Acta Diabetologica最新文献

In patients with Type 1 Diabetes Mellitus (T1DM), diabetic gastroparesis is associated with increased risk of severe hypoglycemia, pronounced glycemic variability and higher HbA1c. Data concerning the efficacy and safety of Automated Insulin Delivery systems (AID) in these patients are extremely limited. We present the case of a patient with T1DM, asymptomatic diabetic gastroparesis, multiple chronic diabetes complications and suboptimal glycemic control successfully treated with MiniMed 780 hybrid insulin pump.

Aims: Genome-wide association studies (GWAS) have identified the IGF2BP2 (Insulin-like Growth Factor 2 mRNA binding protein 2) gene as a susceptibility locus for Type 2 diabetes mellitus (T2D). This study aimed to evaluate the IGF2BP2 mRNA levels in the blood of a cohort of T2D patients and to quantify the expression levels of non-coding RNAs (ncRNAs) that are predicted to interact with it.

Methods: We extracted RNA from peripheral blood mononuclear cells of 50 T2D patients and 30 healthy controls (CTRL) and quantified, by qPCR, the IGF2BP2 expression levels. Using bioinformatics tools, we predicted its main ncRNAs target and quantified it.

Results: The expression study showed a significantly higher IGF2BP2 level in T2D subjects than in CTRL. In silico analysis identified hsa-let7b-5p as a potential microRNA regulator of IGF2BP2, with reduced expression levels observed in T2D patients. Additionally, three lncRNAs (SNHG5, HOTAIR, and MEG3) were predicted as potential targets of IGF2BP2. Their expression levels were significantly elevated in T2D patients. In vitro assays demonstrated that inhibiting hsa-let7b-5p in HeLa cells resulted in increased expression of IGF2BP2 and the three lncRNAs.

Conclusion: These findings highlight a potential regulatory network involving IGF2BP2, hsa-let7b-5p, and lncRNAs. This network may contribute to dysregulation of insulin/IGF signaling and glucose metabolism pathways, providing insights into T2D pathogenesis.

Background: Periodontal disease (PD) is common in type 1 diabetes mellitus (T1DM); however, studies related to oral microbiome in PD in type 1 diabetes is limited.

Methods: In this cross-sectional study,60 participants were enrolled in three groups. T1DM with PD (DMPD, n = 20), T1DM without periodontal disease (DM, n = 20)), and siblings without diabetes but with PD (PD, n = 20)). All the participants underwent comprehensive periodontal examination. Gingival plaque samples were collected for DNA isolation and next-generation sequencing to quantify microbiological abundance.

Results: In total, 3294 operational taxonomic units were identified and analysed. Significant difference was observed across the groups, notably Prevotella, Megasphaera, Dialister, and Camphylobacter, Aggregatibacter, and Corynebacterium showed difference in abundance. Prevotella was found to have a very high and statistically significant abundance in DMPD. Prevotella, Veillonella, and Selenomonas were significantly higher in the poorly controlled glycemic group. Subjects with severe Gingival Index (GI) exhibit higher abundance of Capnocytophaga, Neisseria and Rothia compared to those with non-severe GI.

Conclusion: The Oral microbiome composition of individuals with T1DM varied significantly in the presence of periodontal disease. The oral microbiome also varies according to glycemic status of T1DM and severity of PD. The markedly increased abundance of certain phyla and genera in subjects with PD and diabetes suggests a role for the relevant microbiota in the development of periodontal infection in T1DM subjects.

Objective: This study aimed to investigate gut microbiota composition and metabolic functions in patients with type 2 diabetes mellitus (DM) complicated by myocardial infarction (MI) and to explore potential mechanisms linking the gut microbiome to MI development.

Methods: Sixty patients with DM complicated by MI and 52 patients with DM alone were initially recruited. After quality control, 29 DM + MI patients and 33 DM patients were included in the final analysis. Gut microbial profiles were characterized using shotgun metagenomic sequencing and bioinformatics analyses. Microbial diversity, composition, and gene functions were compared between groups based on KEGG, COG, and CAZy annotations.

Results: Overall microbial diversity and metabolic profiles were comparable between the two groups; however, significant differences were observed in specific taxa and functional genes. Taxa enriched in the DM + MI group included Bacteroidales, Prevotellaceae, and Lachnospiraceae. In total, 510 KEGG orthology (KO) units and 21 pathways-including ABC transporters, quorum sensing, and general metabolic pathways-differed significantly between groups. Carbohydrate transport and metabolism, as well as glycoside hydrolase activity, represented the most enriched functional categories. Random forest models based on selected microbial species, KO units, and KEGG pathways achieved areas under the curve (AUCs) of 0.868, 0.885, and 0.820, respectively.

Conclusion: Patients with DM complicated by MI exhibit distinct gut microbial compositions and functional gene signatures compared with patients with DM alone. These microbiome-based markers may contribute to early risk stratification and provide potential targets for microbiota-focused interventions to mitigate MI risk in patients with diabetes.

Aims: To evaluate whether continuing versus reducing metformin at imeglimin initiation is associated with 24-week changes in HbA1c and body weight in routine practice, and to describe 48-week outcomes.

Methods: Single-center retrospective study of adults with type 2 diabetes who started imeglimin 2000 mg/day (September 2022-August 2024). For the primary 24-week efficacy analysis, metformin users who tolerated and continued imeglimin through week 24 were classified as metformin continuation (no change) or metformin reduction (≥ 250 mg/day decrease, including discontinuation). The primary endpoint was 24-week ΔHbA1c. Associations were assessed with nonparametric tests and ANCOVA adjusting for age, sex, diabetes duration, and baseline HbA1c; sensitivity models additionally adjusted for baseline metformin dose and major concomitant glucose-lowering drug classes (SGLT2i, GLP-1RA, insulin, and sulfonylureas).

Results: Seventy metformin users were included (continuation n = 34; reduction n = 36). At 24 weeks, HbA1c decreased by - 0.6% versus - 0.2% (median difference - 0.5%, 95% CI - 0.6 to - 0.3), and body weight by - 1.2 kg versus - 0.4 kg (median difference - 0.9 kg). The absolute metformin dose reduction correlated with ΔHbA1c (Spearman ρ = 0.52). Metformin continuation remained associated with greater adjusted HbA1c reduction in sensitivity ANCOVA (adjusted difference - 0.57%, 95% CI - 0.88 to - 0.26; P = 0.0006). In a 48-week cohort (n = 65) continuing imeglimin, metformin dose reduction remained associated with ΔHbA1c in multivariable analysis.

Conclusions: Continuing metformin at imeglimin initiation was associated with greater improvements in HbA1c and body weight than dose reduction. Findings are associative and may reflect residual confounding.

Telomere length serves as a critical biomarker of ageing, and diabetes is associated with shorter telomeres. This study aims to investigate the association and underlying molecular mechanism between telomere attrition rate in healthy individuals and patients with type 2 diabetes who consume the anti-diabetic drug metformin. Leukocyte telomere length was measured using the telomere restriction fragment assay in 111 healthy individuals and in 73 individuals with type 2 diabetes who were consuming metformin. Telomere length-regulating mRNA and protein expression studies were performed. The BJ fibroblast cell line was treated with different concentrations of metformin, and telomere length analysis, gene expression and chromatin immunoprecipitation (ChIP) were performed. Compared to healthy volunteers, telomere attrition was markedly reduced in diabetic patients who were on metformin. Diabetic females, in particular, showed an increase in telomere length, while males showed a reduction in the telomere attrition rate. In the BJ fibroblasts, metformin slowed telomere attrition in a dose-dependent manner. Molecular studies revealed that metformin treatment resulted in increased expression of telomeric protein RAP1 via enhanced PGC1α-dependent Foxo3a recruitment to the RAP1 promoter. Metformin is associated with decreased telomere attrition and increased telomeric protein RAP1 expression in both diabetic patients and in the fibroblast model. The effect is particularly significant in females. To our knowledge, this is the first study to identify a PGC-1α-FOXO3a-RAP1 signaling axis linking metformin exposure to telomere protection in human diabetic cohorts and to mechanistically validate this pathway using a fibroblast model.