The global burden and serious outcomes of coronary heart disease (CHD) highlight the need for further comprehensive research. This study explored the predictive value of glycated apolipoprotein A-1 (G-apoA1) and glycated low-density lipoprotein cholesterol (G-LDL-C) levels for coronary artery obstruction severity and future major adverse cardiovascular events (MACEs) among patients with type 2 diabetes mellitus (T2DM). This study included 3,292 patients with T2DM who were followed up for 5 years. Patients were stratified into quartiles of G-apoA1 and G-LDL-C, and associations with the incidence of MACEs were assessed by comparing quartile groups. Logistic regression and Spearman's correlation analyses were conducted to evaluate the associations of G‑apoA1 and G‑LDL‑C with CHD risk, while Cox regression was used to estimate the risk of MACEs. G-apoA1 and G-LDL-C levels were significantly higher in patients with T2DM and CHD than in those with T2DM without CHD and were identified as independent risk factors for CHD [G-apoA1: odds ratio (OR) = 2.021, 95%CI: 1.622-2.519, p < 0.001; G-LDL-C: OR = 2.038, 95%CI: 1.616-2.570, p < 0.001]. These levels were also positively correlated with the number of obstructed coronary arteries and the Gensini score (GS). During the 5-year follow-up period, 443 patients experienced MACEs. An analysis using restricted cubic spline models revealed that the incidence of MACEs increased with higher G-apoA1 and G-LDL-C levels. Multivariate Cox regression analysis showed a significantly higher risk of MACEs among patients in the highest quartile than among those in the lowest quartile [G-apoA1: hazard ratio (HR):2.183, 95%CI: 1.630-2.923, p < 0.001; G-LDL-C: HR:2.798, 95%CI: 2.053-3.812, p < 0.001]. This study showed that G-apoA1 and G-LDL-C levels were associated with CHD in patients with T2DM and correlated with the severity of coronary obstruction. Moreover, higher G-apoA1 and G-LDL-C levels were associated with an increased incidence of MACEs.

The study aimed to characterize the oral microbiota of patients with nasopharyngeal carcinoma (NPC) before and after radiotherapy (RT), and to compare the differences in microbiota between patients with and without radiation-related caries (RRC). Saliva and tongue swab samples were collected from 29 NPC patients pre-RT (baseline) and 3–9 months post-RT. Patients were categorized into the RRC group (those who developed new radiation-related caries post-RT) or the non-RRC group (those without new caries) based on clinical diagnosis. Oral microbiota composition was assessed via 16S rRNA gene sequencing. The permutational multivariate analysis of variance (PerMANOVA) and linear discriminant analysis (LDA) effect size (LEfSe) were used to compare the oral microbiota composition before and after RT and between patients with and without RRC after RT. There were no significant differences in alpha diversity between patients before and after RT, nor between the RRC and non-RRC groups after RT. The beta diversity analyses detected significant differences on post-RT saliva samples between the RRC and non-RRC groups (R2 = 0.062, F = 1.720, P = 0.005). There were also significant differences in the beta diversity of both saliva samples (R2 = 0.099, F = 2.192, P = 0.001) and tongue swab samples (R2 = 0.118, F = 2.671, P = 0.002) before and after RT in the RRC group, as well as in saliva (R2 = 0.062, F = 2.183, P = 0.005) and tongue swab (R2 = 0.099, F = 3.639, P = 0.001) samples in the non-RRC group. The LEfSe analysis showed no substantial difference when comparing microbiota composition of saliva and tongue swab samples between RRC and non-RRC groups before RT. However, an enrichment of Streptococcus mutans and Ligilactobacillus salivarius was detected post-RT in both the salivary and tongue swab samples of the RRC group. RT was associated with significantly altered oral microbiota composition of NPC patients, while RRC was associated with tooth decay related microbiota enrichment after RT.

BACKGROUND:Data on the efficacy and safety of sacubitril/valsartan in hemodialysis patients with heart failure and preserved left ventricular ejection fraction (≥ 50%, HFpEF) or mildly reduced left ventricular ejection fraction (41%-49%, HFmrEF) were analyzed, as well as cardiac functional parameters and safety after withdrawal of sacubitril/valsartan. METHODS:Ninety-eight maintenance hemodialysis patients with heart failure with preserved or mildly reduced ejection fraction were included in the present study. Patients were divided into sacubitril/valsartan and control groups according to whether they had been, or were being, treated with sacubitril/valsartan. Patients were further divided into continuation and discontinuation groups based on whether sacubitril/valsartan was discontinued at the end of follow-up. Laboratory examination results, echocardiographic parameters, and the occurrence of major adverse cardiac events were recorded and analyzed. RESULTS:There were 50 patients in the control group and 48 in the sacubitril/valsartan group. The median follow-up time was 14.5 months. Compared with the control group, the serum B-type natriuretic peptide levels and echocardiographic parameters in the sacubitril/valsartan group significantly decreased from baseline at 6-month follow-up (p < 0.05). In the sacubitril/valsartan group, there were 28 patients in the continuation group and 20 in the discontinuation group. The reduction in left ventricular end-diastolic diameter in the sacubitril/valsartan group reversed in the discontinuation group (by 10%) after drug withdrawal, whereas it was stable in the continuation group (change 0.66%, p = 0.030). Patients with lower left ventricular end-diastolic diameters at the end follow-up (≤ 50 mm) exhibited a lower incidence of major adverse cardiac events compared to those with higher diameters (>50 mm; p = 0.012). CONCLUSION:Sacubitril/valsartan improved cardiac function in patients on hemodialysis with heart failure and preserved or mildly reduced left ventricular ejection fraction. Long-term continuous use of sacubitril/valsartan may reduce left ventricular end-diastolic diameter and positively impact prognosis.

OBJECTIVE:Polyols, natural nutritive sweeteners, are often found in the diet during pregnancy. This study investigates the association between maternal serum polyol levels and the risk of gestational diabetes mellitus (GDM) and large-for-gestational-age (LGA) infants. METHODS:This nested case-control study matched 218 women (with GDM vs. without GDM) by age and body mass index. After exclusions, the final analytic sample comprised 194 women for glucose metabolism outcomes and 177 women for birth weight and LGA outcomes. Serum polyols (sorbitol, erythritol, xylitol, and maltitol) were quantified using gas chromatography coupled with time-of-flight mass spectrometry. LGA was defined as a birth weight ≥90th percentile or ≥4000 g. Logistic regression was used to assess the associations between polyols and GDM and LGA, with adjustment for confounders. RESULTS:Among the participants, 23.7% had LGA infants, and maternal serum polyol levels were significantly higher in this group. After adjusting for confounders, a 1-standard deviation increase in serum polyol levels was associated with increased odds of LGA (odds ratio=1.71, 95% confidence interval [CI]:1.22 to 2.40) and GDM (OR=1.52, 95% CI: 1.09 to 2.14). Erythritol and sorbitol were significantly associated with the odds of LGA, whereas xylitol and maltitol had no significant associations. Furthermore, a 1-standard deviation increase in serum polyol levels was linked to higher birth weight (beta [β]=95 g, 95% CI: 33 to 157 g) and elevated homeostasis model assessment for insulin resistance (β=0.32, 95% CI: 0.12 to 0.52). CONCLUSIONS:Elevated maternal serum polyol levels were positively associated with the risk of GDM, LGA infants, and higher birth weight.

Akkermansia muciniphila is a promising target for managing obesity and type 2 diabetes (T2D), but human studies are limited. We conducted a 12-week randomized, double-blind, placebo-controlled trial involving 58 participants with overweight or obese T2D, who received A. muciniphila (AKK-WST01) or placebo, along with routine lifestyle guidance. Both groups showed decreases in body weight and glycated hemoglobin (HbA1c), without significant between-group differences. In participants with low baseline A. muciniphila, AKK-WST01 supplementation showed high colonization efficiency and significant reductions in body weight, fat mass, and HbA1c, which were not found in the placebo group. However, AKK-WST01 supplementation showed poor colonization and no significant clinical improvements in participants with high baseline A. muciniphila. These findings were verified in germ-free mice receiving feces with low or high A. muciniphila. Our study indicates that metabolic benefits of A. muciniphila supplementation could depend on its baseline intestinal levels, supporting the potential for gut microbiota-guided probiotic supplementation. (ClinicalTrials.gov number, NCT04797442).

Dyslipidemia has been found to promote platelet activation and aggregation, contributing to the formation of atherosclerotic plaques. This study aims to explore the relationship between lipid profiles and platelet indices (PI) among middle-aged and older people without cardiovascular disease (CVD) history. The study employed a cross-sectional design, a total of 10,060 participants from Chongming District, Shanghai, were enrolled in the study. Serum lipids (total cholesterol[CHOL], low-density lipoprotein cholesterol[LDL-C], triglycerides[TG], and high-density lipoprotein cholesterol[HDL-C]) were measured on an automatic analyzer and platelets indices (platelet count[PLT], mean platelet volume[MPV], platelet distribution width[PDW], and plateletcrit[PCT]) were measured using an automatic blood cell analyzer. Lasso regression was used to select significant covariates. Multiple linear regression models were then constructed to evaluate the impact of lipids on platelet indices, adjusting for these selected covariates. Restricted cubic spline (RCS) models were utilized to explore potential nonlinear relationships and subgroup analyses stratified by gender were conducted to enhance the robustness of the findings. After applying exclusion criteria, 9,396 participants aged 40 to 70 were included, with a median age of 56 years, of whom 32.5

Anti-vascular endothelial growth factor (anti-VEGF) therapies are effective treatment of severe diabetic retinopathy (DR) and macular edema, but a significant subset of people showed inadequate response to anti-VEGF intervention. Since elevation or overexpressing retinol binding protein 3 (RBP3) decreased risks for retinal pathologies and progression to severe DR, we compared the therapeutic profile of RBP3 and anti-VEGF to normalize retinal dysfunctions induced by diabetes. Intravitreous injection of recombinant human RBP3 (rhRBP3) and anti-VEGF antibodies (bevacizumab) inhibited retinal vascular permeability in Lewis rats induced by VEGF-A or after 2 months of diabetes induced by streptozotocin, in parallel with reductions of retinal VEGF and VEGFR2 expressions and tyrosine phosphorylation of VEGFR. Only rhRBP3 ameliorated diabetes induced reduction of neural retinal function, measured by electroretinogram. Further, rhRBP3 reduced retinal expressions of inflammatory cytokines (TNFα and IL6) in retinal pigmented epithelial and Müller cells exposed to hyperglycemia. Metabolic studies, using Seahorse, showed only rhRBP3 normalized retinal glycolytic rates in diabetic rats. Thus, both intravitreous anti-VEGF antibodies and RBP3 injections normalized retinal vascular dysfunctions caused by diabetes. Only RBP3 targeted both neural and vascular retina to reduce glycolytic rates, reversed neural-retinal dysfunctions, and reduced inflammatory cytokines induced by diabetes, to delay early changes of DR.

Introduction and Objective: This study aims to investigate the association between maternal serum polyol levels and the risks of gestational diabetes mellitus (GDM) and large for gestational age (LGA) infants. Methods: In a population-based nested case-control study, we matched pregnant women with GDM (n=89) and those without GDM (n=89) based on age and pre-pregnancy body mass index (BMI). We excluded cases of preterm birth, low birth weight, gestational hypertension, and missing data, and a final sample of 175 women (89 with GDM and 86 without GDM) were included. 75g oral glucose tolerance test (OGTT) and insulin release test (IRT) were measured during the gestation period of 20-28 weeks. Pre-pregnancy weight was self-reported by the pregnant woman, and body weight was remeasured at the last prenatal visit in the third trimester. Serum levels of polyols (sorbitol, erythritol, xylitol, and maltitol) were quantified using gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF/MS). Results: Among the 175 participants, 24.0% had LGA infants. Maternal serum polyol levels were significantly elevated in the LGA group. After adjusting for confounders, a 1-SD increase in serum polyol levels was associated with increased odds of LGA (OR 1.76, 95% CI: 1.19-2.59) and GDM (OR 1.52, 95% CI: 1.09-2.14). Notably, erythritol and sorbitol were significantly associated with LGA risk, while xylitol and maltitol showed no significant correlation. Additionally, a 1-SD increase in serum polyol levels was linked to higher birth weight (β= 89 grams, 95% CI: 16-161 grams) and increased values of homeostasis model assessment for insulin resistance (HOMA-IR) (β= 0.26, 95% CI: 0.07-0.46) in the fully adjusted model. Conclusion: Our findings indicated that elevated maternal serum polyol levels were positively associated with the risks of GDM, LGA infants, and high birth weight. T. Tan: None. M. Wang: None. Y. Qi: None. Y. Liu: None. L. Qin: None. J. Ma: None. Science and Technology Commission of Shanghai Municipality-Science and Technology Program (20DZ2201500); Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20181807)

Emerging evidence indicates associations between serum vitamin D (VD) levels and metabolic profiles in obesity. This study aimed to investigate the relationship between VD and metabolic health and body composition, with a specific focus on exploring sex-specific differences. Data were sourced from a cohort. A linear regression model was used to explore the relationship between VD and various health indicators. Consensus clustering algorithm (CCA) identified the potential subtypes in male and female obese populations. Dose–response relationship was determined using a restricted cubic spline (RCS) model. Mediation effects of metabolic indicators between VD and obesity subtypes were explored. A total of 1507 participants were included in this study. The linear regression model revealed an inverse relationship between VD and fasting blood glucose, HbA1c, triglycerides, and homeostatic model assessment for insulin resistance (HOMA-IR) in males. VD demonstrated a positive association with high-density lipoprotein cholesterol (HDL-C) in females. CCA identified two clusters, named unhealthy and relatively healthy obesity. RCS suggested that individuals with serum VD levels exceeding 37.7 and 30.0 μmol/mL were more likely to be relatively healthy obese in the male and female populations, respectively. For mediation analysis, HOMA-IR mediated 31

Hemifacial microsomia (HFM) is a rare congenital disorder that affects facial symmetry, ear development, and other congenital anomalies. However, known causal genes account for only approximately 6% of patients, indicating the need to discover more pathogenic genes. Association tests demonstrated an association between common variants in SHROOM3 and HFM (P = 1.02E-4 for the lead SNP), while gene burden analysis revealed a significant enrichment of rare variants in HFM patients compared to healthy controls (P = 2.78E-5). We then evaluated the expression patterns of SHROOM3 and the consequences of its deleterious variants. Our study identified 7 deleterious variants in SHROOM3 among the 320 Chinese HFM patients and 2 deleterious variants in two HFM trios, respectively, suggesting a model of dominant inheritance with incomplete penetrance. These variants were predicted to significantly impact SHROOM3 function. Furthermore, the gene expression pattern of SHROOM3 in the pharyngeal arches and the presence of facial abnormalities in gene-edited mice suggest that SHROOM3 plays important roles in facial development. Our findings suggest that SHROOM3 is a likely pathogenic gene for HFM.

It is important to detect the predictors of prediabetes progressing to diabetes. Although polyols affect glycometabolism, little is known about the association between fasting serum polyol levels of participants with habitual diet and the risk of prediabetes progressing to type 2 diabetes. In this nested case-control study, 180 participants who developed from prediabetes to type 2 diabetes (progressors), and 180 matched controls (non-progressors) with prediabetes during a 3.5-year follow-up were enrolled. The baseline levels of serum polyols in the fasting state were quantified using time-of-flight mass spectrometry. Multivariate conditional logistic regression was performed to assess the effects of the differential polyol levels on the risk of incident diabetes from prediabetes. The baseline fasting xylitol levels, but not sorbitol or erythritol levels, were higher in non-progressors than in progressors (P < 0.001). Non-progressors, in comparison with progressors, had significantly higher proportions within the third tertile of xylitol levels (71/180 non-progressors [39.4

This retrospective cohort study assessed the predictive value of routine clinical indicators for diabetic nephropathy (DN) in elderly patients (≥60 years) with type 2 diabetes mellitus (T2DM) and hypertension. A total of 102 hospitalized patients (January 2022-December 2023) were divided into DN and non-DN groups. Fasting blood glucose (FBG), 2-h postprandial glucose (2hPG), HbA1c, systolic blood pressure (SBP), urinary microalbumin (UMA), and urinary albumin-to-creatinine ratio (UACR) were analyzed using univariate and multivariate logistic regression to identify independent predictors. A nomogram based on these indicators was developed and evaluated by receiver operating characteristic (ROC) analysis. All six factors independently predicted DN (p < 0.05), with 2hPG showing the strongest association (OR = 8.922). The combined model achieved high predictive accuracy (AUC = 0.906), outperforming any single indicator. This model offers a practical tool for early DN risk stratification in elderly T2DM patients with hypertension, supporting individualized prevention and intervention.

Beyond the Thyroid Imaging Reporting and Data System (TIRADS) classification of thyroid nodules, additional factors must be weighed in the decision to perform fine needle aspiration (FNA). In this study, we aimed to identify risk factors for malignancy in patients with ultrasound-classified Chinese-TIRADS (C-TIRADS) 4 A nodules. Patients who underwent thyroid FNA at our institution between May 2021 and September 2022 were enrolled. We collected demographic data, including age, sex, previous radiation exposure, and family history. An in-person questionnaire was used to collect lifestyle data, such as smoking habits and alcohol consumption. Body mass index (BMI) was calculated. The serum levels of thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured. Prior to FNA, ultrasonic inspection reports were reviewed. The cytologic diagnoses for FNA of thyroid nodules followed the Bethesda System for Reporting Thyroid Cytopathology (2017). Among the 252 C-TIRADS 4 A nodules, 103 were malignant. Compared to those in the benign group, the patients in the malignant group had a younger age (42.2 ± 13.6 vs. 51.5 ± 14.0 years, P < 0.001). Logistic regression showed that advanced age was associated with a lower risk of malignancy in C-TIRADS 4 A nodules (OR = 0.95, 95

Context Sugar alcohols (also called polyols) are regarded as a "healthy" sugar substitute. One of the possible reasons for their safe use in pregnant women is their natural origin and the presence of polyols in maternal and fetal samples during normal human gestation. But little is known about the association between circulating sugar alcohols levels and maternal metabolic disorders during pregnancy.Objective We aimed to detect the concentration of the polyols in participants with and without gestational diabetes mellitus (GDM), and to investigate the association between maternal serum levels of polyols and GDM, as well as newborn outcomes.Methods A nested population-based case-control study was conducted in 109 women with and without GDM. Maternal concentrations of serum erythritol, sorbitol, and xylitol in the fasting state were quantified using a time of flight mass spectrometry system.Result In women with GDM, serum concentrations of erythritol and sorbitol were higher, but serum concentrations of xylitol were lower than those in women without GDM. Per 1-SD increment of Box-Cox-transformed concentrations of erythritol and sorbitol were associated with the increased odds of GDM by 43% and 155% (95% CI 1.07-1.92 and 95% CI 1.77-3.69), while decreased odds were found for xylitol by 25% (95% CI 0.57-1.00). Additionally, per 1-SD increase of Box-Cox-transformed concentrations of serum sorbitol was associated with a 52% increased odds of large for gestational age newborns controlling for possible confounders (95% CI 1.00-2.30).Conclusion Maternal circulating sugar alcohols levels during pregnancy were significantly associated with GDM. These findings provide the potential roles of polyols on maternal metabolic health during pregnancy.

Background The etiology of Hashimoto's thyroiditis (HT) involves genetic and environmental factors. There is a lack of clarity regarding the relationship between Vitamin D and HT. This study aimed to investigate the effect of Vitamin D and gene polymorphisms on thyroid peroxidase antibody (TPOAb) positivity. Methods A total of 9,966 participants were included from a survey conducted in East China from 2014 to 2016. We measured the levels of 25(OH)D, thyroid hormones and autoimmune antibodies. rs11675434, rs9277555, and rs301799 were genotyped. Based on these 3 SNPs, a weighted genetic risk score was calculated for TPOAb. Results The proportion of females in the TPOAb-positive group was greater than that in the TPOAb-negative group (74.2% vs. 57.2%, P<0.001). Vitamin D levels were lower in the TPOAb-positive group than in the TPOAb-negative group (40.07±11.87 vs. 40.80±12.84, P=0.01). The GG genotype of rs9277555 and the TT genotype of rs11675434 were correlated with the risk of TPOAb positivity (OR=1.34, 95% CI 1.13-1.59, P=0.001; OR=1.29, 95% CI 1.06-1.58, P=0.01). TPOAb-GRS was associated with TPOAb positivity (OR=3.17, 95% CI 1.72-5.84; P<0.001). When stratified by Vitamin D group, the association between TPOAb-GRS and TPOAb positivity existed only in the Vitamin D deficiency group (OR=3.41, 95% CI 1.73-6.70 P<0.001) but not in the control group (OR=2.45, 95% CI 0.59-10.19, P=0.22). Conclusions This study suggested that TPOAb-GRS was associated with TPOAb positivity in the Han Chinese population, mainly due to rs9277555 and rs11675434. The hereditary effect of TPOAb positivity differed depending on Vitamin D status.

CONTEXT:Advanced glycation end products (AGEs) are a group of molecules formed through nonenzymatic reactions. These compounds are associated with several age-related diseases, including sarcopenia and osteoporosis. OBJECTIVE:This work aimed to investigate the relationships between AGEs, osteoporosis, and sarcopenia in community-dwelling older adults. METHODS:This cross-sectional study included 1991 older adults aged 72.37 ± 5.90 years from China. AGE levels were measured by the AGE Reader device. Bone mineral density was assessed using dual-energy X-ray absorptiometry, and osteoporosis was diagnosed based on a T score of less than -2.5. Sarcopenia was defined as loss of muscle mass plus loss of muscle strength and/or reduced physical performance. Presarcopenia was defined as low muscle mass with normal muscle strength and normal physical performance. RESULTS:The prevalence of sarcopenia was 18.5%, and that of osteoporosis was 40.5%. Compared to the lowest AGE quartile, the highest AGE quartile showed a significant association with sarcopenia (odds ratio [OR] 2.42; 95% CI, 1.60-3.66) (P for trend <.001), but not with presarcopenia. Per-SD increase in AGE was associated with higher odds of sarcopenia (OR 1.44; 95% CI, 1.26-1.66). Additionally, in the mediation analysis, when AGEs were treated as a continuous variable (the mediation effect is denoted by Za*Zb = 18.81; 95% CI, 8.07-32.32]-the 95% CI does not contain zero, representing a significant mediating effect) or a categorical variable (the mediating effect is expressed as Zmediation = 3.01 > 1.96, which represents a significant mediating effect), osteoporosis played a partial mediating role in the association between AGEs and sarcopenia. CONCLUSION:Elevated AGEs are associated with sarcopenia but not with presarcopenia. This association was partially mediated by osteoporosis.

Purpose To investigate the effect of nicotinamide (Nam) on diabetic kidney disease (DKD) in mice and explore its mechanism. Methods Thirty DBA/2 J mice were randomly assigned to three groups. After 8 weeks of hyperglycemia induced by streptozocin (STZ), Nam and saline were administrated to STZ + Nam and STZ + NS mice, respectively, for 8 weeks. Non-diabetic mice (NDM) were used as control group. Twenty In2 −/− Akita mice were randomly divided into two groups. After 8 weeks of hyperglycemia, Nam and saline were administered to Akita + Nam and Akita + NS mice, respectively, for 6 weeks. Wild-type littermates were used as control group. Markers of renal injury were analyzed, and the molecular mechanisms were explored in human proximal tubular HK2 cells. Results Urinary albumin-to-creatinine ratio (UACR) and kidney injury molecule 1 (KIM-1) decreased in the STZ + Nam and Akita + Nam groups. Pathological analysis showed that Nam improved the structure of glomerular basement membrane, ameliorated glomerular sclerosis, and decreased the accumulation of extracellular matrix and collagen. Compared to the diabetic control group, renal fibrosis, inflammation, and oxidative stress were reduced in the Nam-treated mice. The expression of sirtuin 1 (Sirt1) in human proximal tubular HK2 cells was inhibited by high glucose and Nam treatment enhanced its expression. However, in HK2 cells with Sirt1 knockdown, the protective effect of Nam was abolished, indicating that the beneficial effect of Nam was partially dependent on Sirt1. Conclusions Nam has a renoprotective effect against renal injury caused by hyperglycemia and may be a potential target for the treatment of DKD.

AIMS:Follicle-stimulating hormone (FSH) is associated with higher risks of metabolic syndrome and diabetes in menopausal women. We aimed to investigate whether FSH was associated with the lipid profile in women older than 55 years.DESIGN:The data were obtained from a cross-sectional study.PARTICIPANTS:Our data were from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (China, including Shanghai and Zhejiang, Jiangxi and Anhui provinces). A total of 1795 women older than 55 years were selected.METHODS:Morning serum sex hormones and lipid profiles were measured. Linear and logistic regression analyses were used to analyse the data.RESULTS:Lower FSH was associated with lower high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TG), total cholesterol (TC)/HDL-C ratio and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio (all p for trend <0.05) after adjusting for age and other sex hormones. After further adjustment for body mass index, diabetes and hypertension, the associations of FSH with the lipid profile weakened, but the associations of FSH quartiles with HDL-C and the TC/HDL-C ratio were still significant (both p for trend <0.05). Compared with women in the highest FSH quartile, the odds of low HDL-C (HDL-C<1.04 mmol/L) in women in the lowest FSH quartile were 5.25 (95% CI 1.60 to 17.26) (p for trend <0.05) in the fully adjusted model, and the odds of TC≥6.22 mmol/L, TGs≥2.26 mmol/L and LDL-C≥4.14 mmol/L were not significant. Luteinising hormone did not show a significant association with dyslipidaemia.CONCLUSION:Lower FSH was associated with a worse lipid profile in women older than 55. Diabetes, adiposity and hypertension mostly explained the association of FSH with TGs and the LDL-C/HDL-C ratio but only partially explained the associations of FSH with HDL-C and the TC/HDL-C ratio.

Background Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. Methods Patients with T2DM were randomized to receive fotagliptin ( n = 230), alogliptin ( n = 113) or placebo ( n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. Results After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. Conclusions In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. Trial registration ClinicalTrail.gov NCT05782192.