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.

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.

Analytical performance of free testosterone calculated by direct immunoluminometric method compared with the Vermeulen equation: results from a clinical series.

INTRODUCTION: Testosterone (T) is a hormone that is crucial for primary and secondary sexual development in both males and females. Free testosterone (FT) represents the biologically active form of T, and its measurement is of great importance in clinical practice. While application of either equilibrium dialysis or ultrafiltration is considered to be the gold standard for FT assessment, these methods are expensive and not widely accessible. As an alternative, the Vermeulen formula is a commonly utilized calculated method. METHODS: This clinical study, including 190 consecutive patients, was carried out to compare FT levels obtained through direct immunoluminometric assay and the Vermeulen formula. The comparison was performed using Passing-Bablok and Deming regression as well as the Bland-Altman plot. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were assessed. RESULTS: The calculated method employing the Vermeulen formula was considered the gold standard. Passing-Bablok regression indicated a good agreement between the two methods, with slopes close to 1 for the whole series. Although the Bland-Altman plot demonstrated overall agreement, a potential proportional bias was observed in females. Deming regression confirmed excellent agreement and reliable estimates. Sensitivity and specificity analysis revealed that the direct method had a sensitivity of 75.0% and a specificity of 93.4% in all patients. However, sensitivity improved to 81.0% in males and dropped to 18.2% in females likely due to the low number of true positive cases. CONCLUSION: The direct method exhibited comparable performance to the calculated method, but caution should be exercised when interpreting results, particularly in females. Further studies are necessary to validate its sensitivity and specificity in larger series.

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.

Alteration of Serum Proteome in Levo-Thyroxine-Euthyroid Thyroidectomized Patients.

The monotherapy with levo-thyroxine (LT4) is the treatment of choice for patients with hypothyroidism after thyroidectomy. However, many athyreotic LT4-treated patients with thyroid hormones in the physiological range experience hypothyroid-like symptoms, showing post-operative, statistically significant lower FT3 levels with respect to that before total thyroidectomy. Since we hypothesized that the lower plasmatic FT3 levels observed in this subgroup could be associated with tissue hypothyroidism, here we compared, by a preliminary proteomic analysis, eight sera of patients with reduced post-surgical FT3 to eight sera from patients with FT3 levels similar to pre-surgery levels, and six healthy controls. Proteomic analysis highlights a different serum protein profile among the considered conditions. By enrichment analysis, differential proteins are involved in coagulation processes (PLMN-1.61, -1.98 in reduced vs. stable FT3, p < 0.02; A1AT fragmentation), complement system activation (CFAH + 1.83, CFAB + 1.5, C1Qb + 1.6, C1S + 7.79 in reduced vs. stable FT3, p < 0.01) and in lipoprotein particles remodeling (APOAI fragmentation; APOAIV + 2.13, p < 0.003), potentially leading to a pro-inflammatory response. This study suggests that LT4 replacement therapy might restore biochemical euthyroid conditions in thyroidectomized patients, but in some cases without re-establishing body tissue euthyroidism. Since our results, this condition is reflected by the serum protein profile.