Acta Diabetologica最新文献

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.

PDX1-MODY is a rare, dominantly inherited form of monogenic diabetes resulting from pathogenic variants in the PDX1 (IPF1) gene. It typically presents with early-onset, non-ketotic hyperglycemia and variable insulin dependence. This report describes two unrelated families carrying confirmed PDX1 variants (c.313G > T [p.Glu105*] and c.492G > T [p.Glu164Asp]) that illustrate the clinical and genetic heterogeneity of PDX1-MODY. Comprehensive next-generation sequencing (NGS) including a 36-gene panel for monogenic diabetes confirmed the variants, which were classified according to ACMG/AMP 2015 guidelines as "pathogenic" (p.Glu105)* and "likely pathogenic" (p.Glu164Asp). Clinically, both pedigrees exhibited preserved C-peptide secretion over decades, absence of autoimmune markers, and progressive β-cell dysfunction, confirming the variable but characteristic phenotype of PDX1-MODY. These cases expand the mutational and phenotypic spectrum of PDX1-MODY and highlight the importance of considering monogenic diabetes in early-onset, antibody-negative cases.

Aims: Diabetic Autonomic Neuropathy (DAN) and Diabetic Peripheral Neuropathy (DPN) are distinct complications of diabetes, but their co-existence remains underexplored. This study aimed to investigate the symptom-driven co-existence of DAN, DPN, and painful DPN.

Methods: In November 2022, an electronic survey was distributed to everyone with diabetes in the North Denmark Region (n = 29,155). The survey included demographic data, and validated questionnaires: the Michigan Neuropathy Screening Instrument (MNSI), Composite Autonomic Symptom Score-31 (COMPASS-31), and Douleur Neuropathique 4 Interview (DN4i). DPN was defined as MNSI ≥ 4, painful DPN as bilateral foot pain with DN4i ≥ 3, and DAN as COMPASS-31 ≥ 16. DAN was further stratified into: symptoms of autonomic dysfunction (SAD)- (< 16), SAD + (16-31), and SAD +  + (≥ 32).

Results: Of 9,913 respondents, 7,321 provided complete data. Mean age was 64.8 yearsand 86.3% had type 2 diabetes. DPN prevalence among those with DAN was 44.6% in type 1 and 39.6% in type 2 diabetes. DPN prevalence rose with DAN severity: 11.1% in SAD-, 26.4% in SAD + , and 58.6% in SAD +  + (p < 0.01). Painful DPN followed a similar trend, increasing from 8.0% in SAD- to 50.2% in SAD +  + (p < 0.01). Linear regression demonstrated a strong association between COMPASS-31 and MNSI scores (p < 0.001), indicating that higher autonomic symptom burden was associated with greater severity of peripheral neuropathy.

Conclusions: DAN, DPN, and painful DPN frequently co-exist. Increasing DAN symptom severity is associated with higher prevalence of both DPN and neuropathic pain and showed a strong linear association with the severity of peripheral DPN, suggesting shared pathophysiological mechanisms beyond isolated small fiber involvement.

Background: Despite advances in therapeutic strategies a significant proportion of acute coronary syndrome (ACS) patients experience early coronary artery disease (CAD) progression, particularly those with diabetes.

Aim: To evaluate CAD progression in diabetic patients treated with glucagon-like peptide 1 receptor agonists (GLP-1Ra) over 1 year after an ACS.

Methods: Patients presenting with non-ST-elevation ACS between 2019 and 2022 were enrolled in a prospective registry and underwent serial coronary computed tomography angiography (CCTA) at baseline (after revascularization, during the index hospitalization) and at 1-year follow-up. The primary endpoint was the absolute change (1 year - baseline) in non-culprit lesion plaque burden (ΔPB) on CCTA, with the absolute change in patient percent atheroma volume (ΔPAV) as a key secondary endpoint. A comprehensive lipidomic, metabolomic, and proteomic plasma assessment was also performed in all GLP-1Ra-treated patients and four randomly selected controls.

Results: Of 28 diabetic patients, 7 (25%) with 22 coronary plaques were treated with GLP-1Ra, and 21 (75%) with 65 plaques received other antidiabetic agents. In the 1-year observation frame, both ΔPB (-5.8 ± 12.8% vs. -1.1 ± 13.6%, p = 0.041) and ΔPAV (-6.1% [-7.3, -1.8] vs. -0.7% [-2.4, 9.8], p = 0.039) were significantly lower in GLP-1Ra-treated patients. Total atheroma volume also showed a numerically greater reduction in the GLP-1Ra cohort (0.7 mm³ [-2.5-8.7] vs. 25.0 mm³ [4.8-39.7]), primarily due to a decrease in plaque fibrofatty volume percentage (-2.9 ± 10.1% vs. 1.0 ± 6.8%, p = 0.042). Lipidomic, metabolomic, and proteomic analyses identified reductions in monoacylglycerols and triacylglycerols, increases in diacylglycerols and phosphatidylethanolamine, a shift from carbohydrate metabolism toward lipid metabolism and hormone regulation, and differential expression of proteins involved in complement activation, endothelial function, and cytoskeletal organization in GLP-1Ra-treated patients compared with controls.

Conclusions: In diabetic patients with ACS, GLP-1Ra therapy was associated with a significant regression in coronary plaque burden at 1 year, supported by favorable lipidomic, metabolomic, and proteomic changes. These findings suggest a potential role for GLP-1Ra in modifying atherosclerosis progression beyond glycemic control.

Diabetic neuropathy (DN) is one of the most common chronic complications of diabetes, severely impacting patients' quality of life. Recent studies have demonstrated that endoplasmic reticulum stress (ERS) plays a key role in the development and progression of DN. This article systematically reviews the activation mechanisms of the ERS pathway, its pathological role in DN, and potential therapeutic strategies targeting this pathway. The ER, a crucial site for protein synthesis, folding, and modification in eukaryotic cells, is homeostatically imbalanced, triggering the unfolded protein response (UPR). In the diabetic state, chronic hyperglycemia, oxidative stress, inflammatory factors, and other factors lead to persistent activation of ERS. Through signaling pathways such as PERK, IRE1α, and ATF6, ERS ultimately causes neuronal and Schwann cell apoptosis, mitochondrial dysfunction, and neuroinflammation, promoting the progression of DN. A deeper understanding of the relationship between ERS and DN will not only help elucidate disease mechanisms but also provide a theoretical basis for the development of novel targeted therapies.Diabetic neuropathy (DN) is one of the most common chronic complications of diabetes, severely impacting patients' quality of life. Recent studies have demonstrated that endoplasmic reticulum stress (ERS) plays a key role in the development and progression of DN. This article systematically reviews the activation mechanisms of the ERS pathway, its pathological role in DN, and potential therapeutic strategies targeting this pathway. The ER, a crucial site for protein synthesis, folding, and modification in eukaryotic cells, is homeostatically imbalanced, triggering the unfolded protein response (UPR). In the diabetic state, chronic hyperglycemia, oxidative stress, inflammatory factors, and other factors lead to persistent activation of ERS. Through signaling pathways such as PERK, IRE1α, and ATF6, ERS ultimately causes neuronal and Schwann cell apoptosis, mitochondrial dysfunction, and neuroinflammation, promoting the progression of DN. A deeper understanding of the relationship between ERS and DN will not only help elucidate disease mechanisms but also provide a theoretical basis for the development of novel targeted therapies.

Aim: This study aims to investigate the interplay between post-percutaneous coronary intervention (PCI) microvascular dysfunction and diabetes mellitus (DM) in patients with ST-segment elevation myocardial infarction (STEMI) and their combined impact on prognosis.

Methods: This retrospective study included 1,629 STEMI patients who successfully underwent PCI across three centers. Angio-IMR (angiography-derived index of microcirculatory resistance) was retrospectively measured. The primary endpoint was 2-year major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for heart failure, myocardial re-infarction, and target vessel revascularization.

Result: Among the 1,629 patients, 448(27.5%) had diabetes. Post-PCI angio-IMR value did not differ significantly between DM and non-DM group (33.04 [interquartile range (IQR) 22.20-43.20] vs. 32.02[IQR 22.57-41.60]; P = 0.420). Patients with post-PCI angio-IMR > 40 had significantly higher rates of MACE, irrespective of diabetes status (DM group: 23.1% vs. 6.7%; P < 0.001. Non-DM group: 19.0% vs. 4.8%; P < 0.001. P for interaction = 0.771). Patients with both diabetes and angio-IMR > 40 had the highest hazard ratio (HR) for MACE after adjustment (HR 5.076; 95% confidence interval, 3.157-8.161; P < 0.001).

Conclusions: Post-PCI angio-IMR is an independent predictor of 2-year MACE in STEMI patients, regardless of diabetes status. Patients with both diabetes and post-PCI angio-IMR > 40 had the highest 2-year adverse event rates, underscoring the need for targeted risk assessment and management.

Purpose: This study aimed to provide an economic analysis of the Local Health Authority Turin 5 (ASL TO 5) teleophthalmology diabetic retinopathy screening program.

Methods: A retrospective chart analysis was performed on the diabetologists' digital folder to compare the costs of ASL TO5 screening program to the Italian standard of care based on in-office examination by ophthalmologist . The total cost was calculated for the two methods of screening. Mean annual unadjusted cost data per patient have been calculated by type of cost component.

Results: The study included 3,635 patients with diabetes mellitus screened for diabetic retinopathy (DR) in 2023-24. The total (direct and indirect) cost for teleophthalmology screening program was € 48,976 while the estimated cost for the same quantity of patients screened with traditional examination by ophthalmologist would have been € 148,486. The mean cost per patient of telescreening was € 13.5 ± 5.3 . Conversely traditional screening would have a mean cost € 40.9 ± 28 per patient (p-value < 0.001).

Discussion: Advances in telemedicine are enhancing the DR screening strategies. Telescreening showed cost-savings of approximately € 100,000 for the Local Health Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Authority ASL TO5 over a period of 2 years and for a screened population of 3,635. Telemedicine-based screening emerges as a less costly solution for the Italian National Health Service and can improve accessibility and compliance to this procedure.

Conclusions: This study provides an economic analysis of teleophthalmology DR screening program and highlights significant implications for patients, healthcare professionals and policymakers.