Acta Diabetologica最新文献

Aims: Ageing in people with type 1 diabetes is identified as a research gap. Therefore, the aim of our study is to characterize above 65-year-olds with type 1 diabetes, and to identify potential protective factors or factors related to increased risk of mortality in this age group.

Methods: This observational study includes 864 participants aged 55 years or older with type 1 diabetes (age at onset below 40) from the Finnish Diabetic Nephropathy Study, grouped according to age into three categories: 55-60, 60-65, and > 65 years old. Multivariable logistic regression analysis was used to identify factors independently associated with age above 65. Cox regression analysis was conducted to assess how these factors impact survival.

Results: Factors that were independently associated with age above 65 years included: higher diabetes onset age, higher pulse pressure, lower mean arterial pressure, absence of current smoking and diabetic kidney disease, history of severe diabetic retinopathy and cardiovascular events, lower daily insulin dose, lower HbA_1c, and lowerApoB-100 concentrations. Of these factors, the ones associated with mortality in above 65-year-olds during follow-up were presence of diabetic kidney disease, higher HbA_1c, and history of cardiovascular events.

Conclusion: Above 65-year-olds were characterized by both factors generally related to positive and negative health outcomes. Additionally, different factors were found to be associated with reaching older age and with survival beyond the age of 65.

Aims: To investigate the association between depression and refill adherence to cardioprotective medications in a representative cohort of type 1 diabetes adults.

Methods: This Finnish Diabetic Nephropathy (FinnDiane) sub-study included 1,588 adults with type 1 diabetes who had purchased antihypertensive or lipid-lowering drugs within ± 0.5 years from study baseline. The proportion of days covered (PDC) method was used to calculate overall refill adherence over a 10-year follow-up. Adherence was classified into good (> 80%), intermediate (≥ 50 and < 80%), and poor (< 50%). Participants were considered to have depression, if they had a diagnosis of depression or had purchased antidepressive agents at any time point from 1995 until the end of follow-up, identified from national registries. Multinomial logistic regression analysis, adjusted for age, sex, duration of diabetes, education level, HbA_1c, BMI, diabetic kidney disease, smoking, and alcohol consumption was performed.

Results: Of the cohort 37% had depression during the study period. Those individuals with depression were more often women (P = 0.0001), and had lower adherence to cardioprotective medication (P = 0.02) than those without depression. Individuals with depression had 72% higher odds ([95% CI 1.09, 2.70], P = 0.02) of having poor versus good adherence, compare to those without depression. The results persisted after excluding antidepressants potentially used for neuropathic pain (OR 1.61 [95% CI 1.02, 2.55], P = 0.04).

Conclusions: Healthcare professionals should assess presence of depression and monitor medication adherence at regular consultations, and whenever needed, should implement strategies to manage the depression in order to enhance adherence, which might ultimately lead to improved cardiovascular outcomes in type 1 diabetes.

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.