Depends on which Penn shows up. The unmotivated Penn who started off strong against GSP, then faded away? Maybe, but Diego's cardio would probably win him(Diego) the fight.
If the Penn who decimated Gomi shows up, then Diego is in big trouble. Hell, the Penn who showed up against Hughes the second time would decimate Diego.
Cardio is the only big factor. Diego is really good, but he's no Penn.