Previous studies identified subtypes among individuals at elevated risk of type 2 diabetes mellitus (T2DM), yet the molecular signatures distinguishing these subtypes remain poorly characterized. We aimed to identify and characterize T2DM risk subtypes using routine and non-routine clinical variable lists, and to compare their metabolomic, proteomic, and lifestyle profiles.

In the Netherlands Epidemiology of Obesity study (median age 56 years; median BMI 29 kg/m²), we applied partitioning around medoids (PAM) clustering using two variable lists (routine, N = 5235; non-routine, N = 1510), both including variables derived from a liquid mixed meal challenge. Cox proportional hazards models estimated associations between subtypes and T2DM incidence. Random forest models identified discriminative metabolites and proteins across subtypes.

Each variable list yielded four subtypes ranging from an insulin-sensitive and lean profile (subtype 1) to an obese profile with ectopic fat accumulation and insulin resistance (subtype 4), with a graded increase in T2DM risk (hazard ratios ranging from 1.9 [95% confidence interval (CI): 0.4-9.8] to 19.5 [95% CI: 9.1-41.6]). Both subtyping schemes captured metabolic heterogeneity beyond conventional weight-by-glycemia categories, e.g., redistributing overweight or obese but normoglycemic individuals across subtypes with divergent metabolic profiles and T2DM risks. While multi-omics profiling revealed shared metabolic and proteomic markers across higher-risk subtypes (e.g., glycoprotein acetyls, glucose, hepatocyte growth factor), subtype assignment was predominantly driven by fasting glucose and lipoprotein levels (e.g., very-low-density lipoprotein [VLDL]), with additional subtype-specific molecular signatures (e.g., branched-chain amino acids). Individuals in the higher-risk subtypes also exhibited less healthy lifestyle characteristics, including poorer dietary quality.

Four metabolic subtypes with graded T2DM risk were identified in a predominantly overweight or obese, middle-aged population, revealing metabolic heterogeneity among individuals who appear homogeneous under conventional weight-by-glycemia categories. Although subtype differentiation was largely driven by fasting glucose and lipoproteins, multi-omics profiling uncovered additional molecular signatures, suggesting that data-driven subtyping may complement conventional risk markers and inform targeted prevention.

Direct superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass is used for selected haemodynamic cerebrovascular disorders, but comparative data between moyamoya and non-moyamoya disease remain limited in Indonesia.

Consecutive patients undergoing direct STA-MCA bypass from 2021 to 2025 were retrospectively analysed. Clinical and operative outcomes were assessed in 68 patients; paired CT perfusion data were available in 41.

The cohort included 40 patients with moyamoya disease and 28 with non-moyamoya disease, predominantly intracranial atherosclerotic disease [27/28 (96%)]. Patients with moyamoya were younger [41 (29-49) vs 48 (38-59) years; p = 0.003] and had lower rates of diabetes mellitus [7% vs 29%; p = 0.041] and hypertension [42% vs 86%; p < 0.001]. Bypass patency was documented in 90% versus 100% (p = 0.226). Paired modified Rankin Scale scores improved in both cohorts: from 2.08 ± 1.51 to 1.38 ± 1.39 in moyamoya (mean difference 0.70; p < 0.001) and from 2.82 ± 1.19 to 1.86 ± 1.33 in non-moyamoya disease (mean difference 0.96; p < 0.001). M4 frontal clipping time was longer in moyamoya [33 (31-37) vs 26 (24-32) minutes; p = 0.002]. Postoperative seizure occurred in 15% versus 7% (p = 0.455), and ischaemic stroke in 0% versus 11% (p = 0.065). In the CT perfusion cohort, pre-bypass Tmax was higher in non-moyamoya disease [2.17 (1.25-3.34) vs 1.31 (1.10-1.92); p = 0.048], while infarct volume was higher in moyamoya [8.65 (1.41-17.23) vs 5.63 (3.35-7.32) mL; p = 0.034]. No follow-up CT perfusion parameter differed significantly.

Direct STA-MCA bypass was followed by functional improvement in both cohorts and comparable follow-up CT perfusion profiles.

Impaired skin wound healing and fibrosis are common complications in diabetic patients, closely associated with impaired health and reduced quality of life. Aloe vera is a natural plant known for promoting skin regeneration, with its primary active component being aloe polysaccharides. We modified purified aloe polysaccharide solution via membrane permeation and induced it to self-assemble to obtain Aloe barbadensis polymeric acemannan 2 (ABPA2), which was further emulsified with silicone oil to form a stable emulsion named Aloe vera barbadensis extract regenerator (AVBER). In this study, we found that compared to the control group and the basic fibroblast growth factor (bFGF) group, treating burn wounds in diabetic Bama miniature pigs with AVBER for 21 days significantly increased the wound healing rate, restored skin structure, and reduced dermal thickness and fibrosis deposition. Histological and proteomic data indicated that AVBER regulates cellular metabolism and related signaling pathways at the wound site, modulates multiple fibrosis-associated pathways such as TGF-β, Wnt, and Hippo, and improves collagen fiber ratio and deposition. This may explain the dual mechanism of AVBER in promoting wound healing and exerting anti-fibrotic effects. Our findings demonstrate that AVBER can serve as an effective aloe polysaccharide-based formulation for treating diabetes-related skin injuries and ameliorating fibrosis.

We evaluated the long-term risk of childhood autoimmune diseases following neonatal total parenteral nutrition (TPN) exposure using a massive nationwide cohort.

Using the South Korean National Health Insurance Service database (2005-2010), we analyzed 2,362,290 neonates. To neutralize "sick kid bias" and ensure temporal separation, a 1-year landmark design with entropy balancing was used to align 101 maternal and neonatal covariates (standardized mean difference <0.01). Five major autoimmune conditions-inflammatory bowel disease, juvenile arthritis, systemic lupus erythematosus, psoriasis, and type 1 diabetes mellitus-were evaluated using weighted Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Among 8601 TPN-exposed neonates, neonatal TPN exposure was not significantly associated with the long-term risk of childhood autoimmune diseases (Weighted HR 1.00; 95% CI, 0.87-1.15; P = 0.996). This lack of independent association remained consistent across all individual conditions, including inflammatory bowel disease (HR 1.17; P = 0.404) and type 1 diabetes mellitus (HR 1.01; P = 0.970). Furthermore, subgroup analyses confirmed the immunological safety of TPN across clinically vulnerable populations, such as infants requiring mechanical ventilation (HR 0.98; P = 0.917) or NICU admission (HR 0.90; P = 0.638), and across both infant sexes (male sex: HR 0.61, P = 0.085; female sex: HR 1.25, P = 0.342).

Neonatal TPN exposure was not independently associated with childhood autoimmune diseases. These findings strongly reassure clinicians that perceived long-term immunological risks reflect baseline clinical severity rather than the TPN intervention itself.

As societies age worldwide, diabetic sarcopenia has become increasingly common. The development of this disorder involves intricate pathophysiological processes, with contributions from multiple mechanisms: insulin resistance, ongoing inflammatory responses, oxidative damage, buildup of advanced glycation end products (AGEs), compromised mitochondrial function, and alterations in gut microbial composition. The present review comprehensively analyzes the epidemiological patterns and pathological processes associated with diabetic sarcopenia, with special attention to the therapeutic benefits and mechanistic insights of traditional Chinese medicine (TCM). Rooted in substantial clinical experience, TCM implements multitargeted therapeutic approaches using both classical compound formulas (e.g., Sijunzi decoction, Buzhong Yiqi decoction, Bazhen decoction, and Shenling Baizhu powder) and purified bioactive constituents from individual herbs (including astragalus polysaccharide, puerarin, Lycium barbarum extract, and magnesium tanshinate). The therapeutic effects encompass optimization of glucose metabolism, stimulation of muscle protein synthesis, inhibition of proteolysis, and reduction of inflammatory and oxidative damage-demonstrating the holistic TCM advantage of "co-treatment of glucose metabolism and muscle function." This work provides scientific rationale and clinical evidence to support TCM-based strategies for preventing and treating diabetic sarcopenia.

Hyperglycaemia and/or type 2 diabetes (T2D) can have a detrimental effect on women with breast cancer (BC) undergoing or post-cytotoxic chemotherapy. This systematic review aims to evaluate the short and long-term consequences of hyperglycaemia and/or T2D on treatment outcomes in women with breast cancer receiving cytotoxic chemotherapy.

Studies published between 2018 and 2024 across four electronic databases were identified. The JBI critical appraisal tool was adopted to select high-quality studies.

Nine papers met the criteria for review. Thematic analysis identified two themes: 1) short-term consequences of hyperglycaemia and/or T2D, specifically its impact on healthcare utilisation, treatment toxicity, and treatment modification, and 2) long-term consequences of hyperglycaemia and/or T2D, such as effects on pathological response, prognosis, and mortality.

Proactive identification and rigorous management of hyperglycaemia and/or T2D are essential to reducing complications and improving outcomes in women with BC receiving chemotherapy. Evidence demonstrates that poor glycaemic control clearly impairs treatment response. The current research gap and fragmented care pathways demand strengthened multidisciplinary collaboration and the delivery of personalised care. These measures are necessary to significantly improve the quality of living with and beyond a diagnosis of BC.

Tubulointerstitial fibrosis (TIF) plays an important role in the deterioration of diabetic kidney disease (DKD). Epithelial-to-mesenchymal transition (EMT) in tubular epithelial cells (TECs) leads to TIF in the progression of DKD. Hypoxia-inducible factor-1α (HIF-1α; HIF1A) has been elucidated to promote EMT and TIF through inducing transforming growth factor-β1 (TGF-β1) pathway. In this study, we aimed to explore the mediation effect of key genes in HIF‑1α‑induced EMT and TIF in DKD. Tubulointerstitial gene expression profiling data from DKD patients and healthy controls (HCs) were acquired from the GEO database, R packages were used for bioinformatics analysis, and the db/db mice and proximal TEC line (HK-2) were used to validate the bioinformatic findings. Consequently, we focused on cathepsin S (CTSS). Functional enrichment indicated that HIF1A and CTSS were jointly involved in inflammatory activation, extracellular matrix deposition, and cellular interaction. In vitro and in vivo experiments validated that in DKD models, HIF‑1α could upregulate Cathepsin S to promote partial EMT-associated phenotypic shift and fibrotic remodeling in TECs, thereby deteriorating diabetic kidney injury. Conclusively, CTSS may serve as a downstream effector of HIF‑1α participating in the regulation of partial EMT-associated phenotypic shift and fibrotic remodeling of TECs in diabetic kidney disease models.

Interactions between the gut microbiota and inflammatory pathways contribute to intestinal alterations associated with type 1 diabetes mellitus (T1DM). Annexin A1 (AnxA1) is a pro-resolving protein implicated in epithelial homeostasis and inflammasome regulation. This study investigated the role of AnxA1 in intestinal epithelial alterations and NLRP3 inflammasome-associated responses during T1DM. Wild-type (WT) and AnxA1-deficient mice were assigned to control or diabetic groups following streptozotocin-induced diabetes. Intestinal tissues were analyzed using histological, immunohistochemical, molecular, and multiplex cytokine/growth factor approaches. Diabetes induction reduced goblet cell density in both genotypes, whereas AnxA1 deficiency was associated with increased epithelial thickness and reduced E-cadherin expression. ZO-1 levels were decreased in both diabetic groups compared with controls. Diabetic WT mice exhibited increased inflammatory mediator production, whereas AnxA1-deficient mice displayed attenuated classical inflammatory responses but increased expression of NLRP3 inflammasome-associated proteins, including NLRP3, ASC, and cleaved caspase-1. Epidermal growth factor levels were reduced only in AnxA1-deficient diabetic mice. Collectively, these findings indicate that AnxA1 contributes to the regulation of intestinal epithelial homeostasis and inflammatory responses during diabetes. Furthermore, AnxA1 deficiency was associated with increased expression of NLRP3, inflammasome-related components, suggesting a potential role for AnxA1 in modulating inflammasome-associated pathways in the diabetic intestine. These findings highlight AnxA1 as a potential therapeutic target for intestinal complications associated with T1DM.

Whether hair repigmentation during cancer therapy is driven by immune checkpoint inhibitors (ICIs) or chemotherapy remains unclear. This study aimed to quantitatively identify the primary driver using a controlled design.

In this prospective study, 29 patients with thoracic malignancies were divided into an immunotherapy group (n = 18) and a chemotherapy group (n = 11). Standardized dermoscopic images were captured before and after treatment. Hair pigmentation was quantified via grayscale analysis.

Grayscale values decreased significantly posttreatment in the immunotherapy group (p = 0.0008) but not in the chemotherapy group (p = 0.1427). The magnitude of change (ΔGrayscale) was significantly greater with immunotherapy than with chemotherapy alone (23.5 ± 24.67 vs. 4.32 ± 9.01; p = 0.0065), representing a large effect size (Cohen's d = 0.90).

This controlled study provides quantitative evidence suggesting that immunotherapy, rather than chemotherapy, is closely associated with hair repigmentation. It establishes an objective methodological framework for future investigation of this phenomenon.

Elderly oral cavity cancer patients form a unique cohort with multiple therapeutic considerations. The Oral Cancer Survival Calculator^® has been used to estimate the risk of cancer-specific deaths in patients with oral cancer. The aim of our study was to evaluate surgical outcomes and cancer-specific survival in elderly oral cavity cancer patients using the calculator.

Retrospective outcome analysis of elderly (>/=70 years) oral cavity cancer patients undergoing surgery at a rural-based tertiary academic institution was performed. The calculator was used to decipher health adjusted age (HAA), estimated 1-, 2- and 5-year overall survival (OS) and cancer specific deaths. Chronological age and HAA-related outcomes were analysed.

Ninety-seven elderly patients (median age: 74 years) underwent surgery. Post-operative complications were noted in 18.6%, with an overall mortality of 14.4%. Presence of comorbidities (p < 0.001) and the need for tracheostomy (p < 0.001) significantly increased complication rates. Using the calculator, the estimated 1-, 2- and 5-year OS and cancer-related deaths was 84%, 71% and 37% and 14%, 26% and 37% respectively. However, the accuracy of the calculator in predicting deaths was 55.5%. HAA, obtained from the calculator, was lower than the corresponding chronological age in 57.7% of patients and was associated with lower post-operative complications (7.1%) and re-admission (1.8%) rates.

HAA was predictive of lower complication and re-admission rates after surgery in elderly oral cavity cancer patients. The Oral Cancer Survival Calculator ^® showed a moderate prediction for mortality. However, larger studies are needed to validate these findings.