Melatonin, an indoleamine, has been reported to exert cardiovascular protective effects; however, its influence on endothelin-1 (ET-1)–induced vascular reactivity in diabetic endothelial dysfunction remains incompletely...Melatonin, an indoleamine, has been reported to exert cardiovascular protective effects; however, its influence on endothelin-1 (ET-1)–induced vascular reactivity in diabetic endothelial dysfunction remains incompletely understood. The present study aimed to evaluate the functional effects of melatonin on ET-1–mediated vasoreactivity and the involvement of ETA- and ETB-dependent responses in the aortas of streptozotocin (STZ)-induced diabetic rats. Thoracic aortic rings were isolated from non-diabetic, diabetic, and melatonin-treated diabetic rats (30 mg/kg orally for 14 days) and mounted in an automatic organ bath system. Cumulative concentration–response curves to ET-1 were generated in the presence or absence of acute melatonin preincubation and selective ETA (BQ123) and ETB (BQ788) receptor antagonists. Vascular responses were assessed using maximal contraction (Emax), potency (pD₂), and area under the curve (AUC) as functional outcome measures. Diabetes significantly enhanced ET-1–induced vasoconstriction, evidenced by a leftward shift of the concentration–response curve and increased Emax, indicating augmented vascular reactivity. In non-diabetic aortas, acute melatonin preincubation significantly attenuated ET-1–induced contraction, whereas this inhibitory effect was markedly reduced in diabetic vessels. Chronic melatonin treatment partially normalized ET-1 responsiveness in diabetic aortas, reflected by reduced maximal contraction and altered sensitivity to ETA and ETB receptor antagonism. Functional blockade studies further demonstrated that diabetes impaired ETB-dependent vasodilatory responses, which were partially restored following melatonin administration. In conclusion, this study demonstrates that melatonin improves ET-1–induced vascular dysfunction in experimental diabetes by attenuating exaggerated vasoconstrictor responses and modulating ETA- and ETB-dependent functional pathways. These findings support the use of melatonin as a functional vasoprotective agent and highlight its potential as an adjunct strategy for mitigating diabetic vascular complications.
Type 2 Diabetes Mellitus (T2DM) is increasingly recognized as increasingly recognized as not only a metabolic disorder, but also a disease of microbiome–host dysregulation. While the role of the gut microbiota in T2DM ha...Type 2 Diabetes Mellitus (T2DM) is increasingly recognized as increasingly recognized as not only a metabolic disorder, but also a disease of microbiome–host dysregulation. While the role of the gut microbiota in T2DM has been extensively studied, the emerging convergence of precision medicine and microbiome modulation has not been systematically integrated into prior reviews. This work provides a critical synthesis that unites the classical concepts of dysbiosis with cutting-edge insights into microbial metabolites, strain-specific effects, and host–microbe–drug interactions, including the influence of metformin on microbial ecology and the therapeutic potential of Akkermansia muciniphila. We further discuss the underexplored domains, such as the gut virome, microbial gene editing, and short-chain fatty acid subtype-targeted interventions, which may transform T2DM management. We propose a novel conceptual framework for microbiome-guided, individualized T2DM care by framing gut microbiota as a dynamic, patient-specific therapeutic target. The review concludes with a roadmap for translating microbiota signatures into predictive biomarkers and tailored interventions, emphasizing standardized methodologies, multi-omics integration, and cross-disciplinary clinical trials. This perspective shifts the field from descriptive correlations to actionable precision-guided microbiome therapeutics in T2DM. Notably, this review extends beyond existing summaries by integrating emerging concepts, including gut virome contributions, microbial metabolite engineering, and host–microbe–drug interaction frameworks, to position the gut microbiota as a precision-modifiable therapeutic axis. This synthesis not only reviews established associations but also identifies underexplored therapeutic frontiers, including the gut virome, mycobiome, and microbial genome editing, which could reshape precision T2DM management.
Tumminia A, Romano R, Frasca F
… +14 more, Galeano F, Baratta R, Oteri V, Longo A, Frittitta L, Le Moli R, Piticchio T, Di Pino A, Di Marco M, Piazza L, Picardo MC, Magnano San Lio P, Fimognari FL, Romano M
Acta Diabetol
· 2026 May · PMID 41843082
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BACKGROUND: Pain may be absent in a substantial proportion of elderly patients with acute abdominal conditions. This study explored the association between type 2 diabetes mellitus (T2DM) and asymptomatic presentation. M...BACKGROUND: Pain may be absent in a substantial proportion of elderly patients with acute abdominal conditions. This study explored the association between type 2 diabetes mellitus (T2DM) and asymptomatic presentation. METHODS: We conducted a cross-sectional analysis of 215 patients aged ≥ 65 years admitted with acute abdominal conditions. Demographic, clinical, and laboratory data were extracted from medical records. Descriptive statistics and multivariable logistic regression were used to identify associative predictors of asymptomatic acute abdomen (AAA). RESULTS: The median age was 82 years [77-86]; 54.4% (n = 117) were female; 31.2% (n = 67) had T2DM. Overall, 33.5% (n = 72) presented without abdominal pain. T2DM prevalence was higher in AAA than symptomatic patients (44.4% vs. 24.5%, p < 0.01). In multivariable analysis, T2DM (OR 1.95, 95% CI 1.10-3.45, p = 0.02), lower heart rate (OR 0.83, 95% CI 0.71-0.96, p = 0.01), and absence of fever (OR 0.50, 95% CI 0.26-0.95, p = 0.03) were associated with AAA. Among patients with T2DM, longer diabetes duration (12.5 years [10.5-14.5] vs. 8.8 years [5.0-11.0]; p < 0.01) and higher HbA1c (8.2% [7.2-8.7] vs. 7.5% [6.8-7.6]; p = 0.02) were associated with asymptomatic presentation. CONCLUSIONS: Asymptomatic acute abdomen is common among elderly patients. Long-standing and poorly controlled T2DM is associated with absent pain. Prospective studies are needed to clarify causal mechanisms, and early glyco-metabolic assessment may aid recognition of at-risk patients.
AIMS: Diabetes induces skeletal muscle atrophy and capillary regression, especially in oxidative muscles, such as the soleus (SOL). Capillary regression impairs oxygen and substrates delivery, and contributes to metaboli...AIMS: Diabetes induces skeletal muscle atrophy and capillary regression, especially in oxidative muscles, such as the soleus (SOL). Capillary regression impairs oxygen and substrates delivery, and contributes to metabolic dysfunction and vascular complications. Although protective effects of antioxidants have been demonstrated in disuse models, their role in diabetes-induced capillary regression remains unclear. We examined whether dietary astaxanthin supplementation attenuates capillary regression in the SOL muscles of rats with streptozotocin-induced diabetes. METHODS: Twenty-four male Wistar rats (6 weeks old) were randomly divided into three groups: control (CON), streptozotocin-induced diabetes (STZ), and STZ with astaxanthin supplementation (STZ + AST). Diabetes was induced by a single tail vein injection of streptozotocin (STZ; 50 mg/kg). Astaxanthin (100 mg/kg/day) was orally administered to the STZ + AST group for 6 weeks. The SOL muscles were analyzed for the capillary-to-fiber (C/F) ratio, oxidative stress (dihydroethidium [DHE] staining), and expression of angiogenesis- and AGEs-related proteins by western blotting. RESULTS: Rats in the STZ group exhibited decreased muscle C/F ratio, increased DHE fluorescence, and elevated FOXO1 and TSP-1. Astaxanthin supplementation significantly improved the C/F ratio and reduced excessively generated ROS and anti-angiogenic protein expression. In addition, the VEGF-A/TSP-1 ratio improved in the STZ + AST group rats. Although the RAGE levels remained elevated, a downward trend was observed following astaxanthin treatment. DISCUSSION: Astaxanthin supplementation attenuated diabetes-induced capillary regression in the SOL muscles by suppressing oxidative stress and modulating angiogenic signaling. These findings suggest a therapeutic potential for protecting the skeletal muscle microvasculature under diabetic conditions.
Szeliga-Krol J, Betlejewska A, Buraczynska M
… +1 more, Zaluska W
Acta Diabetol
· 2026 May · PMID 41739226
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AIMS: Our study aimed to evaluate the association between the erythropoietin gene rs1617640 polymorphism and diabetic retinopathy (DR) in diabetes patients. METHODS: In this preliminary retrospective study the genotyping...AIMS: Our study aimed to evaluate the association between the erythropoietin gene rs1617640 polymorphism and diabetic retinopathy (DR) in diabetes patients. METHODS: In this preliminary retrospective study the genotyping was performed on 860 DNA samples from Caucasian patients with type 2 diabetes mellitus (T2DM). For analyzing the effect of the polymorphism, patients were assigned into three phenotypic subgroups: non-DR (without retinopathy), NPDR (with non-proliferative diabetic retinopathy) and PDR (with proliferative diabetic retinopathy). The rs1617640 polymorphism was analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and direct DNA sequencing procedures. RESULTS: A statistically significant difference in the polymorphism distribution was observed between T2DM patients with DR (both NPDR and PDR) and those without DR. The minor G allele was associated with the increased risk of DR. In the NPDR subgroup subjects carrying the G allele had 1.53-fold higher risk of developing retinopathy. Similarly, in the PDR subgroup patients carrying the G allele showed almost twofold increased risk of PDR in a dominant model of inheritance. CONCLUSION: Our results demonstrate that in T2DM patients the EPO rs1617460 polymorphism is associated with significantly increased risk of developing DR. This finding can provide a new insight into the role of EPO gene in the pathophysiology of microvascular complications of diabetes.
Balducci S, Haxhi J, Vitale M
… +12 more, Mattia L, Calvi F, Marini M, Ciocca E, Auccello F, Gentile A, Bollanti L, Sacchetti M, Orlando G, Nicolucci A, Pugliese G, Italian Diabetes, Exercise Study (IDES) Investigators
AIMS: To assess the effect of a 1-year supervised exercise training program on long-term mortality in people with type 2 diabetes. METHODS: This is a post hoc analysis of the Italian Diabetes and Exercise Study randomize...AIMS: To assess the effect of a 1-year supervised exercise training program on long-term mortality in people with type 2 diabetes. METHODS: This is a post hoc analysis of the Italian Diabetes and Exercise Study randomized clinical trial, which enrolled 606 physically inactive and sedentary individuals with type 2 diabetes from October 2005 to March 2006. Participants were randomized 1:1 to either an exercise group (EXE) receiving a twice-weekly, progressive, supervised aerobic and resistance exercise training plus a physical activity (PA) counseling or a control group (CON) receiving counseling alone for one year. The vital status of participants was verified on 30 June 2024 by interrogating the Italian Health Card database. RESULTS: A similar number of EXE and CON participants died over a mean 16.2-year follow-up (88 vs. 95, p = 0.536). Likewise, no between-group differences were detected in death rates (unadjusted, 17.62 [95% confidence interval, 14.30-21.71] vs. 19.59 [16.02-23.96] per 1,000 patient-years, p = 0.483; and age- and sex-adjusted, 16.46 [12.81-21.13] vs. 17.93 [13.92-23.09], p = 0.563). Kaplan-Meier estimates (Log Rank = 0.647, p = 0.421) and mortality risk (unadjusted, hazard ratio, 0.888 [95% confidence interval, 0.664-1.187], p = 0.442; and age- and sex-adjusted, 0.922 [0.689-1.233], p = 0.584). A significant relation with mortality was observed for baseline maximal oxygen uptake (VO), but not lower body muscle strength, regardless of study arm, whereas no association was detected for changes from baseline in leisure-time PA, total PA volume, VO, and lower body muscle strength. CONCLUSIONS: In people with type 2 diabetes, a one-year supervised exercise training program had no significant effect on long-term mortality. TRIAL REGISTRATION: isrctn.com; ISRCTN-04252749; URL https://www.isrctn.com/ISRCTN04252749 .
BACKGROUND: Diabetic cardiomyopathy (DCM) is characterized by oxidative stress and a critical loss of myocardial metabolic flexibility, yet therapies targeting these intrinsic disease drivers remain limited. We investiga...BACKGROUND: Diabetic cardiomyopathy (DCM) is characterized by oxidative stress and a critical loss of myocardial metabolic flexibility, yet therapies targeting these intrinsic disease drivers remain limited. We investigated whether cardiac-restricted activation of nuclear factor erythroid 2-related factor 2 (Nrf2) protects against DCM by orchestrating metabolic rewiring beyond its canonical antioxidant role. METHODS: This study integrated human bulk and single-nucleus transcriptomics with a cardiomyocyte-specific Nrf2 gain-of-function mouse model subjected to streptozotocin (STZ)-induced diabetes. RESULTS: Human transcriptomic analysis revealed that Nrf2 suppression is a hallmark of the DCM gene signature and correlates with mitochondrial dysfunction. In vivo, cardiomyocyte-restricted Nrf2 overexpression significantly attenuated diabetes-induced systolic and diastolic dysfunction, preventing ventricular dilation and myocardial fibrosis. At the single-cell level, Nrf2 activation preserved sarcomere shortening kinetics and mitochondrial respiration while reducing oxidative injury. Mechanistically, Nrf2 prevented the metabolic collapse typical of diabetic hearts by sustaining two parallel signaling axes: it restored Akt phosphorylation to maintain glycolytic competence and preserved AMPK-PGC-1α signaling to support fatty acid oxidation (FAO) capacity. Crucially, pharmacological inhibition of PI3K/Akt or AMPK abolished the Nrf2-mediated preservation of glycolysis and FAO, respectively, confirming that Nrf2 confers protection through this coordinated metabolic regulation. CONCLUSION: These findings identify a novel Nrf2–Akt–AMPK–PGC-1α signaling axis that safeguards the heart against diabetic injury. By re-establishing metabolic flexibility and redox homeostasis, cardiomyocyte-restricted Nrf2 activation represents a potential disease-modifying strategy for DCM.
BACKGROUND: Obesity includes a wide range of metabolic conditions. Some patients remain metabolically healthy despite excess body weight (MHO phenotype), while others develop metabolic syndrome and metabolic dysfunction–...BACKGROUND: Obesity includes a wide range of metabolic conditions. Some patients remain metabolically healthy despite excess body weight (MHO phenotype), while others develop metabolic syndrome and metabolic dysfunction–associated fatty liver disease (MAFLD). These differences may determine the risk of diabetes and cardiovascular disease. The present study compared clinical and biochemical characteristics between people with MHO and those with MetS combined with MAFLD, and evaluated the effects of six months of metformin therapy in the latter group. METHODS: A total of 78 adults with obesity (BMI ≥ 30 kg/m2) were examined. Participants were classified as MHO (n = 26) or as having metabolic syndrome with MAFLD (n = 52). Anthropometric data, glucose and lipid metabolism indicators, liver enzymes, and non-invasive measures of hepatic steatosis and fibrosis (CAP, FIB-4, HSI) were recorded. Patients with MetS + MAFLD were randomized to lifestyle modification (Mediterranean diet and moderate exercise) or the same program plus metformin (500 mg twice daily) for six months. RESULTS: After six months, patients in the metformin group showed significant improvements in fasting glucose (− 0.9 ± 0.4 mmol/L, p < 0.001), HbA1c (− 0.5 ± 0.2%, p < 0.001), and HOMA-IR (p < 0.001), accompanied by modest weight reduction (− 1.6 ± 0.8 kg, p = 0.02). ALT and AST decreased (p = 0.001 and p = 0.003, respectively), and CAP values fell by 9% (p = 0.004). Fibrosis indices FIB-4 and HSI both improved (p < 0.001). Triglycerides (p = 0.01) and blood pressure (p < 0.05) decreased, while HDL-cholesterol increased (p = 0.02). CONCLUSIONS: People with MHO showed preserved metabolic function and no signs of fatty liver despite similar BMI. In patients with metabolic syndrome and MAFLD, metformin treatment for six months led to meaningful improvement in glucose control, liver function, and lipid profile.
Sarlak H, Shakir K, Rogati G
… +3 more, Leardini A, Berti L, Caravaggi P
Acta Diabetol
· 2026 May · PMID 41706181
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BACKGROUND: Therapeutic footwear plays an important role in preventing ulceration in people with diabetes. Despite guidelines recommending offloading footwear for individuals at risk of ulceration, limited data are avail...BACKGROUND: Therapeutic footwear plays an important role in preventing ulceration in people with diabetes. Despite guidelines recommending offloading footwear for individuals at risk of ulceration, limited data are available on the alignment between current industrial practices, clinical expectations, and evidence. This study explored current practices, priorities and challenges associated with diabetic footwear from manufacturers’ and clinicians’ perspectives across Europe. METHODS: An exploratory cross-sectional survey was conducted between May and October 2025 to gather insights from diabetic footwear manufacturers and clinicians involved in diabetic foot care across Europe. A 26-item questionnaire was developed to explore product design, materials, innovation, and adherence to guidelines among manufacturers. Additionally, a separate 14-item questionnaire for clinicians examined footwear prescription, patient barriers, and industry communication. Quantitative data were analysed descriptively, and open-text responses underwent thematic analysis. RESULTS: Nine manufacturers and twelve clinicians participated in the survey. While only half of the Manufacturers that completed the survey reported having a research and development department, most reported adopting data-driven design approaches (n = 8) and scientific literature (n = 7). Offloading, internal volume, and toe protection were the highest-ranking priorities for manufacturers, whereas aesthetics ranked lowest. Clinicians, conversely, prioritised accommodation of deformities, offloading, and comfort, and highlighted poor aesthetics and shoe weight as major limitations to adherence. CONCLUSIONS: This exploratory study suggests partial alignment between diabetic footwear manufacturers and clinicians on functional and offloading features but highlights gaps in aesthetics, materials, and sustainability. Better collaboration, data-driven innovation, and clearer product specifications could improve user adherence, prescription efficacy, and the preventive role of therapeutic footwear in diabetes care.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have profoundly reshaped the therapeutic landscape of type 2 diabetes mellitus (T2DM). In this narrative review,...Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have profoundly reshaped the therapeutic landscape of type 2 diabetes mellitus (T2DM). In this narrative review, we critically appraise the published literature on the combined effects of these two classes on cardiovascular outcomes, heart failure, and kidney disease. Randomized controlled trials indicates that combination therapy achieves greater reductions in HbA1c compared with either agent alone. Meta-analyses demonstrate that both GLP-1RAs and SGLT2i reduce the risk of major adverse cardiovascular events (MACE) to a comparable extent, while SGLT2i provide superior benefits in mitigating hospitalization for heart failure and slowing chronic kidney disease progression. However, cardiovascular outcome trials (CVOTs) have not demonstrated a synergistic or additive protective effect of combined therapy on MACE or renal endpoints. In contrast, real-world evidence suggests incremental benefits across MACE, heart failure, and renal outcomes, supporting the hypothesis that complementary mechanisms of action may translate into broader protection in clinical practice. In this context, the aim of the present work is to summarize the existing meta-analyses that have evaluated both real-world studies and randomized controlled trials assessing the combination therapy of GLP-1 receptor agonists and SGLT2 inhibitors.Globally, GLP-1RAs and SGLT2i should be regarded as complementary rather than alternative therapeutic strategies. Randomized evidence supports the individual efficacy of each class and real-world data increasingly endorse their combined use to optimize cardiovascular and renal protection in patients with T2DM.
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by insulin resistance, chronic hyperglycemia, and oxidative stress. Recent research has highlighted the therapeutic potential of gut micro...BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by insulin resistance, chronic hyperglycemia, and oxidative stress. Recent research has highlighted the therapeutic potential of gut microbiota-derived metabolites in regulating glucose homeostasis. AIM: This study evaluated the antidiabetic effects of indole propionic acid (IPA) in a streptozotocin-induced diabetic rat model. METHOD: Male Wistar rats (n = 30) were divided into Control, T2DM, T2DM + IPA, T2DM+metformin, and IPA-only groups. Following four weeks of oral IPA administration, biochemical, histological, molecular, and metabolomic assessments were performed. RESULTS: IPA treatment significantly reduced fasting blood glucose levels, improved body weight, and normalized food intake in diabetic rats. Histopathological analysis revealed that IPA preserved pancreatic islet architecture and increased both islet cell counts and diameter. Furthermore, IPA markedly enhanced antioxidant defenses by elevating superoxide dismutase (SOD) and catalase (CAT) activities while reducing malondialdehyde (MDA) content in pancreatic tissue. Molecular analysis showed that IPA upregulated the expression of key insulin signaling genes—PI3K, Akt, and GLUT4—in skeletal muscle and downregulated mTOR expression in pancreatic tissue, indicating improved insulin sensitivity. Molecular docking suggested a potential direct interaction between IPA and GLUT4/PI3K, supporting the gene expression data. CONCLUSION: These findings highlight the multifaceted antidiabetic potential of IPA, supporting its use as a promising therapeutic agent for managing T2DM and its associated metabolic dysfunctions.
Płoszaj T, Skoczylas S, Gadzalska K
… +25 more, Gorządek M, Jakiel P, Juścińska E, Borowiec M, Mojsak P, Oto A, Ołubiec A, Chobot A, Cypryk K, Głowińska-Olszewska B, Iwaniszewska B, Jarosz-Chobot P, Kasznicki J, Kowalska I, Mazur A, Moczulski D, Myśliwiec M, Nazim J, Robak-Kontna K, Skowrońska B, Stawerska R, Szadkowska A, Urbańska-Kosińska M, Walczak M, Zmysłowska A
Despite years of experience from scientific teams around the world, diagnosing the cause of monogenic diabetes (MD) remains a challenge, mainly due to the proper definition of the patients' phenotype and the multitude of...Despite years of experience from scientific teams around the world, diagnosing the cause of monogenic diabetes (MD) remains a challenge, mainly due to the proper definition of the patients' phenotype and the multitude of molecular causes. Our goal was to present the results of the efforts to make the molecular diagnosis of patients with suspected MD as precise as possible from the last few years of our Rare Disease Center for Children and Adolescents and Diabetogenetics using the NGS (Next Generation Sequencing) method. We used a targeted NGS panel and whole exome sequencing (WES) data. The study group consisted of 644 individuals, including 501 patients who were referred from 17 Polish diabetes centers with suspected MD and who were diagnosed between January 2020 and December 2023, as well as their 143 family members. The median age for the patients was 14 years (IQR: 9-18). Overall, MD was confirmed by identifying the causative genetic variant in 43.3% of probands. We identified causative variants in 16 genes, most commonly in GCK and HNF1A (85.7%), mainly of the SNV (single nucleotide variant) type, and CNV variants in the GCK and HNF1B genes (1.4%). Using WES data, we could also identify the 17q12 syndrome in one patient. The subgroups of MD and unresolved patients differed in regard to age of clinical and genetic diagnosis (p = 0.00714 and p = 0.00004), birth weight (p = 0.00255), BMI (p = 0.00075), and HbA1c (p = 0.00001). Analysis of WES data (44%) and targeted gene panels (43%) provided similar results in successful diagnosis of MD. However, WES data offer a more complete molecular picture for the diagnosis of MD, especially for large rearrangements, and allow for kinship and ethnicity analysis, which can expand the scope of the diagnosis.
BACKGROUND: Sleeve gastrectomy (SG) induces substantial metabolic improvement in patients with type 2 diabetes (T2DM), but glycemic remission remains heterogeneous. We evaluated metabolic, continuous glucose monitoring (...BACKGROUND: Sleeve gastrectomy (SG) induces substantial metabolic improvement in patients with type 2 diabetes (T2DM), but glycemic remission remains heterogeneous. We evaluated metabolic, continuous glucose monitoring (CGM), and quality-of-life (QoL) outcomes after SG according to remission status. METHODS: Prospective observational study of patients with severe obesity and T2DM undergoing SG that were evaluated preoperatively and at 12 months. Patients were analyzed in T2DM remission (RG) and persistent diabetes (PG) groups. RESULTS: RG included 15, while PG 18 patients. Weight loss and excess BMI loss were comparable between groups. RG demonstrated greater improvement in fasting glucose and HOMA-IR at follow-up, while HOMA-B decreased significantly in RG but increased in PG, suggesting divergent β-cell adaptation. CGM showed significant postoperative improvement in both groups, with consistently lower mean glucose and fewer hyperglycemic readings in RG. Hypoglycemia indices increased in both groups. QoL improved substantially across BAROS and SF-36 domains, with more pronounced physical improvements; between-group differences in QoL were modest despite distinct metabolic trajectories. CONCLUSIONS: SG provided meaningful metabolic and quality-of-life benefits, particularly in patients achieving remission, suggesting potential benefits of earlier surgical referral before advanced β-cell deterioration limits the potential for metabolic recovery, and highlighting the value of CGM for individualized postoperative de-escalation of therapy.
AIMS: Genome-wide association studies (GWAS) have identified the IGF2BP2 (Insulin-like Growth Factor 2 mRNA binding protein 2) gene as a susceptibility locus for Type 2 diabetes mellitus (T2D). This study aimed to evalua...AIMS: Genome-wide association studies (GWAS) have identified the IGF2BP2 (Insulin-like Growth Factor 2 mRNA binding protein 2) gene as a susceptibility locus for Type 2 diabetes mellitus (T2D). This study aimed to evaluate the IGF2BP2 mRNA levels in the blood of a cohort of T2D patients and to quantify the expression levels of non-coding RNAs (ncRNAs) that are predicted to interact with it. METHODS: We extracted RNA from peripheral blood mononuclear cells of 50 T2D patients and 30 healthy controls (CTRL) and quantified, by qPCR, the IGF2BP2 expression levels. Using bioinformatics tools, we predicted its main ncRNAs target and quantified it. RESULTS: The expression study showed a significantly higher IGF2BP2 level in T2D subjects than in CTRL. In silico analysis identified hsa-let7b-5p as a potential microRNA regulator of IGF2BP2, with reduced expression levels observed in T2D patients. Additionally, three lncRNAs (SNHG5, HOTAIR, and MEG3) were predicted as potential targets of IGF2BP2. Their expression levels were significantly elevated in T2D patients. In vitro assays demonstrated that inhibiting hsa-let7b-5p in HeLa cells resulted in increased expression of IGF2BP2 and the three lncRNAs. CONCLUSION: These findings highlight a potential regulatory network involving IGF2BP2, hsa-let7b-5p, and lncRNAs. This network may contribute to dysregulation of insulin/IGF signaling and glucose metabolism pathways, providing insights into T2D pathogenesis.
In patients with Type 1 Diabetes Mellitus (T1DM), diabetic gastroparesis is associated with increased risk of severe hypoglycemia, pronounced glycemic variability and higher HbA1c. Data concerning the efficacy and safety...In patients with Type 1 Diabetes Mellitus (T1DM), diabetic gastroparesis is associated with increased risk of severe hypoglycemia, pronounced glycemic variability and higher HbA1c. Data concerning the efficacy and safety of Automated Insulin Delivery systems (AID) in these patients are extremely limited. We present the case of a patient with T1DM, asymptomatic diabetic gastroparesis, multiple chronic diabetes complications and suboptimal glycemic control successfully treated with MiniMed 780 hybrid insulin pump.