Polycystic ovary syndrome (PCOS) is a prevalent endocrine-metabolic disorder among women of reproductive age, associated with hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Insulin resistance and lipid metabolism abnormalities are common in PCOS, increasing the risk of metabolic syndrome and type 2 diabetes mellitus (T2DM). Isthmin-1 (ISM1) is a novel adipokine that regulates glucose and lipid metabolism, but its role in PCOS remains unknown.  This study aimed to investigate whether serum ISM1 levels are altered in women with PCOS compared to healthy controls and whether ISM1 is associated with key metabolic (e.g., insulin resistance, homeostasis model assessment of insulin resistance [HOMA-IR]) and hormonal parameters (e.g., follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol [E2], testosterone, dehydroepiandrosterone sulfate [DHEA-S]). Emerging evidence highlights the role of novel adipokines in the metabolic dysregulation associated with PCOS. Among these, ISM1 has gained attention due to its insulin-mimetic effects and its role in glucose and lipid metabolism. Given the central role of insulin resistance and obesity in PCOS pathogenesis, investigating whether ISM1 is altered in women with PCOS could provide new insights into its potential role in disease mechanisms. Furthermore, exploring its association with insulin resistance markers may help determine whether ISM1 can serve as a supportive metabolic biomarker. Therefore, this study aimed to compare serum ISM1 levels between women with PCOS and healthy controls, and to examine the relationship between ISM1 levels and key metabolic and hormonal parameters.

This case-control study included 60 women aged 18-45 years: 30 women with PCOS diagnosed using the Rotterdam 2003 criteria and 30 age-matched healthy controls. Anthropometric measurements (body mass index [BMI], waist circumference), metabolic parameters (fasting/postprandial glucose, fasting insulin, HOMA-IR, hemoglobin A1c [HbA1c], lipid profile), and hormonal markers (FSH, LH, estradiol, testosterone, DHEA-S, prolactin, thyroid-stimulating hormone [TSH], free thyroxine [FT4]) were assessed. Serum ISM1 concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses included independent t-tests, Mann-Whitney U tests, Spearman correlation, and ROC analysis.

Median ISM1 concentration was significantly higher in the PCOS group (1.60 ng/mL) compared to the control group (1.34 ng/mL, p = 0.03). ISM1 levels positively correlated with fasting insulin (r = 0.26, p = 0.04) and HOMA-IR (r = 0.29, p = 0.03). No significant correlation was found between ISM1 and reproductive hormones or lipid profile components. ROC analysis demonstrated that ISM1 had moderate diagnostic performance in identifying PCOS, with an area under the curve (AUC) of 0.658 (95% CI: 0.52-0.77, p = 0.026). At an optimal cut-off value of 1.85 ng/mL, the sensitivity was 43.3% and specificity was 90.0%.

Elevated serum ISM1 levels and their correlation with insulin resistance suggest that ISM1 may contribute to the metabolic pathophysiology of PCOS. Although its diagnostic performance is limited due to low sensitivity, ISM1 may serve as a supportive biomarker in identifying metabolic risk in women with PCOS. Further large-scale and mechanistic studies are needed to validate these findings and clarify the functional role of ISM1.

The association between cumulative endogenous estrogen exposure across the lifespan, especially considering reproductive events, and women's cardiometabolic health remain unclear. We aimed to examine the associations between lifetime endogenous estrogen exposure and the risks of diabetes, hypertension, and cardiovascular disease (CVD) among postmenopausal women.

We used baseline data from the Regional Ethnic Cohort Study in Northwest China. Reproductive factors were self-reported using a structured questionnaire, and surrogate indicators of estrogen exposures-reproductive lifespan, endogenous estrogen exposure, cumulative gestation duration and other proportional indicators-were calculated. Diabetes, hypertension and CVD were defined based on self-reported physician diagnoses at the hospital. Multivariable logistic regression models were employed to estimate adjusted odds rations (aORs) and 95% confidence intervals (CIs).

Among 35,498 postmenopausal women (median age 59.0 years [interquartile range: 54.0-65.0], each additional year of reproductive lifespan was associated with lower risks of diabetes (aOR 0.971; 95%CI 0.961, 0.982), hypertension (aOR 0.969; 95%CI 0.962, 0.975) and CVD (aOR 0.954; 95%CI 0.946, 0.962). Similar inverse associations were observed for endogenous estrogen exposure. In contrast, a higher ratio of gestation-to-reproductive lifespan duration was positively associated with increased risks of diabetes, hypertension, and CVD. Multiple incomplete pregnancies were associated with increased diabetes risk, while multiple complete pregnancies were linked to elevated risks of hypertension and CVD.

Longer exposure to endogenous estrogen was associated with decreased risk of cardiometabolic disease, while a higher burden of gestational events was associated with increased risks. Reproductive history could be considered as an indicator for risk stratification and management of cardiometabolic disease in women.

This study aimed to assess the influence of type 2 diabetes mellitus (T2DM) on clinical features and adverse outcomes in COVID-19 patients and to develop a predictive model for adverse outcomes in this population.

A retrospective analysis was conducted from December 2022 to February 2023, involving 1058 COVID-19 inpatients at two hospitals. Patients were divided into T2DM (n = 363) and non-T2DM (n = 695) groups. Demographic and laboratory data were collected, and univariate analyses were performed. Logistic regression analysis was employed to identify risk factors associated with ICU admission, and a predictive model was constructed and validated using ROC curves.

T2DM patients exhibited higher levels of certain inflammatory and biochemical markers and a greater incidence of ICU admission compared to non-T2DM patients. Neutrophil count and lactate dehydrogenase were identified as independent risk factors for ICU admission.

T2DM is associated with increased levels of inflammatory and biochemical markers and a higher risk of ICU admission in COVID-19 patients. The predictive model, incorporating neutrophil count and lactate dehydrogenase, offers clinical utility. The study's findings can inform clinical strategies for managing COVID-19 patients with T2DM, particularly in predicting and mitigating adverse outcomes.

Cardiometabolic multimorbidity (CMM), the co-occurrence of two or more cardiometabolic conditions, poses a growing health concern as populations age. Linked to adverse outcomes like cognitive decline, poor COVID-19 prognosis, and higher mortality, its prevalence is rising due to shared risk factors among conditions such as diabetes, heart disease, and hypertension. While CMM is well-studied in high-income countries, data from low- and middle-income countries, particularly from India, is limited. This study investigates the prevalence and correlates of CMM among older Indian adults.

We analyzed data from 59,764 participants aged 45 years and older from the Longitudinal Ageing Study in India (LASI), wave 1, conducted from 2017 to 2019. CMM was defined as the co-occurrence of two or more of the following conditions: hypertension, diabetes, coronary heart disease, stroke, obesity, and hypercholesterolemia. Descriptive statistics were employed to calculate the prevalence of CMM with 95% confidence intervals to predict uncertainty. Multivariable logistic regression was used to examine the associations between CMM and various socio-demographic correlates, with results reported as adjusted odds ratios (AOR).

We observed higher CMM prevalence among females 27.3% (95% CI: 26.8%-27.8%) compared to males 23.04% (95% CI: 22.5%-23.5%), particularly in the 60-74 age group. CMM was more prevalent in urban areas, wealthier socioeconomic groups, and those with higher education. Increased odds of CMM were found among males from the OBC and other castes and females from SC, OBC, and "Others" castes, while ST males had lower odds. Significant correlates for both genders included not working, urban residence, and higher wealth. Regionally, CMM rates were highest in the Southern and Western regions, and lowest in the North-East and Central regions of India.

This study reveals a rising burden of CMM among middle-aged and older adults in India, with higher prevalence in females, urban residents, and wealthier groups. Regional and caste disparities highlight the need for targeted interventions. Effective management of CMM requires early screening and comprehensive primary care, especially as India ages and develops.

Individuals with metabolic syndrome are at an increased risk of developing chronic kidney disease (CKD) or accelerating the progression of pre-existing CKD. Further, such individuals are predisposed to developing diabetes mellitus, increasing their susceptibility to diabetic kidney disease (DKD). Current DKD treatments have expanded to include renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRA), and glucagon-like peptide-1 receptor agonists (GLP1-RA), which confer significant renoprotection. Nevertheless, DKD continues to persist and progress, underscoring the need for the development of novel therapeutic strategies that additionally target the underlying pathophysiological mechanisms in DKD. This mini-review highlights several emerging targets from pre-clinical models of DKD and metabolic-associated kidney disease and provides a brief overview of the pathways involved in their mechanisms of renoprotection.

Healthy diet is essential to reduce the increased risk of developing type 2 diabetes mellitus (T2DM) among women with previous gestational diabetes mellitus (GDM). This study investigates dietary changes and predictors of dietary improvement during first year after childbirth among women with GDM.

This post-hoc longitudinal analysis used data from the Face-it randomised controlled trial, which evaluated a health promotion intervention for women with recent GDM. As the intervention had no effect on diet, data from both intervention and usual care groups were pooled, collected at baseline and follow-up (3 and 12 months after childbirth). Dietary quality score (DQS) was used to assess self-reported dietary habits. Predictor variables included body mass index (BMI), risk perception of T2DM, self-perceived dietary habits, social support, breastfeeding status and mental well-being. Paired t-test and ordinal logistic regression adjusted for randomisation group were conducted.

This study included 232 women. The overall mean DQS did not change from baseline to follow-up; however, 66% women modified their dietary quality, with an equal split between improvement and decline. Higher odds of dietary improvement were seen in women with baseline BMI ≥30 kg/m² (OR: 3.29, 95% CI: 1.60-6.80) and BMI 25-29.9 kg/m² (OR: 2.41, 95% CI: 1.28-4.54) compared to those with a BMI <25 kg/m². Women who perceived their diet as unhealthy had increased odds of improvement compared to those who perceived it as healthy (OR: 3.84, 95% CI: 1.40-10.56). Fully breastfeeding women at baseline had lower odds of dietary improvement than non-breastfeeding women (OR: 0.39, 95% CI: 0.18-0.84). No associations were found for risk perception of T2DM, social support, and mental well-being.

Dietary patterns after a GDM affected pregnancy are heterogeneous, underscoring the importance of tailored dietary interventions addressing individual needs to improve dietary quality and reduce the risk of T2DM.

Acute-on-chronic liver failure (ACLF) is a rapidly progressive syndrome marked by high short-term mortality. While diabetes mellitus (DM) is known to worsen liver-related outcomes, its specific impact on alcohol-related ACLF (ALD-ACLF) remains underexplored. This study aimed to assess the prognostic impact of DM on 90-day outcomes in ALD-ACLF using data from the APASL ACLF Research Consortium (AARC) database.

This observational study involved data from 5612 ACLF patients with documented 90-day outcomes. We identified 2096 patients with ALD-ACLF precipitated by alcoholic hepatitis. Patients with non-ALD etiologies, mixed etiologies, or non-alcoholic precipitants were excluded. Diabetic and non-diabetic patients were compared using 1:2 propensity score matching based on key baseline covariates. Survival outcomes were assessed using Kaplan-Meier analysis and multivariable Cox regression.

After matching, 109 diabetic patients were compared with 218 well-matched non-diabetic controls. Diabetic patients had significantly lower overall survival (32 vs. 57%) and transplant-free survival (31 vs. 50%) compared to non-diabetics (log-rank p < 0.001). On multivariable Cox regression, DM was independently associated with increased 90-day mortality (HR 1.739, 95% CI 1.262-2.395, p < 0.001), along with elevated serum lactate (HR 1.187 per mmol/L, p < 0.001) and creatinine (HR 1.267 per mg/dL, p < 0.001).

Diabetes mellitus is a significant independent predictor of mortality in patients with ALD-ACLF. These findings highlight the need for early identification and integrated management of diabetes in ACLF care pathways to improve clinical outcomes.

Podocyte injury is a key event in the progression of diabetic kidney disease (DKD), and the role of long noncoding RNAs (lncRNAs) in DKD and podocyte injury is emerging. RNA sequencing, fluorescence in situ hybridization and real-time PCR results revealed that the expression of the lncRNA ENST00000532153.1 (lncRNA 153) was downregulated in patients with DKD and correlated with clinical parameters. Moreover, the overexpression of lncRNA 153 mitigated podocyte injury caused by high glucose (HG) stimulation. Following RNA-pulldown and mass spectrometry analysis, KEGG enrichment analysis revealed that the lncRNA 153 binding protein is primarily involved in protein processing in the endoplasmic reticulum (ER). Poly (ADP-ribose) polymerase 1 (PARP1) was subsequently identified as the binding protein of lncRNA 153. PARP1, a marker protein for apoptosis, was found to be upregulated in the kidneys of patients with DKD. Knockdown of PARP1 in podocytes under HG conditions resulted in the inhibition of ER stress and apoptosis, leading to the alleviation of podocyte injury both in vitro and in vivo. Furthermore, this study revealed that activating transcription factor 3 (ATF3) is a novel protein that interacts with PARP1, and that the interaction between them is involved in the regulation of gene transcription. Mechanistic studies demonstrated that lncRNA 153 binds to PARP1, inhibiting its interaction with ATF3 and subsequently reducing the transcriptional activity of ATF3, ultimately alleviating podocyte injury in DKD by suppressing ER stress and apoptosis. Therefore, our study suggests that lncRNA 153 and PARP1 may be attractive therapeutic targets for DKD.

Inflammatory bowel disease (IBD) is a chronic condition with a rising incidence linked to inflammation and oxidative stress. This disorder includes two main subtypes: ulcerative colitis (UC) and Crohn's disease (CD). Current treatment plans lack effectiveness; as a result, finding novel approaches is encouraged. Various groups of oral anti-diabetic medications are employed in clinical practice, and they have shown beneficial effects against conditions beyond diabetes mellitus (DM). This review is aimed at evaluating the hypothesis that oral anti-diabetic medications may serve as potential therapeutic agents for IBD due to their anti-inflammatory and antioxidant effects. The current study investigated the protective effects of these agents against IBD. In this review, we gathered evidence from cellular, animal, and clinical studies within the scientific databases Medline, Scopus, and Web of Science regarding the favorable impacts of anti-diabetic drugs on IBD. We explored these databases from their inception to May 2024. Studies focusing on the therapeutic impacts of these medications on diverse models of IBD were included and reviewed. Biguanides, sulfonylureas, thiazolidinediones (TZD), dipeptidyl peptidase 4 inhibitors (DPP4I), and sodium-glucose cotransporter inhibitors (SGLT2I) exhibited protective effects against IBD. These medications promoted gut microbiome balance and the function of tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin. Moreover, they affected key cytokines (tumor necrosis factor (TNF), malonaldehyde (MDA)), enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPX), myeloperoxidase (MPO)), and signaling pathways (nuclear factor erythroid 2-related factor (Nrf2) transcription factor/hemoxygenase 1 (HO-1), high mobility group box 1 (HMGB1)/receptor for advanced glycation end-products (RAGE)/nuclear factor kappa B (NF-κB)). Anti-diabetic medications demonstrated positive effects against IBD. However, further comprehensive clinical assessments are necessary to confirm their efficacy and safety as an adjunctive therapy for IBD.

Definitive prevention for type 1 diabetes (T1D) is not yet available, but we are now entering a new era where disease-modifying therapies are becoming available in T1D to halt disease progression. In this review, we present up-to-date knowledge related to the prevention of T1D in youth, involving disease-modifying therapies at different T1D stages. A narrative literature review utilising the PubMed/MEDLINE database was performed using the keywords 'screening', 'prevention', 'Disease-modifying therapy', and 'Diabetes Mellitus, Type 1' [Mesh] in youth aged 0-18 years. Only teplizumab has been approved by the FDA as the first drug shown to delay the onset of Stage 3 T1D. Other monoclonal antibodies targeting specific immune cells, agents targeting specific cytokines, antigen-specific therapies, and immunomodulant and/or immunosuppressive agents have been studied alone or in combination to control or delay the progression of beta-cell destruction. In individuals with Stage 3 T1D, several intervention trials have led to a temporary improvement in beta-cell function, but this benefit has consistently been short-lived. Ongoing and future research will be essential to refine patient selection, identify additional therapeutic targets, and optimise the timing and durability of immunotherapy responses.