Serum levels of pancreatic stone protein (PSP)/reg1A as an indicator of beta-cell apoptosis suggest an increased apoptosis rate in hepatocyte nuclear factor 1 alpha (HNF1A-MODY) carriers from the third decade of life onward

We analysed serum PSP/reg1A levels and correlated with clinical and biochemical parameters in subjects with HNF1A-MODY, glucokinase (GCK-MODY), and type 1 diabetes mellitus. A control group of normoglycaemic subjects was also analysed.PSP/reg1A serum levels were significantly elevated in HNF1A-MODY (n？=？37) subjects compared to controls (n？=？60) (median？=？12.50？ng/ml, IQR？=？10.61-17.87？ng/ml versus median？=？10.72？ng/ml, IQR？=？8.94-12.54？ng/ml, p？=？0.0008). PSP/reg1A correlated negatively with insulin levels during OGTT, (rho？=？？0.40, p？=？0.02). Interestingly we noted a significant positive correlation of PSP/reg1A with age of the HNF1A-MODY carriers (rho？=？0.40 p？=？0.02) with an age of 25？years separating carriers with low and high PSP/reg1A levels. Patients with type 1 diabetes mellitus also had elevated serum levels of PSP/reg1A compared to controls, however this was independent of the duration of diabetes.Our data suggest that beta cell apoptosis contributes increasingly to the pathophysiology of HNF1A-MODY in patients 25？years and over. PSP/reg1A may be developed as a serum marker to detect increased beta-cell apoptosis, or its therapeutic response.