Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery.

OBJECTIVE: This retrospective cohort study aimed to assess the effectiveness of semaglutide 2.4 mg in patients with severe obesity (BMI ≥ 40 kg/m2 ) who had previously undergone bariatric surgery (BS) but failed to achieve satisfactory weight loss or experienced weight regain compared with patients without a history of BS with similar BMI. METHODS: The authors analyzed data from 129 patients with a BMI ≥ 40 kg/m2 , including 39 with (BS+) and 90 without (BS-) a history of BS. The patients received semaglutide treatment for 24 weeks starting at 0.25 mg/wk and gradually increasing to reach a final dose of 2.4 mg/wk. The treatment outcomes were assessed based on the percentage of weight loss, changes in BMI, and waist circumference. RESULTS: Semaglutide treatment resulted in significant 9.1% weight loss in the BS+ group, with no significant difference in weight loss between the BS+ and BS- groups. CONCLUSIONS: This study is the first, to the authors' knowledge, to compare the effectiveness of semaglutide treatment in patients with versus those without a history of BS, providing valuable evidence of its efficacy. By focusing on individuals with severe obesity (BMI > 40 kg/m2 and associated comorbidities), it fills a gap in the current literature and highlights the potential of semaglutide 2.4 mg as a treatment option for this specific population.

Modification of Muscle-Related Hormones in Women with Obesity: Potential Impact on Bone Metabolism.

Lean body mass (LBM) is a determinant of areal bone mineral density (aBMD) through its mechanical actions and quite possibly through its endocrine functions. The threefold aims of this study are: to determine the effects of obesity (OB) on aBMD and myokines; to examine the potential link between myokines and bone parameters; and to determine whether the effects of LBM on aBMD are mediated by myokines. aBMD and myokine levels were evaluated in relation to the body mass index (BMI) in 179 women. Compared with normal-weight controls (CON; n = 40), women with OB (n = 139) presented higher aBMD, myostatin and follistatin levels and lower irisin levels. Except for irisin levels, all differences between the OB and CON groups were accentuated with increasing BMI. For the whole population (n = 179), weight, BMI, fat mass (FM) and LBM were positively correlated with aBMD at all bone sites, while log irisin were negatively correlated. The proportion of the LBM effect on aBMD was partially mediated (from 14.8% to 29.8%), by log irisin, but not by follistatin or myosin. This study showed that myokine levels were greatly influenced by obesity. However, irisin excepted, myokines do not seem to mediate the effect of LBM on bone tissue.

Vitamin D status is not related to insulin resistance in different phenotypes of moderate obesity.

Low plasma 25-hydroxy-vitamin D (25OHD) and high levels of parathyroid hormone (PTH) are associated with obesity and could play a role in the occurrence of complications such as insulin resistance. The objective of the study was to evaluate whether the relationship between 25OHD status and phosphocalcic parameters differs between metabolically healthy obese (MHO) and insulin-resistant obese (IRO). This cross-sectional study included 158 consecutive adults (121 females) with obesity (body mass index (BMI) 35.15 ± 2.8 kg/m2), aged 43.21 ± 13.6 years. Serum 25OHD, calcemia, phosphatemia, PTH, plasma lipids, fasting plasma glucose, insulin levels, and body composition were measured. Participants were classified as MHO (n = 65) or IRO (n = 93) based on homeostatic model assessment insulin-resistance value. IRO patients had a higher BMI (p = 0.001), waist circumference (p = 0.03), and trunk fat mass (p = 0.007) than MHO patients. Mean HbA1c (p = 0.03), triglycerides (p = 0.02), and hsCRP (p = 0.04) plasmatic levels were increased in the IRO group. No between-group difference was found on 25OHD, PTH, calcium, or phosphorus plasmatic levels. Only age-predicted 25OHD levels were identified among IRO participants, whereas no factors were identified in MHO. No predictive factors of PTH plasmatic level were identified in the IRO and MHO groups. Although MHO and IRO patients have different metabolic profiles, we did not detect any difference regarding either 25OHD or PTH. Insulin resistance was not a predictive factor of vitamin D status. Our results confirm the absence of link between vitamin D status and insulin resistance in moderate obesity.

Leukotriene production is increased in abdominal obesity.

Obesity is a major risk factor for insulin resistance and type-2 diabetes. A chronic low grade inflammatory state has been described during obesity and associated with insulin resistance pathogenesis. Results from animal studies are in favor of a role of the leukotriene (LT) pathway in obesity induced-insulin resistance. However, there is a paucity of data regarding this association in human obesity. Therefore, the aim of this study was to investigate whether LT production was associated with insulin resistance and other metabolic parameters in a cohort of obese subjects. Forty-six (70% females) obese subjects (BMI≧30 kg/m2) without known diabetes and without inflammatory disease (CRP<10 mg/l) were included. Median age was 44 years (16-80) with a median BMI of 36.8 kg/m2 (30-51). Insulin resistance was evaluated by HOMA-IR index and glucose tolerance test. Urinary LTE4 (U-LTE4) concentration was measured by enzyme immune assay. Screening for obstructive sleep apnea was performed. There was a positive association of U-LTE4 with waist to hip ratio, systolic blood pressure and HOMA-IR in univariate analysis. Further, waist to hip ratio remained the only parameter significantly correlated with U-LTE4, in adjusted multivariate analysis. Taken together, these results confirm the previously established notion of chronic low grade inflammation in obesity and further suggests a role for the LT pathway in obesity-associated development of insulin resistance in humans.