| Title: |
Molecular cross-talk via extracellular vesicles for the characterization of young subjects with type 1 diabetes unravels new potential markers of insulin resistance and double diabetes |
| Authors: |
Maria Concetta Cufaro; Ilaria Cicalini; Paola Irma Guidone; Paola Lanuti; Francesca D’Ascanio; Maria Alessandra Saltarelli; Lorenza Sacrini; Anna Piro; Domenico De Bellis; Gessica Di Carlo; Luca Natale; Serena Veschi; Damiana Pieragostino; Piero Del Boccio; Claudia Rossi; Stefano Tumini |
| Source: |
Diabetology & Metabolic Syndrome, Vol 18, Iss 1, Pp 1-15 (2025) |
| Publisher Information: |
BMC |
| Publication Year: |
2025 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
Double diabetes; Extracellular vesicles; FACS-Proteomics; Acylcarnitines; Insulin resistance; Nutritional diseases. Deficiency diseases; RC620-627 |
| Description: |
Background Insulin resistance (IR) is commonly calculated using a simple mathematical formula, the eGDR (estimated Glucose Disposal Rate), but in the paediatric type I diabetes (T1DM) population this value has provided contrasting information. We aimed to provide a clearer metabolic “fingerprint” in children with “double diabetes”, focusing on the molecular cross-talk mediated by extracellular vesicles (EVs). Methods Paediatric patients were classified based on the eGDR value in: insulin-resistant (T1DM+, eGDR < 8 mg/Kg/min, n = 29) and non-insulin-resistant (T1DM-, eGDR > 8 mg/Kg/min, n = 35). Venous blood collected from them, and 30 healthy controls was used to obtain dried blood spots (DBS) for AAs and ACs analysis by FIA-MS/MS and for EV by a patented flow cytometry method. Then, EVs were subjected to shotgun proteomics analysis by LC-MS/MS. Results Our data showed that T1DM + EVs were packaged with proteins involved in fatty acid metabolism suppression through STAT3 inhibition and related to possible liver damage. ACs on DBS samples corroborated these data, demonstrating a significant increase in oleoylcarnitine (C18:1), linoleoylcarnitine (C18:2), and myristoylcarnitine (C14) in T1DM+. The combination of clinical and metabolic data led to the identification of a statistical model with an out-of-bag error of 0.115%, demonstrating that palmitoleoylcarnitine (C16:1) and C18:1 are the metabolites that best distinguish children with T1DM + from T1DM- ones. C16:1 correlated significantly with eGDR (p = 0.0023). Conclusions Combined “omics” approach allowed us to identify a new metabolic “photograph” in a complex context involving diabetes complications related to obesity and IR in a paediatric population that is not yet fully characterized, identifying EVs as well-organized and functionalized shuttles. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1186/s13098-025-02042-7; https://doaj.org/toc/1758-5996; https://doaj.org/article/42a734fcea034b6a8a515ab27900f0ea |
| DOI: |
10.1186/s13098-025-02042-7 |
| Availability: |
https://doi.org/10.1186/s13098-025-02042-7; https://doaj.org/article/42a734fcea034b6a8a515ab27900f0ea |
| Accession Number: |
edsbas.FF852E87 |
| Database: |
BASE |