Diabetes & metabolism最新文献

Stem cell-based therapies are a leading frontier in diabetes treatment, aiming to restore insulin-producing β-cell function beyond symptomatic management. Clinical progress has evolved from donor islet transplantation, such as the Edmonton Protocol, to pluripotent stem cell-derived β-cell replacement. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can differentiate into insulin-producing cells, while mesenchymal stem cells (MSCs) provide immunomodulatory and metabolic support. Landmark trials by ViaCyte, Vertex, and Sernova tested ESCs- and iPSCs-derived progenitors with encapsulation devices and bioengineered niches, yielding insights into safety, differentiation, and immune responses. Vertex's VX-880 program achieved insulin independence, and a 2024 Cell study reported the first functional cure of type 1 diabetes using chemical induced iPSCs (CiPSCs)-derived islets. Encapsulation technologies dominate trials, aiming to shield transplanted cells from rejection without systemic immunosuppression, though fibrosis and vascularization remain obstacles. MSCs therapies across Phase 1-3 trials improved glycemic control and β-cell preservation, underscoring their complementary role. Despite promising outcomes, no clinical stem cell-derived therapy is yet routine, with tumorigenicity, immune rejection, and scalability as key challenges. Future directions focus on gene-edited immune-evasive cells, advanced biomaterials, scalable bioreactors, and harmonized regulation to achieve durable insulin independence and global accessibility.

Aim: Monogenic diabetes is a group of disorders arising from single gene mutations with a clear pathophysiology, most of which present with impaired beta cell function rather than insulin resistance. This study aims to evaluate the ability of TyG index and polygenetic risk score (PRS) to identify multi-type beta cell monogenetic diabetes (beta-cell-MgD) in Chinese early-onset type 2 diabetes (EOD) population.

Methods: A prediction model for beta-cell-MgD was established by logistic regression analysis in Cohort 1 (92 beta-cell-MgD, 512 EOD). Model performance was evaluated by receiver operating characteristic curves (ROC) and validated in an independent case-control sample (Cohort 2, 35 beta-cell-MgD, 50 EOD) and a newly diagnosed drug-naive EOD cohort (Cohort 3, 7 beta-cell-MgD, 176 EOD). PRS was constructed based on Genome-wide genotyping data from participants in Cohort 3. The ability of PRS to identify beta-cell-MgD was tested by ROC.

Results: The TyG-MgD score based on age at diagnosis, BMI and TyG presented a good performance to distinguish beta-cell-MgD (AUC=0.769), and achieving AUCs of 0.966 and 0.754 respectively in validation cohorts. At the optimal cutoff point -16.19, the model achieved a sensitivity of 66.3% and a specificity of 75.39%, allowing one case of beta-cell-MgD identified among every three patients. -16.85 could be used as the screening threshold prioritizing 80% sensitivity (with 59% specificity). Models combining TyG-MgD with East Asian PRS and beta-cell dysfunction-high proinsulin partitioned polygenetic score showed AUCs of 0.842 and 0.834 respectively for indentifying beta-cell-MgD.

Conclusion: We developed a clinical prediction model as a simple screening tool for multi-type beta-cell-MgD, identifying who are most likely to benefit from next genetic sequencing in Chinese population. PRS might be helpful for further screening of MgD.

Aims: The association between sodium glucose cotransporter-2 (SGLT2) inhibitors and the risk of urothelial carcinoma (UC) remains controversial. This study aimed to investigate this relationship in Asian populations where upper tract urothelial carcinoma (UTUC) is prevalent.

Methods: Using Taiwan's National Health Insurance Database from 2016 to 2021, we conducted a nationwide cohort study comparing SGLT2 (n = 150,278) and dipeptidyl peptidase-4 (DPP4) inhibitor users (n = 363,178). Inverse probability of treatment weighting was applied to balance baseline characteristics, including demographics, comorbidities, and concurrent medications. Cumulative drug days were used to evaluate medication exposure. The primary outcome was the incidence of UC, including bladder cancer and UTUC. To avoid reverse causation and consider cancer latency, outcomes were assessed starting one year after treatment initiation.

Results: During a mean follow-up of 2.62 years, we found no significant association between the use of SGLT2 inhibitors as a class and the risk of UC compared to DPP4 inhibitors (adjusted hazard ratio = 0.99, 95 % confidence interval: 0.77-1.27). This null association was consistent for both bladder cancer and UTUC. Furthermore, no significant associations were observed when analyses were stratified by individual drug type or cumulative drug days. Although some trends were noted in exploratory sensitivity analyses, no findings remained robustly significant after accounting for multiple comparisons.

Conclusion: SGLT2 inhibitor use was not associated with an increased risk of UC, with potential protective associations in specific subgroups requiring further investigation.

Introduction: The main objective : To assess the efficacy of Intact fish skin graft (IFSG) for the closure of University of Texas (UT) Grade 2 and 3 Diabetic foot ulcers (DFUs) versus local standard of care (SOC).

Methods: In the French subgroup of a multinational randomized trial, 180 (179 in primary endpoint analysis) patients with UT grade 2 and 3 DFUs (8 centers) were randomized to receive IFSG or SOC, that adhered to the International Working Group on the Diabetic Foot (IWGDF) guidelines. Primary endpoint was complete epithelialization at 16 weeks. Secondary endpoints were healing curve, percentage of wounds healed to 80 % or more in an average of 16 weeks, percentage healed at 20 weeks.

Results: The primary endpoint was 41.6 % closure rate in IFSG group versus 22.2 % in SOC group (P = 0.0053). In the intent to treat analysis (ITT), there was a statistically significant difference (P < 0.05) in mean relative wound area between the IFSG and SOC arms at weeks 6.The proportion of patients with complete epithelialization at 20 weeks was 2.11 times higher in the IFSG group than in the SOC group. For those patients that healed a median of 7 graft applications was required.

Conclusions: In France, the addition of IFSG to the care plan of patients with deep diabetic foot wounds improved the closure rate by 41.6 % in IFSG group versus 22.2 % in SOC.

Autism spectrum disorders (ASD) encompass a collection of neurodevelopmental disorders that exhibit impaired social interactions and repetitive stereotypic behaviors. Although the exact cause of these disorders remains unknown, it is widely accepted that both genetic and environmental factors contribute to their onset and progression. Recent studies have highlighted the potential negative impact of maternal diabetes on embryonic neurodevelopment, suggesting that intrauterine hyperglycemia could pose an additional risk to early brain development and contribute to the development of ASD. This paper presents a comprehensive analysis of the current research on the relationship between various forms of maternal diabetes, such as type 1 diabetes mellitus, type 2 diabetes mellitus, and gestational diabetes mellitus, and the likelihood of ASD in offspring. The study elucidates the potential mechanisms through which maternal hyperglycemia affects fetal development, involving metabolic hormones, immune dysregulation, heightened oxidative stress, and epigenetic alterations. The findings of this review offer valuable insights for potential preventive measures and evidence-based interventions targeting ASD.