The feline diabetic–friend or foe?(Proceedings)

Is the feline diabetic patient every veterinarian's nightmare? Since diabetes mellitus is one of the most common endocrinopathies in cats, it is likely you will face this disease many times in your veterinary career. The focus of this presentation will be to discuss the problems you may encounter with your feline diabetic foes using case studies to illustrate how these feline diabetics can be your friends.

Monitoring:

      Clinical signs – water consumption, urination habits, appetite, activity, weight gain/loss

      Blood glucose curves – useful to find nadir (low point), identify Somogyi effect but overall frustrating and difficult to interpret. Use sparingly.Some clients are willing to follow blood glucose readings at home, which has its advantages and disadvantages. The personal blood glucometers are sufficiently accurate, though some meters are more accurate than others. I rely on my in-house readings to adjust insulin doses.

      Fructosamine levels – Reliable; useful for all cats, especially fractious ones...! These levels inconjunction with spot blood glucose readings have replaced blood glucose curves in my hands.

      Urine glucose monitoring – urine glucose test squares (Glucotest Feline Urinary Glucose Detection System; Ralston Purina, St. Louis, MO) can be mixed in cat litter. Useful for non-insulin dependent patients to determine if glucosuria has recurred; persistent glucosuriasuggests inadequate control and the need for reevaluation. Do not have owners adjustinsulin levels based on urine glucose measurements.

Suspect insulin resistance when:

      Dose of insulin is 6-8U (cat) q.12h and all BG levels >300 mg/dl

      Dose of insulin is >2.2U/kg to maintain BG < 300 mg/dl

Insulin resistance problems: The hunt for the problem(s) begins...

Insulin administration problems are the most common problems identified in poorly regulated diabetics. Over 80% of poorly regulated diabetic patients are due to administration issues...!

     • Vary location of injection sites.

     • Shave injection sites. (Eliminate the "fur" injection problem.)

     • Spend time training/testing clients on insulin administration. Make sure all the familymembers who will be giving the injections are trained.

     • Have the client obtain a new bottle of insulin every 4 weeks for all insulin types except Lantus.Lantus should remain potent for up to 4-6 months. If diabetic control with Lantus is poor, have the Client change to a new bottle every 2-3 months.

     • When poor diabetic control is present, review insulin administration techniques with the client and everyone giving the insulin injections. Don't forget to include the petsitter.

Every diabetic cat, especially those that are difficult to regulate, should have a full physical examination, complete diagnostic evaluation (CBC, biochemistry profile, serum T4, urinalysis), blood pressure measurement, and fructosamine level.

Imaging studies (radiographs, ultrasound) and more extensive testing may be needed to rule out concurrent diseases.

Don't forget to check for urine ketones.

Ketones are the end-product of rapid or excessive fatty-acid breakdown.

     • Acetoacetic acid

     • Acetone

     • Beta-hydroxybutyrate

Glomeruli freely filter ketones and the tubules then resorb them completely. If the tubular resorptive capacity is saturated, then the ketones are incompletely resorbed, resulting in ketonuria. Ketonuria occurs quickly in younger animals and is more easily detected than ketonemia. Ketonuria does not signify renal disease, but rather excessive lipid or defective carbohydrate metabolism. Ketones will be present in the urine when the ketones in the blood go above a certain level.

The ketone present in the largest amount, beta-hydroxybutyrate, does not register on the urine dipstick. Dipstick tests are semiquantitative and only detect acetone and acetoacetic acid. Reagent strips contain nitroprusside that does not react with beta-hydroxybutyric acid. However, you can perform a simple chemistry maneuver to determine if any ketones are present. One drop of urine plus one drop of hydrogen peroxide will convert beta-hydroxybutyrate to acetoacetic acid which does register on the urine dipstick.

Causes of insulin resistance other than management problems:

     • Hyperthyroidism

     • Acromegaly

     • Bacterial infections (especially urinary)

     • Dental disease

     • Renal, hepatic, and cardiac insufficiency

     • Hyperadrenocorticism

     • Drugs (Corticosteroids, progestins)

     • Chronic pancreatitis

     • Toxoplasmosis

     • Exocrine pancreatic insufficiency

     • Neoplasia

     • Obesity

     • Hyperlipidemia

     • Diestrus

Treat/manage concurrent diseases (hyperthyroidism, inflammatory bowel disease (IBD), eosinophilic granuloma complex, chronic kidney disease, neoplasia).

You can use corticosteroids in diabetic pets when needed to treat other ongoing diseases such as IBD, asthma, allergic dermatopathy, eosinophilic ulcers or cancer.

Expect some degree of insulin resistance, requiring higher insulin doses.

Try to lower the corticosteroid dose to lowest effective level when/if possible.

      Treatment options:

      Prednisolone instead of prednisone

      Budesonide

      Inhalant corticosteroids.

Complications to be aware of in diabetic patients:

Infections, especially urinary tract progressing to kidneys if not adequately treated (bacteria love the extra sugar in the urine = excellent media for growth)

Neuropathy due to poor diabetic control (long-standing)

Systemic hypertension

     • Don't forget systemic hypertension in diabetic patients

     • Can be a cause of acute blindness (retinal hemorrhages/detachment)

     • Can also be a silent killer

     • Blood pressure measurements - Goal: 145 mmHg or less (systolic)

Treatment of choice:

Varies based on doctor's experience and individual patient response. If a pet is not responding well to one therapy, try another one.

Insulin therapy (Insulin Insanity):

     • **The ideal insulin preparation has not been identified for diabetic cats.**

     • Short-acting insulin: Regular, primarily used in ketoacidotic cats

     • Intermediate-acting insulins: NPH, Vetsulin

     • Long-acting insulins: ProZinc, Lantus (glargine), Levemir (detemir)

     • AVOID compounded insulins of any type. Too much variability in preparations.

     • **My preference: Lantus 0.5U/kg q. 12h to start (long-acting insulin)**

Lantus - Insulin Glargine

This is the "insulin du Jour", but it is very effective at controlling diabetes mellitus in cats. Insulin Glargine is a long-lasting human insulin analog produced by recombinant DNA technology using a non-pathogenic strain of E coli. This insulin requires U-100 syringes. The bottle of insulin may remain potent for 2-6 months once opened.

Study results: Diabetic cats treated with Lantus had lower serum fructosamine levels and achieved diabetic remission earlier than cats treated with PZI or lente.

Dose: 0.25 – 0.5 U/kg q 12 - 24 hours. Adjust dose as needed. Dose may decrease after 2 weeks of starting therapy (or sooner) in new diabetic patients.

     • Higher probability of diabetic remission using higher BID dosing.

     • Low risk of clinical hypoglycemia.

     • Glargine has a very long duration of action whether dosed once or twice daily.

Oral hypoglycemic drugs (cats): Limited use as single therapy; can be used in conjunction with insulin or other oral drugs to obtain better glycemic control.

      Transition metals

      Vanadium (Super Vanadyl Fuel (TwinLab)) ½ capsule once daily

      Chromium 200 micrograms/cat daily

      Alpha-glucosidase inhibitors

      Acarbose 12.5-25 mg/cat with meals

      Sulfonylureas

      Glipizide 2.5 – 5 mg/cat PO 2-3 times daily

Diet: Cats are carnivores.

Feed diet high in protein, low in carbohydrates (canned food preferred)

      Kitten food

      Purina DM

      Prescription diet m/d

      Evo

Some cats still do better on the high fiber diets (w/d, r/d, OM).Use high protein diets with caution in cats with evidence of chronic kidney disease.Each cat is an individual and will respond differently to different diets.

Try to maintain consistent feeding schedule.Let "nibbler" cats continue to nibble throughout the day and night.

Manage obesity! Encourage hunting activity. Take out portion of kibble from daily measured amount. Place kibble in favorite places initially and then place kibble in less frequented areas.

Hunting = activity = calories burned.

Follow-up plan for diabetic patients:

Recheck the patient one week after starting insulin therapy. Perform blood glucose curve to determine nadir if using insulin other than Lantus. Adjust insulin based on these readings.

Lantus is a peakless insulin. It is released at a relatively steady, constant rate with no pronounced peak. Blood glucose curves are not useful for cats on Lantus.

If using diet alone, recheck blood glucose & ketones after 3-4 weeks on the diet. ( fructosamine level).

Recheck pet every 1-2 weeks at nadir and adjust insulin based on blood glucose and clinical signs.

Consider running a fructosamine level when clinical signs are more normal and blood glucose levels are improving. I usually run a fructosamine level monthly until good control is obtained. This allows me to follow the trend in the levels. A steady decline should be seen. If not, review insulin administration or consider looking for complicating factors/diseases/diet.

Once the diabetic cat is well-controlled, recheck blood glucose and fructosamine levels every 3 months. Recheck full blood work, urinalysis, and blood pressure every 6 months.

Selected readings

Appleton DJ, Rand JS, Sunvold GD, et al: Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats. J Feline Med Surg 4:13-25, 2002.

Behrend EN, Greco DS: Treatment of feline diabetes mellitus: Overview and therapy. Comp Cont Educ Pract Vet 22:423-439, 2000.

Behrend EN, Greco DS: Treatment of feline diabetes mellitus: Evaluation of treatment. Comp Cont Educ Pract Vet 22:440-452, 2000.

Berg RI, Nelson RW, Feldman EC, et al: Serum insulin-like growth factor-I concentration in cats with diabetes mellitus and acromegaly. J Vet Intern Med 21(5):892-898, 2007.

Biourge V, Nelson RW, Feldman EC, et al: Effect of weight gain and subsequent weight loss onglucose tolerance and insulin response in healthy cats. J Vet Intern Med 11:86-91, 1997.

Cohn LA, McCaw DL, Tate DJ, et al. Assessment of five portable blood glucose meters, as point-of-care analyzer, and color test strips for measuring blood glucose concentrations in dogs. J Am Vet Med Assoc 216(2):198-209, 2000.

Crenshaw KL, Peterson ME, Heeb LA, et al: Serum fructosamine concentration as an index of glycemia in cats with diabetes mellitus and stress hyperglycemia. J Vet Intern Med 10:360-364, 1996.

Elliott DA, Nelson RW, Reusch CE, et al: Comparison of serum fructosamine and blood glycosylated hemoglobin concentrations for assessment of glycemic control in cats with diabetes mellitus. J Am Vet Med Assoc 214:1794-1798, 1999.

Feldman EC, Nelson RW: Feline diabetes mellitus. In Feldman EC, Nelson RW (eds): Canine and Feline Endocrinology and Reproduction, 3rd ed. Philadelphia, W.B. Saunders, 2004, pp 539-579.

Feldman EC, Nelson RW: Diabetic ketoacidosis. In Feldman EC, Nelson RW (eds): Canine and Feline Endocrinology and Reproduction, 3rd ed. Philadelphia, W.B. Saunders, 2004, pp 580-615

Feldman EC, Nelson RW, Feldman MS: Intensive 50-week evaluation of glipizide administration in 50 cats with previously untreated diabetes mellitus. J Am Vet Med Assoc 210:772-777, 1997.

Goosens MMC, Nelson RW, Feldman EC, et al: Response to insulin treatment and survival in104 cats with diabetes mellitus (1985-1995). J Vet Intern Med 12:1-6, 1998.

Gunn-Moore D: Feline endocrinopathies. Vet Clin Small Anim 35:171-210, 2005.

Kirk CA: Feline diabetes mellitus: low carbohydrates versus high fiber? Vet Clin North Am Small Anim Pract 36(6):1297-306, 2006.

Marshall RD, Rand JS, Morton JM. Glargine and protamine zinc insulin have a longer duration of actionand result in lower mean daily glucose concentrations than lente insulin in healthy cats, J Vet Pharmacol Therapeut 31:205-212, 2008.

Marshall RD, Rand JS, Morton JM. Insulin glargine has a long duration of effect following administration either once or twice daily in divided doses in healthy cats. J Feline Med Surg 10:488-494, 2008.

Marshall RD, Rand JS, Morton JM. Treatment of newly diagnosed diabetic cats with glargine insulin improves glycaemic control and results in higher probability of remission than protamine zinc andlente insulin. J Feline Med Surg 11: 683-691, 2009.

Mayer-Roenne B, Goldstein R, Erb HN: Urinary tract infections in cats with hyperthyroidism, diabetes mellitus and chronic kidney disease. J Feline Med Surg 9(2):124-32, 2007.

Mazzaferro EM, Greco DS, Turner AS, et al: Treatment of feline diabetes mellitus using an alpha- glucosidase inhibitor and a low-carbohydrate diet. J Feline Med Surg 5:183-189, 2003.

Nelson, RW: Oral medications for treating diabetes mellitus in dogs and cats. J Small Anim Pract 41: 486-490, 2000.

Nelson RW, Lynn RC, Wagner-Mann CC, et al: Efficacy of protamine zinc insulin for treatment of diabetes mellitus in cats. J Am Vet Med Assoc 218:38-42, 2001.

Niessen SJM, Petrie G, Gaudino F, et al: Feline acromegaly: an underdiagnosed endocrinopathy? J Vet Intern Med 21(5):899-905, 2007.

Prahl A, Guptill L, Clickman NW, et al: Time trends and risk factors for diabetes mellitus in cats presented to veterinary teaching hospitals. J Vet Med Surg 9(5):351-8, 2007.

Rand JS, Marshall RD: Diabetes mellitus in cats. Vet Clin Small Anim 35:211-224, 2005.

Reusch CE, Kley S, Casella M: Home monitoring of the diabetic cat. J Feline Med Surg 8(2):119- 27, 2006.

Roomp K, Rand JS. Intensive blood glucose control is safe and effective in diabetic cats using homemonitoring and treatment with glargine. J Feline Med Surg 11:668-682, 2009.

Sellon RK, Fidel J, Houston R, Gavin PR. Linear-accelerator-based modified radiosurgical treatment of pituitary tumors in cats: 11 cases (1997-2008). J Vet Intern Med 23:1038-1044, 2009.

Weaver KE, Rozanski EA, Mahony OM, Chan DL, Freeman LM. Use of glargine and lente insulins in cats with diabetes mellitus. J Vet Intern Med. 20(2):234-238, 2006.

Wess G, Reusch C. Capillary blood sampling from the ear of dogs and cats and use of portable meters to measure glucose concentrations. J Small Anim Pract 41(2):60-66, 2000.