World Journal of Diabetes最新文献

Interleukin-35 (IL-35) is a novel protein comprising IL-12α and IL-27β chains. The IL12A and EBI3 genes are responsible for its production. The study of IL-35 has experienced a substantial increase in interest in recent years, as demonstrated by many research papers. Recent clinical studies have shown that individuals who do not have a C-peptide have notably reduced amounts of IL-35 in their blood serum. This is accompanied by a drop in the percentage of IL-35⁺ Treg cells, regulatory B cells, and CD8⁺ FOXP3⁺ cells that produce IL-35. This article em-phasizes the potential significance of IL-35 expression in governing the immune response and its involvement in chronic inflammatory autoimmune diabetes in pancreatic inflammation. It demonstrates IL-35's ability to regulate cytokine proportions, modulate B cells, and protect against autoimmune diabetes. However, further investigation is necessary to ascertain the precise mechanism of IL-35, and meticulous planning is essential for clinical studies.

In this editorial, we discuss an article by Wang et al, focusing on the role of mitochondria in peripheral insulin resistance and insulin secretion. Despite numerous in vitro and pre-clinical studies supporting the involvement of mitochondrial dysfunction and oxidative stress in the pathogenesis of diabetes and its complications, efforts to target mitochondria for glycemic control in diabetes using mitochondria-targeted antioxidants have produced inconsistent results. The intricate functionality of mitochondria is summarized to underscore the challenges it poses as a therapeutic target. While mitochondria-targeted antioxidants have demonstrated improvement in mitochondrial function and oxidative stress in pre-clinical diabetes models, the results regarding glycemic control have been mixed, and no studies have evaluated their hypoglycemic effects in diabetic patients. Nonetheless, pre-clinical trials have shown promising outcomes in ameliorating diabetes-related complications. Here, we review some reasons why mitochondria-targeted antioxidants may not function effectively in the context of mitochondrial dysfunction. We also highlight several alternative approaches under development that may enhance the targeting of mitochondria for diabetes treatment.

Current treatment strategies for diabetic retinopathy (DR), an eye condition that can lead to blindness, have mainly focused on proliferative DR, including vitreous injection, retinal photocoagulation, and vitrectomy. Vitreous injections mainly depend on anti-vascular endothelial growth factor therapy. In this editorial, we comment on the article by Sun et al. We focus specifically on the mechanisms of the protective effect of genipin on the retina. Genipin is a gardenia extract used in traditional Chinese medicine (TCM). In their study, the authors suggest that controlling advanced glycosylation by the intraocular injection of genipin may be a strategy for preventing retinopathy. The innovative use of a Chinese medicine extract injected into the eye to achieve a curative effect has attracted our attention. Although TCM is effective in treating DR, the topical application of DR, especially intraocular injections, is not yet feasible. Herein, we present a brief analysis of effective Chinese medicines for the treatment of DR. The effectiveness of local injections of TCM applied directly into the eyes holds promise as an effective treatment approach for DR.

In this editorial, we comment on the article by Zhang et al. Chronic kidney disease (CKD) presents a significant challenge in managing glycemic control, especially in diabetic patients with diabetic kidney disease undergoing dialysis or kidney transplantation. Conventional markers like glycated haemoglobin (HbA1c) may not accurately reflect glycemic fluctuations in these populations due to factors such as anaemia and kidney dysfunction. This comprehensive review discusses the limitations of HbA1c and explores alternative methods, such as continuous glucose monitoring (CGM) in CKD patients. CGM emerges as a promising technology offering real-time or retrospective glucose concentration measure-ments and overcoming the limitations of HbA1c. Key studies demonstrate the utility of CGM in different CKD settings, including hemodialysis and peritoneal dialysis patients, as well as kidney transplant recipients. Despite challenges like sensor accuracy fluctuation, CGM proves valuable in monitoring glycemic trends and mitigating the risk of hypo- and hyperglycemia, to which CKD patients are prone. The review also addresses the limitations of CGM in CKD patients, emphasizing the need for further research to optimize its utilization in clinical practice. Altogether, this review advocates for integrating CGM into managing glycemia in CKD patients, highlighting its superiority over traditional markers and urging clinicians to consider CGM a valuable tool in their armamentarium.

Background: Diabetic nephropathy (DN) is a severe microvascular complication of diabetes characterized by inflammation, oxidative stress, and renal fibrosis. Asiaticoside (AC) exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties, suggesting potential therapeutic benefits for DN. This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) antioxidant pathway.

Aim: To investigate the renoprotective effects of AC against DN and elucidate the role of the NRF2/HO-1 pathway.

Methods: The effects of AC on high glucose (HG)-induced proliferation, inflammation, oxidative stress, and fibrosis were evaluated in rat glomerular mesangial cells (HBZY-1) in vitro. A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury, inflammation, oxidative stress, and fibrosis. The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model.

Results: AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats, including reduced body weight, and elevated blood glucose, serum creatinine, blood urea nitrogen, and 24-h urine protein. Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, reactive oxygen species, and malondialdehyde levels while increasing superoxide dismutase activity. Additionally, AC suppressed the expression of fibrogenic markers such as collagen I, collagen IV, and fibronectin. AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase (Quinone) 1 protein expression in renal tissues and HG-induced HBZY-1 cells.

Conclusion: AC improves DN by reducing inflammation, oxidative stress, and fibrosis through the activation of the NRF2/HO-1 signaling pathway. These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation.

Background: Dyslipidemia and type 2 diabetes mellitus (T2DM) are chronic conditions with substantial public health implications. Effective management of lipid metabolism in patients with T2DM is critical. However, there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population, particularly concerning non-high-density lipoprotein cholesterol (non-HDL-C).

Aim: To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.

Methods: In this cross-sectional study, thyroid hormone sensitivity indices, the thyroid feedback quantile-based index (TFQI), the thyroid-stimulating hormone index (TSHI), the thyrotrophic T4 resistance index (TT4RI), and the free triiodothyronine (FT3)/free thyroxine (FT4) ratio were calculated. Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels. Random forest variable importance and Shapley Additive Explanations (SHAP) summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.

Results: Among the 994 participants, 389 (39.13%) had high non-HDL-C levels. Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI (OR: 1.584; 95%CI: 1.088-2.304; P = 0.016), TSHI (OR: 1.238; 95%CI: 1.034-1.482; P = 0.02), and TT4RI (OR: 1.075; 95%CI: 1.006-1.149; P = 0.032) but was not significantly correlated with the FT3/FT4 ratio. The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex. An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men (OR: 1.331; 95%CI: 1.003-1.766; P = 0.048) but elevated TFQI levels in women (OR: 2.337; 95%CI: 1.4-3.901; P = 0.001). Among the analyzed variables, the average SHAP values were highest for TSHI, followed by TT4RI.

Conclusion: Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.

Background: Diabetic cardiomyopathy (DCM) is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role. The immunological molecular mechanisms underlying DCM are poorly understood.

Aim: To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes (IFGs).

Methods: Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing (RNA-seq) datasets. Single-sample gene set enrichment analysis (ssGSEA) facilitated the analysis of immune cell infiltration. Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort. Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques. Additionally, single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.

Results: The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes. Four IFGs showed good diagnostic and prognostic values in the validation cohort: Proenkephalin (Penk) and retinol binding protein 7 (Rbp7), which were highly expressed, and glucagon receptor and inhibin subunit alpha, which were expressed at low levels in DCM patients (all area under the curves > 0.9). SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells. High expression of Penk (P < 0.0001) and Rbp7 (P = 0.001) was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro. Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM, especially between mesenchymal cells and macrophages.

Conclusion: The present study identified Penk and Rbp7 as potential DCM biomarkers, and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.

Background: Diabetic foot (DF) is a serious complication of type 2 diabetes. This study aimed to investigate the factors associated with DF occurrence and the role of delayed medical care in a cohort of patients with type 2 diabetes.

Aim: To reveal the impact of delayed medical treatment on the development of DF in patients with type 2 diabetes and to establish a predictive model for DF.

Methods: In this retrospective cohort study, 292 patients with type 2 diabetes who underwent examination at our hospital from January 2023 to December 2023 were selected and divided into the DF group (n = 82, DF) and nondiabetic foot group (n = 210, NDF). Differential and correlation analyses of demographic indicators, laboratory parameters, and delayed medical treatment were conducted for the two groups. Logistic regression was applied to determine influencing factors. Receiver operating characteristic (ROC) analysis was performed, and indicators with good predictive value were selected to establish a combined predictive model.

Results: The DF group had significantly higher body mass index (BMI) (P < 0.001), disease duration (P = 0.012), plasma glucose levels (P < 0.001), and HbA1c (P < 0.001) than the NDF group. The NDF group had significantly higher Acute Thrombosis and Myocardial Infarction Health Service System (ATMHSS) scores (P < 0.001) and a significantly lower delayed medical treatment rate (72.38% vs 13.41%, P < 0.001). BMI, duration of diabetes, plasma glucose levels, HbA1c, diabetic peripheral neuropathy, and nephropathy were all positively correlated with DF occurrence. ATMHSS scores were negatively correlated with delayed time to seek medical treatment. The logistic regression model revealed that BMI, duration of diabetes, plasma glucose levels, HbA1c, presence of diabetic peripheral neuropathy and nephropathy, ATMHSS scores, and delayed time to seek medical treatment were influencing factors for DF. ROC analysis indicated that plasma glucose levels, HbA1c, and delayed medical treatment had good predictive value with an area under the curve of 0.933 for the combined predictive model.

Conclusion: Delayed medical treatment significantly affects the probability of DF occurrence in patients with diabetes. Plasma glucose levels, HbA1c levels, and the combined predictive model of delayed medical treatment demonstrate good predictive value.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are associated with significant cardiovascular benefit in type 2 diabetes (T2D). However, GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities.

Aim: To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D.

Methods: The systematic review was conducted according to PRISMA recommendations. The protocol was registered on PROSPERO (ID: 42022385007). A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment. Effect modification of prior myocardial infarction (MI) and heart failure (HF) was also explored to provide clinical insight as to when the combination treatment should be considered.

Results: The estimated hazard ratios (HR)_{GLP-1RA/SGLT-2I vs Placebo} (0.75-0.98) and HR_{Combination vs GLP-1RA/SGLT-2I} (0.26-0.86) for primary and secondary cardiovascular outcomes suggested that the combination treatment may achieve additional cardiovascular benefit compared with GLP-1RA or SGLT-2I alone. In patients with prior MI or HF, the mono-therapies may not improve the overall cardiovascular outcomes, as the estimated HR_MI+/HF+ (0.57-1.52) suggested that GLP-1RA or SGLT-2I alone may be associated with lower risks of hospitalization for HF but not cardiovascular death.

Conclusion: Considering its greater cardiovascular benefit in T2D, the combination treatment of GLP-1RA and SGLT-2I might be prioritized in patients with prior MI or HF, where the monotherapies may not provide sufficient cardiovascular protection.

Diabetic cardiomyopathy (DCM), a complication of diabetes, poses a significant threat to public health, both its diagnosis and treatment presents challenges. Teneligliptin has promising applications and research implications in the treatment of diabetes mellitus. Zhang et al observed the therapeutic effect of teneligliptin on cardiac function in mice with DCM. They validated that teneligliptin's mechanism of action in treating DCM involves cardiomyocyte protection and inhibition of NLRP3 inflammasome activity. Given that the NLRP3 inflammasome plays a crucial role in the onset and progression of DCM, it presents a promising therapeutic target. Nevertheless, further clinical validation is required to ascertain the preventive and therapeutic efficacy of teneligliptin in DCM.