Q & A: Will Lactulose Affect Blood Sugar Levels In Diabetic Cats?

My problem case is an 14-year old, male-neutered DLH cat that has been on a relatively high dose of lactulose (6 ml, bid) for chronic constipation for many years.

One month ago, he developed weight loss, an increase in appetite, and polydipsia. We diagnosed diabetes mellitus (he had severe hyperglycemia with glucosuria) and started him on insulin glargine (Lantus, Sanofi-Aventis). The owner has kept the cat on Hill's dry Science Diet, which the cat loves.

So far, the cat's glargine insulin dose is up to 4 U twice a day (0.9 units/kg), but he is not yet showing any improvement. His last blood glucose was still high at 381mg/dl, with marked glucosuria but negative ketonuria. A serum fructosamine was high at 630 μmol/L (normal <450 μmol/L). A blood glucose curve demonstrated persistent hyperglycemia throughout the day.

My questions are are 4-fold:

1. Does this cat have insulin resistance?
2. Would lactulose have any bearing on this high of blood glucose? Should I try stopping it to see if hyperglycemia improves on insulin therapy?
3. Should I change his insulin to PZI (ProZinc; Boehringer Ingelheim) or another insulin analogue?
4. Is his present diet acceptable?

My Response:

Lactulose is a synthetic, nondigestible sugar developed as a treatment for chronic constipation. It is a disaccharide formed from one molecule each of the monosaccharides fructose and galactose (see Figure 1).

Because it is not digested, lactulose passes unchanged to reach the colon, where it exerts its osmotic laxative effect.Therefore, the lactulose did not contribute to your cats diabetes since the "sugar" in lactulose is not absorbed. Similarly, the drug would not be an issue contributing to the lack of response to insulin therapy in this cat.

Structure of lactulose, a disaccharide

Recommended Steps in this Cat's Management:

1. Rule out urinary tract infection and other concurrent problems

• To start, I'd recommend a urine culture to rule out an occult urinary tract infection. Cat with diabetes are prone to developing urinary tract infections (UTI), so periodic urine cultures are a good idea.

2. Change to a high-protein, low-carbohydrate diet

• You should also consider switching this cat's diet to a good canned food diet — one with a composition that is low in carbohydrates (<10% of calories) and higher in protein (>40% of calories). By lessening the insulin resistance that is a hallmark of diabetes in cats, that diet change will make cats more sensitive to the effects of insulin. 
• Most of my diabetic cats are doing well on an over-the-counter canned food that are low enough in carbohydrates and high in protein content. Check out this website (binkyspage.tripod.com/canfood), which gives you a breakdown of the composition of the various prescription and over-the-counter diets. It turns out that many of the over-the-counter diets have a better composition of protein and carbohydrates than you might have thought — even better than many of the more expensive prescription diets. Very few of my diabetic cat patients require a prescription diet to fulfill their nutritional needs.
• Almost all dry food cat diets are much too high in carbohydrates and  too low in protein content. That is why I believe it's best to limit the amount of dry food that is fed to diabetic cats, or even better, not feed dry food at all.

3. Consider a change in insulin preparation

• Once you have excluded UTI as a cause of insulin resistance, I would change to a more appropriate "diabetic" diet. If no improvement in insulin dosage or glucose regulation is noted after 2-4 weeks, I would recommend switching from insulin glargine to another insulin preparation.
• If needed, I'd recommend a change to PZI (ProZinc), starting at a lower initial dose (e.g., 2 U, BID), and doing dose regulation as needed. I've now seen a few cats that could not be regulated on glargine do better on this insulin preparation.

References:

1. Rucinsky R, Cook A, Haley S, Nelson R, et al. AAHA diabetes management guidelines for dogs and cats. Journal of the American Animal Hospital Association 2010;46:215-224.
2. Frank G, Anderson W, Pazak H,  et al. Use of a high-protein diet in the management of feline diabetes mellitus. Veterinary Therapeutics 2001;2:238-246.
3. Rand JS, Fleeman LM, Farrow HA, eet al. Canine and feline diabetes mellitus: nature or nurture? The Journal of 2004;134(8 Suppl):2072S-2080S.
4. Nelson RW, Henley K, Cole C, et al. Field safety and efficacy of protamine zinc recombinant human insulin for treatment of diabetes mellitus in cats. Journal of Veterinary Internal Medicine 2009;23:787-793.