Dapagliflozin attenuates fat accumulation and insulin resistance in obese mice with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a common endocrine disorder affecting premenopausal women, is associated with various metabolic consequences such as insulin resistance, hyperlipidemia, obesity, and type 2 diabetes mellitus (T2DM). Insulin sensitizers, such as metformin and pioglitazone, though effective, often leads to significant gastrointestinal adverse effects or weight gain, limiting its suitability for women with PCOS. There is an urgent need for safe, effective and affordable agents. Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, enhances glucose elimination through urine, thereby reducing body weight and improving glucose and lipid metabolism. Nevertheless, it is not currently recommended as a therapeutic option for PCOS in clinical guidelines. In this study, we systematically examined the impact of dapagliflozin on an obese PCOS mouse model, focusing on alterations in glucose metabolism, adipose tissue morphology, and plasma lipid profile. Obese PCOS was induced in mice by continuous dihydrotestosterone (DHEA) injections over 21 days and high-fat diet (HFD) feeding. PCOS mice were then orally gavaged with dapagliflozin (1 mg/kg), metformin (50 mg/kg), or vehicle daily for 8 weeks, respectively. Our results demonstrated that dapagliflozin significantly prevented body weight gain and reduced fat mass in obese PCOS mice. Meanwhile, dapagliflozin treatment improved glucose tolerance and increased insulin sensitivity compared to the control PCOS mice. Furthermore, dapagliflozin significantly improved adipocyte accumulation and morphology in white adipose tissue, resulting in a normalized plasma lipid profile in PCOS mice. In conclusion, our results suggest that dapagliflozin is an effective agent in managing glucose and lipid metabolism disorders in obese PCOS mice.

Obstructive sleep apnea (OSA) is associated with increased risk of early-onset sarcopenia and sarcopenic obesity: Results from NHANES 2015-2018.

OBJECTIVE: This study aims to estimate the prevalence of early-onset sarcopenia and sarcopenic obesity in the United States and its relative risk due to obstructive sleep apnea (OSA). METHODS: Data in this cross-sectional study were extracted from the National Health and Nutritional Examination Survey (NHANES) 2015-2018. Weighted multistage stratified probability sampling design was considered to estimate the prevalence of early-onset sarcopenia and sarcopenic obesity. Weighted multivariable logistic regression analyses and weighted multivariable mediation models were performed to evaluate the association between OSA and early-onset sarcopenia. RESULTS: The prevalence of early-onset sarcopenia and early-onset sarcopenic obesity was estimated to be 5.5% and 4.6%, respectively. A higher prevalence of sarcopenia (12% V.S. 5.5%, P < 0.01) and sarcopenic obesity (10.3% V.S. 4.0%, P < 0.01) was observed among participants with OSA than those without OSA. Multivariable logistic regression models suggested that participants with OSA had higher odds ratios of suffering from early-onset sarcopenia [Odds Ratio (OR): 1.5, 95% confidence interval (CI):1.1-2.7] and early-onset sarcopenic obesity [OR: 1.8, 95% CI: 1.1-3.1] after adjusting for potential confounding variables. Mediation analyses suggested serum chronic reaction protein (CRP) mediated 23.7% (P < 0.01) & 26.2% (P < 0.01), homeostasis model assessment insulin resistance index (HOMA-IR) mediated 24.8% (P < 0.01) & 20.7% (P < 0.05), body mass index (BMI) mediated 46.4% (P < 0.05) & 49.9% (P < 0.01), HEI-2015 mediated 23.3% (P < 0.01) & 25.6% (P < 0.01), and Vitamin D mediated 7.5% (P < 0.01) & 8.5% (P < 0.01) of the potential effects of OSA on early-onset sarcopenia and sarcopenic obesity, respectively. CONCLUSION: Early-onset sarcopenia and sarcopenic obesity were prevalent among young adults in the US. OSA is a significant independent risk factor and may induce muscle loss by unhealthy diet habits, higher BMI, chronic inflammation, insulin resistance, and Vitamin D. It was essential for clinicians to arrange appropriate screening and interventions for patients with OSA to prevent muscle loss as early as possible.

Staying up late increases cardiovascular disease risk in women with polycystic ovary syndrome.

STUDY QUESTION: What is the association between late bedtime, night sleep duration, and lifetime cardiovascular disease (CVD) risk in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Both late bedtime (≥1:00) and short sleep duration (<7 h/night) were independently associated with a high-lifetime CVD risk among women with PCOS. WHAT IS KNOWN ALREADY: Previous studies indicated that sleep disturbances, including altered sleep duration and staying up late (SUL), occurred more frequently among women with PCOS compared to women without PCOS. Studies have shown that both PCOS and sleep disturbances are associated with deterioration in cardiometabolic health in the longer term. However, there are limited data regarding the possible association between sleep disturbances and CVD risk among reproductive-aged women with PCOS. STUDY DESIGN, SIZE, DURATION: From the original 393 women identified at our center, a total of 213 women with PCOS aged 18-40 years were enrolled in a cross-sectional study between March 2020 and July 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Bedtime and night sleep duration were obtained from a standardized self-administered questionnaire. The prediction for atherosclerotic CVD risk in the China risk model was applied to estimate the lifetime CVD risk in the PCOS population. Restricted cubic spline regression was applied to explore the non-linear association between sleep duration and lifetime CVD risk in a series of models. Multivariable logistic regression analyses were performed to determine the association between bedtime, night sleep duration, and lifetime CVD risk. MAIN RESULTS AND THE ROLE OF CHANCE: In our study, we found that the proportion of SUL was 94.25% and the mean (±SD) of night sleep duration was 7.5 ± 1.1 h in women with PCOS. Restricted cubic spline regression analysis showed a U-shaped relation between sleep duration and lifetime CVD risk. After adjusting for occasional drinking, fasting insulin, triglyceride, low-density lipoprotein cholesterol, and testosterone in multivariable logistic analyses, compared with going to bed at 23-24 o'clock, those who went to bed after 1 o'clock were independently associated with high-lifetime CVD risk [odds ratio (OR) = 3.87, 95% CI: 1.56-9.62]; compared with optimal sleep duration (7-8 h/night), short sleep (<7 h/night) was also independently associated with high-lifetime CVD risk (OR = 2.46, 95% CI: 1.01-5.97). LIMITATIONS, REASONS FOR CAUTION: Inferring causality is limited owing to the cross-sectional design. All sleep variables data were obtained from a standardized self-administered questionnaire rather than measurements using objective approaches. Even after adjusting for potential confounders, we still cannot completely rule out the possibility of residual confounding from unmeasured factors such as socioeconomic status. Future studies with larger sample sizes are needed to further explore the relation between long sleep duration and lifetime CVD risk. Although these findings are not generalizable to non-SUL PCOS populations, they could be used for guiding multidimensional treatment. Lastly, there is no non-PCOS group in the current cross-sectional study, which limits the interpretation of the findings from the PCOS group. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to report that both late bedtime (≥1:00) and short sleep duration (<7 h/night) were independently associated with a high-lifetime CVD risk among reproductive-aged women with PCOS, in a sample of Chinese adults. Predicting cardiovascular risk and examining the association between sleep disturbances and predicted CVD risk among women with PCOS help to highlight the need for early interventions on sleep to improve their cardiovascular outcomes. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Natural Science Foundation of Fujian Province (No. 2020J011242), the Fujian provincial health technology project (No. 2022CXB016), the Joint Research Projects of Health and Education Commission of Fujian Province (No. 2019-WJ-39), and the Medical and Health project of Xiamen Science & Technology Bureau (No. 3502Z20214ZD1001). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Anti-Müllerian hormone was independently associated with central obesity but not with general obesity in women with PCOS.

Objective: Anti-Müllerian hormone (AMH) is recognized as the most important biomarker for ovarian reserve. In this cross-sectional study, we aimed to explore the potential association of AMH with central obesity or general obesity in women with polycystic ovary syndrome (PCOS). Methods: In this cross-sectional study, 179 patients with PCOS were enrolled and underwent anthropometric measurements (BMI and waist circumference (WC)) and serum AMH level detection. Pearson's correlation and multivariable logistic regression analyses were performed to determine the associations of AMH with central obesity and general obesity. Results: Subjects with increasing BMI showed significantly lower values of AMH (median (interquartile range (IQR)) 8.95 (6.03-13.60) ng/mL in normal weight group, 6.57 (4.18-8.77) ng/mL in overweight group, and 6.03 (4.34-9.44) ng/mL in obesity group, P = 0.001), but higher levels of systolic blood pressure, fasting insulin, total cholesterol, triglycerides, LDL-c, obesity indices (WC, hip circumferences, waist-to-hip ratio, waist-to-height ratio (WHtR), and Chinese visceral adiposity index (CVAI)). Compared with the group of PCOS women without central obesity, the group with central obesity had significantly lower value of AMH (median (IQR) 8.56 (5.29-12.96) ng/mL vs 6.22 (4.33-8.82) ng/mL; P = 0.003). Pearson's correlation analysis showed that AMH was significantly and negatively correlated with BMI (r = -0.280; P < 0.001), WC (r = -0.263; P < 0.001), WHtR (r = -0.273; P < 0.001), and CVAI (r = -0.211; P = 0.006). Multivariate logistic regression analysis with adjustment for potential confounding factors showed that AMH was independently and negatively associated with central obesity but was not significantly associated with general obesity. Conclusions: AMH was independently and negatively associated with central obesity. Closely monitoring the WC and AMH should be addressed in terms of assessing ovarian reserve in women with PCOS.

Independent associations of thyroid-related hormones with hepatic steatosis and insulin resistance in euthyroid overweight/obese Chinese adults.

PURPOSE: The aim of the study is to explore the independent association of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) with hepatic steatosis and insulin resistance. METHODS: A cross-sectional study of 88 overweight/obese adults who underwent anthropometric measurements [BMI, waist circumference (WC) and waist-to-height ratio (WHtR)], hepatic steatosis assessment (FibroScan) and thyroid-related hormones tests was conducted from 2018 to 2020 in Xiamen, China. RESULTS: Subjects with increasing tertiles of FT3 showed significantly higher levels of controlled attenuation parameter (CAP) ((295.4 ± 44.1, 290.1 ± 68.2 and 331.7 ± 43.6 (dB/m) for tertile 1-3, respectively, p = 0.007) and fatty liver index (FLI) score (47.7 (33.9-60.8), 61.5 (45.1-88.9) and 90.5 (84.5-94.8), respectively, p < 0.001). FT3 significantly and positively correlated with obesity index (BMI, WC, and WHtR), homeostatic model assessment of insulin resistance (HOMA-IR) and hepatic steatosis (CAP and FLI). Multivariable linear regression analyses with adjustment for potential confounding factors showed FT3 was independently associated with BMI (regression coefficient (ß (95%CI): 0.024 (0.004-0.043), p = 0.020), HOMA-IR (ß (95%CI): 0.091 (0.007-0.174), p = 0.034), CAP (ß (95%CI): 25.45 (2.59-48.31), p = 0.030) and FLI (ß (95%CI): 0.121 (0.049-0.194), p = 0.001). Neither FT4 nor TSH was significantly associated with any indicators of obesity, insulin resistance or hepatic steatosis. CONCLUSIONS: Increased FT3, but not FT4 or TSH, was independently associated with higher risks of hepatic steatosis and insulin resistance in euthyroid overweight/obese Chinese adults. Trial registration Registration is not applicable for our study.

[Irradiated porcine skin impregnated with fluorine and silver covered by autogenous granule skin graft for treating severe burn injury].

OBJECTIVE: To study the feasibility of using irradiated porcine skin impregnated with fluorine and silver covered by autogenous skin granule graft in the treatment of severe burn injury. METHODS: Autogenous split-thick skin grafts were cut into small pieces (<1 mm3), which were transferred onto the sheet of porcine skin mounted with a layer of Xinnaxing ointment (2 mm in thickness). After eschar removal, the burn wound was covered with the prepared porcine skin, sutured and fixed with small holes at the lower site for drainage. The growth of autogenous granule skin was then observed and the criteria for therapeutic effect evaluation drafted. RESULTS: The layer of Xinnaxing ointment on the the porcine skin improved the adhesion of the autogenous small skin grafts, therefore full use could be made of the donor skin source. In the 15 patients receiving this treatment, the graft-covered area was (12.3+/-3.5) % that of the wound, with the donor-recipient area ratio of 1: (11.0+/-2.7) and subsequent healing time of 27.5+/-5.5 d. Primary healing was achieved in 9 cases, and secondary healing in 6, demonstrating similar clinical effect to that of allo-skin grafting. CONCLUSION: The method is easy and economic, which saves autogenous skin source and produces satisfactory clinical effect.