Acta Diabetologica最新文献

Background: The uric acid-to-HDL cholesterol ratio (UHR) is a promising non-insulin-based marker for metabolic risk, associated with type 2 diabetes, hypertension, hepatic steatosis, and cardiovascular disease. However, its utility in individuals with altered glucose tolerance remains unclear.

Methods: We investigated the relationship between UHR and insulin sensitivity in two independent cohorts. Sample 1 (n = 1555) from the CATAMERI study, was stratified based on oral glucose tolerance test (OGTT) results, and Sample 2 (n = 332) from the EUGENE2 project, with insulin sensitivity measured via euglycemic-hyperinsulinemic clamp.

Results: In Sample 1, UHR showed positive correlations with BMI, triglycerides, 2-hour plasma glucose, HOMA-IR, fasting plasma insulin (p < 0.0001 for all) and with HbA1c (p < 0.001), and negative correlations with Matsuda index (p < 0.0001) and total cholesterol (p = 0.019). Multivariable linear regression identified HOMA-IR (β = 0.100), Matsuda index (β=-0.146), InsAUC30/GluAUC30 (β = 0.120), and Stumvoll 1st-phase insulin secretion (β = 0.121) as independent UHR predictors. In Sample 2, bivariate analyses, adjusted for age, sex, and BMI, confirmed positive correlations between UHR and HbA1c (p < 0.001), 2-hour post-load glucose (p = 0.001), BMI, triglycerides, and fasting insulin (p < 0.0001 for all) and a negative correlation with Clamp M (glucose disposal, p = 0.0003). Finally, multivariable regression of Clamp M variability (adjusted for age, sex, and BMI) demonstrated significant negative associations with UHR (β= -0.230) and BMI (β= -0.375).

Conclusion: These findings suggest that UHR, derived easily and inexpensively from routine clinical measurements, is a promising indicator of metabolic risk in individuals without diabetes. Its accessibility positions it as a potential tool for early diabetes prevention strategies, potentially reducing reliance on the OGTT.

Introduction: Branched-chain amino acids (BCAA) are essential nutrients involved in protein synthesis. BCAA are absorbed via the L-type amino acid transporter (LAT1) in skeletal muscle where the majority of BCAA are metabolized. Higher circulating BCAA levels have been shown to correlate with insulin resistance. Some speculate that enhanced BCAA metabolism/disposal or reduced BCAA uptake may limit BCAA-mediated anabolic signaling and possibly improve insulin sensitivity.

Aims: This study investigated the effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), a LAT inhibitor, on metabolism and insulin sensitivity in a myotube model of insulin resistance. Because BCAA-mediated anabolic signaling has been linked with insulin resistance, we assessed if reduced BCAA uptake via LAT inhibition would improve insulin sensitivity.

Methods: C2C12 myotubes were cultured in the presence and absence of insulin resistance and treated with and without BCH. Myotube metabolism was assessed via oxygen consumption, and associated gene and protein expression were assessed using qRT-PCR and Western blot, respectively. LC/MS was performed to assess the effect of each condition on extracellular BCAA accumulation.

Results and conclusions: BCH treatment and insulin resistance both increased extracellular BCAA levels which was associated with reduced protein expression/activity of BCAA catabolic enzymes. Additionally, BCH and insulin resistance were both independently associated with reduced mitochondrial function which occurred without significant changes in mitochondrial biogenesis signaling. Importantly, BCH did not alter myotube viability or insulin sensitivity, suggesting reduced metabolism was not a function of reduced viability. These observations demonstrate that reduction of BCAA uptake may not improve insulin resistance and may promote mitochondrial dysfunction.

Aims: This study tested the hypothesis that the anti-diabetes drug dapagliflozin (DAPA) alleviates heart dysfunction induced by type 3 cardiorenal syndrome (CRS-3) by normalizing mitochondrial quality control (MQC). MQC is a stress-activated mechanism, regulated by Dual specificity phosphatase 1 (DUSP1), that maintains mitochondrial homeostasis to support heart function. Due to its known renal and cardioprotective effects, DAPA was investigated as a potential treatment for CRS-3.

Methods: CRS-3 was induced in mice through renal ischemia/reperfusion. The effects of DAPA pre-treatment were assessed by measuring heart function, serum levels of myocardial injury biomarkers, oxidative stress, inflammation, and cardiomyocyte apoptosis. Assays in cardiomqyocytes from CRS-3 mice were used to analyze MQC, including mitochondrial dynamics, mitophagy, and biogenesis. The role of DUSP1 was investigated using DUSP1-knockout mice, and a docking analysis was performed to assess the DAPA-DUSP1 interaction.

Results: DAPA pre-treatment dose-dependently improved heart function and reduced serum markers of myocardial injury, oxidative stress, inflammation, and cardiomyocyte apoptosis in CRS-3 mice. DAPA treatment stabilized MQC in cardiomyocytes, shown by improved mitochondrial dynamics and restored mitophagy and biogenesis. Docking analysis suggested that DAPA directly interacts with DUSP1 and suppresses its nuclear translocation. Notably, in DUSP1-knockout mice, the stabilizing effect of DAPA on MQC was abolished. Furthermore, upon DUSP1 deletion, DAPA failed to prevent CRS-3-related oxidative stress, inflammation, apoptosis, and heart dysfunction.

Conclusions: Defective MQC critically contributes to CRS-3-related myocardial dysfunction. The study proposes that DAPA therapy may normalize DUSP1-dependent MQC and consequently alleviate the cardiac depression associated with CRS-3.

Aims: Autoreactive memory T cells are considered to be a primary contributor to chronic islet inflammation in individuals with type 1 diabetes (T1D). OX40-expressing T cells not only facilitate and sustain the presence of CD4⁺ memory T cells but also promote the generation of CD8⁺ memory T cells. We aimed to investigate the role of OX40⁺CD4⁺/CD8⁺ memory T lymphocytes in the pathogenesis of T1D.

Methods: A total of 35 patients diagnosed with Type 1 diabetes and 40 healthy control individuals were enrolled in this study. Peripheral Blood Mononuclear Cells (PBMCs) were isolated from the study participants and analyzed by flow cytometry. Inflammatory cytokines in the plasma were quantitatively measured. The pancreatic islet autoantibodies as well as islet function were also evaluated.

Results: The frequencies and the mean fluorescence intensity (MFI) of OX40 on CD4⁺  effector memory T (Tem) cells significantly increased in patients with T1D compared to healthy controls. Importantly, the expression of OX40 on CD8⁺ Tem and central memory T (Tcm) cells was also significantly higher in T1D compared with healthy controls. However, the expression of OX40 on CD4⁺ Tem cells was not significantly higher in T1D with two or more autoantibodies than control group. Furthermore, the frequencies of OX40⁺CD8⁺ Tem cells significantly increased in T1D patients with two or more autoantibodies but not in those with one autoantibody, compared with control groups. Meanwhile, the frequencies of OX40⁺CD8⁺ Tcm cells were consistently higher across all three subgroups of T1D patients (AAb^-, 1AAb, ≥2AAb) compared to the control group. Notably, both the frequencies of OX40⁺CD4⁺ and OX40⁺CD8⁺ Tem cells exhibited significant negative correlations with the serum C-peptide levels in T1D patients. Additionally, the expression levels of OX40 on peripheral CD4⁺/CD8⁺ memory T cells were positively correlated with the levels of plasma inflammatory cytokines in patients with T1D.

Conclusions: The elevated expression of OX40 on CD4⁺/CD8⁺ memory T cells was associated with the autoimmune-mediated destruction of islet beta cells in T1D. Our findings indicate that the expression levels of OX40 on peripheral CD4⁺ and CD8⁺ memory T lymphocytes may serve as potential predictive biomarkers for the severity of T1D. Additionally, OX40 expression on memory T cells may serve as a potential biomarker for assessing the efficacy of immunotherapy in T1D patients.

Aims: This study examines the use, perceptions, and inequalities in access to Digital Health Solutions (DHS) among people with diabetes (PwD). It aims to identify factors influencing adoption and explore perceived benefits and barriers to using DHS, focusing on person-important outcomes such as physical health, mental burden, and access to care.

Methods: The primary objective of this feasibility study was to assess the intervention acceptability, feasibility, and app usability. The secondary aim is to explore preliminary intervention effects.

Methods: A cross-sectional online survey was conducted in France from April to July 2022. A total of 301 PwD (149 with type 1 diabetes [T1D], 152 with type 2 diabetes [T2D]) completed the study. The survey assessed the use of three DHS categories: information/education (DHS1), self-management support (DHS2), and data-sharing/collaborative care (DHS3). We used univariate and multivariate logistic regression to identify predictors of DHS use, including demographic, socioeconomic, psychological, and medical variables.

Results: DHS1 was the most commonly used category, followed by DHS2 and DHS3. PwD with T1D were more likely to use multiple DHS. Type of diabetes and perceived health status were the strongest predictors of DHS use. Surprisingly, people in poorer health were less likely to use DHS despite potentially benefiting most from them. DHS-naïve individuals expected more benefits but reported greater concerns, especially about information overload and data security. These concerns were stronger than the perceived benefits. For example, concerns about data security reduced the likelihood of using DHS2 and DHS3 by up to 89%.

Conclusion: The study highlights disparities in DHS adoption and the critical role of perceived barriers. Addressing these concerns-particularly among PwD in poorer health-and aligning DHS with outcomes that matter to patients may improve equitable adoption and diabetes care.

Do-It-Yourself Artificial Pancreas Systems (DIY-APS)-which combine commercially available devices with open-source software-are increasingly used for the management of type 1 diabetes, despite a lack of formal regulatory approval in many jurisdictions, including in Italy. This position statement, endorsed by Italian diabetes societies (Associazione Medici Diabetologici, Societa Italiana di Diabetologia, and Società Italiana di Endocrinologia e Diabetologia Pediatrica) and "Diabete Italia", the national patient association, addresses the efficacy, safety, and legal implications of DIY-APS in Italy. Real-world evidence and clinical trials demonstrate that DIY-APS improves glycemic control and quality of life and reduce fear of hypoglycemia in users. This statement outlines the reasons driving patient adoption of DIY-APS, including limitations of commercial systems and the need for greater personalization. It emphasizes the ethical responsibility of healthcare professionals to support patients using DIY-APS while acknowledging the legal complexities surrounding their unregulated use. The statement concludes with recommendations to enhance education for patients and healthcare professionals and advocates for clearer regulatory pathways to ensure patient safety and optimize care.