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Abstract Context As many sports are divided in male/female categories, governing bodies have formed regulations on the eligibility for transgender individuals to compete in these categories. Yet, the magnitude of change in muscle mass and strength with gender-affirming treatment remains insufficiently explored. Objective This study explored the effects of gender-affirming treatment on muscle function, size, and composition during 12 months of therapy. Design, settings, participants In this single-center observational cohort study, untrained transgender women (TW, n = 11) and transgender men (TM, n = 12), approved to start gender-affirming medical interventions, underwent assessments at baseline, 4 weeks after gonadal suppression of endogenous hormones but before hormone replacement, and 4 and 12 months after treatment initiation. Main outcome measures Knee extensor and flexor strength were assessed at all examination time points, and muscle size and radiological density (using magnetic resonance imaging and computed tomography) at baseline and 12 months after treatment initiation. Results Thigh muscle volume increased (15%) in TM, which was paralleled by increased quadriceps cross-sectional area (CSA) (15%) and radiological density (6%). In TW, the corresponding parameters decreased by –5% (muscle volume) and –4% (CSA), while density remained unaltered. The TM increased strength over the assessment period, while the TW generally maintained their strength levels. Conclusions One year of gender-affirming treatment resulted in robust increases in muscle mass and strength in TM, but modest changes in TW. These findings add new knowledge on the magnitude of changes in muscle function, size, and composition with cross-hormone therapy, which could be relevant when evaluating the transgender eligibility rules for athletic competitions.

Aim Obesity is linked to cardiometabolic diseases, however non-obese individuals are also at risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). White adipose tissue (WAT) is known to play a role in both T2D and CVD, but the contribution of WAT inflammatory status especially in non-obese patients with cardiometabolic diseases is less understood. Therefore, we aimed to find associations between WAT inflammatory status and cardiometabolic diseases in non-obese individuals. Methods In a population-based cohort containing non-obese healthy (n = 17), T2D (n = 16), CVD (n = 18), T2D + CVD (n = 19) individuals, seventeen different cytokines were measured in WAT and in circulation. In addition, 13-color flow cytometry profiling was employed to phenotype the immune cells. Human T cell line (Jurkat T cells) was stimulated by rCCL18, and conditioned media (CM) was added to the in vitro cultures of human adipocytes. Lipolysis was measured by glycerol release. Blocking antibodies against IFN-γ and TGF-β were used in vitro to prove a role for these cytokines in CCL18-T-cell-adipocyte lipolysis regulation axis. Results In CVD, T2D and CVD + T2D groups, CCL18 and CD4 + T cells were upregulated significantly compared to healthy controls. WAT CCL18 secretion correlated with the amounts of WAT CD4 + T cells, which also highly expressed CCL18 receptors suggesting that WAT CD4 + T cells are responders to this chemokine. While direct addition of rCCL18 to mature adipocytes did not alter the adipocyte lipolysis, CM from CCL18-treated T cells increased glycerol release in in vitro cultures of adipocytes. IFN-γ and TGF-β secretion was significantly induced in CM obtained from T cells treated with CCL18. Blocking these cytokines in CM, prevented CM-induced upregulation of adipocyte lipolysis. Conclusion We suggest that in T2D and CVD, increased production of CCL18 recruits and activates CD4 + T cells to secrete IFN-γ and TGF-β. This, in turn, promotes adipocyte lipolysis – a possible risk factor for cardiometabolic diseases.

Background Metabolic and bariatric surgery (MBS) is the most effective and durable approach to treating obesity, yet recurrent weight gain occurs in a subset of patients. Primary care often serves as a routine point of contact for patients following MBS and is a potential gateway for addressing and/or preventing recurrent weight gain. Methods Although guidelines for the management of recurrent weight gain after MBS exist, this narrative review was undertaken to clarify the role of the primary care providers in enhancing long‐term outcomes and preventing weight gain after MBS. Findings Regular follow‐up in primary care provides an opportunity to identify challenges related to weight management and overall health outcomes, which may include concerns related to nutrition, mental or physical well‐being, body image, motivation, and behavior change, for example. The availability of multidisciplinary providers within primary care settings, including behavioral health specialists, dietitians, and physical therapists, is an important strength of this setting in addressing potential post‐MBS concerns such as recurrent weight gain. Conclusion This review outlines clinical considerations for managing recurrent weight gain post‐MBS in primary care and includes recommendations for both primary care providers and specialty clinicians working in primary care to deliver care effectively and mitigate weight stigma post‐MBS.

Aims/hypothesis We aimed to elucidate the impact of fat cell size and inflammatory status of adipose tissue on the development of type 2 diabetes in non-obese individuals. Methods We characterised subcutaneous abdominal adipose tissue by examining stromal cell populations by 13 colour flow cytometry, measuring expression of adipogenesis genes in the progenitor cell fraction and determining lipolysis and adipose secretion of inflammatory proteins in 14 non-obese men with type 2 diabetes and 13 healthy controls matched for age, sex, body weight and total fat mass. Results Individuals with diabetes had larger fat cells than the healthy controls but stromal cell population frequencies, adipose lipolysis and secretion of inflammatory proteins did not differ between the two groups. However, in the entire cohort fat cell size correlated positively with the ratio of M1/M2 macrophages, TNF-α secretion, lipolysis and insulin resistance. Expression of genes encoding regulators of adipogenesis and adipose morphology ( BMP4 , CEBPα [also known as CEBPA ], PPARγ [also known as PPARG ] and EBF1 ) correlated negatively with fat cell size. Conclusions/interpretation We show that a major phenotype of white adipose tissue in non-obese individuals with type 2 diabetes is adipocyte hypertrophy, which may be mediated by an impaired adipogenic capacity in progenitor cells. Consequently, this could have an impact on adipose tissue inflammation, release of fatty acids, ectopic fat deposition and insulin sensitivity.

BackgroundObesity is a major factor behind insulin resistance. The validity of simple biochemical surrogate measures to estimate insulin resistance at the fat cell level is unclear.ObjectiveTo investigate if the surrogate measures HOMA-IR (glucose/insulin product) and Adipo-IR (fatty acids/insulin product) reflect insulin action on glucose/lipid metabolism in fat cells.DesignInsulin-induced lipogenesis and lipolysis inhibition (antilipolysis) in subcutaneous fat cells were investigated for sensitivity (reflecting receptor-near events) and responsiveness (i.e., maximum action reflecting distal post-receptor events) in 363 subjects. Results were compared with log10 transformed values for HOMA-IR and Adipo-IR.ResultsIndividually, the four measures of in vitro insulin action on fat cells correlated significantly (p < 0.0001) but weakly with each other (adjusted r2 0.05–0.23). HOMA-IR and Adipo-IR correlated strongly with each other (adjusted r2 = 0.81). Using Spearman or simple linear regression all in vitro measures except antilipolytic responsiveness expressed per lipid weight, correlated significantly with Adipo-IR or HOMA-IR (p values <0.0001). Similar relationships remained after combined correction for age, body mass index and sex. Together, the four in vitro measures explained 50% of the variability in HOMA-IR and ADIPO-IR (p < 0.0001). Receiver-operating characteristic analysis showed good sensitivity and specificity for Adipo-IR and HOMA-IR to detect combined insulin resistance of antilipolysis and lipogenesis in fat cells (area under the curve = 0.8).ConclusionsInsulin action at the receptor and post-receptor levels on lipolysis and lipogenesis in fat cells correlates significantly with Adipo-IR and HOMA-IR. Both surrogate measures give similar information about insulin resistance of glucose and lipid metabolism in fat cells.

ObjectiveErectile dysfunction (ED) is associated with an increased risk of cardiovascular disease in healthy men. However, the association between treatment for ED and death or cardiovascular outcomes after a first myocardial infarction (MI) is unknown.MethodsIn a Swedish nationwide cohort study all men <80 years of age without prior MI, or cardiac revascularisation, hospitalised for MI during 2007–2013 were included. Treatment for ED, defined as dispensed phosphodiesterase-5 inhibitors or alprostadil, was related to risk of death, MI, cardiac revascularisation or heart failure.ResultsForty-three thousand one hundred and forty-five men with mean age 64 (±10) years were included, of whom 7.1% had ED medication dispensed during a mean 3.3 years (141 739 person-years) of follow­-up. Men with, compared with those without treatment for ED, had a 33% lower mortality (adjusted HR 0.67 (95%CI 0.55 to ­0.81)), and 40% lower risk of hospitalisation for heart failure (HR 0.60 (95% CI 0.44 to 0.82)). There was no association between treatment with alprostadil and mortality. The adjusted risk of death in men with 1, 2–5 and >5 dispensed prescriptions of phosphodiesterase-5 inhibitors was reduced by 34% (HR 0.66 (95% CI 0.38 to 1.15), 53% (HR 0.47 (95% CI 0.26 to 0.87) and 81% (HR 0.19 (95% CI 0.08 to 0.45), respectively, when compared with alprostadil treatment.ConclusionsTreatment for ED after a first MI was associated with a reduced mortality and heart failure hospitalisation. Only men treated with phosphodiesterase-5 inhibitors had a reduced risk, which appeared to be dose-dependent.

Background/objectiveThe development of overweight/obesity associates with alterations in white adipose tissue (WAT) cellularity (fat cell size/number) and lipid metabolism, in particular lipolysis. If these changes differ between early/juvenile (EOO < 18 years of age) or late onset overweight/obesity (LOO) is unknown and was presently examined.Subjects/methodsWe included 439 subjects with validated information on body mass index (BMI) at 18 years of age. Using this information and current BMI, subjects were divided into never overweight/obese (BMI < 25 kg/m2), EOO and LOO. Adipocyte size, number, morphology (size in relation to body fat) and lipolysis were determined in subcutaneous abdominal WAT. Body composition and WAT distribution was assessed by dual-X-ray absorptiometry.ResultsCompared with never overweight/obese, EOO and LOO displayed larger WAT amounts in all examined depots, which in subcutaneous WAT was explained by a combination of increased size and number of fat cells in EOO and LOO. EOO had 40% larger subcutaneous fat mass than LOO (p < 0.0001). Visceral WAT mass, WAT morphology and lipolysis did not differ between EOO and LOO except for minor differences in men between the two obesity groups. On average, the increase in BMI per year was 57% higher in subjects with EOO compared to LOO (p < 0.0001).ConclusionEarly onset overweight/obesity causes a more rapid and pronounced accumulation of subcutaneous WAT than adult onset. However, fat mass expansion measures including WAT cellularity, morphology and fat cell lipolysis do not differ in an important way suggesting that similar mechanisms of WAT growth operate in EOO and LOO.

Introduction: Insulin resistance is prominent in overweight/obesity. We examined if insulin action in fat cells predicts the outcome of therapeutic weight loss. Methods: We investigated 93 adult Swedes with overweight/obesity (body mass index, BMI, 29–50 kg/m2) before and after hypo-energetic high- or low-fat diet for 10 weeks. At baseline, overall insulin resistance (homeostasis model assessment, HOMA-IR) and insulin action on lipolysis and lipogenesis in isolated abdominal subcutaneous fat cells were determined. The participants were divided into tertiles based on their values for the cellular insulin action parameters. The relationship to weight loss parameters (fat mass index, fat free mass index, or BMI) was examined by analysis of variance. The influence of baseline age, sex, waist-to-hip ratio, physical activity, and BMI was investigated by analysis of covariance. Because the body weight loss (on average 8 kg) did not differ between the diets their respective data were combined. Results: The sensitivity (half-maximum effective hormone concentration) of the anti-lipolytic effect of insulin correlated with loss of BMI, body weight, and fat mass index (F ≥ 3.1; p ≤ 0.0495). Body weight loss was about 30% greater in those with highest compared with lowest anti-lipolytic insulin sensitivity, and it was independent of the cofactors mentioned above (F = 8–9; p = 0.004–0.005). However, HOMA-IR, maximum insulin induced anti-lipolysis or lipogenesis and insulin sensitivity of lipogenesis did not associate with loss of BMI or fat mass index. Conclusion: A high anti-lipolytic insulin sensitivity in subcutaneous fat cells independently associates with pronounced weight loss following energy-restricted diet, whereas lipogenesis and overall insulin resistance are not related to weight change.