The Use of Biochemical Parameters Instead of MRI for the Prediction of Pancreatic Iron Loading Among Patients with β-Thalassemia Major

Patients with β-thalassemia major (BTM) are prone to morbidities and mortalities of iron accumulation as a consequence of transfusional iron overload and increased intestinal iron absorption. The use of cardiac and hepatic T2* measurements to pr edict the amount of iron accumulation in these organs have been studied extensively and was suggested to be used reliably. However, although the use of MRI for the assessment of iron status in other organs such as pancreas is possible, it may not be practical to screen all organs with MRI related to economical issues and also the prolonged imaging durations. Herein, we studied fasting glucose, fasting insulin, HOMA-IR, HOMA-B and oral glucose tolerance results among patients with BTM, to detect the correlations of these measurements with pancreas, cardiac and hepatic T2* or R2* MRI values.

Patients with BTM from a single center were included in the study between February 2013 and January 2014. All patients were above seven years of age, and were on regular erythrocyte transfusion programme. Only the patients who were compliant to iron chelation treatments were included in the study. Patients with hepatitis B or C, and/or cirrhosis were excluded. The study included a total of 37 patients who fulfilled the inclusion and exclusion criteria. Cardiac, hepatic T2* and pancreas T2* and R2* MRI was applied with 1.5 T (Siemens, Symphony, Erlangen, Germany) device. Simultaneous to MRI, fasting glucose, fasting insulin, HOMA-IR, HOMA-B and oral glucose tolerance results were obtained. HOMA-B was calculated as: insulin (μU/ml) x 20/glucose (mg/dl) - 3.5 and the normal range is 130-400. HOMA-IR was calculated as: insulin (μU/ml) x glucose (mg/dl) / 22,5 and the normal range is 0.8-1.6. Insulin resistance is defined as HOMA-IR value above 1.6. Two patients had a diagnosis of diabetes mellitus.

The mean age of patients participating in the study was 20.8 ± 6.3 years (7.1-36.8). Of the study group, 43.3 % was above 20 years of age. According to BMI assessments, 32 (86.5%) of the patients had normal BMI, whereas 5 (13.5%) were underweight.

Insulin resistance was found in 7.4% of the patients. Fasting blood glucose has been shown to increase with decreases of pancreatic T2* values, which was indicative of increase in fasting glucose levels in parallel to increased pancreatic iron accumulation (r= -0,55, p=0.016). Also there was a statistically significant positive correlation between fasting insulin and pancreatic R2* values. (r= 0.59, p= 0.01). A positive correlation was found between fasting insulin levels and pancreas R2* measeures, indicating increase in fasting insulin levels, paralleling the pancreatic iron accumulation. Correlation analysis was perfromed for cardiac and hepatic T2*, pancreas T2*, R2* and simultaneously calculated HOMA-IR and HOMA-B values and a negative correlation was found between liver T2* and HOMA-IR values (r=-0.54, p=0.004). A negative correlation was found between pancreas R2* ile cardiac T2* (r=-0.67, p=0.02), indicating increased pancreatic iron loading in parallel with cardiac iron accumulation.

In centers where T2*/R2* MRI fascilities are unavailable, fasting insulin, fasting glucose, HOMA-IR measurements may be used to predict pancreatic iron overload. Since hepatic iron loading correlated with insulin resistance development, the insulin resistance among patients with BTM may partially be explained with decreased hepatic insulin clearance from heavily iron loaded liver. Additionally, disorders of glucose metabolism should be taken as a sign for the need to exercise caution in terms of cardiac iron overload and just vice versa patients with cardiac iron loading should be examined thoroughly for consequences of pancreatic iron loading. These biochemical tests may be used dynamically and more frequently throughout the control visits, whereas MRI is ordered at most once or twice a year which may cause a delay for the earlier diagnosis.