The Exchange Server is losing awareness of it's site and DC/GC information. This is first noticed when MB users lose site of Free Busy information.
Free-Busy agent may appear to lock while it trying to get to other Admin Groups.
Switched Outlook users in cache-mode may see extremely slow download times for new mail.
Mis-configured Exchange connector.
One of the first things that happens when Outlook starts up (and before actually downloading mail) is that it tries to download data from public folders (like OAB) and these clients are connecting (or attempting to) to Admin Groups far outside of the local Admin Group.
On the Exchange Connector, check the box to "Do not allow Public Folder referrals"