Therapeutic Advances in Endocrinology and Metabolism

The WATCH-DM integer-based risk score (WATCH-DM(i)) was originally developed and validated to predict heart failure (HF) hospitalization risk in patients with type 2 diabetes mellitus (T2DM). However, its potential association with all-cause mortality in patients without HF remains unclear.

This study aimed to evaluate the prognostic utility of the WATCH-DM(i) score for all-cause mortality in a real-world outpatient cohort of T2DM patients without known HF.

This was a retrospective observational cohort study with national mortality registry linkage performed at a single center.

We analyzed data from 449 adults with T2DM enrolled in a hospital-based cohort between 2016 and 2022. The WATCH-DM(i) score was calculated according to the original published integer-based model reported by Segar et al., using clinical and laboratory parameters. Patients were stratified into four risk groups based on their score. All-cause mortality data were obtained via national linkage. Cox regression models, Kaplan–Meier survival analysis, landmark analysis, and time-dependent receiver operating characteristic curves were used to assess mortality risk.

Over a median follow-up of 61 months, 39 patients (8.7%) died. Each 1-point increase in the WATCH-DM(i) score was associated with a 29% higher risk of all-cause mortality (HR: 1.287, 95% CI: 1.151–1.439, p < 0.001). Higher risk groups showed progressively greater mortality, especially after 24 months. The score demonstrated good discrimination for 5-year mortality (C-index: 0.751). Metformin use was independently associated with lower mortality risk (HR: 0.410, p = 0.019).

The WATCH-DM(i) score is a robust prognostic marker of 5-year all-cause mortality in T2DM patients without HF and may serve as a practical tool for risk stratification in outpatient settings.

Loss-of-function alterations in Makorin Ring Finger Protein 3 (MKRN3) and Delta-like Non-Canonical Notch Ligand 1 (DLK1) genes are associated with familial central precocious puberty (CPP) and can result in reduced serum levels of these proteins.

This study aimed to evaluate the potential of serum MKRN3 and DLK1 levels for predicting genetic variants associated with CPP.

Retrospective study.

This retrospective cross-sectional study included 26 girls with CPP: 11 receiving treatment (Group 1) and 15 not yet treated (Group 2). The control group consisted of 26 healthy girls. Serum MKRN3 and DLK1 levels were measured by ELISA, and MKRN3 and DLK1 genes were analyzed by Sanger sequencing.

A known pathogenic MKRN3 gene variant (c.482dupC/p.(Ala162Glyfs*15)) was found in one patient with a notably low MKRN3 level of 0.127 ng/mL, consistent with paternal inheritance. Median MKRN3 and DLK1 levels were 1.32 (0.7) and 0.62 (0.4) ng/mL in Group 1, and 1.2 (0.6) and 0.62 (0.2) ng/mL in Group 2 (excluding the patient with the variant). No significant differences were observed between Group 1 and Group 2 (p = 0.279; p = 0.338). Control group median serum levels were 1.177 (0.76) ng/mL for MKRN3 and 0.67 (0.44) ng/mL for DLK1, with no significant differences from the CPP cohort (p = 0.917; p = 0.756).

MKRN3 and DLK1 levels do not significantly differ between treated, untreated CPP patients, and healthy controls. Identifying a known MKRN3 variant with low serum levels suggests serum measurements can help predict variants. Familial studies are recommended as these variants may be inherited even in isolated cases.

Proper storage of insulin and accuracy of injection technique are essential for maintaining the effectiveness of insulin and optimizing glycemic control. In resource-poor countries like Ethiopia, poor storage conditions and incorrect injection techniques are prevalent, and hence, less than desired glycemic results are obtained. Interventional studies aimed at addressing these problems in Ethiopia are lacking.

This study aimed to evaluate the effect of an educational intervention on glycemic control, insulin storage behavior, and injection practices among diabetic patients at Debre Tabor Hospital.

A quasi-experimental pre- and post-intervention study design was employed.

The study was conducted at Debre Tabor Hospital from January to June 2024. Baseline data on insulin storage, injection practices, and fasting blood glucose levels were collected using structured questionnaires and clinical records. The intervention was educational conferences with demonstrations and take-home materials on appropriate injection and storage practices. A follow-up after 3 months was carried out to determine changes in glycemic control and practice change. The intervention’s efficacy was determined by analyzing data using STATA version 17 with logistic regression and McNemar’s test.

There were 330 diabetic patients enrolled with a mean age of 42.87 ± 13.76 years, of which 59.39% had type 1 diabetes. Insulin injection technique improved from 48.68% to 72.46% following the intervention (p = 0.001). Lipohypertrophy occurred in 40.9% of patients, predominantly in the arm. Poor glycemic control at the baseline was significantly associated with variables like age (adjusted odds ratio (AOR) = 2.254), polypharmacy (AOR = 2.321), poor injection angle (AOR = 2.311), and inappropriate storage (AOR = 2.675). After the intervention, only age (AOR = 1.504) and polypharmacy (AOR = 1.976) maintained significance.

The educational intervention successfully enhanced the insulin injection and storage procedures, thereby achieving improved glycemic control results. However, glycemic outcomes were still adversely affected by enduring factors of age and polypharmacy. This justifies the need for continuous education and individualized interventions to handle both unchangeable patient factors and mutable behaviors.

Metabolic syndrome (MetS) is a common condition marked by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. It has significant health and economic impacts, highlighting the need for early predictive markers.

To compare the prognostic performance of various obesity indices in the 1-year incidence of MetS among adult employees of a private educational institution.

Cohort study.

A prospective cohort study was conducted using data from adults employed at a private educational institution in Lima, Peru. Participants were enrolled in 2019 and followed for 1 year to monitor anthropometric and biochemical parameters. The outcome was the development of MetS at the end of follow-up, defined according to the criteria of the Latin American Diabetes Association. Receiver operating characteristic curves were plotted, and the area under the curve (AUC) with 95% confidence intervals (CI) was calculated to assess the predictive utility of each index for MetS after 1 year.

Of the 792 adults initially enrolled, 475 were included in the final analysis after exclusions and loss to follow-up. Their average age was 38.4 years, and 54.3% were women. The overall incidence of MetS was 7.4%, with 12% for males and 4% for females. The highest AUC values for predicting MetS were observed for the body mass index (AUC: 0.88; 95% CI: 0.84–0.92), waist-to-height ratio (WHtR; AUC: 0.89; 95% CI: 0.85–0.92), abdominal volume index (AVI; AUC: 0.89; 95% CI: 0.86–0.92), and body roundness index (BRI; AUC: 0.89; 95% CI: 0.85–0.92). In sex-stratified analyses, results were consistent for males. Among females, the body adiposity index also showed good discrimination (AUC: 0.91; 95% CI: 0.83–1.00). The wide 95% CI reflects the small number of incident MetS cases among women (n = 10) and should be interpreted with caution.

In conclusion, the incidence of MetS after 1 year of follow-up was 7.4%, with a higher rate among males. The WHtR, BRI, and AVI were the most useful anthropometric indices for predicting MetS.

Stress-induced hyperglycemia ratio (SHR) has shown strong correlations with diabetes risk. However, its relationship with gestational diabetes mellitus (GDM) remains an area of limited research.

Based on the National Health and Nutrition Examination Survey (NHANES) database, this cross-sectional study aims to explore the association between SHR and GDM.

The study included 461 pregnant women from NHANES between 1999 and 2016. Logistic regression analysis was performed to investigate the relation between SHR and GDM, as well as the weighted tertiles of SHR. Stratified and subgroup analyses assessed the association between SHR and GDM. Restricted cubic splines (RCS) delineated the nonlinear relationship between SHR and GDM. Moreover, a two-segment linear regression model was employed to test the threshold effect of SHR on GDM. Stratified analysis was conducted by stratifying by months of pregnancy.

Among the 461 eligible women included in the study, SHR was a critical risk factor for GDM. Higher SHR values were associated with an elevated likelihood of developing GDM after accounting for other variables (OR: 1.77, 95% CI: 1.37–2.28, p < 0.001). This relationship was maintained across different SHR levels when analyzed in tertiles (p < 0.05). Further subgroup analyses based on education level and alcohol consumption status showed a consistent positive correlation between SHR and GDM risk in each group. A nonlinear relationship between SHR and GDM risk was confirmed by RCS. Threshold effect analysis further revealed a significant positive association between SHR and GDM when SHR was ≤ 15.75, whereas no significant association was observed beyond this threshold. The results of stratified analysis showed a significant positive correlation between SHR and GDM from 1 to 5 months of pregnancy (OR = 2.16, 95% CI: 1.12–4.16, p = 0.026). However, no significant SHR-GDM association was observed from 6 to 10 months of pregnancy.

SHR is significantly positively correlated with an increased risk of GDM in early pregnancy. These results highlight the potential utility of SHR as a clinical marker for early identification and intervention in GDM risk cases.

Overactive bladder (OAB) is a common condition that affects both men and women, but its relationship with central obesity and the dietary intake has not been adequately elucidated.

Our study aims to investigate associations between central obesity replacement indices, dietary intake of sugar and lipids, and OAB risk using National Health and Nutrition Examination Survey 2005–2016 data.

Cross-sectional study.

This study analyzed 24,675 adults (4848 OAB cases). Weight, body mass index, and other central obesity replacement indices (waist circumference, weight-adjusted waist index, waist-to-height ratio (WHtR), body roundness index (BRI)) and dietary nutrients intake (carbohydrate, sugars, fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (PUFAs), and cholesterol) were assessed. Propensity score matching (1:2) balanced covariates. Multivariable logistic regression and generalized additive models evaluated dose-response relationships.

All central obesity indices showed significant positive associations with OAB (p < 0.001), with WHtR and BRI demonstrating the strongest effects (adjusted odds ratio (OR) = 2.04, 95% confidence interval: 1.80–2.30). Nonlinear relationships were observed, particularly for WHtR (degrees of freedom = 3.30–6.16). Dietary analysis revealed that OAB patients had significantly higher consumption of total energy, carbohydrates, and sugars (all p < 0.05), and higher sugar intake increased OAB risk (OR = 1.32, p = 0.0016), while PUFAs were protective (OR = 0.79, p = 0.0159).

Central obesity replacement indices, especially WHtR and BRI, strongly predict OAB risk. Dietary modifications, including reducing sugars and increasing PUFAs intake, may complement abdominal fat reduction for OAB prevention. These findings highlight the importance of combined weight management and dietary modifications for OAB prevention in high-risk populations.

Cushing’s syndrome (CS) is a rare endocrine disorder caused by long-term exposure to excess cortisol and is linked to significant morbidity. Data from multiple centers in Latin America remains limited.

To describe the clinical, diagnostic, and treatment characteristics of patients with CS in a regional Colombian cohort and to assess surgical outcomes in patients with Cushing’s disease (CD) based on neurosurgical expertise.

Multicenter retrospective cohort study.

Medical records from six hospitals in Antioquia, Colombia, were reviewed, including adult patients with biochemically confirmed endogenous CS diagnosed between 2010 and 2024. Data collected included sociodemographic, clinical features, diagnostic tests, etiological classification, treatments, and outcomes. In patients with CD, surgical remission, recurrence, persistence, and postoperative complications were compared based on neurosurgical expertise.

A total of 130 patients were included; 86.9% were women, with an average age of 50.7 years. The most common presenting features were weight gain (79.2%), moon face (36.9%), and striae (29.2%). CD was the leading cause (74.6%), followed by adrenal CS (17.6%) and ectopic adrenocorticotropic hormone syndrome (1.5%). The most frequently used diagnostic tests were 24-h urinary free cortisol and the 1-mg overnight dexamethasone suppression test, while late-night salivary cortisol and inferior petrosal sinus sampling were less commonly performed. Transsphenoidal surgery in CD achieved an initial remission rate of 63.3%, with no significant differences based on neurosurgical experience. All cases of adrenal CS underwent unilateral adrenalectomy.

In this Colombian multicenter cohort, the clinical features, etiological distribution, and surgical outcomes in CS and CD were similar to those reported in specialized international centers. These findings highlight the importance of early detection, better access to diagnostic tools, and multidisciplinary care to improve outcomes in this rare disease.

Cardiovascular-kidney-metabolic syndrome (CKM) is a major public health challenge. While obesity is a central driver of CKM, body mass index (BMI) fails to adequately reflect body fat distribution and its associated prognostic heterogeneity.

To evaluate the prognostic value of emerging anthropometric indices reflecting fat distribution in predicting all-cause mortality risk among individuals in the early and intermediate stages of CKM (stages 0–3).

A population-based retrospective cohort study utilizing data from the National Health and Nutrition Examination Survey (NHANES) 1999–2006, with mortality linkage follow-up through 2019.

We analyzed 5907 adults with CKM stages 0–3. Eleven adiposity indices were evaluated using four machine learning algorithms (LASSO-Cox, RSF-Boruta, RSF, survival XGBoost) to identify key mortality predictors. Statistical analyses incorporated multivariable Cox proportional hazards regression, restricted cubic splines, false discovery rate (FDR) correction for multiple testing, and a sensitivity analysis across the entire CKM continuum (stages 0–4).

Four indices reflecting peripheral-to-central adiposity predominance (TCWR, CWR, AWR, SWR) were consistently identified as key predictors. Higher levels independently correlated with lower all-cause mortality (all FDR-adjusted p < 0.05). TCWR and CWR showed linear inverse trends, whereas AWR and SWR exhibited nonlinear threshold effects. These associations persisted across BMI subgroups and remained robust in the full CKM continuum subanalysis. The combined index model yielded improved discriminative ability (AUC = 0.769) compared to single indices (TCWR AUC = 0.731) and conventional BMI-based models, providing higher net clinical benefit.

Peripheral-to-central adiposity indices are strong predictors of mortality in CKM stages 0–3, providing prognostic information beyond BMI and serving as practical tools for early risk stratification. Future studies should evaluate their dynamic changes and validate their applicability across diverse populations.

Latent autoimmune diabetes in adults (LADA) is a form of diabetes that shares clinical features with type 2 diabetes mellitus (T2DM), often leading to misdiagnosis and delayed treatment. Early detection is critical to prevent the progression of the disease.

This study aims to analyze the risk factors of LADA and develop a predictive model to enhance early diagnosis.

A retrospective study was conducted on T2DM patients treated at our hospital between June 2019 and June 2024. The study focused on identifying risk factors for LADA and developing a predictive model.

Clinical data of 728 patients (651 non-LADA, 77 LADA) were analyzed. LASSO regression was used for variable selection, followed by logistic regression to identify risk factors. The model’s performance was assessed using the receiver operating characteristic curve and the Hosmer–Lemeshow test.

Significant differences were found between the non-LADA and LADA groups in terms of thyroid disease history, diabetic ketoacidosis, fasting plasma glucose (FPG), 2-hour postprandial glucose (2hPG), and glycated hemoglobin (HbA1c) levels (p < 0.05). Logistic regression identified thyroid disease history, FPG, 2hPG, and HbA1c as key risk factors for LADA. The model achieved an area under the curve of 0.907, with a sensitivity of 76.6% and specificity of 91.9%, indicating strong discrimination and robust calibration (p = 0.275).

The predictive model based on thyroid disease history, FPG, 2hPG, and HbA1c demonstrates excellent predictive ability in our cohort for early identification of LADA, suggesting its potential to aid in timely intervention and improved patient outcomes.

Trial registration: Not applicable.

Metformin is the first-line pharmacological treatment for type 2 diabetes mellitus. Metformin-associated lactic acidosis is uncommon; however, subclinical increases in lactate levels can yield considerable clinical consequences, warranting regular surveillance in high-risk patients. Limited data exist on the patterns of metformin dosing and specific patient factors that may elevate lactate levels, indicating a critical need for further investigation.

This study aimed to determine the patterns of metformin dosing and identify patient-specific factors associated with higher lactate levels.

A retrospective, cross-sectional study.

Patients who attended the endocrinology and internal medicine clinic between January 2021 and December 2022 were included. Patients’ data, including demographics, comorbidities, prescribed medications, and laboratory tests, were collected from electronic health records. Patients were categorized based on age (middle-aged <65 years and older ⩾65 years) and metformin dosage (low, medium, and high). Univariable analyses were performed to assess the difference between the comparison groups. Multivariable linear regression analysis was performed to identify factors associated with elevated lactate levels.

Among 3304 diabetic patients, 2329 were metformin users. Metformin users exhibited significantly higher lactate levels (1.9 vs 1.0 mmol/L, p < 0.001) compared to nonusers. Older patients had a higher prevalence of comorbidities such as heart failure (74 vs 55, p < 0.001) and renal disease (3 vs 1, p = 0.01) but received lower metformin doses compared to middle-aged patients. Increasing metformin dosage (β = 0.66, p < 0.001), renal impairment (β = 0.2, p < 0.001) and co-prescription of diuretics (β = 0.2, p < 0.001) and nonsteroidal anti-inflammatory drugs (β = 0.1, p = 0.001) were associated with elevated lactate level, whereas co-prescription of renin-angiotensin-aldosterone inhibitors showed negative association with high lactate level (β = −0.25, p < 0.001).

Metformin users demonstrated higher lactate levels, with increasing doses and renal impairment being key risk factors. This study calls attention to the importance of routine lactate monitoring, particularly in older adults and patients with renal dysfunction or polypharmacy.

Several negative outcomes have been documented post-COVID-19 pandemic, including many cardiometabolic abnormalities associated with metabolic syndrome (MetS).

The study aims to evaluate the prevalence of MetS among Jordanian adults post-COVID-19 and compare these results with previous findings.

A cross-sectional study.

A total of 5188 adults of both sexes (age >18 years) were recruited. Body weight, height, waist circumference (WC), fasting plasma glucose, high-density lipoprotein cholesterol (HDL-C), triglycerides, and blood pressure were measured.

The crude prevalence of MetS, using both the International Diabetes Federation (IDF) and the Adult Treatment Panel III (ATP III) diagnostic criteria, was 42.9% (32.5% in males and 46.9% in females). There was no change in the crude prevalence of MetS among the total population between 2017 (48.2% and 44.1%) and 2024 (48.1% and 45.0%) by IDF and ATP III criteria, respectively (p > 0.05). In comparison, the age-standardized prevalences were 44.6% (95% CI 43.3%–45.9%) for ATP III and 47.7% (95% CI 46.4%–49.0%) for IDF. The main contributing factors for MetS, according to ATP III, were low HDL-C (65.4%) and enlarged WC (60.4%). However, according to IDF criteria, enlarged WC (76.9%) was followed by low HDL-C (65.4%).

Although the crude prevalence of MetS stayed relatively stable before and after COVID-19, age-standardized data show a noticeable upward trend, pointing to an increasing cardiometabolic burden. These findings highlight the urgent need for wide-ranging, population-level strategies that emphasize lifestyle modifications, screening, and early intervention to address metabolic risks.

Epigenetic biomarkers may provide novel insights into long-term health risk. DNA methylation (DNAm) predicted leptin has been proposed as an epigenetic proxy related to metabolic regulation, but its association with mortality remains underexplored.

To examine the association between DNAm-predicted leptin levels and all-cause, cardiovascular, and cancer mortality among US adults using The National Health and Nutrition Examination Survey (NHANES) data.

Population-based cohort analysis with linkage to the National Death Index.

We analyzed 2531 participants from NHANES 1999–2002 with available DNAm-predicted leptin derived from whole-blood methylation profiles. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality outcomes across quartiles of DNAm-predicted leptin, with sequential adjustment for potential confounders. Subgroup and sensitivity analyses were performed to evaluate robustness.

Over a mean follow-up of 17.1 years, 1360 deaths occurred. DNAm-predicted leptin showed a J-shaped association with all-cause mortality. In fully adjusted models, HRs for all-cause mortality were 1.28 (95% CI: 1.00–1.62) for Quartile 1, 1.00 (reference) for Quartile 2, 1.32 (95% CI: 1.01–1.73) for Quartile 3, and 1.35 (95% CI: 1.11–1.64) for Quartile 4. After full adjustment, DNAm-predicted leptin was not statistically significantly associated with cancer mortality, while cardiovascular mortality risk was higher in Quartile 4 compared with Quartile 2.

DNAm-predicted leptin was associated with all-cause mortality in a J-shaped pattern, with elevated risk at both lower and higher levels. Associations with cancer mortality were not statistically significant after adjustment, and evidence for cardiovascular mortality was limited to the highest quartile. Larger studies are needed to validate these findings and clarify cause-specific associations.

Not applicable.

A prolonged QT interval is a recognized risk factor for life-threatening arrhythmias and sudden cardiac death. In patients with type 2 diabetes, identifying clinical markers associated with myocardial repolarization abnormalities is essential for risk stratification.

To investigate the association between multiple non-invasive atherosclerosis indicators and corrected QT interval prolongation in patients with type 2 diabetes.

Retrospective cross-sectional analysis.

We evaluated 96 patients with type 2 diabetes admitted for glycemic control. The QTc interval was calculated using the Bazett (QTcB), Fridericia (QTcF), and Framingham (QTcFra) formulas. We examined the association between QTc and multiple atherosclerosis indicators, including the ankle-brachial index (ABI), cardio-ankle vascular index (CAVI), carotid intima-media thickness (IMT), and flow-mediated dilatation (FMD).

Among all participants, 2 women (7%) and 10 men (15%) had prolonged QTcB. In univariate analyses, FMD was negatively correlated with QTcB (r = −0.28, p = 0.0054), whereas ABI, CAVI, mean, and maximum carotid IMT did not exhibit significant associations. In multivariable linear regression analyses, FMD was independently associated with QTcB (unstandardized coefficient β = −1.95 ms per 1% increase in FMD; 95% confidence interval −3.60 to −0.30; p = 0.021). Subgroup analysis revealed that this association was prominent specifically in the non-obese group (body mass index, <25 kg/m²). Notably, these findings remained consistent regardless of the correction formula used.

Vascular endothelial dysfunction, as measured by FMD, is independently associated with QTc prolongation, particularly in non-obese patients with type 2 diabetes. This suggests a significant link that may help identify individuals at higher risk for life-threatening arrhythmias.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used across the glycemic spectrum, yet their thyroid safety profile remains debated. Prior studies have shown inconsistent findings, and evidence across prediabetes, type 1 diabetes (T1D), and type 2 diabetes (T2D) is lacking.

To evaluate diabetes-type-specific associations between GLP-1RA therapy and thyroid outcomes, including thyroid dysfunction, autoimmune thyroiditis, nontoxic goiter, and thyroid cancer.

A real-world, retrospective target-trial emulation using electronic health records (EHR) from a large multicenter network.

We used the TriNetX US Collaborative Network to identify adults with prediabetes, T1D, or T2D initiating GLP-1RAs. Active comparators included usual care and sodium–glucose cotransporter two inhibitors (SGLT2i). Propensity score matching with extensive covariate adjustment was applied. Participants were followed for incident thyroid outcomes for up to 5 years. Sensitivity and subgroup analyses were conducted to assess robustness.

Across glycemic states, GLP-1RA therapy demonstrated distinct thyroid safety patterns. In prediabetes and T1D, GLP-1RA use was associated with reduced risks of thyroid dysfunction and all-cause mortality, suggesting potential metabolic or immunomodulatory benefits. By contrast, among individuals with T2D, GLP-1RA exposure was linked to modest increases in autoimmune thyroiditis and nontoxic goiter, particularly among those with obesity or without hypertension. Importantly, no increased risk of thyroid cancer was observed in any glycemic state, providing reassuring evidence regarding long-term endocrine safety.

In this large-scale target-trial emulation, GLP-1RAs showed favorable thyroid safety profiles in prediabetes and T1D, while modestly increasing selected nonmalignant thyroid outcomes in T2D. The absence of elevated thyroid cancer risk across glycemic states supports the overall endocrine safety of GLP-1RAs. These findings highlight the importance of individualized monitoring, particularly in metabolically high-risk T2D populations.

Prediabetes comprises three heterogeneous glucometabolic phenotypes and is associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the association of different prediabetes phenotypes with the presence of MAFLD and liver fibrosis remains underexplored.

To examine the association of different prediabetes phenotypes with MAFLD and liver fibrosis.

Population-based cross-sectional study.

Prediabetes was stratified as an isolated defect (impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired hemoglobin A1c (IA1c)), two defects (IFG + IGT, IFG + IA1c, or IGT + IA1c), or all three defects (IFG + IGT + IA1c). Hepatic steatosis and liver fibrosis were assessed by vibration-controlled transient elastography. Multivariate logistic regression analysis was conducted to estimate the odds ratio (OR) and 95% confidence interval (CI) for different prediabetes phenotypes associated with MAFLD and liver fibrosis.

A total of 1599 subjects (394 with normal glucose tolerance (NGT) and 1205 with prediabetes) were included. The prevalence of MAFLD and liver fibrosis was higher in prediabetes than in NGT. The odds of MAFLD in prediabetes with two or three glucometabolic defects were increased compared with those with a single glucometabolic defect, with insulin resistance as a possible mediator. Compared with isolated IA1c, isolated IGT had an increased prevalence of MAFLD (p < 0.05). Moreover, glucose-defined prediabetes had higher odds of MAFLD than HbA1c-defined prediabetes (OR 1.72, 95% CI 1.00–2.96). However, there was no significant difference in the odds of liver fibrosis across different prediabetes phenotypes (p = 0.58).

The odds of MAFLD but not liver fibrosis were increased with the increasing number of glucometabolic defects in participants with prediabetes.

Not applicable.

Type 2 diabetes mellitus (T2DM) is common in Nepal, where many people seek primary care through Ayurveda, a widely practiced traditional medical system. However, concerns remain about variability in clinical practice and the quality of care provided by Ayurvedic practitioners. No evidence-based clinical practice guideline (EB-CPG) currently exists for managing T2DM in Ayurveda. To address this, an EB-CPG was developed, and a feasibility trial was conducted to inform a future definitive cluster randomized controlled trial evaluating whether the EB-CPG would improve T2DM management compared to usual clinical practice.

To explore the experiences and perspectives of Ayurvedic practitioners and patients regarding the two treatment groups (EB-CPG-based care versus usual clinical practice) and participation in the feasibility trial.

Constructivist qualitative study.

Semistructured interviews were conducted with Ayurvedic practitioners and patients. Data were analyzed thematically using an inductive approach and the framework method.

A total of 41 Ayurvedic practitioners and patients were interviewed. Common themes identified across both groups included facilitators and challenges in the trial patient recruitment, challenges in usual clinical care, experiences with EB-CPG-based care (predominantly positive), ease and difficulties of monthly follow-ups, and pros and cons of patient diaries for assessing medication compliance. Practitioner-specific themes included the diverse populations they serve; patients’ motivations for choosing Ayurveda over Western medicine; their motivations for trial participation; balancing clinical duties with the trial demands; confusion about trial roles and responsibilities; and other trial-related issues such as understanding processes and documentation, support and communication, coordination with data collectors, and finances and other resources.

The EB-CPG-based approach for managing T2DM by Ayurvedic practitioners in Nepal was well-received and perceived as more beneficial than usual clinical practice. Trial experiences and perspectives were largely positive; however, several challenges related to trial conduct should be addressed in future studies, including the definitive cluster trial.

The pathogenesis of diabetes is affected by a complex interplay between numerous environmental and genetic factors. While single-nucleotide polymorphisms (SNPs) are not directly used as biomarkers of the disease, they can be considered an important guide for determining predisposition.

To investigate the roles of raftlin, malondialdehyde (MDA), superoxide dismutase (SOD), and the vitamin D receptor (VDR) BsmI (rs1544410 A>G) polymorphism, in the clinical progression of type 2 diabetes mellitus (T2DM).

A retrospective observational case–control study.

A total of 300 subjects were included in the study: 104 with T2DM, 85 with prediabetes, and 111 healthy controls. The VDR BsmI polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, while serum MDA, SOD, and raftlin were analyzed via the enzyme-linked immunosorbent assay (ELISA) method.

No statistically significant differences were observed in the allelic and genotype frequencies of the VDR gene BsmI polymorphism between T2DM prediabetes patients and controls (p = 0.97, p = 0.58, respectively). MDA levels were higher, while raftlin levels were lower in patients with T2DM and prediabetes compared to controls (p < 0.05). Within the T2DM cohort, HbA1c (p = 0.014), MDA (p = 0.001), and raftlin (p < 0.001) differed significantly between the BB and bb genotypes, with a positive correlation between the bb genotype and HbA1c (p = 0.008, r = 0.287). Receiver operating characteristic (ROC) analysis revealed raftlin’s diagnostic potential among T2DM patients with the BB and bb genotypes, with an area under the curve (AUC) of 0.839, a specificity of 69.2%, and a sensitivity of 81.5%.

To the best of our knowledge, this is the first study to demonstrate that raftlin exhibits significant diagnostic efficacy in individuals with the bb genotype within a clinical T2DM cohort.

Adequate glucose control is an important, yet a challenging task, in the early postoperative care after liver transplantation (LTx). Potential of continuous glucose monitoring (CGM) in this context had not been fully explored because of concerns about sensors’ precision in critical care.

We initiated a trial to assess feasibility, accuracy, and benefit of CGM used in addition to standard blood glucose (BG) management.

Prospective randomized trial.

Patients undergoing LTx were included and randomized to wearing (1) unblinded (“active”) CGM which could help guiding insulin therapy, (2) blinded CGM serving as controls. Dexcom G6 was applied immediately after surgery, arterial BG values measured with blood gas analyzer served as reference and for calibration. We evaluated mean absolute relative difference (MARD), Diabetes Technology Society (DTS) Error Grid zones, bias, 15/15 agreement rate, evolvement of accuracy over time, and possible interfering factors. Fisher test, Mann–Whitney test, DTS software, and linear mixed model were used for statistical analysis.

We included 155 LTx recipients, 13 were excluded (1 died during surgery, 12 experienced sensor failure—6 from each group), data from 142 patients (80 in active and 62 in blinded CGM group) were analyzed. Overall, MARD was 9.1% in active and 10.7% in the blinded group (p < 0.0001). DTS error grid in active group had shown 90% in zone A versus 85.3% in the blinded group. These results were consistent for reference glucose ranges 3.9–10 mmol/L and above 10 mmol/L, with less precision in the low ranges (these values were however rare). Sensor accuracy peaked on days 2–3 and deteriorated over time with significant worsening from day 7 on in both groups.

Our study demonstrates feasibility and acceptable accuracy of CGM comparable to reports from the outpatient care. We believe this could be attributed to sensor calibration, reflected by more favorable outcomes in the active CGM group. In addition, we demonstrate decline in accuracy over time, suggesting their use in critical care could be limited to less days to secure sufficient reliability.

This study is part of an ongoing prospective trial registered on ClinicalTrials.gov (NCT05585801) and was registered on October 12, 2022.

Atherosclerosis (AS) is an important risk factor for macrovascular complications in diabetes mellitus and also serves as an independent risk factor for adverse cardiovascular and cerebrovascular events.

This study aims to investigate the association between serum meteorin-like protein (Metrnl) levels and carotid artery plaques in patients with type 2 diabetes mellitus (T2DM).

This study is a cross-sectional study that recruited patients with type 2 diabetes from our hospital’s endocrinology department and healthy subjects from the physical examination center. Carotid ultrasound and glucose tolerance test were performed, and subjects were grouped and analyzed based on the results of the carotid ultrasound and glucose tolerance test.

A total of 208 participants were enrolled in this study. Serum Metrnl concentrations were measured using an enzyme-linked immunosorbent assay. The predictive value of Metrnl for carotid plaque development in T2DM patients was evaluated using receiver operating characteristic (ROC) curve analysis.

Serum Metrnl levels were elevated in the T2DM with carotid plaque group compared to those without (p < 0.05). Multivariate stepwise regression analysis revealed that Metrnl was an independent influencing factor for carotid intima-media thickness. Logistic regression analysis demonstrated that serum Metrnl remained independently associated with carotid plaque formation after adjusting for multiple confounders. ROC curve analysis indicated that the area under the curve for Metrnl in predicting carotid plaque in T2DM patients was 0.724 (95% confidence interval: 0.648–0.800), with a sensitivity of 71.3% and specificity of 67.9%.

Elevated Metrnl levels are a risk factor for carotid plaque formation in T2DM patients, suggesting a potential role of Metrnl in the initiation and progression of carotid atherosclerosis in diabetic individuals.

Limited studies have explored the relationship between surrogate markers of insulin resistance (IR) with both cardiovascular disease (CVD) risk and CVD mortality in individuals with metabolic dysfunction-associated fatty liver disease (MASLD). This study aimed to assess the associations of various IR surrogates with CVD risk and mortality and to identify effective predictors of cardiovascular outcomes in this population.

This study constituted a population-based cross-sectional investigation, utilizing data derived from six cycles of the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2016. The data were linked to the NHANES public-use linked mortality files up to December 31, 2019, to facilitate follow-up on CVD mortality. Following predefined exclusion criteria, participants diagnosed with MASLD were identified and incorporated into the study. The research assessed the associations between surrogate markers of IR and both the prevalence of CVD and CVD mortality.

The primary outcome of this study was the incidence of CVD in individuals with MASLD, and the secondary outcome was CVD mortality. Weighted multivariate logistic regression was utilized to examine the relationship between surrogate markers of IR with total CVD and other subtypes. Weighted multivariate Cox regression and Kaplan–Meier analysis were used to examine the relationship between surrogate markers of IR and CVD mortality. Restricted cubic spline (RCS) was used to explore potential nonlinear relationships. Receiver operating characteristics (ROC) and calibration curves were plotted to evaluate the discriminability and accuracy of IR surrogate markers in predicting CVD risk. Furthermore, mediation analysis was conducted to determine whether surrogate markers of liver fibrosis play a mediating role in the association of surrogate markers of IR with the risk of total CVD and other subtypes.

This study suggests that in the fully adjusted model, estimated glucose disposal rate (eGDR) was significantly negatively correlated with total CVD, congestive heart failure (CHF), heart attack (HA), and CVD mortality. Metabolic score for IR and triglyceride-glucose-body mass index were significantly positively correlated with CVD mortality, total CVD, and CHF. eGDR was best correlated with total CVD (odds ratio (OR) = 0.40, 95% confidence interval (CI): 0.25, 0.63), CHF (OR = 0.15, 95% CI: 0.06, 0.38), and HA (OR = 0.40, 95% CI: 0.22, 0.71). Weighted multivariate Cox regression indicated that for each unit increase in eGDR, the risk of CVD mortality decreased by 27%. RCS analysis showed that all surrogate markers of IR were linearly related to CVD and CVD mortality (P-nonlinear relationship >0.05). In addition, the ROC curve showed that eGDR had a more robust diagnostic efficacy than other IR markers, and eGDR had a higher accuracy in predicting long-term CVD mortality. Adding eGDR to the base model improved the C statistic, net reclassification improvement, and composite discrimination improvement for most outcome variables. In mediation analysis, Metabolic Dysfunction Associated Fibrosis 5 mediated part of the association between eGDR and total CVD, coronary heart disease, HA, and stroke.

In conclusion, eGDR outperformed other IR surrogates in predicting both CVD risk and CVD mortality in MASLD. Incorporating eGDR into prediction models may enhance risk stratification and facilitate early identification of high-risk individuals in this population. Further studies are warranted to validate these findings in external cohorts.

Comparative evidence on 24-month clinical outcomes and biomarker trajectories with semaglutide, empagliflozin, and sitagliptin in adults with type 2 diabetes (T2D) and obesity remains limited.

To compare 24-month clinical outcomes and longitudinal biomarker trajectories among semaglutide, empagliflozin, and sitagliptin in people with T2D and obesity.

Multicenter retrospective cohort study.

Using TriNetX, we performed an active-comparator, new-user study with three prespecified 1:1 propensity score-matched contrasts: semaglutide versus empagliflozin, semaglutide versus sitagliptin, and empagliflozin versus sitagliptin. Follow-up was intention-to-treat for 24 months. Multiplicity was addressed with Benjamini–Hochberg false discovery rate correction within two prespecified families: (i) clinical time-to-event endpoints (all-cause mortality, MACE, heart failure, MAKE, MALO, atrial fibrillation, stroke) within each comparator pairing, and (ii) window-level laboratory contrasts within each biomarker at baseline, 6, 12, and 24 months.

Versus empagliflozin, semaglutide was associated with lower all-cause mortality (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.51–0.69), major adverse cardiovascular events (MACE; HR 0.76, 95% CI 0.66–0.88), and heart failure (HR 0.62, 95% CI 0.54–0.70). Versus sitagliptin, semaglutide was associated with lower all-cause mortality (HR 0.34, 95% CI 0.27–0.42), MACE (HR 0.64, 95% CI 0.51–0.81), and heart failure (HR 0.54, 95% CI 0.43–0.67). Empagliflozin versus sitagliptin showed lower all-cause mortality (HR 0.48, 95% CI 0.40–0.58) and MACE (HR 0.74, 95% CI 0.59–0.92), whereas heart failure did not differ significantly.

In matched cohorts with T2D and obesity, semaglutide was associated with lower 24-month mortality and heart failure risk than empagliflozin, and both semaglutide and empagliflozin were associated with lower mortality and MACE than sitagliptin.

Not applicable (retrospective cohort); Institutional Review Board approval CS2-24004, Chung Shan Medical University Hospital.

Evidence on the maternal–fetal thyroid hormone (TH) axis is limited, especially regarding how maternal thyroid peroxidase antibody (TPO-Ab) status affects the link between gestational thyroid function and neonatal thyroid-stimulating hormone (TSH).

This study explored how maternal TH in late pregnancy influences neonatal TSH and assessed whether TPO-Ab modifies this relationship.

This retrospective cohort study was conducted at a tertiary specialized hospital.

A total of 10,154 eligible mother–newborn pairs were analyzed. Maternal TSH, free thyroxine (FT4), free triiodothyronine (FT3), and TPO-Ab were measured before birth; neonatal TSH was measured 3–7 days postbirth. Mothers were classified as TPO-Ab positive (>34 IU/mL) or negative.

Maternal TPO-Ab positivity prevalence was 5.5%, while congenital hypothyroidism (CH) screening positivity (TSH ⩾10 mIU/L) occurred in 0.87% of neonates. Among TPO-Ab-negative mothers, maternal TSH positively correlated with elevated neonatal TSH (adjusted β: 0.14, 95% confidence interval (CI): 0.10–0.17, p < 0.001) and CH risk (adjusted odds ratio: 1.21, 95% CI: 1.09–1.33, p < 0.001). A nonlinear dose–response relationship revealed a threshold at 4.85 mIU/L: below this value, neonatal TSH increased sharply with maternal TSH (β: 0.21, 95% CI: 0.16–0.26, p < 0.001). No significant associations existed in TPO-Ab-positive mothers. TPO-Ab status reversed the neonatal TSH-maternal FT3/FT4 ratio relationship: negative correlation in TPO-Ab-negative mothers (β: −1.78, 95% CI: −2.70 to −0.87, p < 0.001) versus positive correlation in TPO-Ab-positive mothers (β: 11.31, 95% CI: 2.03–20.58, p = 0.017).

Maternal TSH correlates with neonatal TSH in TPO-Ab-negative pregnancies with a threshold at 4.85 mIU/L. TPO-Ab abolishes this association and reverses the FT3/FT4 ratio-neonatal TSH relationship, establishing TPO-Ab status as a critical modifier of maternal–fetal thyroid interactions. These findings support integrating TPO-Ab screening into prenatal thyroid management to optimize neonatal outcomes. However, the observational design limits causal inference, and further prospective studies are warranted.

Growth hormone and insulin-like growth factor 1 (IGF-1) have recently been linked to temporal muscle thickness (TMT) in acromegaly; however, the relationship between treatment response and TMT remains unclear.

To evaluate whether TMT correlates with treatment response and may serve as a surrogate marker of disease control in patients with acromegaly.

Retrospective longitudinal two-center study.

Patients with acromegaly and non-functioning pituitary adenomas (NFPA) were included. TMT was measured on magnetic resonance imaging scans obtained before treatment initiation and after a 3-year follow-up. Baseline TMT was compared between groups. In patients with acromegaly, TMT was correlated with IGF-1 levels at diagnosis and over time, as well as with treatment response. Mixed-effects regression models adjusted for covariates were used to assess associations.

Imaging studies from 58 subjects were analyzed (40 with acromegaly, 18 with NFPA). Pre-treatment TMT was significantly greater in patients with acromegaly compared with NFPA (mean 10.1 mm (9.3–10.7) vs 8.1 mm (8.0–9.2), p = 0.003). Higher baseline TMT was associated with higher IGF-1 levels at diagnosis (p < 0.01). Following treatment, mean TMT decreased from 9.6 mm at baseline to 8.8 mm at 36 months (p = 0.001). In covariate-adjusted mixed-effects models, higher pre-treatment TMT was independently associated with increased IGF-1 levels at diagnosis and longitudinally (β = 19.59 ng/mL, p = 0.022).

TMT correlates with biochemical disease activity and decreases after treatment, suggesting it may be a useful imaging marker of clinical activity and prognosis in acromegaly.

Not applicable.

The optimal extent of surgery for patients with unilateral multifocal papillary thyroid carcinoma (PTC; ⩽4 cm) and limited lymph node metastasis remains uncertain.

To compare recurrence risk between lobectomy and total thyroidectomy in this population.

Retrospective cohort study with inverse probability weighting regression adjustment (IPWRA) and non-inferiority analysis.

This study included unilateral multifocal PTC (⩽4 cm) patients without bulky nodes (all metastatic <3 cm) treated from 2008 to 2024. IPWRA estimated the average treatment effect (ATE) of lobectomy versus total thyroidectomy on recurrence. A non-inferiority analysis with a prespecified margin of 3% was performed. Sensitivity analyses included traditional multivariable logistic regression, 1:1 propensity score matching, weighted logistic regression, and a 5-year landmark analysis. Recurrence-free survival was analyzed using Kaplan–Meier methods and multivariable Cox regression.

A total of 1373 patients were included (524 lobectomy, 849 total thyroidectomy). After IPWRA, all covariates achieved excellent balance. Over 52.4 months median follow-up, 36 recurrence events occurred (2.6%). The ATE of lobectomy versus total thyroidectomy was 1.19% (95% confidence interval (CI): −1.44% to 3.81%; p = 0.375), indicating no statistically significant difference in recurrence risk between the two procedures. The upper bound of the 90% CI (3.39%) marginally exceeded the prespecified non-inferiority margin of 3%. The 5-year landmark analysis showed a near-zero difference (ATE 0.01%, p = 0.994), and three of four sensitivity analyses yielded nonsignificant results. Subgroup analyses were directionally consistent but underpowered. The multivariable Cox regression was underpowered (minimum detectable hazard ratio (HR): 2.61) and yielded an inconclusive result (HR: 2.04, 95% CI: 0.91–4.62, p = 0.085).

In patients with unilateral multifocal PTC (⩽4 cm) without bulky nodal metastases, lobectomy showed no significant difference in recurrence risk compared with total thyroidectomy, supporting that lobectomy may be a safe alternative in this intermediate-risk population.

Congenital persistent hyperinsulinemic hypoglycemia (HH) is a rare disorder that can lead to severe and recurrent hypoglycemic episodes in neonates and infants. Management often requires intensive glucose infusion via central venous catheters (CVCs), which may increase the risk of thrombosis. While case reports suggest thrombosis can occur in HH, the incidence, risk factors, severity, and outcomes remain poorly understood.

This study aimed to determine the incidence of thrombosis in children with persistent HH and to evaluate potential risk factors associated with thrombotic complications.

A descriptive, retrospective cohort study of patients with persistent HH followed at a university pediatric endocrinology clinic between January 2000 and December 2025.

Twenty patients with persistent HH were included. Data on demographics, clinical characteristics, laboratory results, treatment protocols, CVC use, timing and location of thrombosis were collected. Patients who developed thrombosis were compared with those who did not to identify risk factors.

Among 20 patients, 55% were male, with a median age at diagnosis of 1 day. A total of 23 CVCs were placed in 15 patients, with a median dwell time of 38 days. Thrombosis occurred in nine patients (45%), including six catheter-related and three catheter-independent intracranial thrombosis. Median age at thrombosis detection was 74 days. Patients who developed thrombosis experienced significantly more hypoglycemic episodes and more days with hypoglycemia (p < 0.05). No association was found between genetic mutations (ABCC8, KCNJ11, etc.) and thrombosis development. All four patients treated with enoxaparin achieved complete resolution without complications.

Thrombosis is a frequent and clinically significant complication in persistent HH. Recurrent and severe hypoglycemic episodes are major risk factors. Routine thrombosis screening, particularly in patients with CVCs, may allow early detection and treatment even in asymptomatic cases.

Diabetes in adolescents is usually associated with cardiovascular Autonomic Nervous System (ANS) disorders. The aim of this study was to investigate the effect of exercise and Mindful Self-Compassion Therapy (MSCT) on heart rate variability (HRV), aerobic capacity (VO2peak), and glycemic index of adolescent boys with type 1 diabetes (T1D).

A total of 60 adolescent boys (Age: 12–18 years, Body Mass Index: 19.75 ± 2.26 kg/m²) were enrolled in this semi-experimental research. The participants were allocated into four groups: Control Diabetes (CD, n = 15), Exercise Diabetes (ED, n = 15), MSCT Diabetes (MD, n = 15), and Exercise + MSC Diabetes (EMD, n = 15). The ED group received 3 sessions per week of combined resistance and interval (running) and training, the MD group received 8 sessions of 60 min of MSCT, and the EMD group received exercise training + MSCT during a 12-week intervention period. A two-way multivariate analysis of covariance (MANCOVA) was used with pre-test values as covariate variables to evaluate changes in a range of HRV variables following the interventions.

The ED and EMD groups showed increases in High Frequency (HF), Root Mean Square of Successive RR Interval Differences (RMSSD), Standard Deviation of NN Intervals (SDNN), Very-Low-Frequency (VLF), Low-Frequency (LF), and VO2peak. There was a decrease in resting Heart Rate (HR), LF/HF, and HbA1c levels. The MD group had a substantial increase in HF and RMSSD and a significant decrease in HR and LF/HF (p < 0.05).

The results support the application of combined interval/resistance exercise training and stress control method (MSCT) as an effective non-invasive intervention for enhancing the psychophysiological parameters of HRV in adolescent boys with T1D compared to exercise or MSCT alone.

Pituitary apoplexy (PA) is a neuroendocrine emergency characterized by acute hemorrhage or infarction of a pituitary adenoma. While its initial presentation and management are well documented, data on recurrent PA remain scarce.

To determine the prevalence, clinical characteristics, and predictors of recurrent PA in a national cohort, and to contextualize findings through a structured review of the literature.

Multicenter retrospective cohort study complemented by a structured literature review.

We analyzed 274 patients from the Spanish Pituitary Apoplexy Registry (2010–2023) with complete follow-up. Recurrent PA was defined as a new acute episode with radiological evidence of hemorrhage or infarction within a previously affected lesion. Clinical, radiological, and treatment-related variables were compared between recurrent and non-recurrent cases. A complementary literature review identified published reports of recurrence.

Recurrent PA occurred in 9 patients (3.3%), including 6 of 214 with nonfunctioning adenomas (2.8%) and 3 of 60 with functioning adenomas (5.0%). Compared with nonrecurrent cases, patients with recurrence had significantly larger tumors (median 35 vs 25 mm; p = 0.006), higher rates of cavernous sinus invasion (77.9% vs 37.3%; p = 0.006), and more frequent prior cabergoline therapy (33.3% vs 6.3%; p = 0.020). Median time to recurrence was 18 months (range, 2–108). The literature review identified 11 studies reporting recurrence rates of 2.6%–16.7%, with more consistent estimates (4%–9.6%) in larger series (n ⩾ 50). All recurrent cases showed a favorable clinical course and recovery.

Recurrent PA is uncommon, affecting approximately 3% of patients with a prior apoplexy episode. Given the low frequency of recurrence, the associated factors identified should be interpreted cautiously and considered primarily hypothesis-generating. The second episode was not more severe than the initial event, and the long-term prognosis was favorable.

Not applicable.

Multimorbidity management is crucial in aging populations, particularly for chronic respiratory diseases (CRDs) and diabetes. Their coexistence increases exacerbation and mortality risks. Antidiabetic drugs may differentially impact respiratory outcomes.

To evaluate the effects of antidiabetic drugs on CRDs in individuals with type 2 diabetes (T2D).

Systematic review with conventional and network meta-analyses (NMAs).

We conducted a systematic review with conventional meta-analysis, NMA for drug comparisons, and two-sample Mendelian randomization for genetic evidence. We assessed nine antidiabetic drug classes for associations with CRD exacerbations, incidence, and all-cause mortality in individuals with T2D.

Our analysis of 33 studies (n = 939,064) found that glucagon-like peptide-1 receptor agonists (GLP1RAs) offered the strongest protection against acute exacerbations (hazard ratio vs insulin: 0.40, 95% credible interval 0.29–0.56) and had the highest first-rank probability (72.95%), followed by sodium-glucose cotransporter-2 inhibitors (SGLT2is; 46.19%). Thiazolidinediones reduced incident CRD by 21% (odds ratio (OR) 0.79, 0.69–0.91), while metformin lowered all-cause mortality risk by 16% (OR 0.84, 0.74–0.95). Mendelian randomization confirmed GLP1R expression was associated with reduced asthma risk (OR 0.9987, 0.9979–0.9996).

GLP1RAs provide the strongest protection against CRD exacerbations in T2D patients, with SGLT2is as the second-most effective option. These findings highlight the potential for personalized antidiabetic therapy in multimorbidity management. Further studies should validate these findings and elucidate underlying mechanisms.

PROSPERO (ID: CRD42024542379).

Radiofrequency ablation (RFA) has gained recognition as a highly effective treatment for benign thyroid nodules (BTNs). However, post-procedural thyroid function changes have been reported.

This study specifically focuses on the potential link between changes in thyroid function and the volume reduction ratio (VRR) of treated nodules. Additionally, it seeks to evaluate whether fluctuations in thyroid function at mid-term follow-up can serve as early indicators for the development of long-term hypothyroidism following RFA.

Retrospective cohort study.

In this study, 50 euthyroid individuals (mean age = 47.1 years; 43 females, 7 males) with a total of 72 BTNs (median volume = 4.61 mL) undergoing RFA were evaluated. Comprehensive assessments, including clinical examinations, ultrasound imaging, and blood tests, were conducted at specific intervals (pre-RFA, and at 6 months, 12 months, and annually post-RFA).

The mean follow-up period was 22.3 months. Both medium-term and long-term follow-ups revealed significant reductions in triiodothyronine (T3) levels (p = 0.010, p = 0.036) and elevations in thyroid-stimulating hormone (TSH) levels (p < 0.001, p = 0.006) compared to baseline measurements. A negative correlation was found between medium-term T3 levels and long-term VRR (r = −0.475, p = 0.001). Furthermore, patients with lower T3 levels during medium-term follow-up demonstrated a significantly higher long-term VRR compared to those with higher T3 levels (0.89 vs 0.77, p = 0.030).

Following RFA, notable alterations in thyroid function were observed, without meeting the criteria of hypothyroidism. Additionally, a lower mid-term T3 level may be indicative of a better VRR during long-term follow-up.

The causes of cardiovascular disease are complex, with hyperlipidemia being a major factor in its development. The connection between peptic ulcer disease (PUD) and hyperlipidemia is unclear, and there have been no thorough studies on the effect of anti-PUD medications on the risk of hyperlipidemia, particularly in Asian populations. This study aimed to explore the relationship among PUD, anti-PUD medications, and the risk of developing hyperlipidemia.

Utilizing a population-based cohort study conducted in Taiwan, we investigated the association between PUD, the administration of anti-PUD medications, and the subsequent risk of developing hyperlipidemia.

Retrospective study.

Using data from the Taiwan National Health Insurance Research Database, we conducted a 21-year follow-up study on patients diagnosed with PUD between 2000 and 2021. The Cox proportional hazards regression model was used to analyze the risk of developing hyperlipidemia in relation to PUD and the use of anti-PUD medications.

According to the multivariable Cox proportional hazards regression analysis, patients with PUD had a higher overall incidence of hyperlipidemia (80.7 vs 53.6 per 1000 person-years) than those without PUD. The adjusted hazard ratio was 1.64 (95% confidence interval = 1.62–1.67). Both men and women, as well as different age groups, showed a higher risk of hyperlipidemia among patients with PUD. Patients with PUD who undergo surgery have a higher risk of developing hyperlipidemia than those who do not. The use of anti-PUD medications, such as H2 receptor antagonists, proton pump inhibitors, antibiotics, prostaglandin analogs, anticholinergics, antacids, and carbenoxolone, but not bismuth salts, was associated with a lower risk of developing hyperlipidemia than non-use.

Patients with PUD were more likely to develop hyperlipidemia. However, patients receiving anti-PUD medications had a lower incidence of hyperlipidemia.

Autonomous aldosterone production and mineralocorticoid receptor activation are key pathophysiologic mechanisms underlying primary aldosteronism (PA). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a sensitive biomarker for evaluating cardiac stress and fluid status. This study aimed to investigate the association between NT-proBNP and renin-independent autonomous aldosterone production, as well as potential confounding factors.

We conducted a retrospective cohort study of 443 patients with PA who underwent both a captopril challenge test (CCT) and measurement of NT-proBNP. The CCT was used to evaluate the degree of renin-independent aldosterone production, and the association between NT-proBNP and renin-independent aldosterone production was assessed using multivariable regression analysis. Echocardiography was performed to evaluate cardiac structure and function.

After multivariable regression analysis, post-CCT plasma aldosterone concentration (PAC) and aldosterone-renin ratio (ARR) were identified as independent predictors of NT-proBNP levels. In addition, female sex and lower body mass index (BMI) were significantly associated with higher NT-proBNP levels, compared to men or individuals with higher BMI. NT-proBNP also remained a significant predictor of increased left ventricular mass index and impaired diastolic function after adjustment across multiple models, underscoring its strong association with cardiac remodeling and dysfunction in patients with PA.

Higher post-CCT PAC and ARR were independently associated with NT-proBNP in patients with PA, indicating a pathophysiological link between renin-independent aldosterone production and cardiac stress. Sex and BMI significantly influenced NT-proBNP concentrations, underscoring the importance of considering these factors when interpreting NT-proBNP levels in clinical practice.

To assess the real-world impact of transitioning from the Dexcom G6^® to G7^® system in individuals with type 1 diabetes (T1D) using the Tandem t:slim X2™ with Control-IQ™. Primary outcomes included glycemic control changes, while secondary outcomes evaluated patient-reported outcomes (PROMs) and experiences (PREMs).

A 3-month prospective, multicenter, observational study was conducted in individuals previously using Dexcom G6 and Control-IQ. Glycemic control was assessed via TIR_70–180 and HbA_1c. PREMs and PROMs were measured using validated questionnaires (Diabetes Quality of Life (DQoL), Type 1 Diabetes Life (ViDa1), Diabetes Distress Scale (DDS), and Diabetes Treatment Satisfaction Questionnaire). Statistical analyses were stratified by baseline TIR_70–180 (>70% vs <70%) and sex.

The study included 92 participants (mean age 38 ± 13 years), with a baseline TIR_70–180 of 76% ± 10%. The overall TIR₇₀₋₁₈₀ remained stable throughout the study. However, among participants with baseline TIR_70–180 <70%, a significant increase in TIR₇₀₋₁₈₀ was observed, rising from 61% ± 9% to 65% ± 7% (p = 0.007). In consonance, HbA_1c levels showed a significant decline, from 7.3% ± 0.9% to 7.0% ± 0.6% (p = 0.001). In addition, both glucose management indicator (GMI) and mean glucose levels significantly decreased over time, reflecting an overall improvement in glycemic control. These changes (GMI and glucose levels) were consistent across groups, with no significant differences based on baseline TIR_70-180 stratification. Quality of life and diabetes distress improved (DQoL, ViDa1, and DDS), especially in participants with lower baseline TIR_70-180 and in women. Some reported increased connectivity issues, but none led to treatment discontinuation.

In Control-IQ users, the transition to G7^® did not significantly impact glycemic control overall. However, a subgroup of patients with suboptimal baseline control (TIR_70–180 <70%) may benefit from this change, and enhanced quality of life and diabetes distress, especially in women.