inflammation, suggesting differences in NAFLD etiologies and more aggressive disease progression in the young obese population.

     

Biliopancreatic diversion reduces QT interval and dispersion in severely obese patients

Objectives: The objectives were to evaluate QT interval (QTc) and QT‐interval dispersion (QTd) in severely obese individuals and to determine the effects of biliopancreatic diversion (BPD) and weight loss after BPD on ventricular repolarization parameters. Background: People with severe obesity (SO) have a 50% to 100% increased risk of death associated with a 1.6‐fold increased risk of sudden death. BPD surgery induces rapid and considerable weight loss through severe lipid malabsorption, thus achieving long‐term weight control. Research Methods and Procedures: A total of 85 subjects with SO (age, 42 ± 12 years; 66 females; mean body weight, 120 ± 29 kg; BMI, 45 ± 11 kg/m²) of 330 who had a bariatric surgical consultation between January 2001 and July 2002 were enrolled. Inclusion criteria were sinus rhythm, unremarkable 12 leads surface electrocardiogram, no atrioventricular blocks and/or bundle branch blocks, normal serum electrolyte profile, and no medical therapies exerting known effects on QTc. Exclusion criteria were previous diagnosis of coronary artery disease, known cardiovascular disease, atrial fibrillation or any other known cardiac arrhythmias, cancer, or renal dysfunction. Results: A total of 86% of patients had QTc >440 ms and/or QTd >60 ms. Subjects with SO showed a mean maximum QTc of 446 ± 28 ms and a mean QTd of 52 ± 20 ms. A close correlation was found between QTc and QTd (p < 0.0001; R² = 0.33). One month after BPD, mean QTc was 420 ms and remained stable at follow‐up; QTd was 32 ms at 1 and 6 months and became 35 ms at 1 year. Conclusions: Ventricular repolarization abnormalities are significantly increased in subjects with SO. Reduction of QT abnormalities after BPD is independent of weight loss and is caused by the 100% reduction of glucose plasma shortly after surgery. This effect may be related to surgical interruption of the entero‐insular axis.     

Value of heartburn for diagnosing gastroesophageal reflux disease in severely obese patients

Objective : To evaluate the prevalence of gastroesophageal reflux disease (GERD) in severely obese patients and the association between symptoms and objective data of GERD in this population. Research Methods and Procedures : A total of 158 consecutive severely obese patients (BMI ≥ 40 kg/m²) were prospectively evaluated. Symptoms were evaluated by a structured clinical questionnaire. Objective assessment was made by ambulatory 24‐hour esophageal pH monitoring and endoscopy. GERD was defined by the presence of symptoms or complications (esophagitis). The clinical criterion defining GERD was the presence of at least two episodes of heartburn per week. Results : The mean age of the 138 patients subjected to complete study was 42.6 ± 10.2 years, with a BMI of 50.1 ± 6.9 kg/m² (range, 40.6 to 69.4 kg/m²); 78% were women. The prevalence of GERD evaluated by symptoms and/or esophagitis was 33.3% (46/138). Clinical criteria of GERD were present in 31/138 cases (22.5%), and 26 (18.8%) had esophagitis. In 69/138 patients (50%), pHmetry was abnormal. Fifty‐three patients with esophagitis and/or abnormal pHmetry were asymptomatic. The sensitivity of heartburn as a diagnostic criterion of GERD in patients with severe obesity was 29.3%, with a specificity of 85.7%. No significant association was observed between severe obesity grade and the prevalence of symptoms and/or objective data. Discussion : Asymptomatic gastroesophageal reflux (abnormal esophageal acid exposure and/or reflux esophagitis) is more common than symptomatic gastroesophageal reflux in severely obese patients. Increased BMI is not associated with a greater prevalence of GERD in these patients.     

Relation of left ventricular mass to QTc in normotensive severely obese patients

Prolongation of the corrected QT interval (QTc) has been described in obese subjects. This study assesses the relation of left ventricular (LV) mass to QTc in normotensive severely obese subjects. Fifty normotensive patients whose BMI was ≥40 kg/m(2) (mean age: 38 ± 7 years) were studied. QTc was derived using Bazett's formula. LV mass was calculated using the formula of Devereux et al. and was indexed to height(2.7). Mean QTc was 428.8 ± 19.0 ms and was significantly longer in those with than in those without LV hypertrophy (P < 0.01) QTc correlated positively and significantly with BMI (r = 0.392, P < 0.025), LV mass/height(2.7) (r = 0.793, P < 0.0005), systolic blood pressure (r = 0.742, P < 0.001), LV end - systolic wall stress (r = 0.746, P < 0.001) and LV internal dimension in diastole (r = 0.788, P < 0.0005). Among five variables tested, LV mass/height(2.7) was identified as the sole predictor of QTc by multivariate analysis. In conclusion, LV mass and loading conditions that may affect LV mass are important determinants of QTc in normotensive severely obese subjects.     

New specific equation to estimate resting energy expenditure in severely obese patients

Calculating the estimated resting energy expenditure (REE) in severely obese patients is useful, but there is controversy concerning the effectiveness of available prediction equations (PE) using body weight (BW). We evaluated the efficacy of REE equations against indirect calorimetry (IC) in severely obese subjects and aimed to develop a new equation based on body composition compartments. One hundred and twenty severely obese patients had their REE measured (MREE) by IC and compared to the most commonly used PE (Harris-Benedict (HB), Ireton-Jones, Owen, and Mifflin St. Jeor). In a random sample (n = 60), a new REE equation based on fat-free mass (FFM) was developed and validated. All PE studied failed to estimate REE in severe obesity (low concordance correlation coefficient (CCC) and limits of agreement of nearly 50% of the sample ±10% of MREE). The HB equation using actual BW exhibited good results for all samples when compared to IC (2,117 ± 518 kcal/day by HB vs. 2,139 ± 423 kcal/day by MREE, P > 0.01); these results were blunted when patients were separated by gender (2,771 vs. 2,586 kcal/day, P < 0.001 in males and 1,825 vs. 1,939 kcal/day, P < 0.001 in females). A new resting energy expenditure equation prediction was developed using FFM, Horie-Waitzberg, & Gonzalez, expressed as 560.43 + (5.39 × BW) + (14.14 × FFM). The new resting energy expenditure equation prediction, which uses FFM and BW, demonstrates higher accuracy, precision, CCC, and limits of agreement than the standard PE in patients when compared to MREE (2,129 ± 45 kcal/day vs. 2,139 ± 423 kcal/day, respectively, P = 0.1).The new equation developed to estimate REE, which takes into account both FFM and BW, provides better results than currently available equations.     

Body surface area prediction in normal-weight and obese patients

None of the equations frequently used to predict body surface area (BSA) has been validated for obese patients. We applied the principles of body size scaling to derive an improved equation predicting BSA solely from a patient's weight. Forty-five patients weighing from 51.3 to 248.6 kg had their height and weight measured on a calibrated scale and their BSA calculated by a geometric method. Data were combined with a large series of published BSA estimates. BSA prediction with the commonly used Du Bois equation underestimated BSA in obese patients by as much as 20%. The equation we derived to relate BSA to body weight was a power function: BSA (m(2)) = 0.1173 x Wt (kg)(0.6466). Below 10 kg, this equation deviated significantly from the BSA vs. body weight curve, necessitating a different set of coefficients: BSA (m(2)) = 0.1037 x Wt (kg)(0.6724). Covariance of height and weight for patients weighing <80 kg reduced the Du Bois BSA-predicting equation to a power function, explaining why it provides good BSA predictions for normal-size patients but fails with obesity.     

Insights gained into the interpretation of surface electromyograms from the gastrocnemius muscles: A simulation study

Interpretation of surface electromyograms (EMG) is usually based on the assumption that the surface representation of action potentials does not change during their propagation. This assumption does not hold for muscles whose fibers are oblique to the skin. Consequently, the interpretation of surface EMGs recorded from pinnate muscles unlikely prompts from current knowledge. Here we present a complete analytical model that supports the interpretation of experimental EMGs detected from muscles with oblique architecture. EMGs were recorded from the medial gastrocnemius muscle during voluntary and electrically elicited contractions. Preliminary indications obtained from simulated and experimental signals concern the spatial localization of surface potentials and the myoelectric fatigue. Specifically, the spatial distribution of surface EMGs was localized about the fibers superficial extremity. Strikingly, this localization increased with the pinnation angle, both for the simulated EMGs and the recorded M-waves. Moreover, the average rectified value (ARV) and the mean frequency (MNF) of interference EMGs increased and decreased with simulated fatigue, respectively. The degree of variation in ARV and MNF did not depend on the pinnation angle simulated. Similar variations were observed for the experimental EMGs, although being less evident for a higher fiber inclination. These results are discussed on a physiological context, highlighting the relevance of the model proposed here for the interpretation of gastrocnemius EMGs and for conceiving future experiments on muscles with pinnate geometry.     

Computer-assisted evaluation of surface electromyograms of 8 different arm muscles]

The aim of the present study was, via digitization of the EMG signals and processing them in the computer, to make possible effective evaluation of electromyographically detectable modifications of the activity of the forearm muscles developing during wrist movements under defined conditions of loading. The search for the optimal measuring parameter was of particular importance. In groups of test subjects the electric voltage potentials generated by 8 arm muscles were measured simultaneously on the skin and evaluated using suitable variables (integral, RMS [root mean square] value, mean amplitude, summed amplitude, amplitude peak count [peaks], zero crossings) with the aid of a PC and a computer program specially developed for the task. On evaluation it was found that the parameters reacting sensitively mainly to amplitude size--integral, RMS value, mean amplitude height and summed amplitude--reflected, with gradually decreasing clarity, the activities of each muscle. The correlation among the first three parameters was almost linear. The parameters sensitive primarily to frequency modulations, such as peaks and number of zero crossings, yielded little information under the load applied. They did not adequately reflect the extension and flexion of the hand.     

Tissue leptin and plasma insulin are associated with lipoprotein lipase activity in severely obese patients

The development of metabolic complications of obesity has been associated with the existence of depot-specific differences in the biochemical properties of adipocytes. The aim of this study was to investigate, in severely obese men and women, both gender- and depot-related differences in lipoprotein lipase (LPL) expression and activity, as well as the involvement of endocrine and biometric factors and their dependence on gender and/or fat depot. Morbidly obese, nondiabetic, subjects (9 men and 22 women) aged 41.1+/-1.9 years, with a body mass index (BMI) of 54.7+/-1.7 kg/m(2) who had undergone abdominal surgery were studied. Both expression and activity of LPL and leptin expression were determined in adipose samples from subcutaneous and visceral fat depots. In both men and women, visceral fat showed higher LPL mRNA levels as well as lower ob mRNA levels and tissue leptin content than the subcutaneous one. In both subcutaneous and visceral adipose depots, women exhibited higher protein content, decreased fat cell size and lower LPL activity than men. The gender-related differences found in abdominal fat LPL activity could contribute to the increased risk for developing obesity-associated diseases shown by men, even in morbid obesity, in which the massive fat accumulation could mask these differences. Furthermore, the leptin content of fat depots as well as plasma insulin concentrations appear in our population as the main determinants of adipose tissue LPL activity, adjusted by gender, depot and BMI.     

Gastric bypass surgery reduces plasma ceramide subspecies and improves insulin sensitivity in severely obese patients

Bariatric surgery is associated with near immediate remission of type 2 diabetes and hyperlipidemia. The mechanisms underlying restoration of normal glucose tolerance postoperatively are poorly understood. Herein, we examined the effect of Roux‐en‐Y gastric bypass surgery (RYGB) on weight loss, insulin sensitivity, plasma ceramides, proinflammatory markers, and cardiovascular risk factors before and at 3 and 6 months after surgery. Thirteen patients (10 female; age 48.5 ± 2.7 years; BMI, 47.4 ± 1.5 kg/m²) were included in the study, all of whom had undergone laparoscopic RYGB surgery. Insulin sensitivity, inflammatory mediators and fasting lipid profiles were measured at baseline, 3 and 6 months postoperatively, using enzymatic analysis. Plasma ceramide subspecies (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. At 3 months postsurgery, body weight was reduced by 25%, fasting total cholesterol, triglycerides, low‐density lipoproteins, and free fatty acids were decreased, and insulin sensitivity was increased compared to presurgery values. These changes were all sustained at 6 months. In addition, total plasma ceramide levels decreased significantly postoperatively (9.3 ± 0.5 nmol/ml at baseline vs. 7.6 ± 0.4 at 3 months, and 7.3 ± 0.3 at 6 months, P < 0.05). At 6 months, the improvement in insulin sensitivity correlated with the change in total ceramide levels (r = ?0.68, P = 0.02), and with plasma tumor necrosis factor‐α (TNF‐α) (r = ?0.62, P = 0.04). We conclude that there is a potential role for ceramide lipids as mediators of the proinflammatory state and improved insulin sensitivity after gastric bypass surgery.     

Depot- and gender-related differences in the lipolytic pathway of adipose tissue from severely obese patients.

The present study was performed to analyze in detail gender- and site-related alterations in the adrenergic signal transduction pathway of lipolysis in fat cells isolated from subcutaneous abdominal and visceral fat depots from severely obese patients. The study group consisted of 30 morbidly obese subjects (9 men and 21 women) aged 41.1+/-1.9 years, with a body mass index (BMI) of 54.7+/-1.7 kg/m2, who had undergone abdominal surgery. Protein levels of hormone-sensitive lipase (HSL) and adrenergic receptors (AR), as well as HSL activity and the lipolytic response to adrenergic agents were analyzed. Both fat depots had similar basal lipolysis, but the capacity of catecholamines to activate lipolysis was greater in visceral fat, both at AR and postreceptor levels. Basal lipolysis and lipolytic activity induced by dibutyryl cyclic AMP were higher in men than in women. However, the visceral depot of women showed a higher maximal stimulation by noradrenaline than that of men, in accordance with higher beta1- and beta3-AR protein levels. In conclusion, the main gender-related differences were located in the visceral depot, with women exhibiting a higher sensitivity to catecholamines associated with an increased provision of beta-AR, while men showed an enhanced lipolytic capacity at the postreceptor level.     

Long-term mortality in a cohort of severely obese persons in Italy

Few large studies on Northern European or US populations reported on mortality of severely obese individuals (BMI > or = 40 kg/m(2)). We studied a historical cohort in Italy to compare its mortality with previous findings, to investigate its relationship with BMI in the >40 range, and to provide evidence useful for clinical decision-making on treatment. The cohort comprised 4,837 persons with a BMI > or =40 kg/m(2) and aged > or =18 at first consultation, referred to six centers for obesity treatment between 1975 and 1996. After exclusion of persons with missing personal identification data or those untraceable, 4,498 (972 men, 3,526 women) remained for analyses. We calculated standardized mortality ratios (SMRs) and carried out Cox proportional hazards modeling. General mortality (484 deaths: 153 men, 331 women) was in excess, with SMRs (95% confidence intervals) of 2.78 (2.36-3.26) for men and 2.10 (1.88-2.34) for women. Excess mortality (i) was observed in all BMI categories, except among women weighing 40-42.4 kg/m(2); (ii) increased with increasing BMI; (iii) increased less among persons recruited in recent calendar periods; (iv) was inversely related to age attained at follow-up; and (v) was due to cardiovascular and respiratory diseases and violent deaths but not malignant neoplasms. Excess mortality was similar to that observed in Northern European and US cohorts. Its steady increase with BMI levels > or =40 suggests that benefits proportional to weight reduction are expected and that even limited control may be beneficial. The smaller excess among persons recruited most recently might reflect better treatment.     

Short-term psychological outcomes in severely obese adolescents after bariatric surgery

Bariatric surgery is suggested as a treatment option for severely obese adolescents. Because adolescence is characterized by intense psychosocial adjustment and development, it is important to study the effect of this procedure on adolescents' psychological health. This study examined baseline status and short-term changes in anxiety, depression, anger, disruptive behavior, and self-concept in 37 adolescents (mean age 16.6 ± 1.3). Participants completed the Beck Youth Inventories (BYI) at inclusion and (on average) 4 months after undergoing Roux-en-Y gastric bypass (RYGB). Internalizing (anxiety and depression) and externalizing (anger and disruptive behavior) symptoms were higher at baseline than gender-specific norms. One fifth had a very low self-concept. Four months after surgery, the adolescents showed significantly fewer symptoms of anxiety and depression and significantly improved self-concept from baseline. Anger and disruptive behavior showed no significant changes. An analysis of clinically meaningful changes was conducted, and besides the overall positive outcome, 16% (n = 6) of the adolescents had deteriorated on two or more inventories in BYI shortly after surgery. This impaired group did not show any specific features at inclusion. The results indicate the importance of psychological monitoring immediately after bariatric surgery and the need for additional psychosocial support to be available for vulnerable sub-groups of adolescents. Further studies with larger samples are necessary to identify characteristics predictive of short-term adverse psychological outcomes in adolescents after bariatric surgery.