Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus. Diabetic corneal neuropathy refers to the progressive damage of corneal nerves. Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature. However, growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit, which includes both the retinal vascular structures and neural tissues. Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening. However, diabetic corneal neuropathy is commonly overlooked and underdiagnosed, leading to severe ocular surface impairment. Several studies have found that these two conditions tend to occur together, and they share similarities in their pathogenesis pathways, being triggered by a status of chronic hyperglycemia. This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy, whether diabetic corneal neuropathy precedes diabetic retinopathy, as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy. We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

Exposure to benzene, toluene, ethylbenzene, xylenes, and n-hexane (BTEX-H) may contribute to the development of diabetes. Oil spill response and cleanup (OSRC) workers are exposed to BTEX-H but there are few relevant studies. We studied incident diabetes over 10 years of follow-up among OSRC workers.

This analysis includes 21,726 participants (82.2 % male, mean age 39.9 years; 66.5 % White race) in the Gulf Long-term Follow-up Study - a prospective cohort of Deepwater Horizon (DWH) oil spill OSRC workers followed from 2011 to 2013 through 2021. Individual estimates of cumulative work-related exposures to specific BTEX-H chemicals and an aggregate sum (total BTEX-H) were derived from a job-exposure matrix that linked exposure group estimates derived from exposure measurements to self-reported DWH work histories. We used Cox models to estimate associations of quartiles of exposure to individual BTEX-H chemicals and total BTEX-H with diabetes incidence. We used quantile-based g-computation, quantifying associations with exposure to the BTEX-H chemicals, treating them as separate components in a mixture. We examined differences in associations by neighborhood disadvantage using the Area Deprivation Index (ADI) and by self-classified race in stratified analyses.

Exposure to the BTEX-H chemicals was associated with diabetes, with elevated hazard ratios for third and fourth quartiles of exposure compared to the first quartile. For example, total BTEX-H, Q3 and Q4 HRs were 1.10 95 %CI (0.91, 1.33) and 1.27 95 %CI (1.05, 1.53), respectively. The HR associated with a three-quartile increase in the BTEX-H mixture was 1.31 95 %CI (1.07, 1.59). Stratified analyses showed little variation by race and suggestions of variation by ADI.

Exposures to BTEX-H chemicals were associated with incident diabetes among OSRC workers for the individual BTEX-H chemicals, total BTEX-H, and the BTEX-H mixture. The range of exposures in this study make these findings relevant to other low to moderate exposure settings.

The changes in amino acid (AA) levels have been observed in pregnant women with gestational diabetes mellitus (GDM). However, it remains unclear whether the AA levels in offspring of GDM mothers are affected by GDM. This study aimed to investigate the changes in AA metabolism in offspring of pregnant women with GDM undergoing different glycemic control treatment regimens.

272 pregnant women treated at our hospital were selected and divided into the GDM and the non-GDM groups. The GDM group was further subdivided into three treatment groups: exercise-diet therapy, metformin therapy, and insulin therapy. The levels of 11 AAs of their offsprings were detected using tandem mass spectrometry and the differences in neonatal AA metabolism between the three treatment groups and the non-GDM group were compared.

There were significant differences in the levels of Arg, Cit, Met, Orn, and Pro of their offsprings between different treatment groups and the non-GDM group (P < 0.05). After controlling for relevant confounding factors, the differences in Arg and Orn remained statistically significant in the three treatment groups compared to the non-GDM group (P < 0.05); Cit remained statistically significant in the exercise-diet group (P < 0.05); and Met and Pro remained statistically significant in the exercise-diet group and insulin group (P < 0.05).

Regardless of the glycemic control treatment regimens used for GDM, AA metabolism related to the arginine family is influenced.

This study aimed to investigate the prevalence of diabetes mellitus in patients with Fabry disease using a nationwide population-based dataset. We hypothesised that patients with Fabry disease would have a higher prevalence of diabetes mellitus compared with the general population.

A cross-sectional study.

Taiwan.

We identified a study sample from Taiwan's LHID2010 Database. There were 9408 sampled patients in this study, 2352 study patients with Fabry disease and 7056 propensity-score-matched comparison patients.

Multiple logistic regression analyses were conducted to explore the association between diabetes mellitus and Fabry disease after taking the variables of age, sex, geographic location, monthly income category, urbanisation level of the patient's residence, hyperlipidaemia and hypertension into consideration.

The results revealed significantly higher prevalence of diabetes mellitus among patients with Fabry disease than among comparison patients (35.8% vs 29.6%, p<0.001). The difference was observed, irrespective of gender, males 37.0% vs 30.6%, (p<0.001) and female patients, 34.8% vs 28.7% (p<0.001). The adjusted OR of diabetes mellitus for patients with Fabry disease was 1.424 (95% CI=1.276~1.591) when compared with comparison patients. Classified by sex, the adjusted ORs for diabetes were 1.428 (95% CI=1.213~1.682) for males and 1.424 (95% CI=1.226~1.655) for females. Additionally, among patients aged <65 years, the adjusted OR was 1.489 (95% CI=1.277~1.737), and among patients aged 65 or older, the adjusted OR was 1.361 (95% CI=1.161~1.596).

Our findings suggest the importance of screening for diabetes mellitus in patients with Fabry disease. Physicians should be conscious of this association and be prepared to manage both conditions concurrently.

Diabetic osteoporosis (DOP) can cause abnormal brain neural activity, but its mechanism is still unclear. This study aims to further explore the abnormal functional connectivity between different brain regions based on the team's previous research.

Resting-state functional magnetic resonance imaging (rs-fMRI) data were obtained from 14 participants diagnosed with type 2 diabetes mellitus (T2DM) and osteoporosis. For comparison, data from 13 T2DM patients without osteoporosis were analyzed. The seed regions for functional connectivity (FC) analysis were chosen according to brain areas previously reported to exhibit abnormal regional homogeneity (ReHo).

DOP patients exhibited significantly decreased BMD, T-scores, MoCA scores, and osteocalcin (OC) levels compared to controls (p<0.05). FC analysis revealed: 1) Reduced connectivity between the left middle temporal gyrus (increased ReHo) and middle occipital gyrus; 2) Enhanced connectivity between the right angular gyrus (increased ReHo) and left Rolandic operculum; 3) Weakened the left precuneus (increased ReHo) and right superior/left middle frontal gyri. These alterations correlated with deficits in visual processing, working memory, and executive function.

Distinct FC reorganization in DOP patients reflects synergistic effects of metabolic and skeletal pathologies on neural networks, potentially mediating cognitive decline through visual pathway disruption and prefrontal-default mode network decoupling. The findings highlight neuroimaging biomarkers for metabolic bone disease-related cognitive disorders.

Atherogenicity indices have emerged as promising markers for cardiometabolic disorders, yet their relationship with prediabetes risk remains unclear. This study aimed to comprehensively evaluate the associations between six atherogenicity indices and prediabetes risk in a Chinese population, and explore the predictive value of these atherosclerotic parameters for prediabetes.

This retrospective cohort study included 97,151 participants from 32 healthcare centers across China, with a median follow-up of 2.99 (2.13, 3.95) years. Six atherogenicity indices were calculated: Castelli's Risk Index-I (CRI-I), Castelli's Risk Index-II (CRI-II), Atherogenic Index of Plasma (AIP), Atherogenic Index (AI), Lipoprotein Combine Index (LCI), and Cholesterol Index (CHOLINDEX). To address the natural relationships between the atherogenicity indices and risk of prediabetes, we applied Cox proportional hazards regression with cubic spline functions and smooth curve fitting, using a recursive algorithm to calculate inflection points. Machine learning approach (XGBoost and Boruta methods) to address the high collinearity among indices and assess their relative importance, combined with time-dependent ROC analysis to evaluate the predictive performance at 3-, 4-, and 5-year follow-up.

During follow-up, 11,199 participants developed prediabetes (incidence rate: 3.71 per 100 person-years). Significant nonlinear associations were observed between all atherogenicity indices and prediabetes risk. Through Z-score standardization of atherogenicity indices and comprehensive Cox proportional hazards regression and advanced machine learning techniques, we identified AIP as the most significant predictor of prediabetes [HR = 1.057 (95% CI 1.035-1.080, P < 0.0001)], with LCI emerging as a secondary important marker [HR = 1.020 (95% CI 1.002-1.038, P = 0.0267)]. Our innovative XGBoost and Boruta analysis uniquely validated these findings, providing robust evidence of AIP and LCI's critical role in prediabetes risk assessment. Time-dependent ROC analysis further validated these findings, with LCI and AIP demonstrating comparable discrimination, with overlapping AUC ranges of 0.5952-0.6082. Notably, the combined indices model achieved enhanced predictive performance (AUC: 0.6753) compared to individual indices, suggesting the potential benefit of using multiple atherogenicity indices for prediabetes risk prediction.

This study identifies statistically significant associations between atherogenicity indices and prediabetes risk, highlighting their nonlinear relationships and combined effects. While the predictive performance of these indices is modest (AUC 0.55-0.68), these findings may contribute to improved risk stratification when incorporated into comprehensive assessment strategies.

Previous studies have suggested that pesticide exposure and gut microbiome alterations are associated with gestational diabetes mellitus (GDM) risk. Understanding the complex interactive effect of these factors on GDM is essential. In a cohort of 852 pregnant women, we assessed pesticide levels in serum and analyzed the gut microbiota using 16S rRNA and shotgun metagenomic sequencing. We explored the interactions between pesticides and gut microbiota, assessed their roles in GDM development, and proposed a predictive model based on identified biomarkers. We identified an environmental risk score (ERS), denoting the pesticide mixture level significantly associated with GDM, with the gut microbiota, particularly involving the Dorea branch, playing a crucial mediating role. In addition, we found an interactive effect of pesticide exposure and gut microbiota on GDM risk. Notably, low Prevotella enrichment combined with high ERS arisen from pesticide levels led to a 10.36-fold increased GDM risk. The identified pesticide and gut microbial biomarkers achieved high predictive accuracy for GDM (AUC: 0.833, 95% CI: 0.748-0.918). Collectively, maternal pesticide exposure may induce disrupted microbiome-dependent glycemic alteration, necessitating future assessment of clinical implications. Potential GDM markers can serve as targets for therapeutic intervention caused by pesticides, leading to prevention.

The prevalence of gestational diabetes mellitus (GDM) is currently on the rise globally, which heightens the risk of adverse pregnancy outcomes and subsequently increases the likelihood of cesarean delivery. GDM can induce hyperglycemic conditions in cesarean wounds, leading to delayed wound healing and complications such as itching, pain, and scarring. These complications significantly impact the quality of life and mental health of mothers. Furthermore, there is a lack of effective clinical prevention strategies. Consequently, the need to improve wound healing after cesarean sections in women with GDM is a pressing concern that warrants our attention. To maximize the therapeutic impact and extend the bioavailability of calycosin-7-glucoside (CG), it was integrated into a hybridized hydrogel (GOHA) as a drug carrier to create the GOHACG hydrogel. Bases on our tests, the GOHACG hydrogel demonstrated a strong capacity for water absorption, appropriate pore size, and good biocompatibility to adjust to the in situ surroundings of the wound. GOHACG also promoted epidermal regeneration, collagen deposition, angiogenesis, and the conversion of macrophages from the M1 to M2 phenotype. Indicating a reduction in the inflammatory response, accelerated wound repair, and minimized skin scarring in a postcesarean delivery model involving gestational diabetic mellitus mice. In brief, the GOHACG possesses significant properties that enhance wound healing in GDM model, suggesting its potential effects in treating wound healing of GDM.

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, leading to elevated blood glucose levels. Cellular therapies offer promise for improving hyperglycemia in T2DM. This retrospective study aimed to assess the clinical effectiveness of intravenous allogeneic umbilical cord-derived mesenchymal stem cells (UC-MSCs) infusion in T2DM patients through various clinical evaluations, focusing on systemic inflammation, metabolic dysfunction, and insulin resistance.

The data from a total of 218 T2DM patients who attended for follow-up after 6 months, and 83 patients after 12 months after receiving 50-100×10⁶ allogeneic UC-MSCs were analyzed. Blood and urine samples were collected at baseline and follow-up. Key evaluations included changes in anthropometry, diabetes indices, lipids, liver, renal, hormonal, and inflammatory markers.

All patients demonstrated satisfactory outcomes, without adverse effects. Significant reductions in HbA1c levels were observed at 6-months (p<0.001) and 12-months (p=0.016). Insulin (p=0.048) and HOMA-IR (p=0.007) levels significantly reduced within 6-months, with same trend at 12-months. ALT and GGT levels significantly decreased (p<0.05), indicating a reduction in liver inflammation. hs-CRP level among patients with higher inflammation were also reduced at 6-months (p=0.073) and significantly at 12-months (p=0.016). Testosterone (p=0.050) and estradiol (p=0.043) levels increased in males and females, respectively, during 12-month follow-up. Additionally, estimated glomerular filtration rate (eGFR) and creatinine levels improved in stage 2 chronic kidney disease (CKD) at 6- and 12-month (p<0.05), indicating recovered renal function for those in early stage of CKD.

Allogeneic UC-MSCs infusion is safe for patients with T2DM and is associated with overall health outcomes, with sustained benefits up to 12 months. Notably, the treatment significantly improved metabolic indices including glycemic control, liver and renal profile and systemic subclinical inflammation. These findings provide a basis for further exploration of UC-MSCs in managing T2DM in proper randomized control trial, by addressing both metabolic dysregulation and inflammation.

Background: Dulaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist administered subcutaneously once a week, developed through recombinant DNA technology, and prescribed as an add-on to diet and exercise for managing type 2 diabetes mellitus in adults. In several clinical trials, once-weekly dulaglutide has demonstrated reductions in cardiovascular risk associated with diabetes, as well as improvements in glycemic control and weight reduction. The scope of this study was to evaluate the effect of dulaglutide 1.5 mg on glycemic control, weight management, and LDL-cholesterol levels in patients with uncontrolled type 2 diabetes mellitus. Methods: We retrospectively reviewed the medical records of 55 patients with inadequately controlled type 2 diabetes mellitus who were on oral antidiabetic agents and insulin, and who were additionally treated with dulaglutide 1.5 mg. We monitored fasting plasma glucose and glycated hemoglobin (HbA1c) at baseline and at 6, 12, and 24 months after initiating dulaglutide treatment. Weight, body mass index, and LDL-cholesterol were assessed at baseline and after 24 months of dulaglutide therapy. Results: Treatment with dulaglutide resulted in significant improvements in fasting plasma glucose and HbA1c after 6 months (p < 0.001), 12 months (p < 0.001), and 24 months (p < 0.001). A significant weight reduction was observed after 24 months of dulaglutide therapy (-3.3 kg; p < 0.001). In addition, we observed a significant reduction in LDL-cholesterol after 24 months (p < 0.001). Conclusions: Our data demonstrate that dulaglutide 1.5 mg significantly improves glycemic control, reduces body weight, and lowers LDL-cholesterol in Romanian patients with inadequately controlled type 2 diabetes.

The aim of this study was to evaluate and compare the usefulness of the C-reactive protein (CRP)-triglyceride glucose (TyG) index (CTI) and other insulin resistance (IR) or inflammatory indexes for predicting recurrent cardiovascular events in percutaneous coronary intervention (PCI)-treated patients. In addition, the mediating effects of systemic inflammation, represented by high-sensitive CRP (hs-CRP), on TyG index-associated adverse cardiovascular events across different subgroups were also evaluated.

The formula for calculating the CTI was 0.412 × ln [high-sensitivity CRP (mg/L)] + ln [triglyceride (mg/dl) × fasting glucose (mg/dl)/2]. The primary endpoint was defined as the incidence of major adverse cerebrovascular and cardiovascular events (MACCEs), including cardiovascular death, nonfatal acute myocardial infarction (AMI), nonfatal ischemic stroke and repeat coronary revascularization.

Among the 2383 PCI-treated patients, 413 experienced MACCEs during a median of 34 months follow-up. Correlation analysis showed CTI was significantly associated with cardiometabolic factors. The CTI was the strongest predictor for MACCEs (adjusted HR 1.85, 95% CI 1.44-2.38) among the inflammatory and IR indicators. CTI had an incremental effect on the predictive ability of the prognostic model for MACCEs (NRI: 0.220, p < 0.001; IDI: 0.009, p < 0.001). Subgroup analysis revealed that the prognostic value of the CTI remained significant across all subgroups (all p < 0.05) whereas the predictive abilities of other IR or inflammatory indicators were more or less influenced by the metabolic abnormalities. Finally, mediation analysis revealed that the effects of systemic inflammation on TyG index-associated MACCEs were more prominent in patients with metabolic disorders.

CTI was a practical indicator for evaluating cardiometabolic diseases. Among the IR and inflammatory indicators, CTI was the most promising index for predicting recurrent cardiovascular risks in PCI-treated patients. TyG index-associated cardiovascular risks were partially mediated by systemic inflammation in patients with metabolic abnormalities.

Increasing evidence has suggested that maternal gestational diabetes mellitus (GDM) can influence the neonatal gut microbiota. However, the initial microbial colonization of neonates is still unclear. The discrepancy in results between studies may be due to many other prenatal characteristics. This study aimed to investigate whether perinatal characteristics affect the association between maternal GDM status and early neonatal gut microbiota. This nested case-control study was based on a cohort of mothers and children (2016YFC1000304). Meconium samples were collected from neonates of mothers with (n = 114) and without GDM (n = 133) within 24 h after birth, and then assessed via 16S rRNA gene amplicon sequencing. Differences in the diversity and composition of the neonatal gut microbiota were compared according to maternal GDM status and other perinatal characteristics. The gut microbiota of neonates born to mothers with GDM presented lower alpha diversity with the Chao1 index (P = 0.0235). Principal coordinate analysis revealed that the meconium samples were clustered by maternal GDM status only with unweighted UniFrac distances (R2 = 0.011, P = 0.003). In other groups, such as maternal age ≥ 35 years old and maternal prepregnancy BMI ≥ 24 kg/m2, meconium was not clustered by maternal GDM status. Linear discriminant analysis revealed that 81 taxa were significantly different between the GDM group and the control group. Based on delivery mode, there were 226 representative taxa in the control group, whereas in the GDM group, there were no representative taxa. In addition, based on neonatal sex, there were 79 representative taxa in the GDM group and seven in the control group. Other perinatal characteristics, such as maternal prepregnancy BMI, age, gestational weight gain, and birth weight also influenced the differential taxa of the neonatal gut microbiota between the two groups. In our cohort, newborns from mothers with GDM and without GDM had similar composition but different abundances of the gut microbiota. Maternal prepregnancy BMI, age, gestational weight gain, and neonatal delivery mode, sex, and birth weight had different influences on the diversity and differential taxa of the neonatal gut microbiota. The results of this study suggest that when studying the association between GDM and neonatal gut microbiota, it is necessary to consider the concomitant perinatal characteristics.

This study uses 16S rRNA gene amplicon sequencing to analyze 247 meconium samples with or without maternal gestational diabetes mellitus (GDM) and make a multi-group comparison. We found that newborns from mothers with GDM and normoglycemic mothers had similar compositions but different abundances of the gut microbiota. Other than the maternal diabetes status, maternal body mass index, age, gestational weight gain, and neonatal delivery mode, gender and birth weight all contribute to neonatal gut microbiota. Compared with former related studies, our sample size was larger, and meconium was collected within 24 h after birth to avoid the influence of the living environment, feeding methods, mother's lifestyle, or diet. The results of this study will provide some information on the association between maternal GDM and neonatal gut microbiota colonization in early life and highlight the influence of non-negligible concomitant perinatal characteristics.

Elevated intracranial pressure (ICP) is a veritable and potentially modifiable predictor of adverse stroke outcome. Sonographically measured optic nerve sheath diameter (ONSD), a non-invasive proxy for ICP, could potentially be utilized as an objective measure of severity and outcome among acute stroke patients.

To evaluate the relationship between admission ONSD, stroke severity, and functional outcomes among patients with acute stroke.

A prospective cohort study was conducted among patients with neuroimaging-confirmed acute strokes admitted to a tertiary hospital in Ghana. The ONSD of each patient was measured within 24 h of admission. Multivariable linear regression was conducted to determine the relationship between admission ONSDs, Glasgow Coma score (GCS), and modified Rankin Score (mRS) at days 30, 60, and 90.

We enrolled 116 patients comprising 69 ischaemic strokes, mean (SD) age 62.6 years ± 12.8 versus 47 hemorrhagic strokes, aged 50.9 years ± 12.2 years (p = 0.000). Presence of neuroimaging features of raised ICP was associated with elevated admission ONSD (β 1.253 (95 % CI: 0.229-2.277), p = 0.017). A higheradmission ONSD was an independent predictor of lowerGlasgow Coma scorein individuals with ischemic strokes (adjusted β -8.602 (95 % CI -16.077- -1.127), p = 0.025) but not hemorrhagic strokes. For individuals with hemorrhagic strokes, higher admission ONSD was an independent predictor of month 1 mRS (β 5.363 (95 % CI 0.804-9.922), p = 0.022) and month 2 mRS (β 10.546 (95 % CI 0.595-20.498), p = 0.039). However, for ischemic strokes, elevatedadmissionONSD was an independent predictor of mRS at month 2 (β 16.501 (95 % CI 5.202-27.800), p = 0.005) and month 3(β 16.643 (95 % CI 3.666-29.620), p = 0.014).

Sonographically determined ONSD is an independent predictor of stroke severity and functional outcomes in this Ghanaian cohort. Randomized control trials exploring the potential role of ONSD in guiding clinical decisions during acute stroke management are warranted, especially in resource-limited settings.

Sarcopenia, physical activity (PA), and sedentary behavior are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). The study aimed to evaluate the effects of sarcopenia and PA on the presence and severity of MASLD.

This cross-sectional study analyzed data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). Hepatic steatosis and liver fibrosis were assessed by vibration-controlled transient elastography (VCTE). Sarcopenia was defined based on the Foundation for the National Institutes of Health criteria. PA and sedentary behavior were evaluated using the Global Physical Activity Questionnaire (GPAQ).

Among 1,831 participants, 664 were diagnosed with MASLD, including 482 with severe steatosis and 89 with significant fibrosis. The prevalence of sarcopenia in the MASLD and non-MASLD populations was 11.7% and 3.8%, respectively. Multivariable-adjusted models demonstrated that sarcopenia significantly increased the risk of MASLD (OR 2.45; 95% CI: 1.33-4.52), severe steatosis (OR 2.56; 95% CI: 1.40-4.66), and significant fibrosis (OR 6.10; 95% CI: 2.08-17.84). Additionally, individuals with sarcopenia and low PA had a 7.91-fold increased risk of developing significant fibrosis (OR, 7.91; 95% CI: 1.42-44.16, P = 0.022). Sarcopenia and prolonged sedentary behavior further increased the risk of MASLD (OR 3.75; 95% CI: 1.60-8.76), severe steatosis (OR 17.58; 95% CI: 1.93-159.79), and significant fibrosis (OR 4.32; 95% CI: 1.31-14.31).

Patients with sarcopenia should increase physical activity and reduce sedentary time to decrease the risk and progression of MASLD. Increasing muscle mass and strength through resistance exercise to reduce the risk of significant fibrosis in sarcopenia patients.

Background: This study investigates the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and coronary artery disease (CAD) using the ultrasonographic fatty liver indicator (US-FLI) to assess liver steatosis. Methods: A total of 204 patients were included, with hepatic steatosis evaluated through ultrasound characteristics, diagnosing fatty liver when US-FLI was ≥2. CAD severity was determined using the SYNTAX score (SS), categorizing 100 CAD patients into mild (SS ≤ 22) and moderate-severe (MS) (SS ≥ 23) groups. The association between US-FLI and SS in patients with MAFLD was evaluated through the multivariate logistic regression model. A receiver operating characteristic curve was applied to determine the accuracy, sensitivity, and specificity of US-FLI in predicting SS. Results: In the multivariate logistic regression analysis, US-FLI was an independent predictor of the CAD group (OR = 1.194, 95% CI: 1.008-1.414, p = 0.040) and the MS group (OR = 1.262, 95% CI: 1.025-1.553, p = 0.028). In the receiver operating characteristic curve analysis, a US-FLI value of 2 was found to be the optimal threshold point for diagnosing MS CAD patients (AUC = 0.620, 95% CI: 0.509-0.713, p = 0.039), with a sensitivity of 65.22% and a specificity of 55.56%. The diagnostic performance of MS CAD patients significantly improved when US-FLI was combined with type 2 diabetes mellitus (T2DM) (AUC = 0.732, 95% CI: 0.632-0.832, p < 0.001), with a sensitivity of 65.22% and specificity of 77.78%. Conclusions: US-FLI was independently and positively associated with CAD severity. US-FLI combined with T2DM had better diagnostic performance in patients with MS CAD.

This study assessed the mediating role of cognitive emotion regulation strategies in the relationship between illness uncertainty and diabetes health-promoting self-care behaviours.

A cross-sectional study was conducted with 433 T2DM outpatients using the Mishel Uncertainty in Illness Scale, the Diabetes Health Promotion Self-Care Scale, and the Cognitive Emotion Regulation Questionnaire (CERQ). Data were analysed using SPSS (v.29) for descriptive and Pearson correlation tests, and Process Macro for SPSS (Model 4, v.4.2) for mediation analysis.

There is a statistically significant, weak negative relationship between illness uncertainty and diabetes health promotion self-care scores (r = -0.105, p = 0.029). CERQ showed a weak negative correlation with illness uncertainty scores, whereas the questionnaire demonstrated a statistically significant, moderate positive correlation with diabetes health-promoting self-care (p < 0.05). The relationship between illness uncertainty and diabetes health- promoting self-care was mediated by CERQ such as self-blame (β= 0.083, 95 % CI= 0.019 - 0.155), acceptance (β= -0.031, 95 % CI= -0.061 - -0.007), rumination (β= -0.107, 95 % CI= -0.179 - -0.048), and positive reappraisal (β= -0.043, 95 % CI= -0.091 - -0.001).

Illness uncertainty negatively impacts self-care behaviours in T2DM patients. CERQ, including self-blame, acceptance, rumination, and positive reappraisal, play a mediating role, highlighting their potential in interventions to improve self-care.

Subclinical hypothyroidism is associated with metabolic diseases; however, it remains controversial in older individuals.

This work aimed to investigate the relationship between thyrotropin (TSH) levels and metabolic diseases.

In this cross-sectional study, sampling was conducted from nationally representative general communities from 31 provinces in mainland China. A total of6791 older (aged ≥65 years) and 55 303 young participants (aged 18-64 years) were selected after excluding individuals with overt hyperthyroidism or overt hypothyroidism. According to the kit, TSH reference range (0.27-4.2 mU/L) and the age-specific TSH range previously formulated (an upper limit of 8.86 mU/L for older adults and 6.57 mU/L for young adults), the older adults and young adults were separately divided into 4 groups based on their TSH levels. Main outcome measures included anthropometric assessments, serum concentrations of thyroid functions, and various metabolic parameters.

In contrast to young adults, there was no significant increase in the prevalence of any metabolic disorders assessed in the slightly elevated TSH group (TSH 4.21-8.86 mU/L) compared to the euthyroid group (TSH 0.27-4.2 mU/L) among older adults. After adjusting for interference factors, a TSH level higher than 8.86 mU/L was found to be an independent risk factor for low high-density lipoprotein cholesterol (OR, 1.84; 95% CI, 1.14-2.98) and dyslipidemia (OR, 1.49; 95% CI, 1.09-2.04) when compared to the euthyroid group in older adults.

Slightly elevated TSH levels are not associated with an increased risk of metabolic diseases in older adults. Therefore, we recommend raising the upper limit of the TSH range for individuals aged 65 years and older.

The main purpose of this study was to assess relationships between absolute and relative handgrip strength (HGS) versus other markers of health (body composition) and physical fitness (VO 2 max, vertical jump) in 220 (112 male) healthy young adults (25±10 years). HGS was measured using a hand dynamometer. Absolute HGS represented the highest grip strength measurement (kg) of the right and left hand combined, while relative HGS represented the absolute HGS divided by body weight (kg/kg). Body composition (lean and fat mass) was measured using dual energy x-ray absorptiometry. VO 2 max was measured using a treadmill peak speed protocol (ml/kg/min), while vertical jump was assessed using a countermovement jump (cm). Absolute HGS (mean=86±22 kg) was positively related with lean mass (r=0.82, p<0.001) and vertical jump (r=0.63, p<0.001), while relative HGS (mean=1.2±0.2 kg/kg) was negatively related with body fat (r=-0.69, p<0.001), but positively correlated with VO 2 max (r=0.47, p<0.001), and vertical jump (r=0.45, p<0.001). Linear models suggest that lean mass, body fat, and vertical jump predicted 69% of variance for absolute HGS (adjusted R 2 =0.71, p<0.001), while lean mass and body fat predicted 49% of variance for relative HGS (adjusted R 2 =0.49, p<0.001). Lower relative HGS scores (<1.0 kg/kg) were associated with higher body fat levels and may represent a quick, simple, marker of health.

Background: Alpha-1-acid glycoprotein (AGP) is a glycoprotein synthesized mainly by the liver. Nonalcoholic fatty liver disease (NAFLD) and liver fibrosis (LF) are associated with metabolic disorders. The aim of this study was to examine the potential correlation between AGP and both NAFLD and LF. Methods: The data were derived from the 2017-2023 National Health and Nutrition Examination Survey (NHANES). The linear association between AGP and NAFLD and LF was examined by multivariate logistic regression models. Non-linear relationships were described by fitting smoothed curves and threshold effect analysis. Subgroup analysis was also performed to assess potential regulatory factors. Results: The study included 2270 females. AGP was found to be significantly and positively associated with NAFLD [OR = 12.00, 95% CI (6.73, 21.39), p < 0.001] and LF [OR = 2.20, 95% CI (1.07, 4.50), p = 0.042]. Furthermore, the association between AGP and NAFLD was significantly different in the diabetic subgroup (p < 0.05 for interaction). Additionally, we found an inverted U-shaped relationship between AGP and controlled attenuation parameter (CAP), with an inflection point at 1.20 g/L. Conclusions: We found a significant positive correlation between AGP and both NAFLD and LF, and there was an inverted U-shaped relationship between AGP and CAP.

Human adenovirus 36 (HAdV-36) is associated with obesity, potentially by promoting adipocyte proliferation and differentiation. Although linked to increased fat storage, HAdV-36 is also correlated with improved insulin sensitivity. Given its potential role in modulating adipose tissue and promoting a less inflammatory metabolic profile, its impacts on pro- and anti-inflammatory cytokine secretion remain unclear.

This nested case-control study compared cytokine levels (IL-10, IL-2, IL-6, IL-8, and TNF-α) between patients with and without HAdV-36 infection. A total of 76 participants were included, with 37 in the control group (HAdV-36 negative) and 39 classified as cases (HAdV-36 positive).

HAdV-36 seropositive individuals exhibited significantly lower IL-6 levels and higher IL-8 levels than seronegative participants. Additionally, they had lower glucose levels, suggesting a potential link between HAdV-36 and metabolic regulation.

These findings support the hypothesis that HAdV-36 may influence inflammatory and metabolic responses by modulating cytokine expression and glucose levels. Further research is needed to clarify the underlying mechanisms and their implications for metabolic health.

Acute kidney injury (AKI) following cardiac surgery is common and is associated with poor outcomes. The combination of urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) is a strong predictor of AKI after cardiac surgery. However, most studies have focused on non-Asian populations, and comparisons with other AKI biomarkers or the optimal timing for measurement have yet to be explored.

We prospectively enrolled adult patients at Kochi Medical School Hospital in Kochi, Japan, to assess the predictive values of [TIMP-2]•[IGFBP7], TIMP-2, IGFBP7, neutrophil gelatinase-associated lipocalin (NGAL), and liver fatty acid-binding protein (L-FABP) measured preoperatively and at 2, 4, 6, and 8 h, as well as on day 1 and day 2 after postoperative intensive care unit (ICU) admission, using receiver operating characteristic curve (ROC) analysis.

Of the 38 patients, 13 (34.2%) developed AKI: seven (18.4%) with stage 1, four (10.5%) with stage 2, and two (5.2%) with stage 3. ROC analysis showed that the area under the curve (AUC) for predicting any stage of AKI peaked at 0-4 h, with the highest value at 2 h after ICU admission. Among the biomarkers, [TIMP-2]•[IGFBP7] showed the best AUC at 2 h after ICU admission, followed by TIMP-2, IGFBP7, L-FABP, and NGAL.

Our study demonstrated the good predictive performance of urine biomarkers, including [TIMP-2]•[IGFBP7], TIMP-2, IGFBP7, NGAL, and L-FABP, for any stage of cardiac surgery-associated AKI (CSA-AKI). The combination of TIMP-2 and IGFBP7 measured 2 h after postoperative ICU admission effectively predicted CSA-AKI, identifying patients at higher risk.

Immune imbalance is the core pathophysiological mechanism of the deterioration of β-cell function driven by lipid metabolism disorders. Toll-like receptor 4 (TLR4) inflammatory signaling is a key pathway that mediates lipotoxic injury in β-cells, but the underlying mechanism needs to be further elucidated. Transmembrane protein 24 (TMEM24) is a key transporter that regulates pulsatile insulin secretion, but its pathophysiology in lipotoxicity remains unclear. In this study, we investigate whether TLR4-mediated lipotoxicity is affected by the inhibition of TMEM24 expression. The PPI network shows that TLR4 is associated with both insulin secretion and ER stress proteins in islets from obese rats. Using in vitro lipotoxic β-cell models, we found that TMEM24 is the target signal of palmitic acid (PA)-induced insulin secretion impairment in islet β-cells, and TLR4 plays a mediating role in this process. Mechanistically, TLR4 mediates lipotoxicity by binding to TMEM24 and downregulating its protein expression to suppress PI3K/AKT signaling, leading to β-cell dysfunction. TLR4 knockout ameliorates islet function impairment through TMEM24/PI3K/AKT signaling in HFD-induced obese rats. Taken together, our results show that TLR4 mediates lipotoxicity in islet β-cells by inhibiting the TMEM24/PI3K/AKT pathway, and the mechanism of TLR4-mediated lipotoxicity is elucidated from the perspective of insulin vesicular secretion.

Diabetic patients frequently face difficulty in identifying and adhering to dietary regimen, including its quality and quantity. This study assessed the knowledge and attitude to dietary regimen among patients with type 2 diabetes mellitus in Delta State University Teaching Hospital, Oghara, as implication for glycemic control. The objectives of the study were to evaluate the knowledge on dietary regimen, assess the attitude to dietary regimen among diabetic patients, and determine the relationship between the knowledge and attitude to dietary regimen among diabetic patients.

Descriptive survey design was used for the study. Convenience sampling technique and a sample size of 150 were used. Self-developed questionnaire was administered. Data was collected, analyzed, and presented in tables.

Findings from the study shows that 80% of the respondents have knowledge on adherence to dietary regimen while 61.3% of the respondents finds keeping to dietary regimen for managing diabetes difficult. Meanwhile, highest responses were attributed to family support, this was followed by support group and enlightenment programs, while the least measure was found in mass campaign.

It therefore shows that although there is high knowledge base on dietary regimen, diabetic patients often find difficulty in adhering to the prescribed regimen. Hence, it is important that measures to promote positive attitude to dietary regimen among diabetic patients be devised to enhance management outcomes.

Smoking was identified as a risk factor for the development of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the association between smoking cessation history and the development of liver fibrosis remains unclear. This study was intended to analyze the association between smoking cessation history and significant liver fibrosis in adult MASLD participants in the United States.

This study utilized data from 2643 patients with MASLD from the National Health and Nutrition Examination Survey (NHANES). Significant liver fibrosis was detected based on transient elastography measurements. According to the smoking questionnaire data, patients were categorized as non-smokers, ex-smokers and current smokers. A multivariate logistic regression analysis, adjusted for weights, was performed to investigate the relationship between smoking cessation history and the presence of significant liver fibrosis in participants with MASLD.

A total of 2643 patients with MASLD were included in this study. Compared with non-smokers, ex-smokers had a slightly elevated risk of developing significant liver fibrosis (OR: 1.07, 95% CI: 1.02-1.13). Specifically, a positive correlation was observed between patients who quit smoking for < 20 years and significant liver fibrosis (OR: 1.07, 95% CI: 1.01-1.15). Furthermore, MASLD patients who started regularly smoking at an age of ≤ 20 years (OR: 1.09, 95% CI: 1.02-1.16) and had a smoking duration of ≥ 10 years before quitting (OR: 1.10, 95% CI: 1.02-1.18) were also highly correlated with an increased likelihood of developing significant liver fibrosis.

This study revealed that individuals with MASLD who have ceased smoking exhibit an elevated risk for significant liver fibrosis when compared to those who never smoked. It is highly emphasized that MASLD patients who quit smoking for < 20 years, started regularly smoking at an age of ≤ 20 years, and had a smoking duration of ≥ 10 years before quitting should be extremely vigilant regarding the risk of significant liver fibrosis.

To investigate the effectiveness of maternal hemoglobin A1c (HbA1c) in the diagnosis of gestational diabetes mellitus (GDM) in the second trimester.

A total of 3000 pregnant women between 24 and 28 weeks of gestation were included in the study. Screening for gestational diabetes was performed using maternal HbA1c in 1200 pregnant women who either refused or could not tolerate the OGTT. The HbA1c value for the diagnosis of GDM was set at ≥ 5.7% in accordance with a meta-analysis by Paula B. Renz et al. A total of 154 pregnant women with HbA1c ≥ 5.7% were diagnosed with gestational diabetes, and their data were recorded prospectively. These data were compared with obstetric outcomes in 250 pregnant women diagnosed with diabetes by performing a 100-g OGTT after a 50-g glucose challenge test (GCT).

There were no significant differences between two groups in terms of maternal age, gestational age at diagnosis, gravidity, and parity. Body mass index (BMI) was found to be significantly higher in pregnant women with HbA1c levels ≥ 5.7% (p < 0.001). Polyhydramnios was more common in the HbA1c ≥ 5.7% group and oligohydramnios was more common in the OGTT group (p < 0.001). Neonatal hypoglycemia was found to be significantly higher in the OGTT group (p < 0.05). The median HbA1c value were different in each group (OGTT group 5.6%, HbA1c group 5.8%; p < 0.001).

HbA1c testing has lower accuracy rates than OGTT in diagnosing GDM because it may miss diagnosis in some groups.

Recent evidence links diet and physical activity with type 2 diabetes mellitus (T2DM) remission, but emerging findings suggest that immune system dysregulation may play a crucial role. This study aimed to investigate the associations between neutrophils and T2DM remission.

We conducted a comprehensive analysis of newly-diagnosed T2DM patients (N = 183) from the CORDIOPREV study, without glucose-lowering treatment, and were randomized to follow either a Mediterranean or low-fat diet. Patients were classified into two groups: Responders, who achieved T2DM remission (n = 73), and Non-Responders, who did not achieve remission during the 5-year dietary intervention (n = 110). Neutrophil count and their related-ratio (NER, NBR, NLR and NHR, normalized with erythrocytes, basophils, lymphocytes, and HDL respectively) were measured at the baseline and 5 years of follow-up.

The lowest baseline tertile of neutrophil count was associated with an increased likelihood of T2DM remission among patients following a Mediterranean diet (but not for low-fat diet) when compared with the highest tertile [adjusted HR of 4.23 (95% CI: 1.53-11.69)], in which similar results were observed for NER and NHR. When considering clinical and neutrophil variables, the predictive capacity of this model yielded an AUC of 0.783 (95% CI: 0.680-0.822). Furthermore, after 5-years, Responders exhibited lower neutrophil count compared to Non-responders (p = 0.006) and a significant decrease in neutrophil count (p = 0.001) compared to baseline. This decrease in neutrophil count in Responders who consumed a Mediterranean diet exhibited a significant increase in Insulin Sensitivity and Disposition Index (p = 0.011 and p = 0.018) after the follow-up period.

These findings suggest that neutrophil count can help in identifying patients that are more likely to achieve T2DM remission following a Mediterranean diet, suggesting a role on insulin sensitivity and β-cell function. Further research holds promise for providing valuable insights into the pathophysiology of T2DM.

ID: NCT00924937; URL Clinical trial: https://clinicaltrials.gov/study/NCT00924937?cond=NCT00924937&rank=1 .

C-reactive protein-triglyceride-glucose index (CTI) has been proposed as a novel biomarker for insulin resistance and inflammation. However, the association between CTI and the risk of stroke, particularly in individuals with different glycemic status, remains unclear.

A total of 10,443 middle-aged and elderly participants were enrolled from the China Health and Retirement Longitudinal Study (CHARLS). The primary endpoint was the occurrence of stroke events. The CTI was calculated using the formula 0.412* Ln (CRP [mg/L]) + Ln (TG [mg/dl] × FPG [mg/dl])/2. The Kaplan-Meier curves, Cox proportional hazard models, and restricted cubic spline analysis were applied to explore the association between CTI and the risk of stroke according to gender, age and glycemic status.

During a median follow-up of 9 years, 960 (9.2%) participants experienced a stroke. Our findings revealed a significant positive linear relationship between CTI and the occurrence of stroke. The association was similar between male and female, despite the HR tended to be higher in females (HR 1.22, 95% CI 1.09, 1.36) than males (HR 1.15, 95% CI 1.02, 1.29), and similar in middle-aged (HR 1.25, 95% CI 1.11, 1.41) and elderly participants (HR 1.12, 95% CI 1.00, 1.26). In different glycemic status, high levels of CTI were found to be linked to an increased risk of stroke in individuals with normal glucose regulation (NGR) (HR 1.33, 95% CI 1.11, 1.59) and prediabetes mellitus (Pre-DM) (HR 1.20, 95% CI 1.04, 1.39). However, this association was not observed in individuals with diabetes mellitus (DM).

Our findings revealed a significant positive linear relationship between CTI and the occurrence of stroke. The association between CTI and stroke was similar between male and female, and similar in middle-aged and elderly participants. In different glycemic status, the association was significant in individuals with NGR and Pre-DM.

Preeclampsia (PE) and gestational diabetes mellitus (GDM) are common pregnancy disorders with shared pathophysiological mechanisms. This study examined the association between SIRT1 polymorphisms (rs12778366 and rs7895833) and relative telomere length (RTL) in women with PE and GDM. The DNA from pregnant women with GDM with and without PE was analyzed. The RTL and genotyping were measured using quantitative real-time PCR. The women with GDM and PE had significantly shorter telomeres. The rs12778366 TC genotype was associated with a 4.48-fold increased risk of PE (OR = 4.48; 95% CI 1.54-13.08; p = 0.003). The PE group had a higher prevalence of the heterozygous TC rs12778366 genotype with short telomeres. The SIRT1 variant rs12778366 is associated with shorter telomeres and an increased risk of developing preeclampsia, suggesting it may be a useful biomarker for preeclampsia risk assessment in GDM pregnancies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an elevated risk of cardiovascular conditions, such as lower extremity arterial disease (LEAD). The Fibrosis-4 (FIB-4) index, a non-invasive marker of liver fibrosis, may have predictive value for LEAD in patients with MASLD. This study aimed to explore the association between FIB-4 and LEAD in a cohort of patients with MASLD.

This cross-sectional study included 481 participants with MASLD, selected from a comprehensive health check-up database. Participants were categorized into three groups based on their FIB-4 index (< 1.3, 1.3-2.66, > 2.66) and underwent duplex ultrasonography to diagnose LEAD. Logistic regression models were employed to evaluate the association between FIB-4 and LEAD, adjusting for demographic, metabolic, and lipid-related factors. Subgroup analyses were performed by sex, age, diabetes mellitus status, hypertension, dyslipidemia, smoking status.

The prevalence of LEAD increased with FIB-4 levels, from 51.3% in the low FIB-4 group to 86.5% in the high FIB-4 group (p < 0.001). In fully adjusted models, higher FIB-4 levels were significantly associated with LEAD (adjusted odds ratio [OR]: 3.54, 95% confidence interval [CI]: 1.39-9.01) in the high FIB-4 group compared to the low group. As a continuous variable, each unit increase in FIB-4 was associated with a 66% higher likelihood of LEAD (adjusted OR: 1.66, 95% CI: 1.12-2.26, P < 0.001). Subgroup analyses did not reveal significant interactions (P for interaction > 0.05).

Higher FIB-4 levels are independently associated with the prevalence of LEAD in MASLD patients, although subgroup analyses did not reveal significant interactions. This suggests that further studies with larger sample sizes are needed to explore these relationships more comprehensively.

The prevalence and clinical characteristics of chronic kidney disease (CKD) among patients with ketosis-onset diabetes (also known as ketosis-prone diabetes) remain unclear. Furthermore, the classification of ketosis-onset diabetes remains controversial and requires further investigation.

To investigate the prevalence and clinical features of CKD in patients with newly diagnosed ketosis-onset diabetes.

This real-world study included 217 patients with type 1 diabetes mellitus (T1DM), 698 with ketosis-onset diabetes, and 993 with non-ketotic T2DM. The prevalence and clinical characteristics of CKD were compared among the three groups. Risk factors associated with CKD were evaluated using binary logistic regression for each group.

After adjusting for age and sex, the prevalence of CKD among patients with ketosis-onset diabetes (17.8%) was significantly higher than that in those with T1DM (8.3%, P = 0.007), but was not statistically different compared to those with non-ketotic T2DM (21.7%, P = 0.214). Furthermore, some risk factors for CKD, including age, and serum uric acid and C-reactive protein levels, in patients with ketosis-onset diabetes were similar to those with T2DM, but significantly different from those with T1DM.

The prevalence, clinical characteristics, and risk factors for CKD among patients with ketosis-onset diabetes were more similar to those with non-ketotic T2DM but considerably different from those with T1DM. These findings further support the classification of ketosis-onset diabetes as a subtype of T2DM rather than idiopathic T1DM.

Cardiovascular-Kidney-Metabolic (CKM) syndrome is characterized by the interrelatedness of chronic kidney disease (CKD), cardiovascular disease (CVD), and metabolic disorders. The relationship between estimated glucose disposal rate (eGDR) and CVD risk in CKM syndrome remains unclear.

We analyzed data from 7,849 participants aged ≥ 45 years in the China Health and Retirement Longitudinal Study (CHARLS). The eGDR was calculated using waist circumference, hypertension, and HbA1c. Cox regression and restricted cubic spline (RCS) regression analyses examined the association between eGDR and CVD (stroke or cardiac events).

During a mean follow-up of 8.29 ± 1.67 years, among 7,849 participants (mean age 62.4 ± 8.7 years; 52.82% male), 1,946 CVD events occurred, including 1,504 cardiac events and 663 strokes. CKM stages 0-3 comprised 492 (6.27%), 1,404 (17.89%), 5,462 (69.59%), and 491 (6.26%) of participants, respectively. A U-shaped relationship between eGDR and CVD risk was identified (turning point: 11.82 mg/kg/min). Below this turning point, each unit increase in eGDR decreased CVD risk by 12% (HR: 0.88, 95% CI: 0.86-0.90, P < 0.0001); above it, each unit increase raised the risk by 19% (HR: 1.19, 95% CI: 1.04-1.37, P = 0.0135).

Our findings reveal a U-shaped relationship between eGDR and CVD risk in CKM syndrome stages 0-3. A higher or lower eGDR was associated with an increased CVD risk.

Type 2 diabetes (T2D) complications pose a significant global health challenge. Omics technologies have been employed to investigate these complications and identify the biological pathways involved. In this review, we focus on four major T2D complications: diabetic kidney disease, diabetic retinopathy, diabetic neuropathy, and cardiovascular complications. We discuss advancements in omics research, summarizing findings from genetic, epigenomic, transcriptomic, proteomic, and metabolomic studies across different ancestries and disease-relevant tissues. We stress the importance of integrating multi-omics techniques to elucidate the biological mechanisms underlying T2D complications and advocate for ancestrally diverse studies. Ultimately, these insights will improve risk prediction for T2D complications and inform translation strategies.

Type 1 diabetes (T1D) is an autoimmune disease caused by T-cell mediated destruction of the pancreatic insulin-producing beta cells. Currently, the development of autoantibodies is the only measure of beta-cell autoimmunity used in the clinic. Despite T-cells' well-accepted role in the autoimmune pathogenesis of human T1D, autoimmune T-cell responses against beta cells remain very difficult to measure. An assay capable of measuring beta-cell antigen-specific T-cell responses has been a long-sought goal. Such an assay would facilitate the direct monitoring of T1D-associated T-cell responses facilitating, earlier diagnosis and rapid evaluation of candidate immune therapies in clinical trials. In addition, a simple and robust assay for beta-cell antigen-specific T-cell responses would be a powerful tool for dissecting the autoimmune pathogenesis of human T1D. Here, we review the challenges associated with measuring beta-cell antigen-specific T-cell responses, the current assays which are used to achieve this and, finally, we discuss BASTA, a promising emerging assay for measuring human beta-cell antigen-specific CD4+ T-cell responses.

Gestational diabetes mellitus (GDM) increases maternal risks such as hypertension and future type 2 diabetes while also contributing to fetal complications such as large-for-gestational-age infants and stillbirth. The placenta which is crucial for fetal development, exhibits structural and functional changes in GDM, but the impact of these alterations on placental trophoblast function remains unclear. During their differentiation villous cytotrophoblast display several characteristics of senescent cells however the role of senescence pathways in placental function remains unexplored in GDM. Here we investigate whether placental senescence pathways are altered in GDM, utilizing term villous tissue and primary trophoblasts to assess molecular changes, and determined fetal sex-based differences. Our data suggest that both p21 and p16 mediated senescence pathways are activated during trophoblast differentiation and are dysregulated in GDM placenta in a sexually dimorphic manner. We also provide evidence for increased activation of p53-Lamin A/C and p16-RB pathways in trophoblast from GDM placentas. Reduced expression of p21 and its downstream effects on GCM1 expression and βhCG secretion outline how altered physiological senescence can affect trophoblast differentiation and function. This is a seminal study highlighting how placental senescence pathways are altered in pregnancies complicated by GDM.

Machine learning (ML) models are being increasingly employed to predict the risk of developing and progressing diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). However, the performance of these models still varies, which limits their widespread adoption and practical application. Therefore, we conducted a systematic review and meta-analysis to summarize and evaluate the performance and clinical applicability of these risk predictive models and to identify key research gaps.

We conducted a systematic review and meta-analysis to compare the performance of ML predictive models. We searched PubMed, Embase, the Cochrane Library, and Web of Science for English-language studies using ML algorithms to predict the risk of DKD in patients with T2DM, covering the period from database inception to April 18, 2024. The primary performance metric for the models was the area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI). The risk of bias was assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST) checklist.

26 studies that met the eligibility criteria were included into the meta-analysis. 25 studies performed internal validation, but only 8 studies conducted external validation. A total of 94 ML models were developed, with 81 models evaluated in the internal validation sets and 13 in the external validation sets. The pooled AUC was 0.839 (95% CI 0.787-0.890) in the internal validation and 0.830 (95% CI 0.784-0.877) in the external validation sets. Subgroup analysis based on the type of ML showed that the pooled AUC for traditional regression ML was 0.797 (95% CI 0.777-0.816), for ML was 0.811 (95% CI 0.785-0.836), and for deep learning was 0.863 (95% CI 0.825-0.900). A total of 26 ML models were included, and the AUCs of models that were used three or more times were pooled. Among them, the random forest (RF) models demonstrated the best performance with a pooled AUC of 0.848 (95% CI 0.785-0.911).

This meta-analysis demonstrates that ML exhibit high performance in predicting DKD risk in T2DM patients. However, challenges related to data bias during model development and validation still need to be addressed. Future research should focus on enhancing data transparency and standardization, as well as validating these models' generalizability through multicenter studies.

https://inplasy.com/inplasy-2024-9-0038/, identifier INPLASY202490038.

Lipoprotein(a) [Lp(a)] is associated with the development of coronary artery calcification (CAC), yet its exact function is not fully understood. This study sought to assess the relationship between Lp(a) levels and the risk of CAC in elderly diabetic patients.

This cross-sectional study included 486 elderly diabetic patients. The exposure factor was Lp(a) levels, categorized into three groups (T1, T2, T3). The outcome was the presence of CAC. The relationship between Lp(a) levels and CAC was evaluated using several statistical methods, including univariate and multivariate logistic regression, multivariable stratified analysis, receiver operating characteristic (ROC) curve analysis, and restricted cubic spline (RCS) analysis.

The highest Lp(a) group (T3) showed significantly higher prevalence of CAC compared to the T1 and T2 groups. Univariate logistic regression indicated a significant link between Lp(a) and CAC. Furthermore, multivariate logistic regression supported the finding that elevated Lp(a) levels correlated with a heightened risk of CAC in all models. Specifically, each unit rise in Lp(a) was associated with a notable increase in CAC risk, and Log10Lp(a) and each 1 standard deviation increase in Lp(a) also significantly elevated CAC risk. Multivariable stratified analysis demonstrated significant differences in CAC risk across various subgroups, including age ≤70 years, males, females, smokers, hypertensive, non-hypertensive, hyperlipidemic, non-hyperlipidemic, non-stroke, and non-chronic kidney disease patients. ROC curve analysis showed that adding Lp(a) to the baseline model improved the area under the curve from 0.741 to 0.755. RCS analysis indicated a significant, approximately linear association between Log10Lp(a) and CAC risk (p nonlinear = 0.115).

In an elderly diabetic population, elevated levels of Lp(a) were strongly linked to a greater risk of CAC. Integrating Lp(a) measurements with conventional risk factors improves the predictive accuracy for CAC.

Saponins are compounds composed of lipophilic aglycones linked to hydrophilic sugars. Natural saponins are isolated from plants and some Marine organisms. As important cholesterol-lowering drugs, natural saponins have attracted wide attention for their therapeutic potential in a variety of cholesterol-related metabolic diseases. To review the effects of natural saponins on cholesterol-related metabolic diseases, and to deepen the understanding of the cholesterol-lowering mechanism of saponins. The literature related to saponins and cholesterol-lowering diseases was collected using keywords "saponins" and "cholesterol" from PubMed, Web of Science, and Google Scholar from January 2000 to May 2024. The total number of articles related to saponins and cholesterol-lowering diseases was 240 after excluding irrelevant articles. Natural saponins can regulate cholesterol to prevent and treat a variety of diseases, such as atherosclerosis, diabetes, liver disease, hyperlipidemia, cancer, and obesity. Mechanistically, natural saponins regulate cholesterol synthesis and uptake through the AMPK/SREBP2/3-hydroxy-3-methyl-glutaryl coenzyme A reductase pathway and PCSK9/LDLR pathway, and regulate cholesterol efflux and esterification targeting Liver X receptor/ABC pathway and ACAT family. Natural saponins have broad application prospects in regulating cholesterol metabolism, for the development of more cholesterol-lowering drugs provides a new train of thought. However, it is still necessary to further explore the molecular mechanism and expand clinical trials to provide more evidence.

Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant.

A total of 717 MASH cirrhosis patients who had LT (1997-2017) at 7 US centers (NailMASH Consortium) were analyzed. Patients were categorized by estimated glomerular filtration rate (eGFR) at transplant: low (LGFR, eGFR ≤30 mL/min/1.73 m²), medium (MGFR, eGFR >30-≤60 mL/min/1.73 m²), and high (HGFR, eGFR >60 mL/min/1.73 m²). Time-related eGFR intercepts, slopes, and assessments of advanced-stage CKD (aCKD) events, defined as 2 eGFR levels <30 mL/min/1.73 m² separated by ≥90 d, were examined.

Post-LT, LGFR group showed increased eGFR, whereas the HGFR group experienced a decline. The 3-mo mark was identified as a "reset point," signifying a new reference level, beyond which a different rate of decline was observed. After 3 mo, mean eGFRs of the LGFR group approached MGFRs, whereas the mean eGFR of the HGFR group continued to decrease but remained higher than other groups during a 60-mo follow-up. LGFR patients had significantly higher aCKD probability than MGFR and HGFR groups. Subanalysis at 3 mo post-LT revealed more aCKD events in the LGFR group compared with MGFR and HGFR groups ( P  < 0.0001).

The study underscores renal impact of LT in MASH cirrhosis, indicating unique eGFR trajectories post-LT tied to baseline eGFR, with a reset point at 3 mo. Monitoring post-LT renal function, especially in those at aCKD risk, is crucial. Renal-sparing immunosuppression may help, regardless of baseline eGFR. Further studies are needed for interventions addressing renal dysfunction of patients with MASH post-LT.