Is there any way to change difficulty without making a new profile? When I make a new profile all settings are reset including mouse, hotkeys, etc.

In a text editor, open the .plr file in the "player" subfolder of your game (ex. my profile name is "Player," so my file is \player\Player\Player.plr) and modify the number after "diff" on the 2nd line. "diff 0" = Easy, "diff 1" = Medium and "diff 2" = Hard. I haven't verified that it changes the actual difficulty of the game, but it does change what difficulty is listed next to your profile on the profile screen, so it's worth a shot. If it doesn't seem to make any difference, try restarting or completing the current level, since the difficulty might be re-checked/re-set only when a level is started.

If all fails, you can save and load configurations for your controls.