Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy最新文献

Background: Lifestyle-induced weight loss improves metabolic health, but weight regain is common. Its hepatic consequences, particularly in relation to metabolic dysfunction-associated steatotic liver disease (MASLD), remain insufficiently characterized.

Methods: This retrospective observational study included 213 patients categorized as weight regain (≥5% lifestyle-induced weight loss followed by return to or exceeding baseline weight) or weight sustain (weight change within ±5% of baseline) over 3 years. Propensity score matching (PSM) balanced age, sex, weight, and body mass index. Clinical, biochemical, and noninvasive liver indices were compared. In a bariatric surgery subset, liver histology, transcriptomics, quantitative PCR, and immunohistochemistry were performed.

Results: No significant differences were found in metabolic parameters between groups. After PSM, the weight regain group showed higher alanine aminotransferase (ALT) (median 59.00 vs 41.00 IU/L, P=0.007) and aspartate aminotransferase (AST) (33.50 vs 26.00 IU/L, P=0.041). In males, ALT (88.00 vs 47.00 IU/L, P<0.001) and AST (46.00 vs 30.00 IU/L, P=0.004) remained higher. Noninvasive indices of hepatic steatosis (Dallas Steatosis Index, DSI) and fibrosis (NFS, FIB-4) did not differ. In male patients with liver biopsy samples available, liver histology showed comparable NAFLD Activity Scores (NAS) and fibrosis stages, whereas transcriptomic analysis revealed immune-related pathway enrichment. Increased hepatic CD11B and CD68 expression was confirmed by quantitative PCR and immunohistochemistry.

Conclusion: Weight regain after lifestyle-induced weight loss is associated with early liver-related biochemical abnormalities and hepatic innate immune activation in the absence of advanced fibrosis, underscoring the need for early liver risk assessment in individuals with weight cycling.

Purpose: Although eating habits of "vegetables first" have been reported to be effective in suppressing postprandial hyperglycemia, its association with complications in diabetic patients remains unknown. This study aimed to examine the relationship between the habit of eating vegetables first and complications in diabetic patients.

Patients and methods: This cross-sectional study included diabetic patients who were examined as outpatients at the Ise Red Cross Hospital from June to August 2023 and from June to August 2024. The complications were diagnosed according to the clinical guidelines of the Japan Diabetes Society. Participants completed a questionnaire about their eating order, classified into four groups: no order, vegetables first, protein first, and carbohydrates first. Logistic regression analysis was used to calculate odds ratios for complications based on eating order.

Results: The results revealed that 204 patients ate in no order, 438 patients ate vegetables first, 59 patients ate protein first, and 131 patients ate carbohydrates first. The adjusted odds ratios for diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and cardiovascular disease for vegetables first with no order of eating as the reference were 0.64 (95% confidence interval [CI], 0.41-0.98; P = 0.043), 0.80 (95% CI, 0.53-1.20; P = 0.289), 0.47 (95% CI, 0.30-0.71; P < 0.001), and 1.28 (95% CI, 0.76-2.15; P = 0.351), respectively. Neither the protein first nor carbohydrates first groups showed a significant association with complications.

Conclusion: In diabetic patients, the habit of eating vegetables first may indicate a reduced risk of diabetic retinopathy and nephropathy.

Introduction: Diabetes prevalence in Iraq is high, yet culturally adapted and psychometrically validated health literacy (HL) tools for people with diabetes remain limited. The Jordanian Diabetic Health Literacy Questionnaire (JDHLQ) assesses informational and communicative HL but omits numeracy.

Purpose: To adapt and validate the Iraqi Diabetic Health Literacy Questionnaire (IDHLQ), based on the JDHLQ, which incorporates a numeracy domain, for use among adults with type 2 diabetes in Iraq.

Patients and methods: A cross-sectional study recruited 473 adults with type 2 diabetes from endocrinology clinics across Iraq. Participants were 52.7% female with a median age of 50 years (IQR: 31-60). The 11-item IDHLQ was validated using exploratory factor analysis, Rasch modeling, and Cronbach's alpha. Linear regression examined sociodemographic predictors.

Results: A three-factor model emerged, representing informational, numeracy, and communicative health literacy, with internal consistency ranging from α = 0.70 to 0.86. Rasch analysis showed item separation reliability of 0.87-0.95 and person reliability of 0.65-0.82. The median score was 33 (IQR: 28-36) out of 44. Monthly income predicted HL (β = 0.16, p = 0.003), while age, gender, education, and marital status were nonsignificant.

Conclusion: The adapted IDHLQ is a reliable and valid instrument for assessing multidimensional diabetic health literacy among Iraqi adults. Its use in clinical and public health settings could inform patient education strategies and guide policy development to reduce disparities in diabetes outcomes.

Diabetic vascular complications are common and severe, worsening quality of life and long-term outcomes. In diabetes, chronic hyperglycemia together with dyslipidemia and hypertension reshapes endothelial metabolism and homeostasis. Endothelial cells shift the balance of glucose utilization, fatty acid oxidation, and mitochondrial function, and these metabolic changes bias endothelial behavior toward reduced nitric oxide bioavailability, oxidative stress, and a pro-inflammatory, pro-thrombotic state. Over time, maladaptive stress responses promote senescence, cell loss, and endothelial-to-mesenchymal transition, accelerating the initiation and progression of atherosclerotic plaques. This review summarizes how diabetic cues drive endothelial metabolic reprogramming and how this, in turn, links endothelial dysfunction to plaque formation, growth, and instability. We highlight key metabolic pathways and discuss how local hemodynamic forces at athero-prone regions further shape endothelial phenotypes and inflammatory signaling. Finally, we outline therapeutic opportunities that target endothelial metabolism and stress responses-including modulation of glycolytic flux, mitochondrial and redox-directed strategies, and pathway-level interventions that curb hypoxia and inflammatory programs. We emphasize translational priorities such as endothelium-selective delivery, biomarkers of endothelial metabolic state, and rigorous clinical testing to enable earlier and more effective prevention of diabetes-associated atherosclerotic disease.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of chronic liver disease globally, with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show potential for MASH due to their metabolic benefits, but evidence on histological outcomes remains inconclusive.

Methods: We conducted a PRISMA 2020-compliant systematic review and meta-analysis, including 25 randomized controlled trials (RCTs, n=2481). Primary outcomes were resolution of MASH without fibrosis worsening and fibrosis improvement without steatohepatitis worsening. Secondary outcomes included anthropometric and biochemical parameters. Risk of bias was assessed via ROB 2, and evidence certainty via GRADE. Trial sequential analysis (TSA) addressed random errors.

Results: GLP-1 RAs significantly increased MASH resolution without fibrosis worsening (OR=4.04; 95% CI [2.69-6.05]; P<0.00001; 7 RCTs, n=1456). No significant improvement in fibrosis was observed (OR=1.54; 95% CI [0.95-2.48]; P=0.08; 5 RCTs, n=1277). Secondary outcomes showed reduced BMI (MD=-0.52 kg/m²; P=0.05) but no significant changes in weight, waist circumference, liver enzymes, or lipids. TSA confirmed sufficient evidence for MASH resolution (RIS=197) but not fibrosis improvement (RIS=1693). GRADE indicated high certainty for primary outcomes.

Conclusion: GLP-1 RAs promote MASH resolution but do not significantly improve fibrosis. Their benefits appear to be driven by metabolic mechanisms rather than direct antifibrotic effects. Larger RCTs targeting fibrosis endpoints are warranted.

Trial registration: The protocol for our meta-analysis and systematic review was registered and recorded in PROSPERO (registration no. CRD420251090801).

Purpose: Using latent profile analysis (LPA) based on Self-Determination Theory (SDT), this study aimed to explore the profiles of health behavior motivation among Chinese patients with prediabetes and examine the relationship between these profiles and self-management ability.

Patients and methods: A cross-sectional study was conducted involving 335 patients with prediabetes. The questionnaires were used to assess health behavior motivation, self-management ability, satisfaction of basic psychological needs and disease knowledge level. Latent profile analysis was performed based on five subscale scores of the health behavior motivation measure.

Results: Three distinct latent profiles were identified: a "Self-Determined" profile (C1,29.55%, n=99), a "Non Self-Determined" profile (C2, 55.82%, n=187), and a "Conflicted" profile (C3, 14.63%, n=49). Patients in the C1 profile demonstrated higher levels of autonomy and competence. Patients in the C2 profile were characterized by better disease knowledge and lower relatedness. Compared to patients in the C3 profile, patients in both the C1 and C2 profiles exhibited significantly lower self-management ability.

Conclusion: The heterogeneity in health behavior motivation profiles must be considered in the design and clinical practice of personalized interventions for prediabetes. Profile-specific strategies serve as the foundation for enhancing patients' self-management ability and sustaining healthy behaviors.

Background: Diabetic nephropathy (DN), a major contributor to end-stage renal disease, remains poorly understood at the molecular level. While the roles of TRIM proteins in metabolic diseases are emerging, the specific function of Tripartite Motif Containing 14 (TRIM14) in DN and its novel interaction with Kinesin Family Member 1B (KIF1B) have not been explored. This study aims to investigate this uncharted mechanistic axis.

Methods: A rat DN model was established using a high-fat diet and streptozotocin injection. Transcriptome sequencing, functional enrichment, and protein-protein interaction (PPI) network analyses were performed to identify key regulatory genes and novel interactions. In vitro, high-glucose-exposed HK-2 cells were used for functional assays. The interaction between TRIM14 and KIF1B was validated by co-immunoprecipitation (Co-IP) and immunofluorescence. TRIM14 expression was also assessed in DN patient blood samples via qPCR.

Results: Transcriptomic profiling revealed significant enrichment of immune and metabolic pathways in DN, with TRIM14 emerging as a central regulatory gene. TRIM14 expression was markedly elevated in DN rat kidneys (approximately 2-fold increase, p < 0.001), high-glucose-stimulated HK-2 cells (2-fold increase, p < 0.01), and DN patient blood. Knockdown of TRIM14 significantly mitigated high-glucose-induced apoptosis, oxidative stress, and inflammation in HK-2 cells, partially by suppressing the TLR4/NF-κB pathway. Crucially, PPI analysis and Co-IP confirmed KIF1B as a novel and direct TRIM14 interactor, with TRIM14 positively regulating KIF1B expression and co-localizing in HK-2 cells.

Conclusion: We report for the first time that the TRIM14-KIF1B axis acts as a key driver of renal injury in DN. TRIM14 exacerbates tubular epithelial cell damage via KIF1B modulation and TLR4/NF-κB activation. TRIM14 represents a promising diagnostic biomarker and therapeutic target for DN.

Glucose-dependent insulinotropic polypeptide (GIP), once the overlooked sibling of the incretin family, is now experiencing a research renaissance. Historically, its therapeutic development was hindered by a seemingly diminished insulinotropic effect in type 2 diabetes (T2DM), its paradoxical stimulation of glucagon during hyperglycemia, and translational gaps between rodent and human physiology. This review highlights the renewed interest in GIP, driven by a deeper understanding of its pleiotropic actions. GIP stimulates glucose-dependent insulin secretion and, uniquely, also stimulates glucagon secretion during hyperglycemia. Emerging evidence suggests this glucagon release may subsequently enhance insulin secretion through intra-islet α-β cell communication, revealing a more complex role in glucose homeostasis than previously appreciated. Beyond the pancreas, GIP promotes lipid storage in adipose tissue, reduces ectopic fat deposition, modulates bone remodeling, influences cardiovascular lipid metabolism, and exhibits neuroprotective properties. Preclinical and clinical studies indicate that GIP-based therapies can improve glycemic control, alleviate obesity-related inflammation, and enhance insulin sensitivity. Notably, GIP exhibits synergistic effects with GLP-1, exemplified by the dual receptor agonist Tirzepatide, which has demonstrated superior efficacy in clinical trials. Compared to the selective GLP-1 receptor agonist semaglutide (1 mg), the highest dose (15 mg) of tirzepatide achieved a greater reduction in glycated hemoglobin (-2.30 vs -1.86 percentage points) and body weight (an additional 5.5 kg reduction) over 40 weeks. Furthermore, GIP and its analogs show promise in ameliorating pathology and cognitive deficits in neurodegenerative models like Alzheimer's disease, suggesting a potential new therapeutic avenue for central nervous system disorders. This review synthesizes the evolving narrative of GIP from a challenging target to a multifaceted therapeutic agent and identifies key research gaps, particularly in understanding its tissue-specific signaling and optimizing its synergy within multi-agonist therapies for metabolic and neurodegenerative diseases.

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus. The most common type is distal symmetric polyneuropathy, and lesions frequently lead to disabling neuropathic pain and even amputation, increasing the risk of death. At present, the pathogenesis of DPN has not been clarified, and its insidious onset and lack of obvious symptoms in most patients in the early stages often lead to delayed diagnosis, which is unfavourable for prevention and treatment. This article provides an overview of the existing research progress on early diagnostic markers of DPN, especially oxidative stress-related markers, neural tissue damage markers, inflammation-related markers, neurovascular damage markers, and gene-related markers, in the hope that it can provide a reference for early diagnosis and treatment of DPN, and slow down the occurrence and development of DPN.

Aim: This study aimed to investigate effectiveness of multi-radiomics features (RFs) extracted from super-resolution MRI for predicting minor amputation in patients with Wagner 3 diabetic foot ulcers.

Methods: 275 eligible patients with Wagner 3 ulcers were retrospectively included and randomly divided into a training set (n = 192) and a test set (n = 83). A deep-transfer learning network was utilized to process coronal proton density weighted images (PDWI) and generate super-resolution PDWI (SRPDWI). RFs were extracted separately from soft tissues and phalanges. Random forest models were then developed to predict minor amputation.

Results: The minor amputation rate was 36.4% for the left foot and 32.2% for the right foot. All random forest models demonstrated excellent performance in the training set, achieving AUC ranging from 0.91 to 0.99. In the test set, the integrated radiomics model (combining RFs extracted from both soft tissue and phalanges) exhibited superior performance, with an AUC of 0.83, sensitivity of 0.71, and specificity of 0.79. Additionally, the inclusion of clinical indicators did not enhance the predictive performance of the integrated radiomics model.

Conclusion: The multi-RFs extracted from SRPDWI demonstrated promising potential in predicting the risk of minor amputation for Wagner 3 diabetic foot ulcers.