There are some conditions that cause insulin resistance. These conditions cause cats to need a "high" dose of insulin. A "high" dose is considered any dose above 1u insulin per pound of body weight per day. My cat Norton was at 13U BID at one point, and he had Acromegaly. So - he was getting 26u per day and he weighed 16 pounds.
IAA - Insulin Auto-immune Antibodies -- the body rejects the foreign insulin
Acromegaly - a pituitary tumor generates "insulin-like" growth factor which interferes with the normal insulin receptors and causes the diabetes.
Cushings (rare in cats, more common in dogs) - an adrenal tumor that causes the diabetes (I am less familiar with this)
There are two good tests conducted at the same lab for determining if IAA or Acromegaly is present. Since your vet fee for blood draw and shipping are the most expensive part of these two tests --- get BOTH done. The Acro test costs $49 US and the IAA test costs $15
Cushings is very had to diagnose until extreme stages when the skin is very fragile and tears easily.
More details, and links to the tests:
viewtopic.php?f=12&t=375
IGF-1 test:
http://www.animalhealth.msu.edu/Bin/Cat ... ne&Id=1401
IAA test
http://www.animalhealth.msu.edu/Bin/Cat ... ne&Id=1494
It would be great if you could try a more gentle, long-lasting insulin like Lantus or Levemir.
A few of the cats with Acromegaly need over 50 units BID to get healthy blood sugar levels. More commonly, acro-cats need a less scary dose, like 15u BID to 25u BID.
Do you test your kitty's blood sugar at home? That is the best way to understand how your kitty uses the insulin and how much your kitty needs.
What doses of PZI were tried (and how quickly were the doses changed?) and where are you with the Humulin N dosing?
We recommend a "start low and go slow" approach -- starting at 1U BID and holding the dose for several days or even a week before increasing.
Another possibility is that your kitty has been overdosed from Day One, and is in Somogyi Rebound. This is where the kitty's liver dumps extra sugar into the bloodstream to "soak up" the excess insulin. If the dose started out to high and increased from there --- blood sugar crashes from low to high.
Some cats only need a tiny dose -- my adopted diabetic cat, Tiggy, we use Levemir and he gets a tiny dose of 0.5u BID. (adopted him after we lost Norton to cancer).
Where are you located? (city/state) Maybe someone can show you how to test your cat's blood sugar at home. (saves money and the results are more accurate because cats are usually stressed out at the vet's office - causing increased blood sugar)