Journal of Diabetes Research最新文献

Globally, adherence to Type 2 diabetes mellitus (T2DM) medications remains suboptimal. There are limited insights, however, on this issue in the northern region of Ethiopia. This cross-sectional study at Alamata General Hospital investigated the interplay between patients' medication beliefs, diabetes knowledge, adherence, and glycemic control. Data collection was done using structured questionnaires and chart reviews, while descriptive and inferential statistics were for the analysis. Among 305 T2DM patients, poor medication adherence was prevalent (44.6%), alongside suboptimal glycemic control (75.7%). Patients diagnosed for over a decade had an adjusted odds ratio (AOR) of 3.87 for nonadherence, while high concern about medication side effects was associated with a 20.63-fold higher nonadherence risk (AOR = 20.63). Low disease awareness increased nonadherence risk by 4.54 times (AOR = 4.54), while a strong belief in medication necessity was protective (AOR = 0.21). Poor glycemic control was associated with educational background, diabetes awareness, monthly income, and treatment modality. Urgently needed are tailored diabetes education programs in Northern Ethiopia to counteract high rates of poor medication adherence (AOR = 3.87) and glycemic control among T2DM patients. Targeted interventions, emphasizing knowledge enhancement and reinforcing positive beliefs, are essential for improving outcomes in this population.

Modern lifestyle changes, especially the consumption of a diet high in salt, sugar, and fat, have contributed to the increasing incidence and prevalence of chronic metabolic diseases such as diabetes, obesity, and gout. Changing lifestyles continuously shape the gut microbiota which is closely related to the occurrence and development of metabolic diseases due to its specificity of composition and structural diversity. A large number of pathogenic bacteria such as Yersinia, Salmonella, Shigella, and pathogenic E. coli in the gut utilize the type III secretion system (T3SS) to help them resist host defenses and cause disease. Although the T3SS is critical for the virulence of many important human pathogens, its relationship with metabolic diseases remains unknown. This article reviews the structure and function of the T3SS, the disruption of intestinal barrier integrity by the T3SS, the changes in intestinal flora containing the T3SS in metabolic diseases, the possible mechanisms of the T3SS affecting metabolic diseases, and the application of the T3SS in the treatment of metabolic diseases. The aim is to provide insights into metabolic diseases targeting the T3SS, thereby serving as a valuable reference for future research on disease diagnosis, prevention, and treatment.

Objective: This study elucidated the mechanistic role of Cyathulae Radix (CR) in type 2 diabetes mellitus (T2DM) through bioinformatics analysis and experimental validation. Methods: Components and targets of CR were retrieved from the traditional Chinese medical systems pharmacology, while potential T2DM targets were obtained from GeneCards and Online Mendelian Inheritance in Man databases. Intersecting these datasets yielded target genes between CR and T2DM. Differential genes were used for constructing a protein-protein interaction network, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking and dynamics simulations were performed using AutoDock and GROMACS, respectively, and in vitro experiments validated the results. Experiments evaluated the effect of CR on T2DM pancreatic β-cells. Results: Bioinformatics analysis identified four active compounds of CR, 157 related genes, and 5431 T2DM target genes, with 141 shared targets. Key targets such as JUN, MAPK1, and MAPK14 were identified through topological analysis of the PPI network. GO analysis presented 2663 entries, while KEGG analysis identified 161 pathways. The molecular docking results demonstrated favorable binding energy between the core components and the core proteins. Among them, JUN-rubrosterone, MAPK1-rubrosterone, and MAPK14-rubrosterone deserved further investigation. Molecular dynamics results indicated that all of them can form stable binding interactions. CR could inhibit the expression of JUN, MAPK1, and MAPK14, promote insulin secretion, alleviate apoptosis, and regulate autophagy in INS-1 cells. Conclusion: This study suggests CR approach to T2DM management by multitarget and multipathway provides a scientific basis for further research on the hypoglycemic effect of CR.

The relationship between dietary flavonoid intake and mortality in the diabetic kidney disease (DKD) population is unknown. So this study is aimed at investigating the association of total dietary flavonoid intake and their subclasses with all-cause and cardiovascular disease (CVD) mortality. Data of this cohort study were extracted from the NHANES (2007-2010 and 2017-2018). The survival status of participants was determined by linking to the National Death Index through the end of 2019. Flavonoid intake was measured using two 24-h dietary recall interviews. The Kaplan-Meier curves and weighted Cox proportional hazard regression models were used to assess the effect of dietary flavonoid intake on CVD and all-cause mortality, with adjustments for multiple covariates. A total of 1155 participants were included for analysis. After a median follow-up of 76.36 (S.E: 3.24) months, 409 participants died of all-cause mortality, of which 138 died of CVD. In the fully adjusted model, higher total dietary flavonoids intake (HR = 0.69, 95% CI: 0.52-0.92) was associated with lower all-cause mortality and subclasses of higher flavones (HR = 0.60, 95% CI: 0.35-0.85) was also with lower all-cause mortality. In subclasses of flavonoids, higher intake of both anthocyanidins (HR = 0.54, 95% CI: 0.28 to 0.87) and flavones (HR = 0.50, 95% CI: 0.28-0.87) were associated with lower odds of CVD mortality. Higher flavonoid intake was associated with a reduced risk of CVD and all-cause mortality in DKD. Higher flavonoid intake provides a potential opportunity to improve the prognosis of DKD. And future research into the mechanisms between flavonoids and mortality is needed.

Background: Our goal was to examine the causal link between blood metabolites, their ratios, and the risk of developing proliferative diabetic retinopathy (PDR) from a genetic insight. Methods: Summary-level data about 1400 blood metabolites and their ratios, as well as PDR, were sourced from prior genome-wide association studies (GWAS). A two-sample univariate and multivariate Mendelian randomization (MR) approach was utilized. Additionally, metabolic pathway analysis and sensitivity analysis were also conducted. Results: After adjusting for multiple tests, four blood metabolites significantly correlated with PDR risk. Two ceramides, including glycosyl-N-palmitoyl-sphingosine (d18:1/16:0) (odds ratio [OR] = 1.12, 95% confidence interval (CI): 1.06-1.17, p < 0.001, false discovery rate (FDR) = 0.005) and glycosyl-N-behenoyl-sphingadienine (d18:2/22:0) (OR = 1.11, 95% CI: 1.06-1.16, p < 0.001, FDR = 0.017), were linked to increased risk. Additionally, 3-methylcytidine (OR = 1.05, 95% CI: 1.03-1.08, p < 0.001, FDR = 0.021) also posed a risk, whereas (N(1)+N(8))-acetylspermidine (OR = 0.91, 95% CI: 0.87-0.94, p < 0.001, FDR = 0.002) appeared protective. Multivariable MR analysis further confirmed a direct, protective effect of (N(1)+N(8))-acetylspermidine on PDR risk (OR = 0.94, 95% CI: 0.89-1.00, p = 0.040). The sensitivity analysis results indicated that evidence for heterogeneity and pleiotropy was absent. Conclusion: These metabolites have the potential to be used as biomarkers and are promising for future research into the mechanisms and drug targets for PDR.

Aims: According to the gut-kidney axis theory, gut microbiota (GM) has bidirectional crosstalk with the development of diabetic kidney disease (DKD). However, empirical results have been inconsistent, and the causal associations remain unclear. This study was aimed at exploring the causal relationship between GM and DKD as well as the glomerular filtration rate (GFR) and urinary albumin-to-creatinine ratio (UACR). Materials and Methods: Two-sample Mendelian randomisation (MR) analysis was performed with inverse-variance weighting as the primary method, together with four additional modes (MR-Egger regression, simple mode, weighted mode, and weighted median). We utilised summary-level genome-wide association study statistics from public databases for this MR analysis. Genetic associations with DKD were downloaded from the IEU Open GWAS project or CKDGen consortium, and associations with GM (196 taxa from five levels) were downloaded from the MiBioGen repository. Results: In forward MR analysis, we identified 13 taxa associated with DKD, most of which were duplicated in Type 2 diabetes with renal complications but not in Type 1 diabetes. We observed a causal association between genetic signature contributing to the relative abundance of Erysipelotrichaceae UCG003 and that for both DKD and GFR. Similarly, host genetic signature defining the abundance of Ruminococcaceae UCG014 was found to be simultaneously associated with DKD and UACR. In reverse MR analysis, the abundance of 14 other GM taxa was affected by DKD, including the phylum Proteobacteria, which remained significant after false discovery rate correction. Sensitivity analyses revealed no evidence of outliers, heterogeneity, or horizontal pleiotropy. Conclusion: Our findings provide compelling causal genetic evidence for the bidirectional crosstalk between specific GM taxa and DKD development, contributing valuable insights for a comprehensive understanding of the pathological mechanisms of DKD and highlighting the possibility of prevention and management of DKD by targeting GM.

Background: Obesity is a predisposing risk factor for type 2 diabetes mellitus (T2DM). Actually, not only obese/overweight but also nonobese/lean individuals may be prone to T2DM. This study is aimed at identifying the contribution of adipose tissue to the development of nonobese diabetes (NOD) and obese diabetes (OD). Methods: Serum samples from the nonobese nondiabetes (NOND, n = 47, age = 46.8 ± 8.4, BMI ≤ 23.9 kg/m²) controls, NOD (n = 48, age = 50.7 ± 6.5, BMI ≤ 23.9 kg/m²) and OD (n = 65, age = 49.8 ± 10.2, BMI ≥ 28 kg/m²) patients were utilized to measure the expression of metabolic indicators, adipocytokines, inflammatory factors. Different adipose depots from offspring with corresponding blood glucose and obesity levels of a spontaneously diabetic gerbil line with various degrees of diabetic penetrance and body weights were examined for adipocytokines and inflammation factors detected by ELISA and western blot. Adipose tissue volume and fat cell size of the gerbils were evaluated by magnetic resonance imaging and immunohistochemistry, respectively. Results: The study yielded four key findings. Firstly, in comparison to the NOD group, the OD group exhibited more severe insulin resistance (IR) and metabolic dysfunction in both patients and gerbils, attributed to higher visceral adipose tissue mass and larger fat cell sizes. Secondly, in gerbils, gonadal fat deposition was linked to obesity development, whereas kidney fat deposition correlated with obesity and diabetes occurrence. Thirdly, in both patients and gerbils, the interplay between adiponectin and leptin levels in serum may significantly influence the development of obesity and diabetes. Lastly, heightened expression of MCP3 in gerbils' kidney adipose tissue may serve as a pivotal factor in initiating obesity-associated diabetes. Conclusions: Our study, which may be considered a pilot investigation, suggests that the interaction of adipocytokines and inflammation factors in different adipose depots could play diverse roles in the development of diabetes or obesity.

Background: Vitamin E, an essential micronutrient with antioxidant potential, can dramatically reduce the cardiovascular risk in individuals with haptoglobin (Hp) 2-2 genotype diabetes; however, the underlying mechanism remains unclear. Objective: The objective of this study is to evaluate the effect of vitamin E supplementation on high-density lipoprotein (HDL) levels and function in individuals with diabetes stratified by Hp genotype. Methods: All relevant studies published up to May 2023 were systematically reviewed using PubMed, Cochrane Library, Web of Science, Chinese Wanfang, China Science and Technology Journal, and Chinese National Knowledge Infrastructure databases. Randomized controlled trials that evaluated the effects of vitamin E supplementation on HDL levels were included. The outcomes assessed were changes in HDL concentrations, cholesterol efflux, and HDL-associated lipid peroxides. Results: In total, 163 publications were selected. Based on inclusion and exclusion selection and quality assessment, five studies with 463 participants were included. Vitamin E supplementation did not exert any effect on HDL levels in individuals with diabetes with any Hp genotype. Three of the five studies revealed that vitamin E improved cholesterol efflux and HDL lipid peroxides in individuals with Hp2-2 diabetes but did not positively impact HDL function in Hp1 carriers. Conclusions: Although vitamin E supplementation did not significantly impact HDL levels in individuals with diabetes of any Hp genotype, it may improve HDL function in individuals with Hp2-2 diabetes. These findings indicate a pharmacogenetic interaction between vitamin E and the Hp genotype on HDL function. Moreover, vitamin E supplementation may be an effective strategy for specific individuals with diabetes.

Propionate metabolism is important in the development of diabetes, and fibrosis plays an important role in diabetic nephropathy (DN). However, there are no studies on biomarkers related to fibrosis and propionate metabolism in DN. Hence, the current research is aimed at evaluating biomarkers associated with fibrosis and propionate metabolism and to explore their effect on DN progression. The GSE96804 (DN : control = 41 : 20) and GSE104948 (DN : control = 7 : 18) DN-related datasets and 924 propionate metabolism-related genes (PMRGs) and 656 fibrosis-related genes (FRGs) were acquired from the public database. First, DN differentially expressed genes (DN-DEGs) between the DN and control samples were sifted out via differential expression analysis. The PMRG scores of the DN samples were calculated based on PMRGs. The samples were divided into the high and low PMRG score groups according to the median scores. The PM-DEGs between the two groups were screened out. Second, the intersection of DN-DEGs, PM-DEGs, and FRGs was taken to yield intersected genes. Random forest (RF) and recursive feature elimination (RFE) analyses of the intersected genes were performed to sift out biomarkers. Then, single gene set enrichment analysis was conducted. Finally, immunoinfiltrative analysis was performed, and the transcription factor (TF)-microRNA (miRNA)-mRNA regulatory network and the drug-gene interaction network were constructed. There were 2633 DN-DEGs between the DN and control samples and 515 PM-DEGs between the high and low PMRG score groups. In total, 10 intersected genes were gained after taking the intersection of DN-DEGs, PM-DEGs, and FRGs. Seven biomarkers, namely, SLC37A4, ACOX2, GPD1, angiotensin-converting enzyme 2 (ACE2), SLC9A3, AGT, and PLG, were acquired via RF and RFE analyses, and they were found to be involved in various mechanisms such as glomerulus development, fatty acid metabolism, and peroxisome. The seven biomarkers were positively correlated with neutrophils. Moreover, 8 TFs, 60 miRNAs, and 7 mRNAs formed the TF-miRNA-mRNA regulatory network, including USF1-hsa-mir-1296-5p-AGT and HIF1A-hsa-mir-449a-5p-ACE2. The drug-gene network contained UROKINASE-PLG, ATENOLOL-AGT, and other interaction relationship pairs. Via bioinformatic analyses, the risk of fibrosis and propionate metabolism-related biomarkers in DN were explored, thereby providing novel ideas for research related to DN diagnosis and treatment.

The prevalence of T2DM has been increasing dramatically over recent decades, about 537 million people in 2021. LADA type diabetes, a subtype of diabetes that exhibits characteristics of both T2DM and autoimmune beta-cell destruction similar to T1DM, but with a later onset. The aim of this study is to analyze the main research field on LADA type, including analysis of countries, institutions, journals, authors, and keywords. This research utilized a descriptive bibliometric design. We collected and analyzed data from 672 publications indexed in the Web of Science and Scopus databases, covering the period from 1994 to January 2024. The bibliometric analysis included English-language research articles that involved studies on patients with LADA type diabetes, aged 18 years or older. RStudio and the Bibliometrix R package were used for data merging and for performing statistical and visual analyses. The annual publication shows an upward trend over the period, with the highest number of publications per year in 2021. The study showed that China leads in the number of articles, with 101 papers published. The United Kingdom demonstrates significant international collaborations, particularly with Germany. The top institutions in terms of the number of published articles are the Norwegian University of Science and Technology in the Kingdom of Norway, followed by the Central South University in China. Tuomi has shown significant long-term publication impact, while Zhou ranks among the most frequently cited authors. Diabetes Care is one of the most important scientific journals in diabetology with the highest impact factor of 16.2. This abstract summarizes a comprehensive bibliometric analysis that provides insights into the global research field of LADA type, underscoring the importance of international collaboration and the significant contributions of leading countries and institutions in shaping our understanding of this complex subtype of diabetes.