Light exposure at night is linked to increased risk for obesity and insulin resistance in the general population. While sleep health is recognized as a key component of diabetes management, there has been less emphasis on nighttime light exposure. This study aimed to investigate the effects of blue and white light exposure immediately prior to (1 h) and during sleep (LEDS) on glycemic control and psychosocial wellbeing in adults with type 1 diabetes (T1D). Using baseline data from a randomized controlled trial testing a sleep intervention (NCT04506151), we analysed the following data from 170 adults with T1D: light exposure pattern and sleep from one week of wrist-worn actigraphy, glucose levels from one week of continuous glucose monitoring (CGM), and A1C and self-reported psychosocial measures. Generalized linear models, adjusting for covariates, were employed to examine the relationship between log-transformed light variables and glycemic/psychosocial outcomes. The results revealed that greater blue LEDS was significantly associated with higher glucose levels from CGM including less % time spent in glucose range 70-180 mg/dL (B = -7.30; p = 0.022) and greater % time spent above glucose range 180 mg/dL (B = 6.95; p = 0.041), along with greater depressive (B = 4.41; p = 0.016) and anxiety symptoms (B = 2.25; p = 0.008), and worse diabetes quality of life (B = -5.81; p = 0.031). Light exposure one hour prior to sleep was related to increased fatigue. In conclusion, increased blue LEDS is linked to hyperglycemia and worse psychosocial outcomes in T1D. Thus, blue LEDS warrants further investigation as a modifiable risk factor. Trial Registration: NCT04506151, www.clinicaltrial.gov.

Diabetes mellitus (DM) is a multifaceted disease etiologically characterised by dysregulation in glucose homeostasis. The World Health Organization (WHO) global report indicates that over 90% of DM cases are classified as Type 2 DM (T2DM), which is clinically characterized by chronic hyperglycemia. This systemic condition arises predominantly due to the interplay of two key components: (a) compromised insulin production by the pancreatic β-cells, and (b) the failure of insulin-sensitive tissues to react to insulin. Notably, it is well established that glucagon-like peptide-1 (GLP-1), an incretin hormone of the glucagon superfamily, contributes to glucose-dependent pancreatic β-cell insulin secretion. The insulinotropic impacts of secreted GLP-1 are facilitated by its interaction with GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR). However, GLP-1 is proteolytically cleaved by dipeptidyl peptidase 4 (DPP-4), resulting in a plasma half-life of ∼2 minutes, which limits its therapeutic efficacy in patients with T2DM. Therefore, the exogenous administration of DPP-4-resistant GLP-1R agonists (GLP-1RAs) has proven to be a successful therapeutic strategy for managing T2DM. Notably, the currently marketed GLP-1RAs, such as Semaglutide, Liraglutide, and Lixisenatide, are long-chain GLP-1 mimetic peptides, ranging in length from 33 to 39 amino acids.

Skeletal muscle orchestrates systemic metabolism, dynamically coordinating glucose uptake and fuel use to match energy demand. In Duchenne muscular dystrophy, loss of dystrophin is associated with altered metabolic regulation. In the mdx mouse, we show that physiological stress reveals impaired coordination between insulin and stress responses: glucocorticoid signalling increases without a proportional rise in insulin secretion, resulting in systemic hyperglycaemia despite preserved capacity for muscle glucose uptake. These data support a multi-tissue dystrophinopathy associated with altered endocrine-metabolic coordination. Skeletal muscle glycogen is elevated and incompletely mobilised under stress. The heart maintains high glucose uptake, whereas the brain exhibits reduced uptake, highlighting tissue specific differences in metabolic response. Acute insulin supplementation improves systemic glucose control and restores stress-induced behavioural deficits. Likewise, empagliflozin-mediated glucose offloading reduces stress-associated blood glucose spikes and is associated with improved muscle function to levels comparable with standard care prednisolone. These findings identify impaired coordination of endocrine and metabolic responses during stress as a contributor to metabolic vulnerability in DMD and suggest that modulating insulin availability or glucose flux can improve systemic metabolic control.

The genetic architecture of glycemic dynamic metrics derived from continuous-glucose monitoring (CGM) across different populations remains poorly understood. Here, we conducted a trans-ethnic genome-wide association study (GWAS) meta-analysis of 20 CGM-derived glycemic traits, building upon a previously established European-ancestry CGM dataset and extending it through the inclusion of additional cohorts, in up to 9677 individuals originating from 2051 Chinese, 901 Dutch, and 6725 Israelis. Across 20 glycemic traits, we identified 18 genome-wide significant associations, of which 9 met study-wide significance, and three variants were novel. These variants indicated a shared genetic basis for continuous glycemic regulation and exhibited consistent patterns with those of sequential fingerstick glucose tests. Our findings further demonstrated that the identified genetic variants were enriched in pathways related to the nervous system. These findings were further supported by observed associations with brain magnetic resonance imaging (MRI) metrics, high CGM-related gene expression and co-regulation of quantitative trait loci in brain tissues. Additionally, we observed a positive relationship between genetic liability for the coefficient of variation (CV) and total cholesterol and a bi-directional putative causal relationship between hyperglycemia and type 1 diabetes across trans-ethnic populations. Moreover, we established a polygenic risk score (PRS) for additional participants and reported that certain glycemic traits were significantly associated with the risk of diabetes or pre-diabetes. These variants constituting the PRS demonstrated high transferability across general populations and pregnant women. Overall, our study yields unique insights into the high trans-ethnic and generalizable genetic architecture of CGM-derived glycemic profiles, supporting improved characterization of interindividual differences in glycemic dynamics and underscoring the potential for more personalized glucose management.

The intersection of Type 2 Diabetes Mellitus (T2DM) and breast cancer defines a complex onco-metabolic axis where chronic hyperglycaemia, hyperinsulinemia, and oxidative stress synergistically drive malignant transformation, metabolic reprogramming, and chemoresistance. Despite epidemiological evidence linking these conditions, clinical management typically addresses each disease individually according to established protocols; however, the presence of T2DM significantly alters tumour biology, therapeutic response, and outcomes, necessitating greater consideration of metabolic context in breast cancer treatment. This review delineates the molecular underpinnings of the T2DM-breast cancer comorbidity and critically evaluates current metabolism-targeted therapies within this context. We examine the limitations of current therapeutic strategies in addressing the bidirectional metabolic signalling sustaining both pathologies, thereby motivating the exploration of nanoparticle (NP)-mediated therapeutic approaches. NP strategies enable tumour-selective release, dual-action antidiabetic and anticancer payload delivery, and targeted modulation of shared metabolic pathways are surveyed. Additionally, we highlight how NP platforms can be engineered as intrinsically bioactive scaffolds that synergise with multitarget natural compounds, with potentially lower-toxicity, multi-functional therapeutic strategies suited to this complex comorbid condition. We advocate for systematic investigation of dual-action nanotherapeutics in models of breast cancer in patients with T2DM as a necessary step toward a unified approach for this underserved comorbid population.

This study investigated the impact of a high-carbohydrate diet (HC: 25% carbohydrate) on skin wound healing in turbot versus a control diet (CC: 16% carbohydrate). Following 10 weeks of triple replicates of fish (n = 40), standardized 8 mm skin wounds were created and healing assessed macroscopically and molecularly at baseline, 1, 3, and 7 days post-wounding (dpw). While growth performance remained unaffected, HC-fed fish exhibited persistent hyperglycemia and hyperinsulinemia, indicative of systemic insulin resistance. Macroscopic analysis showed significantly impaired wound contraction in the HC group at 3 and 7 dpw compared to CC controls. Histological assessment revealed defective re-epithelialization characterized by aberrant keratinocyte migration, suppressed provisional matrix formation, ill-defined epidermal stratification, and persistent goblet cell aggregation in HC fish. Molecular analyses demonstrated HC-mediated suppression of re-epithelialization markers (suppressed MMP9, EGF, FGF2, and KRT2 gene expression; reduced MMP9 protein distribution), dysregulated inflammation (reduced MPO and NAG activity; lower IL1B, IL6, IL8, TGFB1, and TNF expression; elevated IL10 expression), and impaired tissue form ation and remodelling (downregulated FN1, VEGF, CCN1, LAMB2, and COL1A mRNA; reduced collagen deposition; attenuated CD31-based angiogenesis). Importantly, HC feeding promoted skin AGEs accumulation, which was accompanied by reduced MTOR phosphorylation, decreased HIF1A protein levels, and blunted post-wounding induction of glycolytic genes, including PFK, HK2, and PK. Collectively, these findings indicate that HC feeding compromises multiple phases of skin wound healing in turbot and suggest that AGE-associated suppression of MTOR-HIF1A-mediated glycolytic adaptation is an important metabolic mechanism associated with delayed healing.

Mitochondrial dysfunction and redox imbalance are increasingly recognised as essential factors in the pathophysiology of gestational diabetes mellitus (GDM). Impaired oxidative phosphorylation in the placenta, increased production of reactive oxygen species (ROS), and insufficient antioxidant protection impair bioenergetics and affect maternal-foetal nutrient exchange. Such changes promote excessive foetal growth and metabolic programming while predisposing mothers to future type 2 diabetes. Current research indicates alterations in mitochondrial dynamics and mitophagy as additional risk factors for placental disease. The placenta is not only a passive recipient of maternal hyperglycaemia; it actively participates in metabolic signalling at the maternal-foetal interface. This structure identifies placental mitochondria as potential therapeutic targets. Preclinical studies on mitochondrial antioxidants (SS-31, MitoQ), uncoupling factors, and biogenesis-supporting substances have shown great potential in restoring mitochondrial integrity and reducing oxidative stress. However, there is still no clinical confirmation of their effectiveness during pregnancy. A comprehensive understanding of mitochondrial redox processes during gestational diabetes offers unique potential for improving pregnancy outcomes and may contribute to reducing the intergenerational inheritance of metabolic diseases.

Chronic diabetic wounds remain a major clinical challenge due to persistent hyperglycemia and prolonged inflammation, which severely impairs tissue regeneration. Therefore, wound dressings capable of dynamically interacting with the local microenvironment and adapting their structure and function to pathological cues are urgently needed. Inspired by a Jenga-style hierarchical assembly concept, we developed a biomass-based multifunctional hydrogel network constructed through Schiff base bonding, metal-polyphenol complexation, and hydrogen bonding, forming a multilevel dynamic cross-linking architecture with dual pH/glucose responsiveness. This structure enabled self-adaptive reconstruction and controlled release of nitric oxide (NO), thereby exerting synergistic antibacterial, anti-inflammatory, antioxidative, and proangiogenic effects. In a full-thickness diabetic rat wound model, it accelerated wound closure by promoting epithelial regeneration, collagen deposition, and neovascularization. Overall, this work established a regulatory mechanism based on microenvironment recognition, structural response, and therapeutic release and provided a novel bioinspired strategy for the design of precision hydrogels for chronic wound repair.

Molecular and structural abnormalities triggered by oxidative stress are key determinants of diabetes pathophysiology, and research into natural therapeutic agents targeting these mechanisms is gaining speed. This study aimed to evaluate the effects of Artemisia haussknechtii leaves ethanolic lyophilized and nanoparticle extract forms on glycemic regulation, oxidative stress markers, and tissue integrity in an experimental diabetes model. A total of 48 female rats were divided into six groups; diabetes was induced with 45 mg/kg STZ (i.p.). DYEE and DYNE were administered orally at doses of 50 and 100 mg/kg for 21 days. Weekly fasting glucose and body weight were monitored. At the end of the study, serum biochemistry, erythrocyte and tissue oxidative stress markers (MDA, GSH, CAT, GPx, SOD, GR, TAS, TOS) were analyzed; liver, kidney, and pancreas tissues were evaluated histopathologically. Diabetic rats exhibited persistent hyperglycemia, body weight loss, dyslipidemia, elevated liver and kidney injury biomarkers, increased lipid peroxidation (MDA), and total oxidant status (TOS), accompanied by marked suppression of antioxidant defense systems. Treatment with Artemisia haussknechtii extracts significantly ameliorated these alterations in a dose-dependent manner. Notably, the high-dose nanoparticle formulation (DYNE2) produced the most pronounced improvements, reflected by reduced blood glucose levels, improved lipid profile, normalization of insulin, HbA1c and c-peptide levels, decreased MDA and TOS, and restoration of antioxidant parameters toward control values. Histopathological findings corroborated the biochemical data, demonstrating substantial attenuation of diabetes-induced tissue damage, particularly in the DYNE2 group. Artemisia haussknechtii extract, particularly in its nanoparticle form, has demonstrated antihyperglycemic, antioxidant, and tissue-protective effects in experimental diabetes. The findings suggest that the plant is a promising candidate for complementary treatment against diabetes-related oxidative stress and organ damage.

Diabetic wound healing is critically impaired by multifaceted pathological disturbances, notably persistent hyperglycemia, recurrent infection, and local ischemia-a process distinct from the reparative process in normal wounds. The wound microenvironment undergoes dynamic and phase-dependent fluctuations in key biochemical markers such as pH, glucose, and reactive oxygen species (ROS). These variations render conventional dressings inadequate, often necessitating frequent changes that exacerbate patient discomfort and impose a substantial economic burden. Hydrogels, characterized by high hydration, biocompatibility, and intrinsic extracellular matrix-mimetic properties, have emerged as a highly promising platform for diabetic wound management. Recent research has advanced toward "smart" stimuli-responsive hydrogels capable of sensing subtle pathological cues and responding through physicochemical transformations-including swelling/deswelling, degradation, or morphological remodeling-thereby enabling spatiotemporal control over on-demand therapeutic release for precise, personalized treatment. This review systematically categorizes and evaluates intelligent hydrogel systems according to four stimuli-responsive modalities-chemical, physical, biological, and multi-stimuli. We critically discuss their design rationales, underlying mechanisms, and functional performance, while also addressing persistent translational challenges and future directions, ultimately providing a forward-looking perspective to guide clinical adoption.