Pontiroli AE, Guarino S, Tagliabue M
… +12 more, La Sala L, Centofanti L, Olmi S, Sarro G, Giovanelli A, Asteria C, Galfrascoli E, Mortola U, Bucciarelli L, Zappa MA, Tagliabue E, Folli F
Acta Diabetol
· 2026 Apr · PMID 41222662
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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 diab...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/m), 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.
Resi V, Bianchi C, Burlina S
… +6 more, Grancini V, Manicardi E, Masulli M, Scarpitta AM, Sorice GP, Fresa R
Acta Diabetol
· 2026 Jun · PMID 41212214
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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 adv...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 d...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 homeos...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.
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...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.
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 kidne...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.
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 depe...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.
Rossi G, Bucciarelli L, Mananguite CL
… +2 more, Giovarelli M, Fiorina P
Acta Diabetol
· 2026 Feb · PMID 41201615
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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 i...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.
Gitto M, Catapano F, Francone M
… +13 more, Mincione G, Scialò V, Pivato CA, Lisi C, Regazzoli D, Cao D, Fiorina RM, Petrelli A, Bucciarelli L, Loretelli C, Condorelli G, Fiorina P, Stefanini G
Acta Diabetol
· 2026 Feb · PMID 41186740
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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:...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 rol...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.
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 o...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.
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 (ST...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.
BACKGROUND AND OBJECTIVE: Diabetic complications can significantly affect the quality of life and prognosis of patients with diabetes. This study employed a systematic approach to elucidate the causal relationship betwee...BACKGROUND AND OBJECTIVE: Diabetic complications can significantly affect the quality of life and prognosis of patients with diabetes. This study employed a systematic approach to elucidate the causal relationship between serum metabolites and six prevalent diabetic complications using a Mendelian randomization (MR) strategy. METHODS: Serum metabolite data were obtained from genome-wide association studies, and data on six diabetic complications were acquired from the FinnGen consortium. A two-sample MR approach was used to investigate the association between serum metabolites and common diabetic complications. Reverse MR analysis was conducted to investigate potential causal relationships between diabetic complications and serum metabolite levels. Sensitivity analyses were performed to evaluate the robustness of our findings. Analyses included inverse-variance-weighted, MR-Egger, linkage disequilibrium score regression, and colocalization approaches. RESULTS: We identified 81 causal associations, highlighting the significance of serum metabolites in the context of diabetic complications. The results identified significant causal associations: Bilirubin degradation products were inversely linked to diabetic retinopathy, while androstane sulfate and N-succinyl-phenylalanine increased the risk of retinopathy. Caffeine metabolites and adenosine 5'-monophosphate-to-citrate ratios were positively associated with nephropathy. Reverse MR analysis confirmed unidirectional causality, and sensitivity tests ruled out pleiotropy. Colocalization analyses highlighted shared genetic loci, such as rs2991970, between metabolites and hypoglycemia. CONCLUSION: These findings elucidate metabolite-specific pathways underlying diabetic complications and propose novel biomarkers for risk stratification. The limitations of this study include its European-centric nature and the lack of stratified covariates. This study highlights the value of integrating genetic and metabolomic data to enhance precision medicine in diabetes management.
Russo GT, Nicolucci A, Cuttone A
… +9 more, Ceriello A, Manicardi V, Rocca A, Prattichizzo F, Lucisano G, Corrao S, De Cosmo S, Di Cianni G, Candido R
Acta Diabetol
· 2026 Mar · PMID 41165847
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PURPOSE: Characteristics defining "early" type 2 diabetes (T2D) are unclear, and type and timing of treatment intensification with glucose-lowering drugs (GLD) in these patients are understudied. METHODS: Within the AMD...PURPOSE: Characteristics defining "early" type 2 diabetes (T2D) are unclear, and type and timing of treatment intensification with glucose-lowering drugs (GLD) in these patients are understudied. METHODS: Within the AMD Annals Initiative, we evaluated the prevalence and clinical characteristics of early T2D subjects, evaluated by diabetologists and defined according to a recent Delphi Consensus. Patient characteristics of early T2D subjects were compared to those of non-early patients. We also explored the time and mode of first intensification in a longitudinal cohort from 2010 to 2023. RESULTS: Overall, 127,456 people were seen in 2023, of whom 10,700 (8.39%) showed an early phenotype. Early patients were younger, more often females, had lower HbA1c, used less cardiovascular-related drugs, and had a lower prevalence of cardiovascular disease. CONCLUSION: In real life, T2D could be considered as early in only ~ 8% of people. Among them, less than 10% received treatment intensification during the first year of observation, although the timing of the introduction of add-on GLD improved during time and drugs with cardiovascular benefit were often chosen as second-line GLD. In longitudinal analysis, of 42,786 early patients initially treated with metformin, 9.37% were prescribed an add-on treatment during 12 months, more frequently represented by SGLT2i, followed by GLP1-RAs and DPP4i. Mean level of HbA1c at treatment intensification improved over time, suggesting an encouraging trend through a proactive approach.
Diabetic gastroparesis is characterized by delayed gastric emptying due to diabetes mellitus, affecting up to 50% of patients with type 1 and type 2 diabetes who have poor glycemic control, significantly impairing their...Diabetic gastroparesis is characterized by delayed gastric emptying due to diabetes mellitus, affecting up to 50% of patients with type 1 and type 2 diabetes who have poor glycemic control, significantly impairing their quality of life. IGF-1 presents significant potential as a therapeutic target for DGP due to its neuroprotective effects and its role in inhibiting smooth muscle cell apoptosis. By promoting the survival and regeneration of interstitial cells of Cajal and reducing inflammation, IGF-1 could enhance gastrointestinal regulation, thereby improving gastric motility and alleviating DGP symptoms. Although IGF-1 has not yet been utilized as a targeted therapy for DGP, its ability to modulate key signaling pathways, such as SCF/C-Kit, PI3K/AKT, and ERK/MAPK, suggests promising therapeutic avenues. Future research should focus on investigating these mechanisms to determine IGF-1's precise role in DGP pathophysiology and explore its clinical applications.
BACKGROUND: Gestational diabetes mellitus (GDM) is a common metabolic disorder that creates considerable risks regarding both maternal and fetal health. Conventional screening approaches for GDM which are typically perfo...BACKGROUND: Gestational diabetes mellitus (GDM) is a common metabolic disorder that creates considerable risks regarding both maternal and fetal health. Conventional screening approaches for GDM which are typically performed in the late second trimester; frequently miss an important window for early intervention. METHODS: This meta-analysis seeks to evaluate the diagnostic accuracy of first-trimester maternal serum biomarkers, particularly pregnancy-associated plasma protein-A (PAPP-A) and beta-human chorionic gonadotropin (β-hCG), in the prediction of GDM. This systematic review of observational studies was conducted to assess PAPP-A and/or β-hCG levels during the first trimester, examining their correlation with the subsequent diagnosis of GDM. This meta-analysis collected data from numerous studies to evaluate sensitivity, specificity, likelihood ratios and diagnostic odds ratios; alongside with developing summary receiver operating characteristic (sROC) curves. RESULTS: This diagnostic meta-analysis assessed 23 studies encompassing first-trimester PAPP-A and β-hCG measurements with regards to early prediction of GDM. The overall pooled sensitivity and specificity were found to be 63% (95% CI: 53-73%) and 70% (95% CI: 61-78%), alongside an AUC of 0.72 (95% CI: 0.68-0.76). Substantial heterogeneity was observed regarding both sensitivity and specificity (I² >95%). Unaccompanied PAPP-A showed a sensitivity of 67% (95% CI: 55-77%) and specificity of 66% (95% CI: 54-76%) with AUC of 0.71, while β-hCG alone exhibited low sensitivity of 29% (95% CI: 7-69%) despite a high specificity of 87% (95% CI: 64-96%) with its AUC found to be 0.71. Fagan's analysis revealed modest clinical impact; which was found to be raising post-test probability from 20% to ~ 39% after a positive result. Deek's tests suggested no major publication bias (p = 0.45 for overall, 0.41 for PAPP-A, 0.08 for β-hCG). Subgroup analyses revealed higher sensitivity levels in studies utilizing ADA criteria and in studies with smaller samples, while those with cohort designs generated more conservative estimates upon comparison with their case-control counterparts. CONCLUSION: First-trimester PAPP-A and β-hCG are found to express modest diagnostic accuracy and therefore are best considered as adjuncts to early risk stratification regarding GDM. PAPP-A, as stand-alone, provides balanced though moderate levels of sensitivity and specificity, whereas β-hCG shows high specificity levels but very low sensitivity level; thus, limiting its independent predictive value. Neither biomarker is found to be sufficient as a stand-alone diagnostic tool, but both may contribute to comprehensive risk models which might inform timely intervention. Future research should emphasize standardized methodologies and validation in large, diverse populations in order to improve clinical applicability.