Diabetic Postmenopausal Women Research Articles

Follicle-Stimulating Hormone and Diabetes in Postmenopausal Women: A Systematic Review and Meta-analysis.

Today, co-occurrence of hormonal changes during menopause and the risk of cardio-metabolic disorders have been well studied. We aimed to explore the association of circulating levels of follicle-stimulating hormone (FSH) with diabetes (DM) among postmenopausal women. In this Systematic review and meta-analysis the search was performed on PubMed, Scopus, Web of sciences, Epistemonikos, and Cochrane library until the September 2023. Risk of bias was assessed by Newcastle-Ottawa Quality Assessment Scale. Pooled estimates of mean differences in FSH levels among diabetic postmenopausal women compared to those without diabetes were performed. Also, the correlation between FSH and fasting blood glucose (FBG)/Insulin/Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) as well as the pooled effect sizes with their 95% confidence intervals (CIs) for risk of DM were calculated. In this study, 14 articles, including 7,878 postmenopausal women, met eligibility criteria and were further analyzed. Most of the included studies had a low/moderate risk of bias. Women with DM had significantly lower FSH levels than those without DM (standardized mean difference [95% CI] -0.751, 95% CI-1.129 to -0.372, I2 = 82.46%, n = 1416). The pooled effect size (ES) for diabetes was 0.861 (95% CI: 0.740-1.001; I2 = 80.11%). The pooled risk estimate for DM based on the categorical FSH levels (high versus low) was (HR = 0.550; 95% CI, 0.356 to 0.850, I2 = 0). The significant inverse correlation was found between FSH levels and glycemic parameters [FBG (r= -0.285; 95%CI -0.441 to -0.113; n = 1229), HOMA-IR (r = -0.241; 95%CI -0.378 to -0.0924; n = 1229) and Insulin (r = -0.337; 95%CI -0.434 to -0.232; n = 959)]. There were no statistically significant differences between estradiol levels among diabetic and non-diabetic groups; however the SMD for luteinizing hormone was similar to that reported for FSH. The available data indicated an indirect association between FSH levels and glucose disturbances among postmenopausal women; notwithstanding heterogeneity among included studies, and the complexity of various influential factors needs to be considered. Further efforts should be made to clarify the underlying mechanisms.

GPER activation attenuates cardiac dysfunction by upregulating the SIRT1/3-AMPK-UCP2 pathway in postmenopausal diabetic rats.

Postmenopausal diabetic women are at higher risk to develop cardiovascular diseases (CVD) compared with nondiabetic women. Alterations in cardiac cellular metabolism caused by changes in sirtuins are one of the main causes of CVD in postmenopausal diabetic women. Several studies have demonstrated the beneficial actions of the G protein-coupled estrogen receptor (GPER) in postmenopausal diabetic CVD. However, the molecular mechanisms by which GPER has a cardioprotective effect are still not well understood. In this study, we used an ovariectomized (OVX) type-two diabetic (T2D) rat model induced by high-fat diet/streptozotocin to investigate the effect of G-1 (GPER-agonist) on sirtuins, and their downstream pathways involved in regulation of cardiac metabolism and function. Animals were divided into five groups: Sham-Control, T2D, OVX+T2D, OVX+T2D+Vehicle, and OVX+T2D+G-1. G-1 was administrated for six weeks. At the end, hemodynamic factors were measured, and protein levels of sirtuins, AMP-activated protein kinase (AMPK), and uncoupling protein 2 (UCP2) were determined by Western blot analysis. In addition, cardiac levels of oxidative stress biomarkers were measured. The findings showed that T2D led to left ventricular dysfunction and signs of oxidative stress in the myocardium, which were accompanied by decreased protein levels of Sirt1/2/3/6, p-AMPK, and UCP2 in the heart. Moreover, the induction of the menopausal state exacerbated these changes. In contrast, treatment with G-1 ameliorated the hemodynamic changes associated with ovariectomy by increasing Sirt1/3, p-AMPK, UCP2, and improving oxidative status. The results provide evidence of the cardioprotective effects of GPER operating through Sirt1/3, p-AMPK, and UCP2, thereby improving cardiac function. Our results suggest that increasing Sirt1/3 levels may offer new therapeutic approaches for postmenopausal diabetic CVD.

Asprosin is a Reliable Predictor of Osteoporosis in Type 2 Diabetic Postmenopausal Women: A Case–Control Study

Asprosin is a Reliable Predictor of Osteoporosis in Type 2 Diabetic Postmenopausal Women: A Case–Control Study

Adverse pregnancy outcomes and risk of type 2 diabetes in postmenopausal women

Although gestational diabetes mellitus and delivering high-birthweight infants are known to predict a higher risk of future type 2 diabetes mellitus, the association of hypertensive disorders of pregnancy and other adverse pregnancy outcomes with type 2 diabetes mellitus is not well established. This study aimed to examine the associations between different types of adverse pregnancy outcomes and incident type 2 diabetes mellitus among postmenopausal women. The Women's Health Initiative, a nationwide cohort of postmenopausal women, collected self-reported history of adverse pregnancy outcomes, including gestational diabetes mellitus, hypertensive disorders of pregnancy, preterm birth, and delivering low- birthweight (<2500 g) or high-birthweight (>4500 g) infants. Participants were followed up annually for self-reported incident type 2 diabetes mellitus treated with medication from baseline (1993-1998) to March 2021. This study used logistic regression to examine the associations of any and individual adverse pregnancy outcomes with diabetes mellitus. Stratified analyses were performed to assess effect modification by body mass index, race and ethnicity, education, parity, breastfeeding, and age at first birth. This analysis included 49,717 women without a history of diabetes mellitus at enrollment who had a least 1 pregnancy and responded to the questionnaire about adverse pregnancy outcomes. After adjusting for body mass index, demographic, lifestyle, and reproductive factors, gestational diabetes mellitus (odds ratio, 2.26; 95% confidence interval, 1.94-2.63), high birthweight (odds ratio, 1.30; 95% confidence interval, 1.18-1.44), and hypertensive disorders of pregnancy (odds ratio, 1.18; 95% confidence interval, 1.08-1.30) were independently associated with higher odds of type 2 diabetes mellitus, whereas preterm birth and low birthweight were not associated with diabetes mellitus risk. A history of ≥2 adverse pregnancy outcomes was associated with higher odds of type 2 diabetes mellitus (odds ratio, 1.55; 95% confidence interval, 1.28-1.88). This study further observed higher odds of type 2 diabetes mellitus (odds ratio, 3.69; 95% confidence interval, 2.38-5.70) among women with a history of both gestational diabetes mellitus and hypertensive disorders of pregnancy than those without any adverse pregnancy outcomes. Postmenopausal women with a history of gestational diabetes mellitus, those delivering high-birthweight infants, or those with hypertensive disorders of pregnancy are at risk of future type 2 diabetes mellitus. In addition, women with ≥2 conditions had an augmented risk and might be prioritized for screening and prevention efforts for type 2 diabetes mellitus.

Insulin therapy combined or not with metformin is associated to a reduced bone mineral density and content in type 2 diabetic postmenopausal women

Anti-diabetic drugs may have negative, positive or neutral effect on bone health. The aim of this study was to compare the effect of combined treatment of metformin and insulin, metformin monotherapy and insulin monotherapy on Bone Mineral Density (BMD)

The Association between Postmenopausal Hormone Use and Risk of Type 2 Diabetes in Postmenopausal

Background: 100 postmenopausal women were examined for their usage of postmenopausal hormones and their risk of Type 2 diabetes. The findings demonstrated a significant association between the use of postmenopausal hormones and the incidence of Type 2 diabetes (odds ratio, 2.7; 95% confidence range, 1.4-5.1; P 0.001). Compared to women who did not take postmenopausal hormone treatment, those who did had a nearly 3-fold increased risk of diabetes. So, this research showed how crucial it is to consider postmenopausal hormones as a risk factor for Type 2 diabetes in postmenopausal women. Objectives: This study's main goal was to determine postmenopausal hormone usage and the likelihood of developing Type 2 diabetes in 100 postmenopausal women at the Hayatabad Medical Complex in Peshawar, Pakistan; the specific goals were to define the features of the research population, evaluate the relationship between diabetes and postmenopausal hormone usage, and pinpoint risk factors for Type 2 diabetes in postmenopausal women. Methods: The research was carried out at the Hayatabad Medical Complex's Department of Endocrinology in Peshawar, Between January 2022 And January 2023. The research's participants included 100 postmenopausal women, aged 50 to 65, from the same institution who had been on postmenopausal hormone treatment for at least three months before the trial. Through blood tests (fasting glucose and hemoglobin A1c), participants' risk of developing diabetes was evaluated. Additionally evaluated were other variables, including medical history, body mass index, and lifestyle choices that can influence the chance of getting Type 2 diabetes. Data were gathered using a semi-structured questionnaire, and descriptive statistics and logistic regression were used to analyze the results.

QTC PROLONGATION, AN EARLY PREDICTOR OF CARDIOVASCULAR AUTONOMIC NEUROPATHY (CAN) IN POSTMENOPAUSAL DIABETIC WOMEN

To evaluate QTc interval in postmenopausal diabetic women in predicting cardiovascular autonomic neuropathy (CAN). A comparative cross-sectional study was conducted in the Cardiology Department of CMH Lahore and Sir Ganga Ram Hospital, Lahore, from April 2022- April 2023. A total of 80 women were included in the study, which was categorized into 40 pre and 40 postmenopausal women. Both groups were further divided into 20 diabetic and 20 non-diabetic women. A cut-off of 3-5 years was selected for natural menopause and 5-7 years for the available duration of type 2 diabetes. Blood samples were taken to determine serum estradiol levels in all 4 groups. Autonomic neuropathy was assessed by corrected QT interval (QTc), heart rate variability (HRV), Valsalva Ratio (VR), and resting heart rate (RHR). All variables were compared among groups by using SPSS version 20.0. Serum estradiol levels were significantly lowered in postmenopausal as compared to premenopausal women (p&lt;0.001). QTc was significantly different (p=0.001) among all four groups. A statistically significant difference was found between premenopausal diabetic and postmenopausal diabetic groups (p=0.001) and between women of premenopausal non-diabetic and postmenopausal diabetic groups (p=0.003). Differences in RHR (p=0.840), HRV (p=0.084), and VR (p=0.129) were statistically nonsignificant among all four groups. A QTc prolongation is an important tool in investigating cardiac autonomic neuropathy (CAN) predisposition in postmenopausal diabetic women. Therefore, assessment of QTc prolongation could aid in early diagnosis of CAN in postmenopausal diabetic women.

Micronutrient deficiencies and functional disorders of postmenopausal diabetic women

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1375340: Correlation of Follicle Stimulating Hormone and Luteinizing Hormone Levels with HbA1c in Post-Menopausal Females

Menopause in female is a normal physiological process however, it is also a well-established risk factor for CVD and osteoporosis. Few studies suggest that low FSH is associated with adiposity and diabetes in post-menopausal women. Aim of this study was to explore correlations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels with HbA1c level in post-menopausal females. The study was conducted at of Dr. S.N. Medical College, Jodhpur, India. Otherwise healthy postmenopausal women attending hospital for preventive health checkup were included in study. Postmenopausal status was confirmed by the absence of menses for at least 12 months. Known case of T2D/T1D, subjects on hormone replacement therapy, acutely sick were excluded from study. The baseline fasting blood samples were collected. Samples was assayed for FSH, LH, HbA1c and standard biochemical profile (glucose, lipid profile, Live function tests and renal function tests) using standard methods. The participants were classified as having diabetes or prediabetes using ADA criterias. Total 229 postmenopausal women were enrolled. Mean age of subjects was 63.2±9.9 years. Mean Hba1c was 6.2±1.4 gm% and subjects were further divided in to non-diabetes (68/229), prediabetes (104/229) and diabetes group (57/229) according to Hba1c levels. Mean LH was 25.8±15.6, FSH was 61.1±30.1 and LH/FSH ratio was 0.47±0.35. Mean LH was 31.4±15.8, 26.0±16.3, 19.5±12.6 in non-diabetes, prediabetes and diabetes group respectively. Mean FSH was 75.9±29.3, 59.6±27.6, 46.9±29.0 in non-diabetes, prediabetes and diabetes group respectively. The LH and FSH values in non-diabetes and diabetes group were statistically significant (p<0.01). In this study low FSH and LH levels were associated with higher level of HbA1c and increased risk of T2D.

Relation between aortic elasticity parameters and SYNTAX score in postmenopausal diabetic women

BackgroundPostmenopausal women are at increased risk of coronary artery disease (CAD). Diabetes Mellitus is a major risk factor for CAD. The stiffening of the aorta is associated with increased cardiovascular morbidity and mortality. We aimed to investigate the relation of aortic elasticity parameters to CAD severity assessed by SYNTAX score (SS) in diabetic postmenopausal women. The study prospectively included 200 consecutive diabetic postmenopausal women with CAD who underwent elective coronary angiography. Patients were classified into 3 groups based on SS, low-SS ≤ 22, intermediate-SS ≥ 23– ≤ 32, and high-SS ≥ 33. Echocardiographic aortic elasticity parameters, including aortic stiffness index (ASI), aortic strain (AS) (%) and aortic distensibility (AD) were obtained in all patients.ResultsPatients in the high SS group were older age and had a higher aortic stiffness. After adjusting different co-variates AD, AS, and ASI could be used as independent predictors of high SS with the following P-values (0.019, 0.016 and 0.010) and cut-off values (2.5, 3.6 and 2.9), respectively.ConclusionsIn diabetic postmenopausal women, the simple echocardiography-derived aortic elasticity parameters might predict the severity and complexity of angiographic coronary lesions assessed by the SS.

Diagnostic markers of insulin resistance to discriminate between prediabetes and diabetes in menopausal women.

Menopause is an important transition period in a woman's reproductive life during which hormonal changes occur, resulting in an increased risk of cardiovascular disease and type 2 diabetes. In this study, we assessed the possibility of using surrogate measures of insulin resistance (IR) to predict the risk of insulin resistance in perimenopausal women. The study involved 252 perimenopausal women living in the West Pomeranian Voivodeship. The methods employed in this study were diagnostic survey based on the original questionnaire, anthropometric measurement, and laboratory tests performed to determine the levels of selected biochemical parameters. In the entire study population, the highest area under the curve was found for the homeostasis model assessment-insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). Triglyceride-glucose index (TyG index) showed a higher diagnostic value as a distinction tool between prediabetes and diabetes in perimenopausal women than the other markers. HOMA-IR significantly positively correlated with fasting blood glucose (r = 0.72; p = 0.001), glycated hemoglobin (HbA1C, r = 0.74; p = 0.001), triglycerides (TG, r = 0.18; p < 0.005), and systolic blood pressure (SBP, r = 0.15; p= 0.021), and negatively with high-density lipoprotein (HDL, r = -0.28; p = 0.001). QUICKI negatively correlated with fasting blood (r = -0.051; p = 0.001), HbA1C (r = -0.51; p = 0.001), TG (r = -0.25; p = 0.001), low-density lipoprotein (LDL, r = -0.13; p= 0.045), and SBP (r = -0.16; p = 0.011), and positively with HDL (r = 0.39; p = 0.001). Anthropometric and cardiometabolic parameters were found to significantly correlate with IR markers. HOMA-beta, the McAuley index (McA), visceral adiposity index (VAI), and lipid accumulation product (LAP) may be useful as predictors of pre-diabetes and diabetes in postmenopausal women.

Assessment of endothelial dysfunction and inflammation in type 2 diabetic postmenopausal women

Objective: Vascular complications in type 2 diabetes mellitus are an important cause of morbidity and mortality. Also, endothelial dysfunction arises with vascular ageing during the postmenopausal period. Our objective in this study was to evaluate inflammation and endothelial function parameters and their possible diagnostic roles in type 2 diabetic postmenopausal patients. Material and Methods: The study was conducted on four groups, including type 2 diabetic premenopausal (n:20), non-diabetic premenopausal (n:20), type 2 diabetic postmenopausal (n:20), and non-diabetic postmenopausal subjects (n:20). Serum endothelin-1 (ET-1), endothelial nitric oxide synthetase (eNOS), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and chitinase-3-like protein 1 (YKL-40) levels were determined as inflammatory and endothelial function markers using ELISA kits. Results: Serum ET-1, IL-6, and YKL-40 levels were higher in the type 2 diabetic postmenopausal group compared to the non-diabetic premenopausal group (p&lt;0.01, p&lt;0.05, and p&lt;0.01, respectively). ET-1, IL-6, and YKL-40 levels were higher in the type 2 diabetic postmenopausal group compared to the non-diabetic postmenopausal group (p&lt;0.001, p&lt;0.05, and p&lt;0.01 respectively). ROC analysis revealed serum ET-1 (AUC 0.933, sensitivity 87.5%, specificity 85.7%), IL-6 (AUC 0.812, sensitivity 56.3%, specificity 92.8%), and YKL-40 (AUC 0.880, sensitivity 81.2%, specificity 92.8%), as good diagnostic parameters, especially in the type 2 diabetic premenopausal vs. non-diabetic premenopausal cohorts. Conclusion: Serum ET-1, IL-6, and YKL-40 levels were at the highest levels in the 2 diabetic postmenopausal group, and the increase in these markers was remarkable in diabetes compared with menopausal periods. Also, ET-1, IL-6, and YKL-40 were good diagnostic parameters for detecting endothelial function and inflammation in type 2 diabetic postmenopausal and non-diabetic premenopausal cohorts.

Homoeopathic management of diabetes mellitus among post-menopausal women by Helonias dioica: A case series

A sample of 15 cases of post-menopausal diabetic women from OPD of Sarada Krishna Homoeopathic Medical College and Hospital were selected, detailed case taking was done and Helonias Dioica in different potencies was administered as per the directions of 5th and 6th editions of Organon of medicine, including its repetition and dosage. FBS and serum HbA1c levels of the individual were measured on the first visit itself. Advices were given to follow a healthy diet. The cases were followed up for 12 weeks to obtain correct changes in serum HbA1c. FBS was analysed in follow ups of every 2 weeks and the repetition of dose, change in potency/medicine was decided based on the overall condition of the patient. After 3 months, HbA1c level was taken and in about 80% of the cases had their HbA1c levels reduced.

Association of Serum Uric Acid with Diabetes in Premenopausal and Postmenopausal Women-A Prospective Cohort Study in Shanghai, China.

There have been few prospective studies on the association between serum uric acid (SUA) and the risk of diabetes in women, and there have been few large-scale Chinese studies based on menopause to investigate the association. Therefore, the present study aimed to investigate the above relationship in Chinese female adults without diabetes. Methods: Data from 5743 premenopausal women and 11,287 postmenopausal women aged 20−74 years were obtained from the Shanghai Suburban Adult Cohort and Biobank (SSACB) study conducted in China. Cox regression models were applied to evaluate the association between SUA levels and the risk of diabetes. Restricted cubic spline analysis and stratified analysis on the basis of menopausal status were performed to explore the dose−response association between SUA levels and diabetes. Results: Among 17,030 participants, incidence rates of diabetes were 3.44/1000 person-years in premenopausal and 8.90/1000 person-years in postmenopausal women. The SUA levels in postmenopausal women were higher than that in premenopausal women (p < 0.0001). In Cox regression analysis, after adjusting for confounding factors, for each 10 µmol/L increase in SUA levels, the adjusted HR of diabetes was 1.01 (95% CI: 0.97−1.04) in postmenopausal women, and 1.03 (95% CI: 1.01−1.04) in premenopausal women. Compared with the lowest quartile of SUA levels, the HR (95% CI) of diabetes in the highest quartile was 0.99 (0.55−1.79) in premenopausal women and 1.39 (1.07−1.81) in postmenopausal women. Compared with those without hyperuricemia, the HR (95% CI) for diabetes was 1.89 (0.67−5.31) in premenopausal women with hyperuricemia, and 1.55 (1.19−2.02) in postmenopausal women. Moreover, restricted cubic splines models showed that there was a linear relationship between SUA levels and diabetes risk in premenopausal (p for nonlinear = 0.99) and postmenopausal women (p for nonlinear = 0.95). Furthermore, the restricted cubic spline graph showed that the risk of diabetes in postmenopausal women increased with an increase in SUA levels (p = 0.002). Conclusions: In a cohort of Chinese adult women, SUA levels are associated with diabetes risk in postmenopausal women, but this association was not observed in premenopausal women.

Increased risk of non-alcoholic fatty liver disease fibrosis is closely associated with osteoporosis in women but not in men with type 2 diabetes.

BackgroundThis study aimed to investigate the association of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis with osteoporosis in postmenopausal women and men over 50 years of age with type 2 diabetes (T2DM).MethodsIn this study, 1243 patients with T2DM (T2DM with coexistent NAFLD, n = 760; T2DM with no NAFLD, n = 483) were analysed. Non-invasive markers, NAFLD fibrosis score (NFS) and fibrosis index based on four factors (FIB-4), were applied to evaluate NAFLD fibrosis risk.Results There was no significant difference in bone mineral density (BMD) between the NAFLD group and the non-NAFLD group or between males and females after adjusting for age, BMI and gender. In postmenopausal women, there was an increased risk of osteoporosis (odds ratio (OR): 4.41, 95% CI: 1.04–18.70, P = 0.039) in the FIB-4 high risk group compared to the low risk group. Similarly, in women with high risk NFS, there was an increased risk of osteoporosis (OR: 5.98, 95% CI: 1.40–25.60, P = 0.043) compared to the low risk group. Among men over 50 years old, there was no significant difference in bone mineral density between the NAFLD group and the non-NAFLD group and no significant difference between bone mineral density and incidence of osteopenia or osteoporosis among those with different NAFLD fibrosis risk.Conclusion There was a significant association of high risk for NAFLD liver fibrosis with osteoporosis in postmenopausal diabetic women but not men. In clinical practice, gender-specific evaluation of osteoporosis is needed in patients with T2DM and coexistent NAFLD.

Vulvar Pruritus in Postmenopausal Diabetic Women With Candidiasis Secondary to Sodium-Glucose Cotransporter Receptor-2 Inhibitors.

Vulvar pruritus with external rash in postmenopausal women on sodium-glucose cotransporter receptor-2 inhibitors may indicate vulvovaginal candidiasis, which requires early yeast culture for prompt diagnosis and management. Objective/Purpose We present a case series of recurrent vulvovaginal candidiasis (RVVC) secondary to sodium-glucose cotransporter receptor-2 (SGLT2) inhibitor-induced glucosuria in postmenopausal women that resulted in extensive vulvar skin involvement. Materials and Methods We describe 5 cases of RVVC presenting primarily with vulvar pruritus and external rash, in type 2 diabetic, postmenopausal women on SGLT2 inhibitor therapy. This work was exempt from institutional review board approval in compliance with the university guidelines for determining human subject research. All patients consented to the use of pictures for educational and research purposes. Results All patients developed RVVC, with vulvar cultures positive for Candida albicans and resolution of symptoms after treatment with oral fluconazole. All patients presented primarily with severe vulvar pruritus that developed after beginning treatment with SGLT2 inhibitors (range: 4 wk–16 mo). Given the intermittent nature of symptoms, variable degree of activity at presentation, lack of vaginal discharge, atypical population, and extensive skin involvement, RVVC was not considered initially. Three patients were misdiagnosed with lichen sclerosus and treated with topical steroids, which may have allowed for disease progression. Two patients were prescribed topical estrogen creams for presumed vaginal atrophy. One patient was misdiagnosed with improper vulvar hygiene and neuropathic itch. Because of these diagnostic missteps, 4 patients endured symptomatically for extended periods (range: 2–6 years) without adequate treatment. Four patients have discontinued their SGLT2 inhibitor, all with resolution of vulvar symptoms. Conclusions Postmenopausal, diabetic women taking SGLT2 inhibitors presenting with vulvar pruritus and rash require early evaluation for RVVC to prevent misdiagnoses and need for diabetic medication alterations.

Metformin prevents age-associated ovarian fibrosis by modulating the immune landscape in female mice.

Ovarian fibrosis is a pathological condition associated with aging and is responsible for a variety of ovarian dysfunctions. Given the known contributions of tissue fibrosis to tumorigenesis, it is anticipated that ovarian fibrosis may contribute to ovarian cancer risk. We recently reported that diabetic postmenopausal women using metformin had ovarian collagen abundance and organization that were similar to premenopausal ovaries from nondiabetic women. In this study, we investigated the effects of aging and metformin on mouse ovarian fibrosis at a single-cell level. We discovered that metformin treatment prevented age-associated ovarian fibrosis by modulating the proportion of fibroblasts, myofibroblasts, and immune cells. Senescence-associated secretory phenotype (SASP)-producing fibroblasts increased in aged ovaries, and a unique metformin-responsive subpopulation of macrophages emerged in aged mice treated with metformin. The results demonstrate that metformin can modulate specific populations of immune cells and fibroblasts to prevent age-associated ovarian fibrosis and offers a new strategy to prevent ovarian fibrosis.

Circulating amino acids and acylcarnitines correlated with different CAC score ranges in diabetic postmenopausal women using LC–MS/MS based metabolomics approach

BackgroundDiabetes mellitus (DM) and its cardiovascular disease (CVD) complication are among the most frequent causes of death worldwide. However, the metabolites linking up diabetes and CVD are less understood. In this study, we aimed to evaluate serum acylcarnitines and amino acids in postmenopausal women suffering from diabetes with different severity of CVD and compared them with healthy controls.MethodsThrough a cross-sectional study, samples were collected from postmenopausal women without diabetes and CVD as controls (n = 20), patients with diabetes and without CVD (n = 16), diabetes with low risk of CVD (n = 11), and diabetes with a high risk of CVD (n = 21) referred for CT angiography for any reason. Metabolites were detected by a targeted approach using LC–MS/MS and metabolic -alterations were assessed by applying multivariate statistical analysis. The diagnostic ability of discovered metabolites based on multivariate statistical analysis was evaluated by ROC curve analysis.ResultsThe study included women aged from 50–80 years with 5–30 years of menopause. The relative concentration of C14:1, C14:2, C16:1, C18:1, and C18:2OH acylcarnitines decreased and C18 acylcarnitine and serine increased in diabetic patients compared to control. Besides, C16:1 and C18:2OH acylcarnitines increased in high-risk CVD diabetic patients compared to no CVD risk diabetic patients.ConclusionDysregulation of serum acylcarnitines and amino acids profile correlated with different CAC score ranges in diabetic postmenopausal women. (Ethic approval No: IR.TUMS.EMRI.REC.1399.062).

Increased eHSP70-to-iHSP70 ratio in prediabetic and diabetic postmenopausal women: a biomarker of cardiometabolic risk.

Decreased estrogen levels in menopause are associated with anthropometric, metabolic, and inflammatory impairments, predisposing women to cardiometabolic risk factors such as diabetes. Menopause and type two diabetes (DM2) are marked by altered heat shock response (HSR), shown by decreased expression of the 70-kDa heat shock protein in the intracellular milieu (iHSP70). While iHSP70 plays an anti-inflammatory role, extracellular HSP70 (eHSP70) may mediate pro-inflammatory pathways and has been associated with insulin resistance in DM2. Considering the roles of these proteins according to localization, the eHSP70-to-iHSP70 ratio (H-index) has been proposed as a biomarker for HSR. We, therefore, evaluated whether this biomarker is associated with glycemic and inflammatory status in postmenopausal women. In this transversal study, 36 postmenopausal women were grouped according to fasting glycemia status as either the control group (normoglycemic, ≤ 99mg/dL) or DM2 (prediabetic and diabetic, glycemia ≥ 100mg/dL). DM2 group showed higher triglyceride/glucose (TyG) index and plasma atherogenic index (PAI), both of which are indicators of cardiometabolic risk. In addition, we found that the eHSP70-to-iHSP70 ratio (plasma/peripheral blood mononuclear cells-PBMC ratio) was higher in the DM2 group, compared with the control group. Furthermore, blood leukocyte and glycemia levels were positively correlated with the eHSP70-to-iHSP70 ratio in women that presented H-index values above 1.0 (a.u.). Taken together, our results highlight the eHSP70-to-iHSP70 ratio as a biomarker of altered HSR in DM2 postmenopausal women.

Gallbladder Disease and Risk of Type 2 Diabetes in Postmenopausal Women: A Women's Health Initiative Study.

Studies have suggested that adults with gallbladder disease have increased risk of type 2 diabetes. This prospective cohort study assessed the risk of type 2 diabetes in postmenopausal women with gallbladder disease. Data from women enrolled in the Women's Health Initiative from 1993 to 2005, aged 50-79 years (mean = 63.2; standard deviation, 7.2), were analyzed. Cox proportional hazards regression models were used to estimate the risk of type 2 diabetes associated with gallbladder disease. There were 8,896 new cases of type 2 diabetes after 1,025,486 person-years of follow-up. Gallbladder disease was significantly associated with type 2 diabetes (hazard ratio = 1.52; 95% confidence interval (CI): 1.38,1.67). The observed risk of type 2 diabetes in women with both gallbladder disease and central obesity was 37% higher than expected (relative excess risk due to interaction = 0.37, 95% CI: 0.11,0.63) on the additive scale. The hazard ratios for type 2 diabetes associated with gallbladder disease were 1.25 (95% CI: 1.19,1.32) and 1.48 (95% CI: 1.34,1.63) in women with and without central obesity, respectively, on the multiplicative scale. Results of this study support further studies to determine whether interventions in older women with gallbladder disease would reduce type 2 diabetes risk, especially among those with central obesity. Future research should examine the pathophysiological basis of the association between gallbladder disease and type 2 diabetes.