In humans increase in intrapancreatic adipose tissue predicts beta-cell dedifferentiation score before diabetes onset: A pilot study

• Published in: Diabetes research and clinical practice Vol. 221; p. 112029
• Main Authors: Cinti, Francesca, Mezza, Teresa, Severi, Ilenia, Moffa, Simona, Giuseppe, Gianfranco Di, Capece, Umberto, Ciccarelli, Gea, Soldovieri, Laura, Brunetti, Michela, Morciano, Cassandra, Gugliandolo, Shawn, Senzacqua, Martina, Avolio, Adriana, Quero, Giuseppe, Tondolo, Vincenzo, Nista, Enrico Celestino, Moroni, Rossana, Cinti, Saverio, Alfieri, Sergio, Gasbarrini, Antonio, Pontecorvi, Alfredo, Giaccari, Andrea
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.03.2025
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adult; Aged; Beta cell dedifferentiation; Blood Glucose - metabolism; Cell Dedifferentiation - physiology; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Female; Glucose Intolerance - pathology; Glucose Tolerance Test; Humans; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Male; Metabolism; Middle Aged; Pancreas - metabolism; Pancreas - pathology; Pilot Projects; Precision medicine; Prediabetic State - pathology; Adipose tissue; Diabetes; Precision medicine; Metabolism; Beta cell dedifferentiation
• ISSN: 0168-8227; 1872-8227; 1872-8227
• DOI: 10.1016/j.diabres.2025.112029

•What is already known about this subject?•Dedifferentiation contributes to β-cell loss in T2D.•Various % of intrapancreatic adipose tissue accumulation have been reported.•What is the key question?•Is the accumulation of WAT related to β-cell dedifferentiation prior to T2D onset?•What are the new findings?•The % of WAT predicts the % of dediff. β-cells.•1-h post-load glycemia is related to the % of WAT and dediff. β-cells.•How might this impact on clinical practice in the foreseeable future?•The reduction of WAT might become a new target to curb T2D onset. The role of intrapancreatic fat (WAT) in the development of T2D remains debated. In T2D, β-cell dedifferentiation is one of the mechanisms responsible for β-cell failure but its role in prediabetes is unknown. We aimed to investigate the relation between WAT and β-cell dedifferentiation prior to diabetes onset. We evaluated pancreatic samples from patients without history of diabetes, who had previously undergone an oral glucose tolerance test and hyperglycemic clamp. Subjects were divided into 3 glucose tolerance groups: normal (NGT), altered (IGT) or newly diagnosed diabetes (nDM). Dedifferentiation and WAT% were morphologically assessed. WAT was higher in nDM patients compared to NGT and IGT (WAT nDM 43.79 ± 20.83 %, IGT 10.67 ± 8.5 %, NGT 4.43 ± 4.37 %). We observed a progressive increase in dedifferentiation score, in parallel with worsening glucose tolerance (from NGT to IGT to nDM; 4.8 ± 3.8; 32.37 ± 7.4; 40.38 ± 19 respectively). A strong linear regression established that WAT could statistically significantly predict dedifferentiated β-cells (R = 0.86, p = 0.005), and that the predicted increase in dedifferentiated β-cells was 1.25 points for every extra one-point change in WAT. Interestingly, the WAT and dedifferentiation score variable pair were significantly related to 1-hour post-load glycemia. The accumulation of WAT might be responsible for dedifferentiation, making it a potential new target to curb diabetes onset.