Journal of Diabetes Research最新文献

[This corrects the article DOI: 10.1155/2013/429154.].

Type 1 diabetes mellitus (T1D) is a disease of complex inheritance where genetic, immunological, and environmental factors interact in rendering the ultimate phenotype. To gain insights into the molecular etiology of the disease in a subset of a population that is sparsely investigated in genetic terms, like in Africa, exome sequence data from a T1D multicase family and a T1D cohort were investigated. The exome analysis identified several candidate genes related to T1D, like human leukocyte antigen (HLA), insulin (INS) gene, Cytotoxic T-lymphocyte-Associated Protein 4 (CTLA4), Protein Tyrosine Phosphatase Nonreceptor Type 22 (PTPN22), and Interferon-Induced Helicase C Domain 1 (IFIH1). A total of eight pathways were significantly overrepresented (p value ≤ 0.05) in target lists analyzed, including WNT, MARS2, TARS, STK36, TYR, TP73, ATIC, and HNF4. Based on Condel functionality scores and centrality positions in genetic interaction networks, two prominent candidates in diabetes mellitus and maturity-onset diabetes of the young (MODY)-HNF1A rs2464195 and HNF4A rs147638455-were identified. The two candidate variants were subsequently genotyped for further replication in a total of 47 T1D cases and 20 unrelated controls. No significant differences were observed (p = 0.73 and p = 1), as the variants turned out to be relatively common among Sudanese and absent or rare in a global sample. Expression analysis of these loci was carried out alongside two miRNAs, miR-105 and miR-518, which were selected based on in silico prediction (p = 0.057 and 0.038, respectively). The results revealed profound miRNA differential expression between T1D cases and controls, suggesting a role for miRNA in the regulation of susceptibility networks, but also the existence of within-family differences in the fold change. Such differences, especially if taken in connection with the clinical differences encountered in this family and the population variation, highlight the potential of both population-based and individualized approaches in fathoming underlying causes of pathogenesis leading to a T1D phenotype.

Cardiovascular disease (CVD) and diabetes mellitus represent major global health challenges, frequently co-occurring and mutually exacerbating. Telehealth interventions offer a promising approach for their management, with potential to improve patient outcomes, enhance access to care, and increase cost-effectiveness. This review synthesized existing evidence from randomized controlled trials (RCTs) and observational studies to evaluate the effectiveness of telehealth interventions for the management of diabetes, focusing on CVD risk, and to identify critical research gaps. A systematic literature search was conducted across major databases (PubMed, Web of Science, and Scopus) to identify studies meeting predefined eligibility criteria, considering digital tools for remote monitoring, consultation, education, and medication management. After the screening of 3041 articles, six studies met the inclusion criteria. Telehealth interventions utilized a range of digital health tools, including mobile applications, artificial intelligence-powered clinical decision aids, electronic consultations, and integrated remote monitoring platforms. Although direct assessment of composite cardiovascular risk was largely absent, the included studies reported several clinical parameters associated with cardiovascular health, namely, blood pressure, lipid profile, and glycated hemoglobin. Telehealth interventions implemented for individuals with Type 2 diabetes mellitus demonstrated promising potential in improving glycemic control and supporting self-management. However, their effectiveness in managing broader cardiovascular risk factors remains less clear due to inconsistent reporting and heterogeneous intervention designs.

Introduction: There is a notable link between diabetes mellitus (DM) and cardiovascular diseases (CVDs), particularly abnormal ventricular repolarization marked by a prolonged QT interval, which significantly contributes to morbidity and mortality in diabetic patients. However, no studies have been conducted in Ethiopia regarding prolonged QT intervals in Type 2 diabetic patients. Therefore, this study is aimed at examining the prevalence of prolonged QT intervals and the associated factors among Type 2 diabetic patients in selected referral hospitals in the Amhara Region, Ethiopia.

Methods: A cross-sectional study was conducted from May 30, 2024, to September 30, 2024, involving 300 participants. Participants were selected using systematic sampling. Data were collected through questionnaires, anthropometric measurements, blood pressure readings, and lipid profile analyses. QTc interval was determined by using digital electrocardiographic machine. The study utilized bivariable and multivariable logistic regression models to identify factors associated with prolonged QT intervals.

Results: The average QT interval was 420 ± 4.8 ms, with 45.6% of patients exhibiting prolonged QT intervals. Multivariable logistic regression analysis identified significant associations between prolonged QT intervals and factors such as age (AOR 1.11, 95% CI: 1.01-2.42), duration of diabetes (AOR 2.52, 95% CI: 1.12-5.31), body mass index (AOR 1.65, 95% CI: 1.21-3.44), fasting blood sugar (AOR 2.21, 95% CI: 1.12-6.21), sulfonylureas drug treatment (AOR 2.42, 95% CI: 1.21-5.94), HbA1c (AOR 2.78, 95% CI: 1.07-6.48), and total cholesterol (AOR 6.21, 95% CI: 4.25-11.25).

Conclusion: This study highlights the significant prevalence of prolonged QT intervals among Type 2 diabetic patients. Several factors significantly contribute to the likelihood of prolonged QT intervals in Type 2 diabetic patients. These include older age, longer duration of diabetes, higher BMI, elevated fasting blood sugar levels, use of sulfonylureas, higher HbA1c levels, and elevated total cholesterol. This significant finding underscores the importance of regular cardiovascular monitoring and effective management strategies to mitigate the risks associated with prolonged QT intervals in this population.

[This retracts the article DOI: 10.1155/2012/851717.].

Diabetic kidney disease (DKD) is a chronic complication that seriously affects the prognosis of diabetic patients and is a primary reason for end-stage renal disease worldwide. The existing treatment strategies have shown unsatisfactory results in the clinical practice of DKD, and there is an immediate need to discover novel and efficacious medicines. Natural products are considered to have the potential for drug design and development due to their diverse pharmacological effects. Astragaloside IV (AS-IV) has a variety of biological activities as a natural product, and existing studies have demonstrated that it can effectively delay the progression of DKD through multiple pathways. Aseptic inflammation is a key characteristic of DKD and is crucial in its pathogenesis. Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an essential regulator of inflammatory amplification. In this review, we focus on the mechanisms by which AS-IV improves DKD by regulating NLRP3 inflammasome activation, including anti-inflammatory, antioxidative stress, reducing endoplasmic reticulum stress (ERS), regulating lipid metabolism disorders, and reducing pyroptosis. These discoveries have provided new ideas for the treatment of DKD.

Artemether (Art) is a derivative of artemisinin, originally sourced from traditional Chinese herbal medicine, with improved bioavailability, and is widely used for malaria treatment. Recently, its potential effects on diabetic complications, particularly diabetic kidney disease (DKD), have attracted increasing attention. This study aimed to evaluate the therapeutic effects of Art on DKD and to explore the underlying mechanisms. Specifically, we investigated the protective role of Art against high glucose (HG)-induced inflammatory biomarkers (transforming growth factor-β1 [TGF-β1], tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], and interleukin-6 [IL-6]) and fibrosis in human renal proximal tubular epithelial (HK-2) cells, focusing on the involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in DKD. To mimic diabetic conditions, HK-2 cells were exposed to HG (30 mM) to induce inflammation and fibrosis. The therapeutic effects of Art (100 and 200 μm) were assessed by immunofluorescence, real-time RT-PCR, and Western blot analyses. Our results demonstrated that Art effectively reversed the HG-induced upregulation of inflammatory and fibrogenic markers in HK-2 cells (∗p < 0.05, ∗∗p < 0.001, and ⁣^## p < 0.001). Additionally, Art pretreatment restored the HG-suppressed expression of PPARγ (∗p < 0.05 and ⁣^## p < 0.001), suggesting that Art exerts its antifibrotic effects by modulating PPARγ and inhibiting the TGF-β/Smad pathway. This hypothesis was further supported by siRNA-mediated knockdown of PPARγ, which significantly diminished Art's antifibrotic effects (∗p < 0.05, ∗∗p < 0.001, and ⁣^## p < 0.001). In conclusion, our study indicates that Art protects renal tubular epithelial cells by partially modulating PPARγ-dependent inhibition of the TGF-β/Smad pathway, thereby mitigating HG-induced inflammation and fibrosis. These findings suggest that Art holds promising therapeutic potential for DKD treatment.

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). The dysregulation of lipoic acid synthase (LIAS) gene, which plays an essential role in the maintenance of mitochondrial function, was reported to participate in DKD pathogenesis. Therefore, the present study aimed to explore the association of LIAS gene methylation with the risk for DKD. DNA methylation has emerged as a potential biomarker for DKD.

Methods: A cohort of 308 patients, comprising 156 patients with Type 2 diabetes mellitus (T2DM) with DKD (DKD group) and 152 with T2DM alone (T2DM group), were involved in the present study. A methylation-sensitive restriction endonuclease (MSRE)-qPCR approach combined with three enzymes (HpaII, AciI, and Hin6I) was developed to examine methylation patterns of the promoter region and exon 1 of LIAS gene. Logistic regression analysis was performed to evaluate the associations between methylation levels and DKD risk, and then the clinical conventional confounders, including age, sex, BMI, hypertension, and lipid profiles, were adjusted.

Results: We successfully identified the methylation sites that can be recognized and digested by HpaII, AciI, and Hin6I, in the CpG islands of LIAS promoter region and exon 1. Applying the MSRE-qPCR approach, significant differences in methylation levels were observed at two CpG sites. Compared with T2DM group, the P3 site in the promoter region exhibited increased methylation level in the DKD group (5.886% vs. 10.229%, p = 0.043), whereas E1 site in exon 1 showed reduced methylation level in the DKD group (11.785% vs. 6.250%, p = 0.023). Furthermore, logistic regression revealed that increased methylation at P3 was associated with increased DKD risk [OR (95% CI) 1.029 (1.011, 1.047), p = 0.002], whereas increased methylation at E1 demonstrated a protective effect [OR (95% CI) 0.940 (0.896, 0.987), p = 0.013]. Then, via including P3 and E1 sites in the same model, we found both sites independently influenced the risk for DKD. In addition, these associations were not significantly altered after adjusted for the confounders.

Conclusion: The findings indicate that LIAS gene methylation participate in DKD pathogenesis, providing novel insights into its pathophysiological mechanisms. It highlighted that LIAS methylation could serve as a promising biomarker for DKD. Also, it supported the utility of MSRE-qPCR in clinical applications.

Aim: The aim of this study was to investigate the relationship between remnant cholesterol inflammatory index (RCII) and new-onset diabetes mellitus in middle-aged and elderly populations in China and United Kingdom.

Methods: The total number of participants included in this study was 9946, comprising members of the Chinese Health and Retirement Longitudinal Study (CHARLS) cohort and the English Longitudinal Study of Ageing (ELSA) cohort. A comparison was made of the baseline characteristics of the two cohorts. Subsequently, a cox regression analysis was performed on the risk factors for diabetes. Subgroup analyses were conducted to explore the potential for effect modification across diverse subgroups.

Results: The application of RCII quartile analyses revealed that the risk observed in the highest quartile (Q4) within the ELSA cohort was 8.49 times higher than that recorded in the lowest quartile (Q1). This finding was particularly significant for males. Similarly, the risk in the CHARLS cohort was 3.1 times higher than that in Q1. Following multi-model adjustment, the risk of diabetes exhibited a progressive increase from the second to the fourth quartile of RCII levels in both cohorts, with all associations demonstrating statistical significance. For each 1 kg/m² increase in body mass index (BMI), the risk of diabetes increased by 13% in the ELSA cohort and by 15% in the CHARLS cohort. Subgroup analyses revealed that within the CHARLS cohort, the association between RCII and diabetes was more pronounced among non-obese individuals, whereas in the ELSA cohort, this link was more evident among middle-aged adults.

Conclusions: Elevated RCII levels have been demonstrated to be significantly associated with an increased risk of future diabetes in middle-aged and older adults.

Background: Diabetic kidney disease (DKD) is a major global cause of end-stage renal disease. Emerging evidence suggests that hypoxia is a critical factor in the advancement of DKD. Traditional Chinese medicine (TCM) is an effective alternative therapy for DKD. The Qi-Gui-Sheng-Jiang-San (QGSJS) decoction is an effective formula for treating DKD clinically, and its mechanism may be related to regulating hypoxia response, necessitating further investigation and a thorough analysis of the underlying biological mechanisms.

Methods: Initially, we employed network pharmacology methods to collect and screen the active constituents of the QGSJS decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and relevant chemical databases. Subsequently, the targets of these active components were predicted via the PubChem and TCMSP databases, while relevant targets associated with DKD were sourced from GeneCards, OMIM, and DrugBank. In the second phase, we built a protein-protein interaction (PPI) network via the STRING database to identify core targets. This was followed by GO and KEGG enrichment analyses to assess if the QGSJS decoction's mechanisms of action are linked to hypoxic response regulation. Finally, in vivo experiments were performed to confirm the findings from the network pharmacology analysis and to comprehensively elucidate the QGSJS decoction's mechanisms of action.

Results: The network pharmacology analysis revealed 57 active components in the QGSJS decoction, capable of influencing 72 targets associated with DKD. Quercetin, kaempferol, and isorhamnetin are likely to be the key constituents of the QGSJS decoction. The PPI network suggests that HIF1A serves as a hub gene, closely associated with IL6, NFKBIA, and VEGFA. Enrichment analysis indicates that the QGSJS decoction modulates the HIF-1 signaling pathway and impacts biological processes and molecular functions linked to HIF-1α. In vivo studies demonstrate the QGSJS decoction's renal protective properties, suppressing the expression of HIF-1α, p-STAT3, p-Akt, VEGF, VEGFR, p-NF-κB, and NOTCH1 in the kidneys without affecting PHD2.

Conclusion: The QGSJS decoction primarily inhibits HIF-1α through non-oxygen-dependent pathways, mitigating damage related to abnormal hypoxic responses, which may be the main mechanism through which it protects the kidneys.