Severe Obese Subjects Research Articles

The effects of laparoscopic Roux-en-Y gastric bypass and one-anastomosis gastric bypass on glycemic control and remission of type 2 diabetes mellitus: study protocol for a multi-center randomized controlled trial (the DIABAR-trial)

BackgroundMetabolic surgery induces rapid remission of type 2 diabetes mellitus (T2DM). There is a paucity of high level evidence comparing the efficacy of the laparoscopic Roux-en-Y gastric bypass (RYGB) and the laparoscopic one-anastomosis gastric bypass (OAGB) in glycemic control. Also, the mechanisms that drive the conversion of T2DM in severe obese subjects to euglycemia are poorly understood.MethodsThe DIABAR-trial is an open, multi-center, randomized controlled clinical trial with 10 years follow-up which will be performed in 220 severely obese patients, diagnosed with T2DM and treated with glucose-lowering agents. Patients will be randomized in a 1:1 ratio to undergo RYGB or OAGB. The primary outcome is glycemic control at 12 months follow-up. Secondary outcome measures are diverse and include weight loss, surgical complications, psychologic status and quality of life, dietary behavior, gastrointestinal symptoms, repetitive bloodwork to identify changes over time, glucose tolerance and insulin sensitivity as measured by mixed meal tests, remission of T2DM, presence of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in liver biopsy, oral and fecal microbiome, cardiovascular performance, composition of bile acids, and the tendency to develop gallstones.DiscussionThe DIABAR-trial is one of the few randomized controlled trials primarily aimed to evaluate the glycemic response after the RYGB and OAGB in severe obese patients diagnosed with T2DM. Secondary aims of the trial are to contribute to a deeper understanding of the mechanisms that drive the remission of T2DM in severe obese patients by identification of microbial, immunological, and metabolic markers for metabolic response and to compare complications and side effects of RYGB and OAGB.Trial registrationClinicalTrials.gov NCT03330756; date first registered: October 13, 2017.

Effect of various weight loss interventions on serum NT-proBNP concentration in severe obese subjects without clinical manifest heart failure

Obesity is associated with a “natriuretic handicap” indicated by reduced N-terminal fragment of proBNP (NT-proBNP) concentration. While gastric bypass surgery improves the natriuretic handicap, it is presently unclear if sleeve gastrectomy exhibits similar effects. We examined NT-proBNP serum concentration in n = 72 obese participants without heart failure before and 6 months after sleeve gastrectomy (n = 28), gastric bypass surgery (n = 19), and 3-month 800 kcal/day very-low calorie diet (n = 25). A significant weight loss was observed in all intervention groups. Within 6 months, NT-proBNP concentration tended to increase by a median of 44.3 pg/mL in the sleeve gastrectomy group (p = 0.07), while it remained unchanged in the other groups (all p ≥ 0.50). To gain insights into potential effectors, we additionally analyzed NT-proBNP serum concentration in n = 387 individuals with different metabolic phenotypes. Here, higher NT-proBNP levels were associated with lower nutritional fat and protein but not with carbohydrate intake. Of interest, NT-proBNP serum concentrations were inversely correlated with fasting glucose concentration in euglycemic individuals but not in individuals with prediabetes or type 2 diabetes. In conclusion, sleeve gastrectomy tended to increase NT-proBNP levels in obese individuals and might improve the obesity-associated “natriuretic handicap”. Thereby, nutritional fat and protein intake and the individual glucose homeostasis might be metabolic determinants of NT-proBNP serum concentration.

Altered GH-IGF-1 Axis in Severe Obese Subjects is Reversed after Bariatric Surgery-Induced Weight Loss and Related with Low-Grade Chronic Inflammation.

Endocrine disorders are common in obesity, including altered somatotropic axis. Obesity is characterized by reduced growth hormone (GH) secretion, although the insulin-like growth factor-1 (IGF-1) values are controversial. The aim of this study was to evaluate the effect of weight loss after bariatric surgery in the GH–IGF-1 axis in extreme obesity, in order to investigate IGF-1 values and the mechanism responsible for the alteration of the GH–IGF-1 axis in obesity. We performed an interventional trial in morbidly obese patients who underwent bariatric surgery. We included 116 patients (97 women) and 41 controls (30 women). The primary endpoint was circulating GH and IGF-1 values. Circulating IGF-1 values were lower in the obese patients than in the controls. Circulating GH and IGF-1 values increased significantly over time after surgery. Post-surgery changes in IGF-1 and GH values were significantly negatively correlated with changes in C-reactive protein (CRP) and free T4 values. After adjusting for preoperative body mass index (BMI), free T4 and CRP in a multivariate model, only CRP was independently associated with IGF-1 values in the follow-up. In summary, severe obesity is characterized by a functional hyposomatotropism at central and peripheral level that is progressively reversible with weight loss, and low-grade chronic inflammation could be the principal mediator.

578-P: A Loss-of-Function Mutation of NRG4 Contributes to the Pathogenesis of NAFLD and Insulin Resistance

Neuregulin 4 (Nrg4), as an adipose tissue-enriched endocrine factor, participates in adipocyte-to-hepatocyte communication which elicits beneficial metabolic effects in NAFLD. We identified a mutation of NRG4 by whole exome sequencing in 151 severe obese subjects and exome array in a community-based population of 2388 subjects. Nrg4 R44H mutation carriers have increased visceral fat area, abnormal liver function and hyperlipidemia. Then we hypothesized that the mutation would affect the function of Nrg4 and accelerated the development of NAFLD. Compared with Nrg4 WT mice, Nrg4 R44H mice gained more weight, accompanied by significantly increased fat mass and lipid accumulation in the liver upon HFD feeding. In vitro, we found that Nrg4 WT activated ErbB4 and stimulated the STAT5 signaling pathway and decreased transcriptional activation of srebp1c. As we hypothesized, the primary hepatocytes treated with Nrg4 R44H purified protein didn’t showed the same activation of cell signaling as Nrg4 WT. In order to reveal the potential mechanisms of loss-of-function of Nrg4 R44H, we performed surface plasmon resonance (SPR) experiments to test the binding affinity of purified Nrg4 and ErbB4 proteins. The SPR results showed Nrg4 WT bind to ErbB4 with an affinity of 2.20uM, while Nrg4 R44H showed no binding. Taken together, these results suggested Nrg4 WT prevented HFD-induced NAFLD and alleviated insulin resistance, and demonstrated Nrg4 R44H lost its ability to bind to the receptor ErbB4, thus losing its physiological function. Disclosure C. Hu: None. Y. Li: None.

Diagnostic of hepatic fibrosis with the XL probe of the Fibroscan versus biopsies in patients candidates to bariatric surgery

The risks of the histological evaluation for metabolic liver disease in severe obese subjects led to the development of the Fibroscan® device. The main objective of our study is to evaluate the diagnostic performance of XL probe for the measurement of hepatic fibrosis compared to histological examination, in obese subjects operated from bariatric surgery. We included patients free from chronic liver diseases. Liver measurement and controlled attenuation parameter (CAP) were carried out using the Fibroscan®. Liver biopsies were performed during bariatric surgery and evaluated by two pathologists. Correlation between vibration-controlled transient elastography (VCTE) and fibrosis stage was assessed using the Kendall correlation coefficient. Diagnosis performance was assessed using receiver-operating-characteristic curve analysis together with its 95% confidence interval. Cut-off value maximizing the Youden index was computed together with specificity, sensitivity, positive and negative predictive values. The average age and body mass index were 41 years and 43kg/m2, respectively (n=108). Forty-one percent of patients presented fibrosis on the histological results. The Kendall correlation coefficient between fibrosis stage and liver stiffness measurement (LSM) was κ=0.33, p<10-5. ROC analysis for the detection of fibrosis indicated the following values: 0.70 [0.60-0.79] for F≥1, 0.83 [0.72-0.92] for F≥2, 0.90 [0.83-0.97] for F≥3. Optimal cut-offs maximizing the Youden index were 7.0kPa for F≥1, 8.1kPa for F≥2 and 8.7kPa for F≥3. Fibroscan® appears to be reliable for detection of significant and severe fibrosis in severe obese patients such as candidates for bariatric surgery. NCT03548597.

Exercise and apulian hypocaloric diet affect adipokine changes and gastric banding-induced weight loss: A prospective study on severe obese subjects.

BackgroundAdiponectin and Resistin correlate with insulin sensitivity and cardiovascular risk, respectively. This study aimed to identify lifestyle factors that modulate changes in Adiponectin and Resistin levels after gastric banding positioning (LapGB).Materials and methodsBefore (T0), 3 months (T3), 6 months (T6), and 12 months (T12) after LapGB, serum Adiponectin and Resistin levels were evaluated in a single-centre prospective study including a cohort of 27 non-diabetic obese subjects (S-Ob, BMI ≥35 kg/m2). After surgery, a dietitian checked the adherence of S-Ob to an Apulian hypocaloric diet (aphypoD)/physical activity (phA) and, according to their high or low compliance to aphypoD/phA, S-Ob were included in group 1 (n = 14) or 2 (n = 13) respectively. Serum Adiponectin and Resistin were also measured in 10 healthy controls.ResultsAt baseline, Resistin levels were significantly higher and Adiponectin levels significantly lower in S-Ob than in controls. After surgery, group 1 showed a 50.2% excess weight loss (%EWL), significantly decreased Resistin levels at T12 and increased Adiponectin levels at both T6 and T12 as compared with baseline. Group 2 showed 24.6 %EWL at T12, decreased Adiponectin levels at T6 and T12 as compared with baseline, but unaltered Resistin levels. After surgery, group 1 followed aphypoD/phA, while group 2 did not.ConclusionsLapGB fails to improve cardiovascular risk markers (Resistin) in S-Ob not improving lifestyle. Future studies might investigate these findings in a larger cohort and display whether aphypoD is more effective than other dietary intervention on cardiovascular risk in subjects undergoing LapGB or other Bariatric procedures.

Bariatric surgery reduces the risk of developing type 2 diabetes in severe obese subjects undergoing sleeve gastrectomy

BackgroundObesity is a major independent risk factor for developing type 2 diabetes (T2D). ObjectivesOur goal in this study was to analyze the impact of laparoscopic sleeve gastrectomy in the risk reduction of developing T2D in middle-aged, severely obese nondiabetes patients. SettingUniversity Hospital, United States. MethodsWe retrospectively reviewed our prospectively collected database from 2010 to 2016. All severely obese patients between 45 and 64 years of age without diabetes at baseline that underwent sleeve gastrectomy were included in our study. The T2D risk score for predicting the incidence of diabetes was measured preoperatively and at 12 months postoperatively and was based on the Framingham Offspring Study that calculates an 8-year risk of developing T2D. ResultsOf the 1330 patients included in this study, 6.5% (n = 86) met the criteria for the T2D risk score calculation. The population was predominantly composed of females (68.9%; n = 59) with a mean age of 52.8 ± 5.3 years. Preoperative body mass index was 43.1 ± 6.9 kg/m2 with a percentage of estimated body mass index loss and percentages of total weight loss were 72.2 ± 26.3% and 26.39 ± 18.15%, respectively, with fasting plasma glucose of 103.3 ± 14.9 mg/dL. The preoperative risk for T2D was 13.9 ± 11.6%, with an absolute risk reduction 12 months after surgery of 10.3%, corresponding to a 74.2% relative risk reduction. When comparing between sexes, risk reduction in females was slightly better than in males; however, this was not statistically significant. At 12-month follow-up, all measured variables were significantly improved, except for diastolic blood pressure. ConclusionsLaparoscopic sleeve gastrectomy significantly decreases the risk of developing T2D in middle-aged severely obese patients. Prospective studies are needed to further understand these findings.

Long-term effect of weight loss induced by bariatric surgery on asthma control and health related quality of life in asthmatic patients with severe obesity: A pilot study

BackgroundThe weight loss induced by bariatric surgery (BS) improves asthma clinical control evaluated usually after a short time. The long-term effects of weight loss attained by BS on asthma control and health related-quality of life (HRQoL) in patients affected by asthma and obesity are not known. ObjectiveTo investigate the five-year effect of weight reduction induced by BS on asthma control, quality of life and pulmonary functional parameters in severely obese intermittent or mild-to-moderate asthmatic patients. MethodsTwenty-six consecutive severe obese subjects with previous diagnosis of asthma with indication for laparoscopic adjustable gastric banding (LAGB) were enrolled into the study. Fifteen of them agreed to undertake the surgery (treatment group, TG) while the remaining eleven non-operated patients represented the control group (CG). Body mass index (BMI), Asthma Control Test (ACT), Mini Asthma Quality of Life Questionnaire (mini-AQLQ) and spirometric parameters were evaluated at baseline and after one and five years from surgery. ResultsMean BMI of TG significantly decreased at one and five years after the surgery, while it remained unchanged in CG. After surgery, both the overall ACT and the mini-AQLQ score significantly improved in TG after one year, persisting improved after 5-years (p < 0.001), while these outcomes remained unchanged in CG. As compared with the pre-surgery values, the percentage of predicted FEV1 and FVC significantly increased at five-year follow-up from surgery in TG, while it remained unchanged in CG. ConclusionsIn severe obese asthmatic patients, the significant improvement of asthma control test and HRQoL, observed one year after LAGB, persists five years after surgery.

Association study between near-MC4R variants and obesity-related variables in Portuguese young adults

The aim of this study was to investigate in a population sample of Portuguese young adults i) the association of near-MC4R variants with obesity measures; and ii) the presence of mutations in MC4R coding region contributing to severe obesity. Polymorphisms rs17782313, rs12970134 and rs9944545 were genotyped in 544 subjects (225 males, 319 females; mean age 20.7years) by TaqMan assay. Body Mass Index (BMI) was calculated (kg/m2) and percentage of body fat (%FAT) was measured using bioimpedance analysis. The coding region of MC4R gene was examined in nine severe obese subjects (BMI>35kg/m2) by Sanger sequencing. Linear regression showed no associations between variants rs17782313, rs12970134 and rs9944545 and BMI (P=0.459, P=0.691 and P=0.611, respectively) or %FAT (P=0.853, P=0.678 and P=0.434, respectively). The logistic regression, in the additive model, revealed no statistically significant interactions with overweight/obesity for any SNP (P=0.717, P=0.771 and P=0.417, respectively). Also, haplotype analysis revealed no significant associations testing for BMI, %FAT or the obesity status. Genomic DNA sequencing of the MC4R coding region revealed no variations explaining the severely obese phenotype. As main conclusion, this study in young Portuguese adults does not replicate previous findings evidencing the association of near-MC4R polymorphisms with human obesity. Nevertheless, the obtained data is in accordance with several studies reporting no such associations.

Editorial: New Translational Insights on Metabolic Syndrome: Obesity, Hypertension, Diabetes and Beyond.

Editorial: New Translational Insights on Metabolic Syndrome: Obesity, Hypertension, Diabetes and Beyond.

Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects

IntroductionObesity is associated with low-grade systemic inflammation which is thought to trigger the development of comorbidities such as type 2 diabetes. The soluble receptor for advanced glycation end products (sRAGE) belongs to the innate immune system and has been linked to obesity, recently. The aim of the present study was to examine whether serum sRAGE concentrations are related to the grade of weight loss and improvement of insulin resistance due to a very low calorie diet (VLCD). Methods22 severe obese subjects (Median Body Mass Index (BMI): 44.5kg/m2) were included in a dietary intervention study of 6month, consisting of a very low calorie formula diet phase (VLCD: 800kcal/d) for 12weeks and a following 12week weight maintenance phase. Fasting glucose, fasting insulin, adiponectin, leptin and sRAGE were determined from sera. Insulin sensitivity was estimated by Homeostasis Model Assessment (HOMA) index and leptin-to-adiponectin-ratio (LAR). ResultsMean body weight reduction by VLCD accounted to 21.7kg with a significant improvement of insulin resistance. At baseline, sRAGE serum levels were significantly inversely related to BMI (rS=−0.642, p=0.001) and HOMA (rS=−0.419, p=0.041). Of interest, sRAGE serum levels at baseline were significantly lower in study subjects with greater reduction of BMI (p=0.017). In addition, a significantly greater HOMA reduction was observed in subjects with lower sRAGE serum levels at baseline (p=0.006). Finally, correlation analysis revealed, that changes of sRAGE serum levels were significantly correlated to changes of BMI (rS=−0.650, p=0.022) during intervention. ConclusionAnti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention.

Inflammation in Adipose Tissue and Fatty Acid Anabolism: When Enough is Enough!

Recent findings in adipose tissue (AT) have uncovered negative interactions among obesity, lipogenesis, and fatty acid (FA) storage, perhaps in response to the increased production of proinflammatory cytokines and transcription factors. Emerging evidence highlights that local hypoxia, generation of reactive oxygen and nitrogen species, increased immune cells infiltration and activation, senescence, inflammation, energy consumption, and decreased lipogenesis in the AT are interrelated and may lead to impaired cytokine and hormonal secretion by adipocytes, and ectopic fat deposition in obesity that strengths the increased risk of suffering metabolic disorders in obese subjects. The information summarized in this review attempts to defend the interdependent relationship of these proofs of concept, supporting the idea that "inflamed" and "dysfunctional" AT are synonymous when referring to obesity. This may happen in severe obese subjects with a large and long-lasting fat excess, when fat depots have reached the point in which excessive fat storage, cell density, and diminished oxygen availability promote decreased lipo/adipogenesis and increased lipolysis and FA release. This response may be induced by an important inflammatory component that promotes angiogenesis and insulin resistance, but also by leptin and the increase of T3 in hyperplastic AT.

Plasma ω-3 fatty acid levels negatively and ω-6 fatty acid levels positively associated with other cardiovascular risk factors including homocysteine in severe obese subjects.

Obesity and homocysteine (tHcy) are important risk factors for cardiovascular diseases (CVD). Plasma omega-3 fatty acids (ω-3 FAs) and omega-6 fatty acids (ω-6 FAs) are essential fatty acids with diverse biological effects in human health and disease. We have investigated the relation of plasma ω-3 FAs and ω-6 FAs levels with other cardiovascular risk factors including tHcy in severe obese subjects. This study was performed on 96 severe obese and 65 normal weight subjects. Plasma fatty acid composition was measured by GC/MS and serum tHcy level was measured by HPLC methods. There were no differences between groups in terms of concentrations of serum tHcy, plasma ω-3 FAs, ω-6 FAs and ω-3/ω-6 ratio, whereas serum vitamin B-12 (p<0.01) and folic acid (p<0.05) levels were lower than those of the normal weight subjects. Homocysteine positively correlated with ω-6 FAs and negatively correlated with ω-3 FAs in severe obese and normal weight subjects. Serum vitamin B-12 positively correlated with ω-3 FAs (p<0.01) and ω-3/ω-6 ratio (p<0.01) and negatively correlated with ω-6 FAs (p<0.05) in severe obese subjects. Serum folic acid positively correlated with ω-3 FAs (p<0.01) in severe obese subjects. Our results suggest an association between the plasma ω-3 FAs and ω-6 FAs and serum tHcy concentrations in severe obese and normal weight subjects. Low levels vitamin B-12 and folic acid may have been responsible for the elevated tHcy levels in severe obese subjects, increasing the risk for future development of cardiovascular diseases.

Association of copy number variation in the AHI1 gene with risk of obesity in the Chinese population

The prevalence of obesity has increased dramatically over the past decade. Gene copy number variants (CNVs) have been recognized as a hereditable source of susceptibility in human complex diseases including obesity. Recent studies have shown that Abelson helper integration site 1 (Ahi1) gene has a significant contribution in the homeostasis regulation in mouse models of obesity. A study was therefore carried out to investigate whether CNVs in AHI1 gene contribute to human obesity. We analyzed samples from 70 Chinese overweight adults and 74 healthy controls for DNA copy number change using the Affymetrix single-nucleotide polymorphism (SNP) 6.0 array. Validation of CNVs of AHI1 was achieved by real-time PCR using the ΔΔC(t) method. Copy number gain analysis revealed significant gains (P=0.0017) of AHI1 gene copy number in 17 of 70 (24.3%) samples but only four of 74 (5.4%) controls overall. Then we studied the frequency distribution of CNVs in AHI1 gene according to body mass index (BMI) grade. Five out of 28 (18.5%) at-risk obese, six out of 26 (26.9%) moderate obese, and six out of 17 (29.4%) severe obese subjects studied showed increased AHI1 gene copy number. The result suggested that there was a significant linear trend for increasing AHI1 gene copy number frequencies with increasing BMI.

Impact of Bariatric Surgery on Pulmonary Function and Nitric Oxide in Asthmatic and Non-Asthmatic Obese Patients

Background. Asthma is an important co-morbidity of obesity. This study evaluated the impact of bariatric surgery on respiratory function in obese patients and compared the outcomes in asthmatic and non-asthmatic subjects. Methods. The study was observational and prospective and included subjects on waiting list for bariatric surgery. Pulmonary function, symptoms, and exhaled nitric oxide were assessed before surgery and 1 year after. Results. Twenty-nine severe obese subjects (age range: 25–66 years) with a mean body mass index of 44.8 ± 4.7 kg/m2 were included. Fourteen of them had also intermittent to moderate asthma. In the whole population, the body mass index decreased from 44.8 ± 4.7 to 41.1 ± 3.9 kg/m2 (p = .0001) and the forced vital capacity increased from 3.05 ± 0.83 to 3.50 ± 0.81 L (p = .043). No change was seen in forced expiratory volume and oxygen saturation. These results remained valid also analyzing asthmatics and non-asthmatics separately. Concerning nitric oxide, the decrease at 1 year was significantly different between the two populations, since in asthma patients exhaled nitric oxide decreased by 4.86 ppb after bariatric surgery and increased by 0.27 ppb in non-asthmatics (p = .04). Conclusions. Bariatric surgery significantly reduces the intake of inhaled corticosteroids and the levels of exhaled nitric oxide, thus bronchial inflammation, in asthmatics.

The effects of weight loss due to gastric banding and lifestyle modification on red blood cell aggregation and deformability in severe obese subjects

To investigate the changes in the aggregation index (AI) and the elongation index (EI), in severe obese subjects (MbObS) undergoing laparoscopic adjustable gastric banding (LAGB). AI and EI are measured by Laser assisted Optical Rotational Red Cell Analyzer (LORCA) and are markers of erythrocyte aggregation and deformability, respectively. Before, 3 and 6 months after LAGB plus lifestyle changes (Mediterranean diet plus daily moderate exercise), we evaluated AI, EI, body mass index (BMI), total (ToT) cholesterol (Chol), high-density lipoprotein (HDL)-Chol, low-density lipoprotein (LDL)-Chol, triglycerides and fasting glucose and insulin levels in 20 MbObS. The Student's t-test was used for comparisons between independent groups and the analysis of variance to assess differences in AI and EI at the 3 time points. Pearson's correlation coefficient was used to assess correlation among continuous variables and multiple linear regression analysis to assess predictive factors for AI and EI changes. BMI and all blood parameters showed a statistically significant decline 3 and 6 months after LAGB as compared with basal, except for EI and HDL-Chol that significantly increased. Stepwise selection of predictors shows that at 3 and 6 months, EI values depended on HDL-Chol values at the same time point. In the EI model, blood glucose was also statistically significant at 6 months. Our data show a significant improvement in EI after LAGB-induced weight loss, which correlates with an improved lipid pattern and support the idea that the rapid weight loss induced by LAGB plus lifestyle changes might reduce the thromboembolic risk and the high mortality risk found in MbObS.

Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects

Obesity is frequently characterized by a reduced vitamin D bioavailability, as well as insulin-resistance and a chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and several circulating inflammatory markers in a cohort of severely obese individuals. Cross-sectional study was carried out among obese patients undergoing a clinical evaluation before bariatric surgery in our University Hospital. Serum 25(OH)D, fasting and post load glucose and insulin, high-sensitive C-reactive protein (hs CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin and lipid profile were collected. Insulin-resistance was assessed by insulin sensitivity index (ISI). Total body fat (FAT kg), total percent body fat (FAT%) and truncal fat mass (TrFAT) were assessed with dual-energy X-ray absorptiometry. A total of 147 obese subjects (89 women, 37.8±7.1years) with mean body mass index (BMI) of 43.6±4.3kg/m(2) were enrolled. Patients in the lowest tertile of 25(OH)D were significantly more obese with a higher amount of TrFAT, more insulin-resistant, and had higher levels of fasting and post-challenge glucose (p<0.05 for all). In a multivariate regression analysis, serum 25(OH)D was inversely related to significant levels of hs CRP, IL-6 and TNF-α after accounting for age, gender, season of recruitment, BMI, FAT kg and TrFAT (p<0.01 for all). In extremely obese subjects, 25(OH)D serum concentrations are inversely associated with several biomarkers of systemic inflammation, regardless of the total quantity of fat mass.

Impaired Pharmacokinetics of Levothyroxine in Severely Obese Volunteers

Suppressive or replacement doses of levothyroxine (LT4) are affected by the rate and extent of the active ingredient absorbed, as well as by the lean body mass. Obesity has reached epidemic proportions worldwide and is related with many comorbidities. The aim of this study was to determine the pharmacokinetic parameters of LT4 in severely obese individuals and compared them with similar data in lean control subjects. We studied 62 euthyroid subjects who had negative tests for anti-thyroid peroxidise antibodies (Ab-TPO). Thirty eight of these subjects were severely obese but otherwise healthy (severe obese subjects [SOS] group). Twenty-four were healthy control subjects (control group), with a body mass index of 23.3 ± 1.7 kg/m(2). Subjects received 600 μg oral sodium LT4 after an overnight fast. Serum triiodothyronine (T3), T4, and thyroid-stimulating hormone were measured at baseline. Serum T4 and T3 was measured 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours after LT4 administration. Baseline serum T4 and thyroid-stimulating hormone concentrations were higher in the SOS group than in the control group; serum T3 was similar in the two groups. The corrected area under the curve and the maximum T4 concentration after LT4 administration were lower, whereas the time to maximum concentration from the baseline was higher in SOS than in the control group. The estimated plasma volume was higher in the SOS than in the control group. Mean serum T3 levels increased gradually during the four hours after LT4 administration in the control group. In contrast, they decreased gradually in the SOS group. Severely obese individuals may need higher LT4 suppressive or replacement doses than normal-weight individuals due, among other factors, to impaired LT4 pharmacokinetic parameters. The latter could be attributed to their higher plasma volume and/or to delayed gastrointestinal LT4 absorption. T4 conversion to T3 might be defective in severe obesity.

New factors of cardiometabolic risk in severely obese children: influence of pubertal status.

The aim of this prospective study was to evaluate the utility of new biochemical markers to assess cardiometabolic risk in severely obese children and adolescents. A total of 107 subjects aged 7 to 14 years, were clinically assessed and anthropometric measures and percentage of fat mass by single frequency bioimpedance analysis were recorded. Of these, 44 were non-overweight and 63 severely obese (body mass index Z-score>2.5) which were stratified by Tanner stages. To estimate the metabolic risk the following variables were considered for analysis: Waist circumference/height>0.5, fasting glucose>100 mg/dL, triglycerides>110 mg/dL, HDL-C<40 mg/dL, and systolic or diastolic blood pressure>95th percentile for age and gender. Fasting insulinemia, apoprotein A1 and B, high-sensitive C-reactive protein, alanine aminotransferase, homocysteine, and folic and uric acids were determined. In severely obese children, metabolic risk was present more frequently in mid puberty. The normalized anthropometric parameters with respect to 50th percentile for age and gender did not differ in the presence of metabolic risk. Insulin resistance was an independent determinant of metabolic risk, adjusted by Tanner stages. Elevated high-sensitive C-reactive protein was noted without any effect of metabolic risk or pubertal stage. Homocysteine, apoprotein B, and alanine aminotransferase values increased with metabolic risk and were not influenced by puberty. Although insulin resistance remains the main factor influencing metabolic risk, biochemical markers as homocysteine, apoprotein B, and alanine aminotransferase, may be useful for identifying severe obese pubertal subjects particularly prone to comorbidities.

Fatty liver disease in severe obese patients: Diagnostic value of abdominal ultrasound

To evaluate the sensitivity and specificity of abdominal ultrasound (US) for the diagnosis of hepatic steatosis in severe obese subjects and its relation to histological grade of steatosis. A consecutive series of obese patients, who underwent bariatric surgery from October 2004 to May 2005, was selected. Ultrasonography was performed in all patients as part of routine preoperative time and an intraoperative wedge biopsy was obtained at the beginning of the bariatric surgery. The US and histological findings of steatosis were compared, considering histology as the gold standard. The study included 105 patients. The mean age was 37.2+/-10.6 years and 75.2% were female. The histological prevalence of steatosis was 89.5%. The sensitivity and specificity of US in the diagnosis of hepatic steatosis were, respectively, 64.9% (95% CI: 54.9-74.3) and 90.9% (95% CI: 57.1-99.5). The positive predictive value and negative predictive value were, respectively, 98.4% (95% CI: 90.2-99.9) and 23.3% (95% CI: 12.3-39.0). The presence of steatosis on US was associated to advanced grades of steatosis on histology (P=0.016). Preoperative abdominal US in our series has not shown to be an accurate method for the diagnosis of hepatic steatosis in severe obese patients. Until another non-invasive method demonstrates better sensitivity and specificity values, histological evaluation may be recommended to these patients undergoing bariatric surgery.