Imaging-informed evaluation of glucose metabolism and β-Cell function in iron overload disorders: A systematic review
Keywords:
pancreatic MRI, T2* relaxometry, Iron overload, Thalassemia, , β-cell function, , Sickle cell disease, , Glucose metabolism,, OGTT,Abstract
Background: Iron overload disorders — including transfusion-dependent β-thalassemia major (β-TDT), thalassemia intermedia or non- transfusion-dependent thalassemia (NTDT), hereditary hemochromatosis (HH), and sickle cell disease (SCD) impose a progressive, multi-organ iron burden that profoundly disrupts glucose homeostasis. Pancreatic β-cell failure, mediated by iron-catalyzed reactive oxygen species (ROS), accounts for the predominant mechanism of diabetes mellitus (DM) in these conditions. Quantitative magnetic resonance imaging (MRI) using T2*/R2* relaxometry has emerged as the non-invasive gold standard for organ-specific iron quantification, offering unique potential to predict glycemic deterioration at a subclinical stage. Objectives: The main goals of our systematic review were: (i) to synthesize evidence on the relationship between MRI-derived pancreatic and hepatic iron quantification and functional indices of β-cell reserve and insulin sensitivity; (ii) to determine validated diagnostic thresholds of pancreatic T2*/R2* for predicting glucose dysregulation; and (iii) to evaluate the impact of iron chelation strategies on imaging-derived iron parameters and concurrent metabolic outcomes.
Methods: A systematic literature search of PubMed/MEDLINE was conducted from January 1995 to December 2024, combining MeSH terms for iron overload, pancreatic MRI, glucose metabolism, OGTT, and β-cell function. Studies employing quantitative T2* or R2* MRI alongside oral glucose tolerance testing (OGTT) and/or HOMA indices were included. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Pooled correlation coefficients and diagnostic accuracy parameters were synthesized using random-effects models where applicable. Results: Thirty-four studies encompassing 4,821 patients met inclusion criteria. Pancreatic T2*/R2* was the single strongest imaging predictor of glucose
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