Quantification of pancreatic iron overload and fat infiltration and their correlation with glucose disturbance in pediatric thalassemia major patients.

Background: Diabetes mellitus affects more than a quarter of patients with thalassemia major (TM) worldwide, and increases the risk for cardiac complications, contributing to significant morbidity. Pancreatic iron overload (IO) and fat infiltration have been correlated with this endocrinal complication in adult TM patients. It has been shown that in adult TM patients, iron accumulation and fat infiltration are found to be heterogeneous in the pancreatic head, body, and tail region. R2* and a fat fraction (FF) generated by gradient-echo imaging can be used as quantitative parameters to assess the iron and fat contents of the pancreas. This study aimed to determine the pattern of pancreatic iron accumulation and fat infiltration in pediatric TM patients with gradient-echo imaging and evaluate the association between pancreatic IO and fat infiltration and glucose disturbances.

Methods: A total of 90 children with TM (10.7±3.1 years) were included. All patients underwent pancreatic magnetic resonance imaging (MRI) using multi-echo gradient-echo sequences. IO was measured by R2* relaxometry in 90 patients, and FF values were measured using iterative decomposition of water and fat with echo asymmetry and the least-squares estimation (IDEAL) method in 40 patients. R2* and FF were assessed in the pancreatic head, body, and tail. The global R2* and global FF values were obtained by averaging the respective values from the pancreatic head, body, and tail. The correlations between global R2*, global FF, and fasting glucose were determined using Spearman's correlation analysis. The Friedman test was used to compare R2* and FF among different pancreatic regions. Receiver operating characteristic (ROC) analysis was used to determine the performance of global R2* and global FF in discriminating impaired fasting glucose from normal fasting glucose patients.

Results: The global R2* was positively correlated with the global FF in the pancreas (r=0.895, P<0.001). No significant differences were found in R2* among the 3 regions of the pancreas (χ=4.050, P=0.132), but significant differences were found in FF among the 3 pancreatic regions (χ=16.350, P<0.001). Both global pancreatic R2* (r=0.408, P<0.001) and global FF (r=0.523, P=0.001) were positively correlated with fasting glucose. ROC analysis showed that global pancreatic R2* and global FF had an area under the curve of 0.769 and 0.931 (both P<0.001), respectively, in discriminating between impaired and normal glucose function patients.

Conclusions: Pediatric TM patients can have homogeneous iron siderosis and heterogeneous fat infiltration in the pancreas as measured by gradient-echo imaging, both of which are risk factors for diabetes.