Acta Diabetologica最新文献

Background: Diabetic retinopathy (DR) is a frequent complication of diabetes, characterized by progressive vision loss, with chronic inflammation being an important contributor in its development. N6-methyladenine (m6A) is a crucial RNA modification within eukaryotes, playing an essential role in different bodily functions and disease states. Nonetheless, the precise mechanism underlying m6A modification in DR remains elusive.

Methods: BV2 cells were stimulated with high glucose (HG) and mice were injected intraperitoneally with streptozotocin (STZ) to induce inflammation. RT-qPCR, Western blot, ELISA, immunofluorescence, CCK-8, Wound Healing, and RIP assays were used to evaluate the effects of methyltransferase-like 14 (METTL14) in these models.

Results: Our study indicated significantly decreased levels of METTL14 in HG stimulated BV2 cells and in STZ models. In addition, METTL14 levels were reduced in peripheral venous samples of DR patients. Meanwhile, the inflammatory factors were inhibited by up-regulation of METTL14 in HG stimulated BV2 cells and STZ models. Mechanistically, METTL14 overexpression inhibited high mobility group box 1 (HMGB1), thereby suppressing nuclear factor kappa-B (NF-κB) signaling pathway activation.

Conclusion: This study suggested that METTL14 may influence inflammation in DR by modulating the HMGB1/NF-κB pathway, providing valuable insights into potential therapeutic approaches for DR.

Aims: To examine trends in prevalence of chronic kidney disease (CKD) and risk management among US adults with diabetes between 2001 and 2020.

Methods and results: This serial cross-sectional study included 4200 adults with diabetes (representing approximately 29.0 million persons) from the National Health and Nutrition Examination Survey (2001 to 2020). Age-adjusted prevalence of CKD G3a among adults with diabetes decreased from 6.6% to 3.0% by 2005-2008, then plateaued. CKD G4-G5 increased from 0.5% to 1.7% by 2009-2012, then decreased to 0.7% by 2017-2020. The prevalence of any CKD decreased from 34.1% to 25.3% by 2009-2012, then increased to 30.6% by 2017-2020. Correspondingly, albuminuria decreased from 28.4% to 21.2% by 2009-2012, then increased to 27.4% by 2017-2020. Among adults with concomitant CKD, proportion of adults achieving blood pressure (BP) < 140/90 mmHg increased from 64.6% to 75.1% by 2005-2008, then decreased to 59.5% by 2017-2020. Low-density lipoprotein cholesterol < 100 mg/dL, non-high-density lipoprotein cholesterol < 130 mg/dL, antidiabetic medication use and antihyperlipidemic medication use increased from 30.4%, 22.8%, 58.6%, and 33.8% to 46.4%, 45.6%, 74.2%, and 38.8%, respectively. Recommended antidiabetic medication use decreased from 37.6% to 24.2% by 2009-2012, then increased to 59.2% by 2017-2020.

Conclusions: After a decade of decline, the prevalence of any CKD and albuminuria increased among US adults with diabetes, while CKD G3a plateaued. CKD G4-G5 peaked during 2005-2012 and decreased thereafter. Lipid control and use of antidiabetic and antihyperlipidemic medications among adults with concomitant CKD increased in the past 2 decades, whereas BP control decreased. This study provided updated trends in the prevalence of chronic kidney disease (CKD) in diabetes and in risk factor control and medication use in diabetes and CKD by using a nationally representative sample of the whole US noninstitutionalized population. Among US adults with diabetes, the prevalence of CKD decreased in earlier years but increased in recent years, while improvements in medication use for diabetes and lipids were observed, though blood pressure control declined.

Background: Studies on morbid obese diabetic and non-diabetic patients' social characteristics and habits, in candidates for bariatric surgery (BS) are few. To gain further insights, we investigated 799 morbid obese diabetic (n = 111) and non-diabetic patients (n = 688).

Methods: Family history of cardiometabolic diseases, personal history, education and occupation, comorbidities, daily habits, previous dietetic treatment, reasons and pathway to BS were investigated. Team members involved and examinations performed were also analyzed.

Results: Family histories of obesity, diabetes and hypertension significantly associated with each other, and clinically overt diseases were also associated with family histories of the same disease, as diabetes and hypertension, and were more frequent in diabetic as compared to non-diabetic (p > 0.05, p < 0.0001 and p < 0.05). Females significantly differed from males for lower body mass index (BMI) (mean 41.2 vs 42.8 kg/m²), and a lower alcohol intake (p < 0.05 to p < 0.001). Knowledge about BS and reasons for BS varied according to age. BS was mostly requested for medical reasons (80.1%).

Conclusions: Patients seeking bariatric surgery have a valid and well structured idea of obesity and are aware of the importance of eating less and physical activity in managing obesity, with differences linked to their educational levels. The interaction between physicians and surgeons improved the overall prognosis of patients seeking BS, based on screening of CV risk factors. Improved patients long term follow-up after surgery, identification of the suitable pre-BS diets, as well and identification of patients who might benefit from non-BS approaches, such as newer medical therapies could improve long term care of obesity.

Over the last 10 years, the number of women with diabetes during pregnancy has increased steadily. Maternal glycaemic control is the most important factor influencing maternal and neonatal outcomes, and technological advances have become integral to the evolution of diabetes care during pregnancy. However, rapid technological development must be accompanied by the equally rapid dissemination of information. In particular, knowledge of the availability of automated insulin delivery (AID) systems for managing type 1 diabetes in pregnancy, and of glucose continuous monitoring (CGM) systems for gestational and type 2 diabetes, needs to be increased. The AMD-SID Italian Diabetes and Pregnancy Study Group, supported by the Technology and Diabetes Study Group, has produced this position paper of expert opinion to review the main international guidelines and current evidence on new technologies for the management of pregnancy in women with GDM, type 1 and type 2 diabetes, and to provide detailed suggestions for the use of commercially available systems in clinical practice.

Aims: Islet transplantation has emerged as a therapeutic option for patients with unstable type 1 diabetes (T1D), but significant islet loss during the peri-transplant period-primarily due to inflammation and substrate deprivation stress-limits its efficacy. Photobiomodulation (PBM), a non-invasive therapy using red or near-infrared light to modulate cellular metabolism, has shown promise in enhancing cell survival under stress. However, its impact on pancreatic beta cells and islets under specific stress conditions remains insufficiently characterized. This study aimed to evaluate the protective and functional effects of PBM (670 nm LED light, 2.8 mW/cm²) when applied as a preconditioning or simultaneous treatment on pancreatic beta cells (MIN6) and rat islets exposed to two major types of stress encountered during islet transplantation: substrate deprivation and inflammatory cytokines. The hypothesis tested was that PBM could improve cell viability and insulin secretion under these stress conditions.

Methods: A series of in vitro experiments were conducted using MIN6 cells and isolated rat islets. PBM was applied either for 24 h before or during stress exposure. Substrate deprivation stress (SDS) was induced by glucose and serum-free medium, while cytokine stress involved incubation with IL-1β, TNF-α, and IFN-γ. Outcomes assessed included cell viability (flow cytometry and confocal microscopy), insulin secretion (GSIS assay), mitochondrial function (mitochondrial membrane potential (MMp), superoxide content, oxygen consumption), and cellular energy metabolism (ATP/ADP content via HPLC). Statistical significance was evaluated using ANOVA and post-hoc tests, with p < 0.05 considered significant.

Results: PBM significantly preserved viability in both MIN6 cells and islets subjected to SDS and cytokine stress. Under SDS, PBM mitigated increases in superoxide production and declines in mitochondrial membrane potential and ATP content in MIN6 cells but did not restore insulin secretion or mitochondrial respiration. In cytokine-stressed cells and islets, PBM restored glucose-stimulated insulin secretion and reduced superoxide content but did not significantly impact MMP or ATP/ADP ratios. Protective effects varied by the timing of PBM application and the type of stress, with some differences observed between cell lines and intact islets.

Conclusions: PBM exerts beneficial effects on pancreatic beta cell and islet viability and function under stress conditions relevant to islet transplantation, although its mechanisms appear to differ depending on the type of stress. These findings support further investigation into PBM as a preconditioning strategy to enhance islet survival and functionality, potentially improving outcomes in islet transplantation for patients with T1D.

Mitochondrial dysfunction plays a crucial role in the pathophysiology of Type 1 Diabetes (T1D), as it compromises beta (β)-cell survival and insulin secretion. Autoimmune-driven inflammation disrupts mitochondrial homeostasis and thereby induces oxidative stress, disturbs calcium signaling, and activates apoptotic cascades that together impair β-cell viability. This review outlines mitochondrial quality control mechanisms, including fusion-fission dynamics, mitophagy, and cardiolipin remodeling, and explains how their dysregulation exacerbates β-cell dysfunction. In particular, mitochondrial proteins such as olfactomedin-4 modulate insulin release and thus provide potential therapeutic targets. Furthermore, crosstalk between the endoplasmic reticulum (ER) and mitochondria also influences β-cell resilience, with ER stress triggering pro-apoptotic signaling, particularly through CHOP-mediated pathways. Pharmacological approaches, including antioxidants, coenzyme Q10, dipeptidyl peptidase IV inhibitors, and imeglimin, together with natural agents such as SIRT3 activators and Vernicia fordii extracts, have shown efficacy in preserving mitochondrial integrity and promoting β-cell functions in animal studies. Further, this review also summarizes critical drug candidates, their mechanisms of action, and cellular outcomes. Collectively, emerging insights underscore mitophagy regulation, lipid metabolism, and calcium balance as promising avenues for restoring mitochondrial function and advancing therapeutic strategies in T1D.

Aim: This study investigated the association between diabetic retinopathy (DR) and histologic features in patients with histologically confirmed diabetic kidney disease (DKD).

Methods: Of 250 patients who underwent kidney biopsy, 108 patients with biopsy-confirmed DKD were included (DKD with DR, n = 71; DKD without DR, n = 37). DKD was classified into classes I-IV using the Renal Pathology Society Classification. Systemic inflammation was assessed using the red blood cell distribution width/albumin ratio (RAR) and C-reactive protein (CRP) levels.

Results: Patients in the DR (+) group were younger and had higher systolic blood pressure. They exhibited significantly lower estimated glomerular filtration rate (36.7 vs. 59.9 mL/min/1.73 m², p = 0.001) and serum albumin (3.4 vs. 3.9 g/dL, p = 0.001). While CRP levels did not differ between groups, RAR was significantly higher in the DR (+) group (3.935 vs. 3.407, p = 0.003). Histologically, kidney injury was more severe in the DR (+) group, with higher frequencies of class III (54.9% vs. 37.8%) and class IV (35.2% vs. 18.9%) disease. Linear deposition of immunoglobulin (Ig) G and light-chain positivity on immunofluorescence staining were also more common in the DR (+) group (IgG: 66.2% vs. 43.2%; light-chain : 53.5% vs. 29.7%).

Conclusion: In biopsy-confirmed DKD, the presence of DR is associated with more severe renal pathology and increased systemic inflammation. These findings support the clinical relevance of DR screening in patients with DKD and highlight the need for prospective validation.

Skeletal muscle wasting is a major yet often overlooked determinant of adverse outcomes in diabetes mellitus and obesity. Loss of muscle mass and strength not only impairs mobility and quality of life, but also worsens insulin resistance, accelerates cardiometabolic decline and increases mortality risk. The convergence of chronic inflammation, mitochondrial dysfunction and altered protein metabolism makes individuals with metabolic diseases particularly vulnerable to sarcopenia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the therapeutic landscape of type 2 diabetes (T2D) and obesity by offering substantial weight loss and cardiometabolic protection. However, clinical trials and real-world evidence consistently show that weight reduction with GLP-1RAs is accompanied by decrease in lean body mass, raising concern in patients already predisposed to muscle wasting and underscoring the need for integrated management strategies. By including all English-language studies on muscle mass loss during GLP-1RA therapy in T2D and obesity from major scientific databases and clinical trial registries, this narrative review synthesizes the current knowledge on the epidemiology and mechanisms of muscle loss in diabetes and obesity, with a focus on the impact of GLP-1RAs therapy. It further examines preventive and therapeutic strategies to preserve muscle health during pharmacological weight loss, with the ultimate aim of providing clinicians and researchers with practical insights and future directions to maximize the benefits of GLP-1RAs while mitigating the risk of sarcopenia.