There is much renewed interest in the arrangement and kinetic of hydrogen bonds in water and heavy water. D2O forms a higher average number of hydrogen bonds per molecule (10% more) compared to the case for H2O, which cause a larger entropic cost for solvating molecules in D2O. Here we used isothermal titration calorimetry (ITC) to investigate the enthalpy of titration of D2O-H2O solutions with different D/H isotope ratios. We found significant enthalpy deviations (exothermic contributions) relative to the computed enthalpy for the limit of ideal mixing both for dilution titration and for concentration titration (injection of solutions with lower D/H ratios into solutions with higher ratios and vice versa). We propose that the observed exothermic deviations might be connected to entropic effects associated with differences in the H and D arrangements that depend on the D/H ratio of the solutions. This ratio varies during the titration processes. leading to the entropy production beyond that of ideal mixing. We also used the ITC in the nonstirring mode to measure the titration kinetics and found long relaxation times of up to tens of minutes for the concentration titrations (but not for the dilution titrations). These observations are consistent with slow propagation of the reaction H2O + D2O <-> 2HDO that involves hopping of deuterium and rearrangements of the H and D bonding.