Assessing the Prevalence of Male Obesity-Associated Gonadal Dysfunction in Severe Obesity: A Focus on the Impact of Bariatric Surgery and Surgical Approaches.

PURPOSE: Obesity is an important risk factor for secondary hypogonadism in men. Several studies evaluated the impact of bariatric surgery on gonadal function in men, proving an improvement in testosterone levels, without yet a global consensus on the impact of different surgical approaches. Objectives of the study are: to estimate the prevalence of obesity-associated gonadal dysfunction among men with severe obesity; to evaluate the response to bariatric surgery in terms of resolution of this condition, distinguishing between restrictive and restrictive-malabsorptive surgery. METHODS: We conducted a retrospective evaluation of 413 males with severe obesity (BMI 44.7 ± 8.3 kg/m2). A subgroup of them (61.7%) underwent bariatric surgery. Anthropometric assessment (weight, BMI, waist and hip circumference), metabolic (glyco-lipidic asset and urate) and hormonal (morning gonadotropin and total testosterone) assessments were carried out at baseline and 3-6 months post-surgery. RESULTS: Using a TT threshold of 2.64 ng/ml, 256 out of 413 (62%) patients were categorized as having biochemical hypogonadism. At multivariate analysis, the only parameter significantly associated with biochemical hypogonadism, was BMI value (p = 0.001). At 3-6 months after surgery, during the acute weight loss phase, only 20.1% of patients still had biochemical hypogonadism. At multivariate analysis, which included age, presurgical BMI, pre-surgical TT, surgical approach and %EWL, presurgical TT levels (p = 0.0004), %EWL (p = 0.04), and mixed restrictive-malabsorptive surgery (p = 0.01), were independently associated with the recovery of gonadal function. CONCLUSIONS: The results of this study underscore the potential reversibility of obesity-associated gonadal dysfunction through bariatric surgery, highlighting the importance of considering surgical approach.

New specific skeletal muscle mass index cut-offs for the assessment of sarcopenia in patients with severe obesity.

Introduction: Bioelectrical impedance analysis (BIA) is the most used tool in clinical practice to evaluate body composition in patients with obesity. The skeletal muscle index (SMI) defined by BIA has been proposed for the identification of sarcopenia, but there are currently no univocal cutoffs for this condition. In this study, we aimed: 1) to determine the prevalence of sarcopenia in patients with severe obesity using the current cutoffs of SMI; 2) to define new specific cutoffs; 3) to validate the new cutoffs; and 4) to re-determine the prevalence of sarcopenia. Methods: A total of 300 patients, 74% women and 26% men (mean age = 42.6 ±; 9 years), with morbid obesity (mean BMI = 46.7 ±; 6.5 kg/m2) followed by the Unit of Endocrinology from January 2014 to December 2020 were retrospectively evaluated. SMI was calculated as the skeletal muscle mass normalized for squared height through the BIA equation by Janssen et al. Results: The prevalence of sarcopenic obesity calculated using the cutoff points reported by De Rosa et al. (7.3 kg/h2 for women and 9.5 kg/h2 for men) was 2.3%. The prevalence of sarcopenia was calculated using the new cutoffs: with the cutoff obtained from the standard deviation method (8.2 kg/h2 for women and 10.2 kg/h2 for men), a prevalence of 14.7% was observed, whereas the prevalence reached 47.6% when using the cutoff calculated through the K-means unsupervised cluster (9.2 kg/h2 for women and 11.3 kg/h2 for men). The new cutoffs were validated with a second sample consisting of 300 patients with morbid obesity (BMI = 44.9 ±; 6.7 kg/m2): the rate of sarcopenic patients was still higher than that observed in the training cohort (56%). After the matching procedure (by BMI and age), the rates of sarcopenic patients were similar in both groups (50.2% in the validation group and 53% in the training group, p = 0.6). Conclusion: The new cutoffs calculated with cluster analysis could better identify sarcopenia in morbidly obese patients. However, further studies are needed to validate these cutoffs in different patient cohorts.

Normalization of Spexin Levels in Patients with Obesity Submitted to Bariatric Surgery.

PURPOSE: Spexin is expressed by white fat tissue and other endocrine organs. A negative correlation between spexin and gluco-lipidic metabolism, energy homeostasis, and food intake has been reported. The objectives of this study are (1) to compare spexin levels between patients with obesity (study group) and normal-weight subjects (control group); (2) to evaluate spexin levels after bariatric surgery; and (3) to identify a correlation between spexin and weight loss/metabolic profile of patients with obesity. MATERIALS AND METHODS: We examined 53 patients with obesity (mean BMI 48.5 ± 9.4 kg/m2) who underwent bariatric surgery, compared to 55 normal-weight subjects. Serum spexin levels were assessed at baseline (study and control group) and at 3 and 6 months after surgery in patients with obesity. RESULTS: Spexin at baseline was significantly lower in the study group (p < 0.0001). At 3 and 6 months after bariatric surgery, spexin significantly increased compared to pre-surgical levels (p < 0.001) reaching control group levels (p = 0.08) at 6 months. In patients with obesity, pre-surgical spexin was similar in patients with and without comorbidities. No correlation between spexin and C-reactive protein (p = 0.8) and HOMA index (p = 0.5) was found. A significant negative correlation between age and pre-surgical spexin was observed (p = 0.03). At multivariable analysis, no correlation between Δ spexin and pre-surgery BMI, HOMA index, age, and 6-month TWL% was found. CONCLUSION: This study demonstrates that patients with obesity have significantly lower spexin levels than healthy subjects. After surgery, spexin levels of the study group become similar to those observed in the normal-weight group.

Follow-up after bariatric surgery: is it time to tailor it? Analysis of early predictive factors of 3-year weight loss predictors of unsuccess in bariatric patients.

Bariatric surgery (BS) is the most effective treatment strategy for obesity. Nevertheless, a subset of patients does not reach a successful weight loss or experience long-term weight regain. Conflicting evidence exists regarding predictors of BS outcomes. We aimed to define the early factors linked to 3 year unsuccessful weight loss in order to promote a tailored close follow-up. We enrolled 443 patients who underwent BS from January 2014 to December 2018 with a 3 year follow-up. An unsuccessful BS outcome was defined as a percentage of total weight loss (%TWL) < 20. We compared the characteristics between successful and unsuccessful patients in order to identify predictor factors of unsuccess after surgery. We found that the proportion of patients with unsuccessful weight loss progressively increased from one to three years after BS. In a multiple regression model, only 1 month %TWL and sleeve gastrectomy (SG) were significantly associated with 3 year unsuccessful weight loss. We stratified our cohort in four groups according to the risk of BS unsuccess, in terms of 1 month %TWL and type of surgery (SG vs gastric bypass). Interestingly, groups showed a significant difference in terms of %TWL at each follow-up point. Patients submitted to SG with lower 1 month %TWL must be considered at higher risk of future weight regain; consequently, they require a tailored and closer follow-up.

Type 2 deiodinase p.Thr92Ala polymorphism does not affect the severity of obesity and weight loss after bariatric surgery.

A single nucleotide polymorphism in the Type 2 deiodinase (DIO2) gene (p.Thr92Ala) was found to be associated with hypertension, type 2 diabetes mellitus (T2DM), insulin resistance, and body mass index (BMI). We retrospectively evaluated 182 patients to assess whether the DIO2 p.Thr92Ala was associated with severe obesity and response to bariatric surgery. Genomic DNA was extracted from peripheral blood leukocytes before surgery. Glycemic control parameters, cardiometabolic risk biomarkers (waist circumference, lipid assessment and blood pressure) and hormonal parameters were assessed at baseline and after surgery. Based on genotype evaluation, 78/182 (42.9%) patients were homozygous wild-type (Thr/Thr), 83/182 (45.6%) heterozygous (Thr/Ala), and 21/182 (11.5%) rare homozygous (Ala/Ala). Age at the time of the first evaluation in our Unit was significantly lower in patients with DIO2 p.Thr92Ala. No significant association was observed between DIO2 p.Thr92Ala and BMI, excess weight, waist circumference, Homa Index. The prevalence of comorbidities was not associated with allele distribution except for hypertension that was more frequent in wild-type patients (p = 0.03). After bariatric surgery, excess weight loss (EWL) % and remission from comorbidities occurred without differences according to genotypes. DIO2 p.Thr92Ala does not affect the severity of obesity and its complications, but it seems to determine an earlier onset of morbid obesity. The presence of polymorphism seems not to impact on the response to bariatric surgery, both in terms of weight loss and remission of comorbidities.

The impact of CPT1B rs470117, LEPR rs1137101 and BDNF rs6265 polymorphisms on the risk of developing obesity in an Italian population.

OBJECTIVE: This study aimed to analyze 11 single nucleotide polymorphisms (SNPs) belonging to 9 genes involved in metabolic pathways (BDNF rs6265; PNPLA3 rs2294918 and rs2076212; CIDEA rs11545881; NTRK2 rs2289658; ALOX12 rs1126667; ALOX12B rs2304908; LEPR rs1137101; CPT1B rs470117 and rs8142477; rs2305507 CPT1A) in obese patients and controls. METHODS: Polymorphisms were analyzed in 300 severe obese patients undergoing bariatric surgery (body mass index >30 kg/m2) and 404 control subjects in order to evaluate their association with obesity and clinical variables. RESULTS: Our findings showed significant differences for the allelic distributions of CPT1B rs470117 and LEPR rs11371010 in obese subjects compared to controls. The BDNF rs6265 correlates with obesity only when associated with the other two SNPs. In particular, for CPT1B rs470117 and LEPR rs1137101, the rare allele was associated with a reduced risk of developing the obese phenotype, whereas the simultaneous presence of the common C allele for rs470117 and A allele for rs1137101 was more frequent in obese patients (p = 0.002, OR = 1.417). A significant association between CPT1B rs470117 and steatosis was found. Moreover, we observed that by associating the rare allele T of the BDNF rs6265 with the most common alleles of the SNPs CPT1B rs470117 and LEPR rs1137101, the combination of T-C-A alleles was associated with a higher risk of developing an obese phenotype (p = 0.001, OR = 1.6679). CONCLUSIONS: Our results suggest that SNPs CPT1B rs470117 and LEPR rs1137101 taken individually and in association with BDNF rs6265 may be involved in an increased risk of developing obese phenotype in an Italian cohort.

Controlling Nutritional Status (CONUT) Score and Micronutrient Deficiency in Bariatric Patients: Midterm Outcomes of Roux-en-Y Gastric Bypass Versus One Anastomosis Gastric Bypass/Mini Gastric Bypass.

BACKGROUND: Two of the most common bariatric procedures performed worldwide are Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB). Comparative data regarding nutritional status are lacking and no previous study focus on malnutrition according to a validated score. METHODS: Retrospective data from a single institution were reviewed. Anthropometric variables and nutritional data were assessed. The primary aim was to analyze and compare the nutritional status before and 3 years after RYGB vs OAGB using the controlling nutritional status (CONUT) score. The incidence of micronutrient deficiency and the remission of comorbidities in each group were defined as secondary outcomes. RESULTS: Fifty-seven patients in each arm were enrolled. A 3-year mild malnutrition (CONUT score 2-3) was found in 38% and 37.05% in the RYGB and OAGB groups, respectively (p > 0.05). In terms of percentage of total weight loss (%TWL) and percentage of adjustable weight loss (%AWL), no differences were found between OAGB and RYGB groups. OAGB and RYGB patients had similar vitamin deficiencies. Anemia, hypoproteinemia, hypoalbuminemia, and hypocalcemia were comparable between groups. At 3-year follow-up, total protein and albumin values were similar between arms while prealbumin deficit was more frequent after OAGB than after RYGB. The rate of type 2 diabetes (87.5% in OAGB and 92% in RYGB), arterial hypertension (51.6% in OAGB and 58.3% in RYGB), and dyslipidemia (69.7% in OAGB and 78.6% in RYGB) remission was not significantly different between the two groups. CONCLUSIONS: Postoperative CONUT score, micronutrient deficiency, comorbidity remission, and improvement of anthropometric parameters 3 years postoperatively were comparable between RYGB and OAGB groups.

Validation of American Thyroid Association Ultrasound Risk-Adapted Approach for Repeating Cytology in Benign Thyroid Nodules.

Background: The 2015 American Thyroid Association (ATA) ultrasound (US) risk stratification system is used to identify thyroid nodules in which fine-needle aspiration cytology (FNAC) should be performed. In addition, this system is used to plan the long-term follow-up of patients with cytological benign thyroid nodules. The aim of our study was to evaluate the ATA US risk-adapted approach for repeating cytology in a large retrospective cohort of consecutive benign nodules with a second FNAC repeated after a median follow-up of 3.8 years (range 1.0-14.2 years). Methods: We retrospectively evaluated 1010 thyroid nodules, with an initial benign cytological diagnosis, that underwent at least one repeat FNAC during the follow-up. Results: The rate of missed cancer in the whole cohort of thyroid nodules was 1.0%, and it increased along by the US risk class (0.8% in very low/low-risk, 1.2% in intermediate-risk, and 3.1% in high-risk nodules). The 2015 ATA US risk stratification system showed a very high accuracy in selecting nodules that did not require a second FNAC (negative predictive value = 99.1%). In addition, the rate of missed cancer significantly increased along with the increase in the US risk class in nodules that showed an enlarged volume (0.4% in the low-risk class and 6.4% in the high-risk class, p = 0.005), while it was very low and not associated with the US features in the subgroup of thyroid nodules that did not grow during the follow-up (p = 0.96). Conclusions: Our results confirm the accuracy of the ATA recommendations in selecting benign nodules for FNAC repetition during the follow-up. An additional cytological evaluation maybe avoided in benign thyroid nodules with low-risk US features, regardless of the evidence of growth during the follow-up. While the utility of the routine repeat FNAC in all benign nodules with high-risk US features remains to be defined, based on our results, repetition of FNAC seems to be indicated in nodules with evidence of growth during the follow-up.

ONE MONTH WEIGHT LOSS PREDICTS THE EFFICACY OF LIRAGLUTIDE IN OBESE PATIENTS: DATA FROM A SINGLE CENTER.

Objective: Liraglutide is a glucagon-like peptide 1 receptor agonist which acts through peripheral and central receptor pathways affecting food intake. Preliminary identification of responder patients represents a crucial point to reduce an inappropriate exposure to the drug and the health expenditure. The primary endpoint of our study was to identify predictors of liraglutide efficacy in the short term follow-up. The secondary endpoint was to evaluate the treatment efficacy stratified by the underlying psychiatric disorder. Methods: We evaluated a cohort of 100 patients (77 females, 23 males, mean body mass index 38.6 ± 3.2 kg/m2) who were evaluated at baseline, and after 1, 3, and 6 months of treatment. Liraglutide efficacy was defined by a weight loss ≥5% of initial weight. Sociodemographic/metabolic parameters, food intake, smoking habit, and physical activity were correlated with liraglutide efficacy. Results: There was a significant weight loss after 1 month of therapy, as well as after 3 and 6 months when compared to the baseline (P<.0001; 27%, 45%, and 57% of patients showed a weight loss ≥5%, respectively). No difference was found in weight loss between the 3 groups of patients (with binge eating, with/without psychiatric disorders). The weight loss at 1 month was the only predictor of a positive response to the treatment. Conclusion: Our results confirm the efficacy of liraglutide even at a lower dose than conventional. The early response to the drug seems to be a good predictor of long-term efficacy and it might be useful in clinical practice to identify patients in whom liraglutide may induce a significant weight loss. Abbreviations: BMI = body mass index; EMA = European Medicine Agency; FDA = Food and Drug Administration; GLP-1 RA = glucagon-like peptide 1 receptor agonist.