Journal of Diabetes Research最新文献

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.

Objective: To evaluate the effectiveness of empagliflozin in reducing all-cause mortality (ACM), hospitalization for heart failure (HHF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), and end-stage renal disease (ESRD) in routine clinical practice in the Nordic countries of the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study. Methods: This noninterventional, multicountry cohort study used secondary data from four Nordic countries (Denmark, Sweden, Finland, and Norway). Propensity score (PS) matched (1:1) adults with type 2 diabetes (T2D) initiating empagliflozin (a sodium-glucose cotransporter-2 inhibitor) during 2014-2018 who were compared to those initiating a dipeptidyl peptidase-4 inhibitor (DPP-4i). Cox proportional hazards regression modelling was used to assess the risk for ACM, HHF, MI, stroke, CVM, and ESRD. Meta-analyses were conducted and hazard ratios (HRs) with 95% confidence intervals (CIs) from random-effects models were calculated. Results: A total of 43,695 pairs of PS-matched patients were identified. Patients initiating empagliflozin exhibited a 49% significantly lower risk of ACM (HR: 0.51, 95% CI 0.40-0.64) compared to DPP-4i. Additionally, empagliflozin was associated with a 36% significantly lower risk of HHF (HR: 0.64, 95% CI 0.46-0.89), a 52% significantly lower risk of CVM (HR: 0.48, 95% CI 0.37-0.63), and a 66% significantly lower risk of ESRD (HR: 0.34, 95% CI 0.15-0.77) compared to DPP-4i. No significant differences were observed in the risk of stroke and MI between patients initiating empagliflozin compared with those initiating a DPP-4i. Results were generally consistent for subgroups (with/without pre-existing CV disease or congestive heart failure) and in sensitivity analyses. Conclusion: Empagliflozin initiation was associated with a significantly reduced risk of ACM, HHF, CVM, and ESRD compared with initiation of DPP-4i in patients with T2D when examining routine clinical practice data from Nordic countries.

Aims: We aimed to assess neurodegenerative changes in the rhinencephalon via magnetic resonance imaging (MRI) and relate it to olfactory function and diabetic peripheral neuropathy (DPN) in adults with type 1 diabetes (T1D). Materials and Methods: Individuals aged 18-65 with T1D duration over 10 years and control healthy subjects underwent olfactory assessment using Sniffin'Sticks and brain MRI to assess volumetric measurements of the olfactory bulbs and piriform cortex thickness. Results: 32 T1D (24 males) aged 43.5 years (IQR: 37.0-48), diabetes duration 24.5 years (IQR: 20.5-27.0), and A1C 7.95% (IQR: 7.4-8.4) were assessed. The control group consisted of 6 healthy adults (4 males) aged 41.0 years (IQR: 36.0-48.0). Significantly lower olfactory test results in TDI (threshold-differentiation-identification) (31.5 (IQR: 28.7-33.6) vs. 34.1 (IQR: 33.2-37.2), p = 0.02) were obtained in the T1D as compared to the controls. Summarized olfactory bulb (OB) volumes and thickness of the left pyriform cortex were significantly smaller in T1D than in controls (65.8 mm³ (IQR: 57.9-71.7) vs. 75.8 mm³ (IQR: 74.8-76.7); p = 0.0005 and 3.1 mm (IQR: 2.7-3.4) vs. 3.6 mm (IQR: 3.5-4.1); p =0.02). Patients with DPN had significantly smaller OB volumes than patients without DPN (58.1 mm³ (IQR: 54.0-70.9) vs. 69.8 mm³ (IQR: 65.0-72.2); p = 0.02). Tobacco smoking (β: -7.89; p = 0.013) and DPN (β:-7.02; p = 0.015) proved to be independent predictors of OB volume. Conclusions: In adults with a long history of T1D, olfactory function and structures are impaired. The presence of diabetic neuropathy and ongoing smoking addiction might be considered predictors of the degradation of rhinencephalon structures in people with T1D.

Aims: This study is aimed at comparing whole exome sequencing (WES) data with the clinical presentation in children with type 1 diabetes onset ≤ 5 years of age (EOT1D). Methods: WES was performed in 99 unrelated children with EOT1D with subsequent analysis to identify potentially deleterious rare variants in MODY genes. High-resolution HLA class II haplotyping, SNP genotyping, and T1D-genetic risk score (T1D-GRS) were also evaluated. Results: Eight of the ninety-nine EOT1D participants carried a potentially deleterious rare variant in a MODY gene. Rare variants affected five genes: GCK (n = 1), HNF1B (n = 2), HNF4A (n = 1), PDX1 (n = 2), and RFX6 (n = 2). At diagnosis, these children had a mean age of 3.0 years, a mean HbA1c of 10.5%, a detectable C-peptide in 5/8, and a positive islet autoantibody in 6/7. Children with MODY variants tend to exhibit a lower number of pancreatic autoantibodies and a lower fasting C-peptide compared to EOT1D without MODY rare variants. They also carried at least one high-risk DR3-DQ2 or DR4-DQ8 haplotype and exhibited a T1D-GRS similar to the other individuals in the EOT1D cohort, but higher than healthy controls. Conclusions: WES found potentially deleterious rare variants in MODY genes in 8.1% of EOT1D, occurring in the context of a T1D genetic background. Such genetic variants may contribute to disease precipitation by a β-cell dysfunction mechanism. This supports the concept of different endotypes of T1D, and WES at T1D onset may be a prerequisite for the implementation of precision therapies in children with autoimmune diabetes.

Background: No comprehensive meta-analysis has evaluated the efficacy and safety of ertugliflozin compared to a placebo in patients with Type 2 diabetes (T2D) until now. This meta-analysis fills this gap in knowledge. Methods: A systematic search was carried out in electronic databases to identify randomized controlled trials (RCTs) that included patients with T2D receiving ertugliflozin in the treatment group and placebo in the control group. The change in HbA1c from the baseline values was the primary outcome, whereas changes in plasma glucose and other metabolic parameters and adverse events (AEs), including hypoglycemia, were the secondary outcomes. Results: Seven RCTs involving 7283 subjects met the inclusion criteria. Ertugliflozin outperformed placebo in reducing HbA1c in both 5 mg (MD -0.62%, 95% CI [-0.80, -0.44], p < 0.00001, I ² = 91%) and 15 mg (MD -0.69%, 95% CI [-0.91, -0.47], p < 0.00001, I ² = 93%) doses. A higher proportion of patients achieved HbA1c < 7.0% with ertugliflozin than with placebo. Ertugliflozin was also superior to placebo in lowering fasting plasma glucose (FPG), body weight, and systolic and diastolic blood pressure (BP). Ertugliflozin and placebo had comparable AE profiles, including urinary tract infection (UTI) and hypoglycemia, except for the greater risk of genital mycotic infections (GMIs) with ertugliflozin. Ertugliflozin 5 and 15 mg have equivalent efficacy and safety profiles except for greater weight reduction with ertugliflozin 15 mg. Conclusion: Ertugliflozin has a good glycemic efficacy and a reassuring safety profile in managing T2D. Trial Registration: Registration number: CRD42023456450.

Aims: This study was aimed at assessing the association of oral glucose tolerance test (OGTT) glucose threshold levels and the requirement of insulin therapy in twin pregnancies with gestational diabetes mellitus (GDM). Methods: In this post hoc analysis of a cohort study spanning 18 years, 446 patients with twin pregnancy and GDM (246 managed with lifestyle modification and 200 requiring pharmacotherapy) were included. We collected and evaluated maternal characteristics, as well as fasting, 1-h, and 2-h glucose concentrations from a standardized 75-g OGTT. The assessment methods included logistic regression analysis, positive and negative predictive values, area under the curve (AUC), and random forest analysis. Results: The fasting (p < 0.01, OR: 1.03 [95% CI 1.01-1.05]) and 1-h (p < 0.01; OR: 1.01 [95% CI 1.00-1.02]) glucose levels during the OGTT were significantly associated with the subsequent need for insulin therapy, with thresholds of 95 mg/dL for fasting glucose and 184 mg/dL for the 1-h OGTT. Additionally, indications for insulin therapy were marked by thresholds of 108 mg/dL at G0, 215 mg/dL at G60, and 86 mg/dL at G120. Conclusion: Identifying threshold values for insulin therapy and risk stratification in twin pregnancy are crucial for optimal patient management.