Implementing best practice guidelines for diabetes and cardiovascular comorbidities is important to reduce the risk of complications for people with type 2 diabetes. The T1D Exchange Quality Improvement Collaborative (T1DX-QI) established a type 2 diabetes quality improvement (T2D-QI) program to reduce cardiovascular risk for people with type 2 diabetes by improving glucose, blood pressure, and lipid management initiation. The program began in 2019 with an adult endocrine center in the Northeast and a primary care center on the West Coast. In 2023, a new equity-focused type 2 diabetes intervention began with 3 adult endocrine centers on the East Coast, with an aim to increase access to and use of continuous glucose monitors. In 2023, 4 primary care centers focused on improving screening measures for adults with type 2 diabetes, prioritizing glycated hemoglobin A1, blood pressure, lipid, and urine albumin-to-creatinine ratio. Each clinic received training in quality improvement (QI) methodology and coaching from QI consultants to develop initiatives tailored to the needs of their clinics. Lessons gathered through qualitative interviews and reports included the importance of training the clinical team in QI methodology; adopting lower effort, higher impact interventions to build momentum and cultivate confidence and engagement among clinical teams; obtaining timely data updates; and engaging partners who could champion the work, influence practice, and navigate system complexities. The expansion of T1DX-QI to include type 2 diabetes demonstrated that standardized QI training and interventions developed through a data-driven iterative process and delivered through multidisciplinary teams can be successful.

Growing public interest in incretin-based therapies for weight loss has been accompanied by increasing availability of research peptides purchasable online. Products may be used without medical assessment or counselling regarding adverse effects, sick-day management or appropriate follow-up. In addition, composition, purity and dosing accuracy may be uncertain. Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and glucagon receptors currently being investigated for obesity and type 2 diabetes mellitus, but has no established role in type 1 diabetes mellitus. We report a man in his mid-30s with longstanding type 1 diabetes mellitus who presented with severe vomiting, diarrhoea, hyperglycaemia, ketonaemia and acute kidney injury shortly after self-administering an online-purchased product marketed as retatrutide for weight loss. His partner, who had taken the same preparation, also developed gastrointestinal symptoms. Both had also consumed a potential foodborne source of infection. In type 1 diabetes mellitus, where patients remain dependent on exogenous insulin to suppress ketogenesis, gastrointestinal illness may rapidly precipitate ketosis when insulin is omitted and oral intake is reduced. Although diabetic ketoacidosis did not develop, peak ketonaemia reached 4.3 mmol/L in the setting of dehydration and insulin omission, requiring intravenous insulin and fluid replacement. During recovery, recurrent hypoglycaemia required intravenous dextrose and insulin dose adjustment, highlighting challenges of glycaemic management in acutely unwell patients exposed to agents with incretin and glucagon receptor activity. Stool culture subsequently grew Shigella flexneri, introducing diagnostic uncertainty regarding the relative contributions of gastrointestinal infection and retatrutide exposure, and complicating counselling regarding future retatrutide use. While causation cannot be established, the temporal relationship, similar symptoms in another exposed individual, and recognised gastrointestinal adverse-effect profile of retatrutide suggest that exposure may have contributed to symptom severity or amplified the metabolic consequences of infection. This case highlights diagnostic and management challenges created by unregulated research peptides obtained outside healthcare pathways, particularly in patients with type 1 diabetes mellitus where evidence to guide management is limited and clinicians in non-specialist settings may be unfamiliar with these agents. As access expands through online vendors and social media, clinicians should routinely enquire about prescribed and non-prescribed agents when assessing unexplained illness or metabolic decompensation.

Diabetic kidney disease (DKD) is the most prevalent microvascular complication of diabetes mellitus and the leading cause of chronic kidney disease and end-stage renal disease, with its global incidence rising continuously and imposing a substantial disease burden and medical strain worldwide. Current conventional Western therapies only retard disease progression via single-target approaches and fail to comprehensively block multi-dimensional renal pathological injuries including renal inflammation and fibrosis as well as podocyte damage. Moreover, individualized intervention regimens tailored for patients with non-proteinuric DKD and genetically susceptible populations remain scarce. Most existing reviews separate modern pathological mechanisms of DKD from traditional Chinese medicine (TCM) theories and lack systematic integration of multi-target regulatory networks, cutting-edge molecular mechanisms, clinical evidence and medication safety of TCM, which leaves prominent research gaps. Against this backdrop, this review takes TCM intervention for DKD as the core research thread. It systematically summarizes the global epidemiology and risk factors of DKD as well as novel early diagnostic biomarkers and imaging techniques, sorts out susceptibility genes and polygenic risk prediction models, and further dissects a full spectrum of pathophysiological injury pathways covering glomerular lesions, tubulointerstitial damage, inflammation and oxidative stress. Based on the core TCM pathogenesis of "deficiency in origin and excess in superficiality" for DKD, this paper emphatically analyzes the multi-pathway molecular mechanisms through which Chinese herbal formulas and active ingredients regulate renal injury, and generalizes core therapeutic principles, standardized treatment protocols and personalized medication strategies under syndrome differentiation. In addition, it objectively summarizes clinical evidence of TCM efficacy and sorts out key points for safety management of herbal medications. This review aims to construct an integrated analytical framework of "Western medical pathological injury-TCM syndrome and pathogenesis-molecular targets of Chinese herbal medicines", clarify the unique holistic advantages of TCM with multi-pathway and multi-target regulatory effects, and illustrate that TCM, as a complementary therapy to Western medicine, can synergistically alleviate renal injuries throughout all stages of DKD. Accumulated studies have verified that TCM can compensate for the deficiencies of single-agent Western treatments and exhibits prominent application potential in the full-cycle prevention and intervention of DKD. Nevertheless, large-sample multicenter clinical trials are still required to deeply explore the underlying action targets of TCM, so as to facilitate the improvement of an integrated precise prevention and treatment system combining Chinese and Western medicine for DKD.

OBJECTIVE: To investigate the association between iron metabolism markers and microalbuminuria in patients with Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: A total of 137 patients with T2DM and MASLD were enrolled and stratified into microalbuminuria-positive and microalbuminuria-negative groups based on the urinary albumin-to-creatinine ratio (UACR). Iron metabolism markers, including serum ferritin, serum iron, total iron-binding capacity (TIBC), transferrin saturation (TS), and hepcidin, were measured. Hepatic iron and fat content were assessed using magnetic resonance imaging (MRI), including R2 mapping (MRI-R2) and proton density fat fraction (MRI-PDFF). RESULTS: Patients with microalbuminuria had significantly higher levels of serum ferritin, serum iron, hepcidin, and MRI-R2 compared with those without microalbuminuria (all < 0.05). Correlation analyses showed that hepcidin ( = 0.208, = 0.015) and MRI-R2 ( = 0.248, = 0.003) were positively associated with UACR. However, after multivariable adjustment for confounding factors, MRI-R2 remained independently associated with microalbuminuria ( = 0.049). CONCLUSIONS: Altered iron metabolism is associated with microalbuminuria in patients with T2DM and MASLD. MRI-R2, a quantitative imaging marker of hepatic iron content, showed an independent association with microalbuminuria after multivariable adjustment and may provide complementary information for early renal injury assessment in this population.

OBJECTIVE: Gestational diabetes mellitus (GDM) is linked to excessive inflammatory activation during pregnancy. Serum amyloid P component (SAP) and proteoglycan 4 (PRG4) participate in inflammatory and placental regulatory processes; however, their relationships with GDM remain insufficiently clarified. This exploratory single-center retrospective study aimed to preliminarily investigate the associations of circulating SAP and PRG4 concentrations with GDM. METHODS: A total of 111 Pregnant women undergoing 24-28 week OGTT screening were enrolled and divided into the GDM group and normal glucose tolerance (NGT) group. Serum SAP and PRG4 levels were measured by ELISA. Baseline characteristics, biomarker concentrations and relevant clinical indices were compared between groups. Receiver operating characteristic (ROC) curve and logistic regression analyses were used to evaluate their associations and predictive value. RESULTS: The median serum levels of proteoglycan 4 (PRG4) and serum amyloid P (SAP) were 1.81 (1.11, 2.60) ng/mL and 308.55 (227.06, 437.02) ng/mL, respectively. The serum SAP level in the GDM group [437.66 (366.69, 543.72) ng/mL] was significantly higher than that in the NGT group [232.22 (203.12, 295.86) ng/mL] (<0.001). The AUC of SAP for predicting GDM was 0.886 (<0.001). No significant difference in serum PRG4 levels was found between the two groups (=0.111), with an AUC of 0.588 (=0.111). Logistic regression analysis showed that serum SAP level ≥386.88 ng/mL was independently associated with GDM (odds ratio (OR)=3.292, 95% confidence interval (CI): 1.270-8.528, =0.014); advanced maternal age (≥30 years), history of induced abortion and history of adverse pregnancy were also independent risk factors for GDM. CONCLUSION: Elevated serum SAP may be correlated with GDM, whereas peripheral PRG4 showed no obvious association with gestational hyperglycemia in this cohort.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic disease that significantly impacts patients' quality of life. Its prevalence is rising globally each year. This study aims to identify potential biomarkers associated with T1DM through comprehensive bioinformatics analysis, further enhancing T1DM early diagnosis and treatment. METHODS: Transcriptome datasets from T1DM patients and the control group were from the Gene Expression Omnibus (GEO) database. Differentially Expressed Genes (DEGs) were identified and subsequently analyzed using Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network analysis. Hub genes were identified using Enzyme-Linked Immunosorbent Assay (ELISA) on clinical samples comprising 17 T1DM patients and 19 controls. Immune cell infiltration was estimated using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm, while the diagnostic performance of the hub genes was evaluated receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 20 up-regulated and eight down-regulated DEGs were identified in the GEO database. Functional enrichment analysis showed that immune activation played an important role in T1DM. The expression levels of the hub genes, and , were further validated in clinical samples. ROC analysis showed moderate diagnostic performance, with AUC values of 0.75 (training set) and 0.67 (validation set). CONCLUSIONS: The results indicate that and may serve as promising diagnostic biomarkers for T1DM. Our study is positioned as exploratory with moderate diagnostic relevance rather than definitive biomarker discovery. The findings are preliminary and require further validation before any clinical application.

OBJECTIVE: This study investigated the associations between five insulin resistance (IR)-related surrogate indices and gout and compared their associations and discriminative abilities for gout. The indices included the triglyceride-glucose (TyG) index, TyG combined with body mass index (TyG-BMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and metabolic score for insulin resistance (METS-IR). METHODS: Data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. Comparisons between the gout and nongout groups were performed using -tests and chi-square tests. Multivariable logistic regression and subgroup analyses were used to assess the associations. RESULTS: Among 14,582 participants (4.80% with gout), adjusted analyses identified the highest METS-IR quartile as the strongest predictor of gout (adjusted OR = 2.823, 95%CI 1.643-4.851), followed by TyG-BMI (OR = 2.290, 95%CI 1.555-3.373). Restricted cubic splines revealed nonlinear associations of TyG and LAP with gout risk, contrasting with linear trends for TyG-BMI, VAI, and METS-IR. Subgroup analyses suggested that elevated TyG and VAI were positively associated with gout in nondiabetic individuals (interaction < 0.05). CONCLUSION: All five IR-related indices showed positive associations with gout, particularly in those with central obesity. These indices showed modest discriminative ability for gout, and further validation is needed.

Adjuvant endocrine therapy for breast cancer - particularly tamoxifen - is commonly associated with weight gain, increased adiposity, and metabolic dysfunction. Lifestyle measures often fail to reverse these effects. Evidence regarding glucagon-like peptide-1 (GLP-1) receptor agonists in this specific context remains limited. Reversal of tamoxifen-associated weight gain with liraglutide has been rarely reported. A 58-year-old postmenopausal woman with stage IIA, hormone-receptor positive breast cancer experienced marked weight gain after 24 months of tamoxifen therapy, despite diet and exercise. She developed prediabetes, insulin resistance (assessed by Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] 4.9), and dyslipidemia. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, was initiated and titrated to 3.0 mg/day. Over 12 months, she lost 18.5 kg, and her metabolic parameters, including HOMA-IR and glycated hemoglobin (HbA1c), normalized. Tamoxifen therapy was continued without adverse effects. This case suggests that liraglutide may reverse substantial tamoxifen-associated weight gain and related metabolic derangements in a breast cancer survivor. The observed improvement exceeded what is typically achieved with lifestyle measures alone. Formal studies are needed to define the role of GLP-1 receptor agonists in managing endocrine therapy-related metabolic complications.

BACKGROUND: Type 1 diabetes (T1D) and type 2 diabetes (T2D) differ in health care needs. Precise prevalence estimates by type are important for health care planning. DATA AND METHODS: This validation study used Norwegian health registry data to develop a T1D/T2D classification method, using the Norwegian Diabetes Register for Adults (NDR-A) as reference standard. Our study population consisted of all individuals 18 years and older residing in Norway in 2022 ( = 4,315,563). We used Cohen's kappa to assess agreement between the classification method and the NDR-A. RESULTS: The established classification method had three key steps: (a) T1D, based on insulin use and specialist health care T1D diagnoses, (b) T2D, based on specialist and primary health care T2D, and (c) T1D, based on primary health care T1D and insulin use, and no T2D. The overall agreement with NDR-A diagnosis was 95.2% for T1D and 97.6% for T2D. For T1D, agreement was 97% or higher in age-groups 18-39 and 40-59, 87.6% for those aged 60-79 and 69.4% for individuals older than 80. For T2D, the agreement was 97% or higher for age-groups 40 and above, and 92.1% for those aged 18-39. Applying the classification method to total population data showed that, in 2022, among 4,315,563 individuals aged 18 and older living in Norway, 31,264 had T1D (0.72%) and 239,120 had T2D (5.5%).

BACKGROUND: Body mass index fails to capture variation in fat and muscle distribution that determines metabolic health and disease risk. MRI enables radiation-free quantification of regional body composition, yet scalable open-source tools applied in pooled cohorts with differing acquisition protocols have been lacking. METHODS: MRSegmentator, an open-source nnU-Net-based pipeline, was applied to quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), gluteofemoral adipose tissue (GFAT), trunk musculature, and the liver mask used for liver fat-fraction estimation in 45,851 adults from the German National Cohort (n = 26,877, 3 T multi-centre Siemens) and UK Biobank (n = 18,974, 1.5 T Siemens). Population-scale compartment volumes were segmented from stitched in-phase gradient-echo (GRE) images in both cohorts; liver fat fraction was calculated from fat-only and water-only images. The annotated development data comprised NAKO T2-HASTE and UKB Dixon reconstructions. A single pooled model was applied without site-specific adaptation. A separate two-reader agreement study used 50 scans from these annotated development-sequence domains. Associations between BMI-adjusted body composition and cardiometabolic conditions were estimated using generalized linear mixed-effects models. Incremental discrimination beyond age, BMI, and waist-to-hip ratio was assessed. RESULTS: Five-fold participant-stratified internal cross-validation against curated human-in-the-loop development references comprising UKB Dixon and NAKO T2-HASTE yielded a mean Dice of 0.91. In a separate 50-scan reader study on these annotated development-sequence images, overall reader-reader Dice was 0.937 and overall algorithm-reader Dice was 0.908. The trained pipeline was then used to segment compartment volumes from stitched in-phase GRE inputs in both cohorts, while liver fat fraction was calculated from fat-only and water-only images; direct sequence-matched validation on NAKO GRE was not performed. VAT showed the strongest positive associations with cardiometabolic conditions, while GFAT showed inverse associations, most prominently for type 2 diabetes (OR 0.69, 95% CI 0.66 to 0.72). Disease-specific body-composition phenotypes were identified, with type 2 diabetes characterized by elevated VAT, reduced GFAT, and increased liver fat. MRI-derived compartments modestly improved discrimination for type 2 diabetes and hyperlipidemia beyond anthropometric measures. CONCLUSIONS: A single open-source deep-learning pipeline enabled pooled body-composition phenotyping in two cohorts and captured distributional variation in fat and muscle beyond BMI. High agreement in internal cross-validation (mean Dice 0.91) and the separate two-reader study support the annotated development-sequence analysis, while the population-scale application identified distinct disease-associated phenotypes and modest incremental discrimination beyond conventional anthropometry.

BACKGROUND: Socioeconomic shifts have increased metabolic disorders, yet long-term trends among Chinese youth (aged 5-24 years) remain under-researched. OBJECTIVES: To examine the disease burden of metabolic disorders in China's population aged 5-24 years (1990-2021) and compare with global levels. DESIGN: A population-based modeling study utilizing Global Burden of Disease (GBD) 2021 data. METHODS: We analyzed disability-adjusted life years (DALYs) and age-standardized DALY rates (ASDR) for hypertension (HTN), non-alcoholic fatty liver disease (NAFLD), obesity, and Type 2 diabetes mellitus (T2DM). Trends were assessed using Joinpoint regression. The Bayesian age-period cohort (BAPC) model predicted trends. Drivers were explored via decomposition analysis. RESULTS: HTN ASDR decreased significantly (average annual percentage change (AAPC) = -2.89%), faster than the global average. Obesity and T2DM ASDRs surged (AAPCs: 3.06% and 3.12%), consistent with global upward trends. Despite lower NAFLD (AAPC = -1.84%), the burden rebounded after the mid-2010s, particularly among females. Males bore higher DALY proportions. BAPC predicted improving HTN but worsening obesity and T2DM by 2030. Epidemiological shifts primarily enhanced DALY increases. Population growth and aging provided mitigating effects. CONCLUSION: Chinese youth face a bifurcated metabolic landscape: improving HTN but worsening obesity and T2DM. The recent NAFLD resurgence among females necessitates targeted public health interventions. IMPACT: Key Message: The study highlights worsening burdens of obesity and T2DM among Chinese youth, alongside improving trends in HTN and NAFLD, with significant sex disparities. Added Value: Provides a comprehensive, sex- and age-stratified analysis of metabolic disease burdens in China, using advanced decomposition and projection methods. IMPACT: Calls for urgent, targeted interventions to address rising obesity and T2DM, emphasizing the need for sex-specific public health strategies.

INTRODUCTION: Randomized controlled trials are the gold standard for evaluating interventions but are resource-intensive and impose considerable burden on participants. Historical control designs, which incorporate data from previous trials into new analyses, could reduce sample size requirements, but their practical application is limited. This study explored the feasibility of constructing a historical control using the Bayesian meta-analytic predictive approach based on data from a systematic review of metformin in type 2 diabetes mellitus. METHODS: We extracted baseline and end point glycated hemoglobin values and participant characteristics from 25 randomized trials (36 comparisons). Using the RBesT package in the R software, meta-analytic predictive priors were constructed, and their contribution to new data was quantified using the effective sample size metric. Between-trial heterogeneity (τ) was initially set to the default conservative value (0.5) and subsequently estimated and replaced in the analysis using the output from the metafor package based on the reported study-level variances. Additional stratified analyses based on follow-up duration and publication year were conducted. RESULTS: Initial models yielded low effective sample size values (1-4), indicating minimal information borrowing from historical data. The presence of a high level of heterogeneity (τ = 0.55-0.85) appeared to limit the priors' influence. Further investigation into a stricter data set showed that four outlier studies reduced the estimated τ from the data to 0.0935, which increased effective sample size from 18 (conservative model) to 52 (data-derived model), while estimated treatment effects remained stable (-1.34% to -1.36% glycated hemoglobin). DISCUSSION: Between-trial heterogeneity (τ) estimation critically influences the informativeness of meta-analytic predictive-based historical control analysis. Despite having 25 trials with the same condition, the effective sample size was very low. Data-driven τ estimation substantially increased effective sample size without altering the treatment effect estimates and could represent a valid alternative to historical controls in clinical trial design compared with default conservative choices.

BACKGROUND: This systematic review and meta-analysis aimed to comprehensively evaluate the prognostic impacts of seven classes of antidiabetic medications in patients with cancer, predominantly in the setting of concomitant type 2 diabetes mellitus (T2DM), and to elucidate their potential differential effects. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and the Web of Science was conducted from inception to May 2025, utilizing keywords including "antidiabetic drugs," "cancer," and "prognosis." Based on predefined criteria, eligible English-language randomized controlled trials and cohort studies were included if they compared the prognostic impacts of metformin, insulin, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and thiazolidinediones in patients with cancer. The primary outcome domain was all-cause survival, represented by all-cause mortality (ACM) or overall survival (OS) according to the terminology of the original studies. Secondary cancer-related outcomes included cancer-specific mortality (CSM), disease-free survival (DFS), progression-free survival (PFS), and recurrence-free survival (RFS). Multiple independent investigators performed data extraction and quality assessment. Statistical analyses were performed using OnlineMeta V1.1. DerSimonian-Laird random-effects models were used for all primary meta-analyses to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), while fixed-effects estimates were examined as complementary sensitivity analyses. Study quality was assessed using the Newcastle-Ottawa Scale and the Cochrane risk-of-bias tool for randomized trials. RESULTS: A total of 61 studies comprising 1,106,966 patients with cancer were included. Metformin use was associated with lower ACM (HR=0.82, 95% CI: 0.74-0.91, P=0.0001) and CSM (HR=0.77, 95% CI: 0.69-0.87, P<0.0001), whereas insulin use was associated with higher ACM (HR=2.03, 95% CI: 1.63-2.51, P<0.0001). Among the drug classes analyzed, SGLT2 inhibitor use showed a nonsignificant inverse trend with ACM (HR=0.44, 95% CI: 0.11-1.71, P=0.24) and was associated with lower CSM (HR=0.21, 95% CI: 0.20-0.22, P<0.0001), although these estimates were based on few observational studies with study-specific comparator groups and do not establish superiority over other drug classes. In adjusted-HR-only sensitivity analyses, the direction of association was generally consistent for the major metformin outcomes and insulin-related ACM, whereas several other comparisons were attenuated or could not be pooled because too few studies reported adjusted estimates. CONCLUSION: This meta-analysis identified heterogeneous associations between antidiabetic drug use and cancer-related survival outcomes, with variation across drug classes, cancer types, and study-level mean age groups. Because the evidence was derived predominantly from observational studies with study-specific comparator groups, substantial between-study heterogeneity, and limited data for newer agents, the pooled estimates should not be interpreted as evidence of treatment superiority or used to rank drug classes. These findings are hypothesis-generating and warrant confirmation in prospective studies using clinically comparable treatment groups, standardized outcome definitions, and rigorous control of confounding.

INTRODUCTION: The pandemic disrupted routine healthcare services, including preventive screening for diabetes. We examined the impact of the pandemic on diabetes screening rates and recovery patterns in a universal healthcare setting. METHODS: We conducted a time-series analysis using linked administrative health care and laboratory data from Ontario, Canada to compare expected versus observed monthly diabetes screening rates during the period from March 2020 to March 2023 in the non-diabetes population overall and among subgroups defined by age, sex, and neighborhood socioeconomic status. Monthly expected screening rates were predicted for the same period based on patterns observed from March 2016 to March 2020. RESULTS: Overall, the eligible, non-diabetes population was 9,359,851 in Mar 2016 and 9,894,353 in Mar 2023. Diabetes screening rates declined sharply by 70.1% during the initial lockdown period in April 2020 compared to February 2020 (1.55 vs. 4.47 per 100, -2.92 per 100) with a gradual increase to pre-pandemic levels. As well, 24.5% fewer individuals were screened during the pandemic period versus pre-pandemic levels. While the overall patterns were consistent by sex, the rate of recovery was greater among women (6.42 vs 4.85 per 100, -1.57 per 100) in March 2023. As well, screening recovery rates appeared to be two to three-fold higher among adults aged 50+. Findings were consistent across income groups with slightly higher recovery rates for those living in higher income communities. CONCLUSIONS: The observed sudden decline in diabetes screening may lead to delays in prediabetes and diabetes diagnosis, resulting in missed opportunities for diabetes prevention and early management.

BACKGROUND: Insulin resistance (IR) is closely associated with metabolic dysfunction-associated steatotic liver disease (MASLD), exhibiting tissue-specific effects in the liver, adipose tissue, and muscle. However, the temporal relationships among tissue-specific IR across MASLD status remain unclear. METHODS: We retrospectively identified 491 participants, including 293 without MASLD and 198 with MASLD, who underwent repeated oral glucose tolerance tests and assessment of tissue-specific IR indices between June 2014 and December 2025. Cross-lagged path analysis was performed separately according to baseline MASLD status to examine temporal associations among hepatic IR, adipo-IR, and muscle IR. Logistic regression was used to explore baseline factors associated with persistent or progressive IR. RESULTS: After a median interval of 22 months (range, 12-32 months), 63 of 293 participants without MASLD (21.5%) developed MASLD, while 47 of 198 participants with MASLD (23.7%) transitioned to an elevated FIB-4 category (>1.3). In the fully adjusted model, baseline hepatic IR was associated with subsequent adipo-IR (ρ = 0.303, P < 0.01) and muscle IR (ρ = -0.211, P < 0.001) in participants without MASLD. In participants with MASLD, hepatic IR (ρ = -0.195, P < 0.01) and adipo-IR (ρ = -0.184, P < 0.05) were associated with subsequent muscle IR, while baseline muscle IR was associated with subsequent hepatic IR (ρ = 0.084, P < 0.05). Body mass index (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01-1.13), HOMA-IR (OR, 1.26; 95% CI, 1.07-1.47), and CT attenuation value (OR, 0.97; 95% CI, 0.94-0.99) were associated with persistent or progressive IR (all P < 0.05). CONCLUSION: The temporal relationships among tissue-specific IR differed according to MASLD status. Hepatic IR preceded peripheral IR in participants without MASLD, whereas more multidirectional relationships were identified in those with MASLD. These findings are hypothesis-generating and do not establish a causal sequence.

The neuropathological diagnosis of hypoglycaemia has long relied on demonstrating the classical pattern of selective neuronal necrosis in affected brain regions. This approach is heavily limited, as hypoglycaemic injury is often indistinguishable from hypoxia-ischaemia. We demonstrate a distinct pattern of beta-amyloid precursor protein (β-APP) immunoreactivity in hypoglycaemic deaths (n = 6), contrasting them with non-hypoglycaemic deaths (n = 8). We also address the temporal relationship between hypoglycaemia and β-APP immunoreactivity. The sample comprised neuropathologically examined medico-legal autopsy cases from Helsinki, Finland, during the years 2023-2025. Hypoglycaemic deaths comprised one accidental and five suicidal insulin intoxications. Non-hypoglycaemic deaths comprised two diabetic ketoacidoses, two other deaths in insulin-treated diabetics, two cases of traumatic axonal injury, and two cases of vascular axonal injury. Detailed characteristics of each case were collected (background information; autopsy, neuropathology, and toxicology findings; photomicrographs of β-APP immunoreactivity in the corpus callosum, capsula interna, pons, and thalamus). Estimates of temporal relationships between hypoglycaemia and β-APP immunoreactivity were based on continuous glucose monitoring records and previous hospitalisations due to insulin intoxications. In our sample, utilisation of β-APP appeared more beneficial for the neuropathological diagnosis of hypoglycaemia than classical assessment of selective neuronal injury. In β-APP, hypoglycaemic deaths consistently exhibited positivity of thalamic and pontine axonal fibres. In contrast, non-hypoglycaemic cases were immunonegative or demonstrated immunoreactivity that was predominantly localised elsewhere. Estimates of temporal relationships suggested that β-APP immunoreactivity developed within a few hours of hypoglycaemia (~2.5-3 h) and was not retained after remote episodes (≥ 1 month). On the basis of our preliminary findings, β-APP immunoreactivity appears to be a promising adjunct marker for hypoglycaemic brain injury. Future studies are needed to corroborate the present findings and further explore potential caveats.

BACKGROUND: Endoscopic lumbar decompression is increasingly used to treat lumbar spinal stenosis, but the impact of obesity on short-term postoperative outcomes remains unclear. This study evaluated the association of BMI and metabolic syndrome with 30-day complications and reoperation following endoscopic lumbar decompression. METHODS: A national database was queried for patients undergoing endoscopic lumbar decompression between 2017-2023. Patients were stratified by BMI category (normal, overweight [25 to <30], class I obesity [30 to <35], class II/III obesity [≥35]). Metabolic syndrome was defined as BMI ≥ 30 with concurrent diabetes mellitus and hypertension. Outcomes included 30-day readmission, reoperation, and composite morbidity, including surgical site infection (SSI), urinary tract infection (UTI), transfusion, pneumonia, or sepsis. Categorical variables were compared using chi-square or Fisher exact tests; continuous variables were analyzed using one-way ANOVA. RESULTS: A total of 398 patients were included (normal n = 70, overweight n = 116, class I obesity n = 137, class II/III obesity n = 75). BMI ≥ 30 was not associated with differences in 30-day readmission, reoperation, or overall morbidity. In contrast, BMI ≥ 35 was associated with higher 30-day morbidity (6.7% vs 1.2%, p = 0.014), higher SSI (4.0% vs 0.6%, p = 0.048), and higher UTI rates (2.7% vs 0.3%, p = 0.033). Metabolic syndrome was associated with increased readmission (9.7% vs 2.7%, p = 0.037) and morbidity (9.7% vs 1.6%, p = 0.026). CONCLUSIONS: Endoscopic lumbar decompression demonstrated low overall 30-day event rates across BMI strata. Class I obesity was not associated with higher short-term adverse event rates; however, exploratory threshold analyses identified higher morbidity among patients with BMI ≥ 35 and metabolic syndrome, driven primarily by wound complications and UTI.

Diabetic cataract (DC) is one of the most common complications of diabetes mellitus, currently lacks effective treatments. Gegen Qinlian Decoction (GQD) is effective against diabetes and its complications, but its efficacy and mechanism against diabetic cataracts remain unclear. In this study, the effects and mechanisms of GQD in treating diabetic cataracts were evaluated in Zucker diabetic fatty (ZDF) rats. All rats were randomly divided into control, model, low/high-dose GQD and metformin groups. Each group was administered the drug or an equal volume of distilled water for 12 weeks. Fasting blood glucose and body weight were measured every two weeks. At the end of the experiment, the degree of lens opacity was examined. Pathological changes in the lenses were observed by hematoxylin-eosin staining. The contents of soluble proteins, malondialdehyde (MDA), superoxide dismutase (SOD) and sorbitol were measured in the lenses. Network pharmacology was employed to predict the signaling pathways of GQD in treating DC. Additionally, the protein expressions of p38, JNK and their phosphorylation levels were evaluated by Western blot. The results showed that GQD significantly alleviated lens opacity, reduced sorbitol accumulation and ameliorated oxidative stress in rats with DC. Network pharmacology revealed that the MAPK signaling pathway is a key regulatory pathway of GQD against DC. Western blot results further confirmed that GQD significantly downregulated the phosphorylation levels of p38 and JNK in the lenses of rats with DC.This study implicates GQD as a potential therapeutic candidate for DC.

Polyendocrine metabolic ovarian syndrome (PMOS), previously known as polycystic ovary syndrome (PCOS), is a complex disorder affecting females of reproductive age. Patients with PMOS can develop several comorbidities, including obesity, hyperlipidemia, arterial hypertension, insulin resistance, infertility, and increased risk for endometrial carcinoma. Venous thromboembolism (VTE) is another complication associated with PMOS, thought in part to be related to chronic inflammation leading to prothrombotic hemostatic changes. Hormonal therapy is the mainstay of management, but the presence of other comorbidities and risk factors such as thrombophilia and/or family history of VTE influences the choice of hormonal therapy. Management of this disorder requires multidisciplinary care of its gynecologic, cardiovascular, endocrine, and hemostatic components. In this review, a summary of the diagnosis and management of PMOS is provided with an emphasis on hemostatic considerations. We highlight 1) the diagnostic criteria and general management of PMOS, 2) Hormonal therapy and VTE risk considerations in PMOS management, and 3) Infertility management and the potential risk for thrombosis in patients with PMOS.

BACKGROUND AND AIMS: The coexistence of liver steatosis in patients with chronic viral hepatitis B (CHB) is growing relevant as the global epidemic of obesity and type 2 diabetes mellitus (T2DM). The aim of this study was to identify the metabolic risk factors linked to steatotic liver disease (SLD) in Romanian patients with CHB. METHODS: In this prospective study, we evaluated 320,000 individuals in the LIVE(RO)2 nationwide screening program in Romania from 2021 to 2023. The majority of the patients had undergone transient elastography using controlled attenuation parameter (CAP) to diagnose liver steatosis, and they belonged to vulnerable categories. Exclusion criteria included heavy alcohol consumption, any other liver disease unrelated to CHB, and the lack of CAP evaluation. RESULTS: 5,321 individuals (1.67%) were found with CHB in the screening program. In the final analysis we included 1,970 patients, with a mean age of 55.87±13.84 years; 57.9% of them were males, with a mean body mass index (BMI) level of 27.26 kg/m², and 61.9% of the patients were vulnerable. The prevalence of SLD was 42.2% in the group of vulnerable individuals, compared with non-vulnerable participants, who had a prevalence of SLD of 26.4%. Moreover, patients with vulnerable conditions have a higher prevalence of T2DM (11.5%), hypertension (41.3%), and raised BMI levels ≥25 kg/m² (71.3%). In our study, vulnerable subjects had a higher prevalence of hepatitis B virus e antigen (HBeAg) positivity of 3%, and it was found to be a protective risk factor for hepatic steatosis development (aOR=0.397). Also, these patients had a higher prevalence of severe liver fibrosis (≥ F3) of 17.1%, compared with those non-vulnerable, with a prevalence of 9.7% of severe liver fibrosis. More than that, we find that the presence of HBeAg-positive increases the risk of severe liver fibrosis progression 6 times higher. CONCLUSIONS: In our study we found a prevalence of hepatic steatosis of 42.2% in the cohort of vulnerable untreated patients with CHB, and the prevalence of severe fibrosis was 17.1%. Presence of HBeAg-positive was found to be a protective risk factor for hepatic steatosis but accelerates the development of severe fibrosis along with T2DM, which is more common in the vulnerable CHB cohort.

Insulin resistance is a major complication of obesity. In adults with obesity insulin resistance is associated with a hyposialylation of the Fc-linked glycan on IgG, and a causal link between IgG hyposialylation and glucose dysregulation has been demonstrated in obese mice. What is unknown is how obesity causes the changes in IgG glycosylation. To avoid factors besides obesity that may influence IgG glycosylation, we sought to fill this knowledge gap by studying adolescents with and without obesity. We demonstrate that in pediatric obesity IgG is hyposialylated and hypogalactosylated, with the changes most apparent in females, and that this is related to an upregulation of B cell WNT3, a GWAS-identified candidate gene for IgG glycosylation whose function in glycan modulation was previously unknown. In parallel, WNT3 is upregulated in B cells from obese mice. Linkage between WNT3 upregulation and decreased IgG galactosylation and sialylation was demonstrated in both a HEK293FS cell model and an ARH-77 B lymphoblast cell line. These observations indicate that obesity causes IgG hypogalactosylation and resulting hyposialylation by previously unrecognized actions of WNT3 which regulate IgG galactosylation in B cells. Better understanding of how obesity alters the unique glycobiology of IgG offers the possibility of identifying additional therapeutic targets in the battle against the insulin resistance that complicates obesity.

INTRODUCTION: Prediabetes is a metabolic state that frequently precedes overt type 2 diabetes mellitus (T2DM) and is associated with an increased risk of micro- and macrovascular complications. Lifestyle modification remains the cornerstone of management, and several pharmacological agents, including metformin, pioglitazone, acarbose and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have demonstrated efficacy in delaying progression to T2DM. Sodium-glucose cotransporter 2 (SGLT2) inhibitors (often referred to as gliflozins) are increasingly being investigated in this context. The aim of this review is to summarise current evidence regarding the use of SGLT2 inhibitors in adults with prediabetes and to discuss the arguments for and against their routine clinical use. METHODS: A narrative review of publications retrieved from the PubMed database, addressing the role of SGLT2 inhibitors in prediabetes, was performed. Original studies, meta-analyses, systematic reviews and high-quality narrative reviews up to February 2026 were considered for inclusion. RESULTS: Multiple studies have demonstrated that SGLT2 inhibitors improve insulin sensitivity, promote modest weight reduction, lower blood pressure and exert favourable effects on hepatic lipid metabolism. Two contemporary meta-analyses confirm that SGLT2 inhibitors reduce the incidence of new-onset T2DM in adults with prediabetes who also have heart failure or chronic kidney disease (CKD), with relative risk reductions of approximately 19-21%. This drug class is generally well tolerated, although it is associated with increased risk of genitourinary infections and rare but serious euglycaemic diabetic ketoacidosis. CONCLUSIONS: SGLT2 inhibitors appear to be a promising class of drugs for the prevention of T2DM, particularly in high-risk populations with concomitant cardiovascular or renal disease. However, dedicated randomised controlled trials in prediabetes-with adequate follow-up and washout periods-are necessary before routine use can be recommended. Current 2026 guidelines do not yet endorse SGLT2 inhibitors as a preventive therapy for prediabetes outside the indications of heart failure and CKD.

PURPOSE: To develop and validate mapping algorithms that estimate EQ-5D health state utility values (HSUVs) from two diabetes-specific patient-reported outcome measures, the Problem Areas in Diabetes (PAID) and Diabetes Distress Scale (DDS), to support economic evaluations when EQ-5D data are unavailable. METHODS: Data from 662 adults with diabetes in Germany included PAID-20, DDS-17, and EQ-5D-5L responses. Direct mapping models predicted EQ-5D utilities using Tobit and censored least absolute deviation (CLAD) regressions, while indirect mapping models used proportional and partial proportional odds regressions to predict EQ-5D dimensions. Six model specifications were tested, incorporating PAID and DDS items with covariates (age, sex, diabetes type), with selection of predictors guided by item correlations and backward stepwise procedure to retain statistically relevant variables. Model performance was assessed using a selection of performance metrics including root mean square error (RMSE) and mean absolute error (MAE). Internal validation of the models employed 10-fold cross-validation. RESULTS: The strongest-performing direct mapping models consisted of a model with a selection of PAID-20 items and covariates (Tobit regression; RMSE: 0.159; MAE: 0.117) and a model that incorporated PAID-20, DDS-17, and covariates (CLAD regression; RMSE: 0.146; MAE: 0.09), and a model based on DDS-17 items and covariates (Tobit regression; RMSE: 0.164; MAE: 0.121). Indirect mapping models demonstrated higher prediction errors overall (RMSE: 0.187-0.21; MAE: 0.124-0.141) than their counterparts. CONCLUSIONS: We present novel algorithms that enable estimation of EQ-5D utilities from PAID and DDS scores, facilitating economic evaluation in diabetes. Preferred models demonstrated predictive accuracy comparable to published mapping studies.

Diabetes mellitus is associated with a persistent prothrombotic state driven by platelet hyperreactivity, endothelial dysfunction, oxidative stress, and chronic low‑grade inflammation, all of which contribute to increased cardiovascular (CV) risk. Importantly, a substantial residual thrombotic risk persists even with optimal glycemic control, indicating that glucose lowering alone is insufficient to prevent vascular complications. In this context, antidiabetic therapies have emerged as important modulators of CV risk beyond their metabolic effects. Several drug classes-including metformin, thiazolidinediones, DPP‑4 inhibitors, SGLT‑2 inhibitors, and GLP‑1 receptor agonists-have been shown to influence platelet activity, endothelial function, and inflammatory pathways. These effects are mediated through mechanisms such as enhanced nitric oxide bioavailability, reduced oxidative stress, attenuation of platelet activation, and modulation of vascular inflammation. Among these, GLP‑1 receptor agonists exert particularly pronounced effects on endothelial function, oxidative stress, and platelet reactivity, alongside robust reductions in CV events. More broadly, accumulating experimental and clinical evidence indicates that several antidiabetic agents exert clinically meaningful antithrombotic actions, contributing to decreased rates of major CV events and heart failure. However, these benefits vary across drug classes and patient populations. This highlights the importance of an individualized therapeutic approach in type 2 diabetes, where treatment selection should account not only for glycemic targets but also for CV and thrombotic risk. Choosing agents with proven CV benefit may optimize overall risk reduction and improve long‑term outcomes. This narrative review aims to critically examine the available experimental and clinical evidence on the effects of antidiabetic drugs on platelet function, thrombosis, and thrombo-inflammatory pathways, highlighting the mechanisms that may contribute to cardiovascular protection beyond glucose lowering.

Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder that shows cerebellar glucose hypometabolism, systemic hypermetabolism and weight loss. This study aimed to explore novel molecular mechanisms of disease for SCA2, based on the assessment of blood glucose homeostasis. A case-control and correlational study was conducted in 79 normoglycemic Cuban patients with SCA2 and 83 sex- and age-matched control subjects during a fasting state. A subset of 20 patients with SCA2 and 19 control individuals underwent an oral glucose tolerance test (OGTT). Several indices for assessing blood glucose homeostasis, derived from the fasting state or the OGTT, were included in the study. Fasting glucose levels showed a small increase, whereas the QUICKI index for insulin sensitivity was slightly decreased among patients. Markers of glucose homeostasis derived from the OGTT were no different between patients and controls. Fasting insulin levels, QUICKI, McAuley´s, HOMA2-%S, HOMA2-IR, and HOMA2-%β indices showed weak to moderate correlations with markers of body composition. McAuley´s, TyG, HOMA2-IR, and HOMA2-%β indices correlated with the age at onset, progression rate, or INAS count. Patients with SCA2 with mild-to-moderate ataxia do not have any major alteration in blood glucose homeostasis. Markers of glucose homeostasis associate with body composition and have nominal modifying effects on disease severity and progression rate in patients with SCA2, with McAuley's index showing effects more consistently. Further studies are needed to describe the changes in blood glucose homeostasis in the different stages of disease, and to delve into its pathophysiological relevance.