Do Pet Owners Need a Prescription for Insulin or Insulin Syringes?

Do we need a prescription to get insulin?

For the "older" recombinant human insulin preparations, such as regular or NPH, a prescription is generally not required (1).  The big exception is the State of Alaska, where a prescription is needed.

So that means that Novolin R and Humulin R (regular insulins); Novolin N and Humulin N (NPH insulins); and Novolin 70/30 and Humulin 70/30 (mixtures of regular and NPH insulins) do not generally require a prescription.

In contrast, federal law dictates that the newer, insulin analogs do indeed require a prescription. These include rapid-acting insulins (Humalog, Novolog, or Apidra),  mixtures of rapid- and long-acting analogs (Humalog Mix; Novolog 70/30),  and longer-acting insulin analogs (Lantus, Levemir). See my previous blog post on insulin preparations for more information about any of these insulin analogs or mixtures (2).

So for diabetic dogs and cats, we need to be concerned primarily with insulin glargine (Lantus) and insulin detemir (Levemir) (3). Obviously, we do not need a prescription for ProZinc (PZI) or Vetsulin/Caninsulin (lente insulin), since those are veterinary products and would not be carried by a human pharmacy.

Do we need a prescription to get insulin syringes?

The requirement for a prescription for insulin syringes is much more variable between State-to-State (1). About a a third of States do have some limitations (e.g., a pharmacy may only dispense 10 syringes at a time or will only sell the syringes with a bottle of insulin).

For more information concerning specific State requirements, see this link that outlines the individual State laws for insulin prescriptions (1).

When in doubt, it is always best to provide your diabetic owners with a prescription for insulin syringes.

References:

1. Web site, Islets of Hope for Persons with Diabetes: State Laws for Insulin and Syringe Prescription 
2. Blog Post, Insights to Veterinary Endocrinology. Insulin Choice for the Diabetic Dog and Cat: Which is Best? 
3. Gilor C, Graves TK. Synthetic insulin analogs and their use in dogs and cats. Veterinary Clinics of North America: Small Animal Practice 2010; 40:297-307. 

Insulin Glargine and Injection Pain in Cats

I have a 10-year-old neutered male diabetic cat that has been on 3 units of insulin glargine (Lantus) twice a day for 3 months. The cat's diabetes has responded very well. Over the past few days, however, the owner says that the cat has been in severe pain and appears to be very sensitive in the back area where the insulin injections are given.

The owner did her own research on-line and found information to suggest that Lantus can cause "shooting pain" in some human diabetics. Could this truely be a cause for the cat's pain, or are we most likely dealing with a hyperesthetic syndrome or an orthopedic problem?

They can not bring the cat to me for an exam for a couple of days. Do you have any other suggestions for insulin therapy if the owner decides that they want to stop the Lantus injections?

My Response:

In man, pain resulting from the injection of insulin glargine (Lantus) certainly can occur (1-3). In clinical studies of adult patients done by the manufacturer of Lantus, there was a higher incidence of treatment-emergent injection site pain in glargine-treated patients (2.7%) compared to NPH insulin-treated patients (0.7%) (1).

The reason for the higher frequency of injection pain appears to be related to the fact that, unlike other insulins, insulin glargine is injected as an acidic solution with a pH of 4 (1-4). Careful investigation in children confirm that some individuals will indeed perceive more pain during subcutaneous injection of acidic insulin solutions than neutral insulin solutions (3).

If you decide that a change in insulin preparation is indicated in this cat, alternative, nonacidic, long-acting insulin options for cats include PZI (ProZinc) insulin and insulin detemir (Levemir) (4-9). Lente or NPH are also nonacidic insulins; however, both are intermediate-acting insulin preparations and may have a duration of action that is too short for the diabetic cat (10).

That all said, the pain you describe sounds like the cat's pain is constant and may not be related to the insulin or insulin injections at all. Again, this cat needs a good old physical examination to help sort out the underlying cause of the pain that the owner is describing.

References:

1. Hirsch IB. Insulin analogues. N Engl J Med 2005;352:174-83.
2. LANTUS (insulin glargine injection), Sanofi-Aventis, Full prescribing information at http://products.sanofi.us/lantus/lantus.pdf
3. Karges B, Muche R, Riegger I, et al. Injection of acidic or neutral insulin and pain: a single-center, prospective, controlled, noninterventional study in pediatric patients with type 1 diabetes mellitus. Clin Ther 2006;28:2094-2101. 
4. Gilor C, Graves TK. Synthetic insulin analogs and their use in dogs and cats. Vet Clin North Am Small Anim Pract 2010;40:297-307. 
5. 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 2001;218:38-42. 
6. Norsworthy G, Lynn R, Cole C. Preliminary study of protamine zinc recombinant insulin for the treatment of diabetes mellitus in cats. Vet Ther 2009;10:24-28. 
7. Nelson RW, Henley K, Cole C. Field safety and efficacy of protamine zinc recombinant human insulin for treatment of diabetes mellitus in cats. J Vet Intern Med 2009;23:787-793. 
8. Gilor C, Ridge TK, Attermeier KJ, et al. Pharmacodynamics of insulin detemir and insulin glargine assessed by an isoglycemic clamp method in healthy cats. J Vet Intern Med 2010;24:870-874. 
9. Roomp K, Rand J. Evaluation of detemir in diabetic cats managed with a protocol for intensive blood glucose control. J Feline Med Surg 2012;14:566-572.
10. Marshall RD, Rand JS, Morton JM. Glargine and protamine zinc insulin have a longer duration of action and result in lower mean daily glucose concentrations than lente insulin in healthy cats. J Vet Pharmacol Ther 2008;31:205-212. 

Top Endocrine Publications of 2011: Feline Diabetes Mellitus

In my sixth compilation of the canine and feline endocrine publications of 2011, I’m moving on to the theme of feline diabetes mellitus.

Listed below are 12 research papers written in 2011 that deal with a variety of topics and issues related to the diagnosis, monitoring, and treatment of diabetes mellitus in cats.

These range from the studies of the prevalence of proteinuria in diabetic cats (1) to evaluation of IGF-1 levels in diabetic cats (2); from studies of continuous glucose monitoring in cats (3, 11) to a comparison of glucosuria detection by two methods (4); from studies of GI hormones that affect insulin secretion (5,6) to the effects of diet and obesity on feline glucose metabolism (7, 12); and finally, studies of the pathogenesis of diabetic remission in cats (9, 10) to insulin resistance (8).

2011 Papers on Feline Diabetes Mellitus:

1. Al-Ghazlat SA, Langston CE, Greco DS, et al. The prevalence of microalbuminuria and proteinuria in cats with diabetes mellitus. Top Companion Anim Med 2011;26:154-157. 
2. Ciftci G, Yarim GF. Evaluation of IGF-I levels and serum protein profiles of diabetic cats and dogs. J Vet Sci 2011;12:325-331. 
3. Dietiker-Moretti S, Muller C, Sieber-Ruckstuhl N, et al. Comparison of a continuous glucose monitoring system with a portable blood glucose meter to determine insulin dose in cats with diabetes mellitus. J Vet Intern Med 2011;25:1084-1088. 
4. Fletcher JM, Behrend EN, Welles EG, et al. Glucose detection and concentration estimation in feline urine samples with the Bayer Multistix and Purina Glucotest. J Feline Med Surg 2011;13:705-711. 
5. Gilor C, Graves TK, Gilor S, et al. The GLP-1 mimetic exenatide potentiates insulin secretion in healthy cats. Domest Anim Endocrinol 2011;41:42-49. 
6. Gilor C, Graves TK, Gilor S, et al. The incretin effect in cats: comparison between oral glucose, lipids, and amino acids. Domest Anim Endocrinol 2011;40:205-212. 
7. Hoenig M, Jordan ET, Glushka J, et al. Effect of macronutrients, age, and obesity on 6- and 24-h postprandial glucose metabolism in cats. Am J Physiol Regul Integr Comp Physiol 2011;301:R1798-1807. 
8. Hoenig M. Insulin resistance in cats: Not all tissues are equal. Nestle Purina Companion Animal Nutritional Summit: Focus on Obesity and Obesity-Related Diseases. Tucson, Arizona, 2011;38-41.
9. Reusch CE, Hafner M, Tschuor F, et al. Diabetes remission in cats: a review. Schweiz Arch Tierheilkd 2011;153:495-500. 
10. Tschuor F, Zini E, Schellenberg S, et al. Remission of diabetes mellitus in cats cannot be predicted by the arginine stimulation test. J Vet Intern Med 2011;25:83-89. 
11. Wiedmeyer CE, DeClue AE. Glucose monitoring in diabetic dogs and cats: adapting new technology for home and hospital care. Clin Lab Med 2011;31:41-50. 
12. Zoran DL, Buffington CA. Effects of nutrition choices and lifestyle changes on the well-being of cats, a carnivore that has moved indoors. J Am Vet Med Assoc 2011;239:596-606. 

ProZinc (PZI Insulin) Supply Status: An Update

As most of you probably already know, ProZinc (PZI insulin), the only insulin preparation specifically made for use in diabetic cats (1,2), has been in short supply for the last few months (see my post about the shortage from last July).  It turns out that the problem has been a shortage of protamine, the protein which slows down the absorption of the PZI insulin and increases its duration of action.

The company that manufacturers ProZinc, Boehringer Ingelheim Vetmedica, had to apply to the FDA for approval to continue to make the insulin using a new source of protamine. The GOOD NEWS is that the company has been granted approval for the insulin formula using the new supplier of protamine. They are now ramping up production of the new ProZinc, but there is a one-month timeline from production to release of an insulin product.

Despite the shortage, current market conditions are better than they have been in awhile. There is still about 4 to 6 weeks of inventory in distribution warehouses at this time. So if you have cats doing well on ProZinc, it should no longer be a problem to obtain the insulin as needed.

References:

1. 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 2001;218:38-42. 
2. Norsworthy G, Lynn R, Cole C. Preliminary study of protamine zinc recombinant insulin for the treatment of diabetes mellitus in cats. Vet Ther 2009;10:24-28. 

Diabetes and Insulin Resistance in Miniature Schnauzers

Association of Hypertriglyceridemia with Insulin Resistance

in Healthy Miniature Schnauzers

Panagiotis G. Xenoulis, Melinda D. Levinski, Jan S. Suchodolski,

and Jörg M. Steiner

Journal of the American Veterinary Medical Association 2011;238:1011–1016.

Primary (idiopathic) hypertriglyceridemia is common in the Miniature Schnauzer breed. A recent study revealed hypertriglyceridemia in almost a third of 192 healthy Miniature Schnauzers in the United States (1). The prevalence of this condition appears to be age-related, with over 75% of older Miniature Schnauzers (> 9 years) suffering from hypertriglyceridemia.

In humans, severe hypertriglyceridemia can induce insulin resistance and may lead to the development of diabetes mellitus (2-5). The Miniature Schnauzer is one of the breeds known to be at risk for developing diabetes (6,7), but the mechanism for why this breed is predisposed to become diabetic has not been investigated.

The purpose of the present study by Xenoulis et al (8) was to determine whether hypertriglyceridemia in Miniature Schnauzers is associated with insulin resistance. To this end, serum glucose and insulin concentrations were measured in two groups of Miniature Schnauzers — one with hypertriglyceridemia and the other without hypertriglyceridemia.

Hypothesis— The hypothesis of this study was that primary or idiopathic hypertriglyceridemia in clinically healthy Miniature Schnauzers is associated with a state of insulin resistance.

Objective—To determine whether hypertriglyceridemia in Miniature Schnauzers is associated with insulin resistance.

Design—Case-control study.

Animals—28 Miniature Schnauzers with hypertriglyceridemia  (study dogs) and 31 Miniature Schnauzers with normal serum triglyceride concentrations (control dogs).

Procedures—All dogs were considered healthy and were not receiving any medications known to affect lipid metabolism or serum insulin concentration. Food was withheld from each dog for ≥ 12 hours; a 5- to 10-ml blood sample was collected and then allowed to clot to obtain serum. Serum insulin and glucose concentrations were measured, and the homeostasis model assessment (HOMA) score was calculated.

Results—Median serum insulin concentration was significantly higher in hypertriglyceridemic Miniature Schnauzers (21.3 mU/L) than it was in the control dogs (12.5 mU/L). The percentage of dogs with high serum insulin concentrations was significantly greater in the hypertriglyceridemic group (28.6%) than it was in the control group (6.5%).

The median HOMA score for hypertriglyceridemic Miniature Schnauzers (4.9) was also significantly higher than that for control dogs (2.8).

Conclusions and Clinical Relevance—Results indicated that hypertriglyceridemia in Miniature Schnauzers is often associated with insulin resistance. Further studies are needed to determine the prevalence and clinical importance of insulin resistance in hypertriglyceridemic Miniature Schnauzers.

My Bottom Line

The results of the present study indicate that Miniature Schnauzers with hypertriglyceridemia often have evidence of insulin resistance, as indicated by higher basal (fasting) serum insulin concentrations and higher HOMA scores.

The HOMA score has been extensively used for the assessment of insulin resistance in humans (9) and has recently also been applied for studies in dogs and cats (10,11). The HOMA score has proven to be very useful for the early detection of insulin resistance in population-based studies and clinical practice because it is simple to determine, accurate, and only requires analysis of a single blood sample.

It is well known that Miniature Schnauzers are at increased risk for the development of diabetes mellitus (6,7). Whether this predisposition of Miniature Schnauzers to diabetes mellitus is associated with the fact that this breed also frequency develops primary hypertriglyceridemia remains to be determined.  However, based on the result of this study, it is certainly plausible that their hypertriglyceride-induced insulin resistance contributes to the glucose intolerance and overt diabetes in these dogs.

In addition, once overt diabetes has been diagnosed, these Miniature Schnauzers are typically difficult to regulate with insulin therapy. As shown in this present study (8), this is likely due to the exogenous insulin resistance that is present in these dogs as a result of their persistent, primary hypertriglyceridemia.

In addition, it is well-established, at least in humans, that insulin resistance itself can lead to secondary hyperlipidemia through the impairment of lipoprotein lipase activity and overactivation of the hormone-sensitive lipase (12). This could also be very important in these dogs because the insulin resistance in hypertriglyceridemic Miniature Schnauzers might contribute to, or worsen, the already present hyperlipidemic state, resulting in an escalation in severity of both conditions (i.e., insulin resistance and hyperlipidemia) in these Miniature Schnauzer dogs.

When most veterinarians see a diabetic dog with suspected insulin resistance, their top list of differentials generally includes hyperadrenocorticism or Cushing's syndrome (13,14). While secondary hypertriglyceridemia, as well as insulin resistance, can develop as a result of hyperadrenocorticism, very few of the "problem diabetic" Miniature Schnauzer dogs that I see have underlying Cushing's syndrome (14).  In fact, I consider hyperadrenocorticism to be a rather uncommon endocrine disorder in the Miniature Schnauzer. One must always remember that we must use caution and be careful not to make a misdiagnosis of Cushing's syndrome in these dogs, which is a common diagnostic problem in any dog with moderate to severe nonadrenal illness (16,17).

References:

1. Xenoulis PG, Suchodolski JS, Levinski MD, et al. Investigation of hypertriglyceridemia in healthy Miniature Schnauzers. J Vet Intern Med 2007;21:1224–1230. 
2. Ascaso JF, Real JT, Merchante A, et al. Lipoprotein phenotype and insulin resistance in familial combined hyperlipidemia. Metabolism 2000;49:1627–1631. 
3. Sane T, Taskinen MR. Does familial hypertriglyceridemia predispose to NIDDM? Diabetes Care 1993;16:1494–1501. 
4. Mingrone G, DeGaetano A, Greco AV, et al. Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids. Diabetologia 1997;40:599–605. 
5. Mingrone G, Henriksen FL, Greco AV, et al. Triglyceride-induced diabetes associated with familial lipoprotein lipase deficiency. Diabetes 1999;48:1258–1263. 
6. Feldman EC, Nelson RW. Canine diabetes mellitus. In: Feldman EC, Nelson RW, eds. Canine and feline endocrinology and reproduction. St Louis: Saunders, 2004;486–538.
7. Hess RS, Kass PH, Ward CR. Breed distribution of dogs with diabetes mellitus admitted to a tertiary care facility. J Am Vet Med Assoc 2000;216:1414–1417. 
8. Xenoulis PG, Levinski MD, Suchodolski JS, et al. Association of hypertriglyceridemia with insulin resistance in healthy Miniature Schnauzers. J Am Vet Med Assoc 2011;238:1011-1016.
9. McAuley KA, Williams SM, Mann JI, et al. Diagnosing insulin resistance in the general population. Diabetes Care 2001;24:460–464.
10. Serisier S, Leray V, Poudroux W, et al. Effects of green tea on insulin sensitivity, lipid profile and expression of PPARalpha and PPARgamma and their target genes in obese dogs. Br J Nutr 2008;99:1208–1216.
11. Appleton DJ, Rand JS, Sunvold GD. Basal plasma insulin and homeostasis model assessment (HOMA) are indicators of insulin sensitivity in cats. J Feline Med Surg 2005;7:183–193. 
12. Ascaso JF, Real JT, Carmena R. Insulin resistance and familial dyslipidaemias. Diabetes Obes Metabol 1999;1:323–330.
13. Melián C, Pérez-Alenza D, Peterson ME. Hyperadrenocorticism in dogs, In: Ettinger SJ (ed): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Seventh Edition). Philadelphia, Saunders Elsevier, 2010; pp. 1816-1840.
14. Peterson ME. The difficult diabetic: Acromegaly, Cushing’s, and other causes of insulin resistance. North American Veterinary Conference (NAVC) Conference 2012: Small Animal & Exotics Proceedings. pp. 873-879.
15. Kaplan AJ, Peterson ME, Kemppainen RJ. Effects of disease on the results of diagnostic tests for use in detecting hyperadrenocorticism in dogs. Journal of the American Veterinary Medical Association 1995;207:445-451.
16. Kaplan A, Peterson ME. Effects of nonadrenal disease on adrenal function tests In: Bonagura JD (ed): Current Veterinary Therapy XIII. Philadelphia, WB Saunders Co., 2000; pp 362-363.

Top Endocrine Publications of 2011: Canine Diabetes Mellitus

Cataract in a diabetic dog

In my fifth compilation of the canine and feline endocrine publications of 2011, I’m moving on to the theme of canine diabetes mellitus.

Listed below are 26 research papers written in 2011 that deal with a variety of topics and issues related to the diagnosis, monitoring, and treatment of diabetes mellitus in dogs.

These range from the studies of the pathogenesis of diabetic cataracts (1) to use of continuous glucose monitoring systems (2, 11, 25); from a survey of owner experiences in managing diabetic dogs (3) to gestational diabetes (4, 12, 24); from a study on the effect of diabetes on the structural arrangement of the cardiac collagen fibers (5) to the effect of obesity on glucose tolerance (7, 21, 22).

Other studies include evaluation of IGF-1 levels in diabetic dogs (8) to the effect of hematocrit on glucometer results (15);  from proinsulin autoantibodies (9) to insulin resistance (21, 22, 26); and finally, from studies of the insulin analogues glargine and detemir in dogs (13, 18) to the causes of secondary diabetes (23).

2011 Papers on Canine Diabetes Mellitus:

1. Abrams KL, Stabila PF, Kauper K, et al. Vascular endothelial growth factor in diabetic and nondiabetic canine cataract patients. Vet Ophthalmol 2011;14:93-99. 
2. Affenzeller N, Thalhammer JG, Willmann M. Home-based subcutaneous continuous glucose monitoring in 10 diabetic dogs. Vet Rec 2011;169:206. 
3. Aptekmann KP, Schwartz DS. A survey of owner attitudes and experiences in managing diabetic dogs. Vet J 2011;190:122-124. 
4. Armenise A, Pastorelli G, Palmisano A, et al. Gestational diabetes mellitus with diabetic ketoacidosis in a Yorkshire terrier bitch. J Am Anim Hosp Assoc 2011;47:285-289. 
5. Benedicto HG, Bombonato PP, Macchiarelli G, et al. Structural arrangement of the cardiac collagen fibers of healthy and diabetic dogs. Microsc Res Tech 2011;74:1018-1023. 
6. Blois SL, Dickie E, Kruth SA, et al. Multiple endocrine diseases in dogs: 35 cases (1996-2009). J Am Vet Med Assoc 2011;238:1616-1621. 
7. Brunetto MA, Sa FC, Nogueira SP, et al. The intravenous glucose tolerance and postprandial glucose tests may present different responses in the evaluation of obese dogs. Br J Nutr 2011;106 Suppl 1:S194-197.
8. Ciftci G, Yarim GF. Evaluation of IGF-I levels and serum protein profiles of diabetic cats and dogs. J Vet Sci 2011;12:325-331. 
9. Davison LJ, Herrtage ME, Catchpole B. Autoantibodies to recombinant canine proinsulin in canine diabetic patients. Res Vet Sci 2011;91:58-63. 
10. Eiki J, Nagata Y, Futamura M, et al. Pharmacokinetic and pharmacodynamic properties of the glucokinase activator MK-0941 in rodent models of type 2 diabetes and healthy dogs. Mol Pharmacol 2011;80:1156-1165. 
11. Fleeman LM. Continuous monitoring of glucose concentration in diabetic dogs. Vet Rec 2011;169:204-205. 
12. Moore MC, Menon R, Coate KC, et al. Diet-induced impaired glucose tolerance and gestational diabetes in the dog. J Appl Physiol 2011;110:458-467. 
13. Moore MC, Smith MS, Turney MK, et al. Comparison of insulins detemir and glargine: effects on glucose disposal, hepatic glucose release and the central nervous system. Diabetes Obes Metab 2011;13:832-840. 
14. Oberg J, Fall T, Lilliehook I. Validation of a species-optimized enzyme-linked immunosorbent assay for determination of serum concentrations of insulin in dogs. Vet Clin Pathol 2011;40:66-73. 
15. Paul AE, Shiel RE, Juvet F, et al. Effect of hematocrit on accuracy of two point-of-care glucometers for use in dogs. Am J Vet Res 2011;72:1204-1208. 
16. Ramnanan CJ, Edgerton DS, Kraft G, et al. Physiologic action of glucagon on liver glucose metabolism. Diabetes Obes Metab 2011;13 Suppl 1:118-125. 
17. Ramnanan CJ, Saraswathi V, Smith MS, et al. Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs. The J Clin Invest 2011;121:3713-3723. 
18. Sako T, Mori A, Lee P, et al. Time-action profiles of insulin detemir in normal and diabetic dogs. Res Vet Sci 2011;90:396-403. 
19. Schoeman JP, Kitshoff AM, du Plessis CJ, et al. Serial plasma glucose changes in dogs suffering from severe dog bite wounds. J S Afr Vet Assoc 2011;82:41-46. 
20. Stojanovic V, Ihle S. Role of beta-hydroxybutyric acid in diabetic ketoacidosis: a review. Can Vet J 2011;52:426-430. 
21. Verkest KR, Fleeman LM, Morton JM, et al. Compensation for obesity-induced insulin resistance in dogs: assessment of the effects of leptin, adiponectin, and glucagon-like peptide-1 using path analysis. Domest Anim Endocrinol 2011;41:24-34. 
22. Verkest KR, Fleeman LM, Rand JS, et al. Evaluation of beta-cell sensitivity to glucose and first-phase insulin secretion in obese dogs. Am J Vet Res 2011;72:357-366. 
23. Verkest KR, Rand JS, Fleeman LM, et al. Distinct adiponectin profiles might contribute to differences in susceptibility to type 2 diabetes in dogs and humans. Domest Anim Endocrinol 2011;41:67-73. 
24. Wejdmark AK, Bonnett B, Hedhammar A, et al. Lifestyle risk factors for progesterone-related diabetes mellitus in elkhounds - a case-control study. J Small Anim Pract 2011;52:240-245. 
25. Wiedmeyer CE, DeClue AE. Glucose monitoring in diabetic dogs and cats: adapting new technology for home and hospital care. Clin Lab Med 2011;31:41-50. 
26. Xenoulis PG, Levinski MD, Suchodolski JS, et al. Association of hypertriglyceridemia with insulin resistance in healthy Miniature Schnauzers. J Am Vet Med Assoc 2011;238:1011-1016. 

Nutritional Management of Idiopathic Hypercalcemia in Cats

Over the last 15 years, idiopathic hypercalcemia has emerged to become the most common cause of hypercalcemia in cats (1-8). Although the underlying cause of this syndrome remains unclear, it is very likely that the cats' diet may be involved, especially the feeding of acidifying, magnesium-restricted diets designed to minimize struvite crystalluria and urolithiasis (9,10). For more information, see my last post on What's Causing Idiopathic Hypercalcemia in Cats?

Before the introduction of high-carbohydrate, magnesium-restricted acidifying diets by the pet food industry, cats did not develop idiopathic hypercalcemia — at least it was never reported until 1999, (1) and I certainly did not see a cat until the mid-1990s.

Nutritional Therapy

I generally start with diet modification as a first-line treatment. If an acidifying diet is being fed, it should be discontinued. However, it may not always be clear that the cat food being fed is an acidifying diet — one should always closely examine the ingredient list to look for the presence of an added urinary acidifier, such as dl-methionine, phosphoric acid, and ammonium chloride.

Although feline urine is normally mildly acidic, feeding cats commercial diets containing high amounts of carbohydrate (e.g., starch and fiber) will result in an alkaline urine pH (11,12). Therefore, many commercial cat food diets contain added acidifiers in order to “counteract” the alkalizing effects of the high carbohydrate diet, even when it is not promoted as a urinary tract diet.

No matter what type of diet is chosen, it is best to feed a wet-only diet to promote urinary dilution and lessen the chance for calcium oxalate stones (13). To this end, we have a variety of different types of cat food diets that have been proposed to help lower calcium in cats with idiopathic hypercalcemia (3-8).

Diets Recommended in the Literature

High-fiber diets
High fiber diets (e.g., Purina OM Overweight Management, Iams Intestinal Plus Low-Residue, Hill’s w/d) will restore normocalcemia in some cats with idiopathic hypercalcemia and calcium oxalate urolithiasis (1,5). The effects of fiber on intestinal absorption are complex and depend on the type and amount of fiber, as well as the interactions with other nutrients in the diet. However, these “high fiber diets” are usually supplemented with extra calcium; therefore, calcium content does not explain why these diets are occasionally helpful in treating idiopathic hypercalcemia. Again, changing from an acidifying diet to any diet that is less acidifying (such as high fiber) would be expected to be beneficial.

Another option, of course, would be to feed a lower calcium diet and add fiber to the diet (e.g., psyllium for a mixed-fiber source or guar gum for an all-soluble source) (8). However, because high-fiber diets tend to be lower in protein, cats with idiopathic hypercalcemia chronically fed these diets can loose lean muscle mass to become muscle wasted (14,15). This is especially true if the cat’s appetite is poor, a sign present in some cats with this syndrome (1-8).

Overall, I do not find high-fiber diets to be helpful in the vast majority of cats with idiopathic hypercalcemia and no longer recommend these diets.

Renal diets
Prescription kidney diets (e.g., Purina NF Kidney Function, Royal Canin Renal LP Modified, Iams Renal Plus, Hill’s k/d) also may result in normocalcemia in some cats with idiopathic hypercalcemia (5,6). Although these renal diets appear less acidifying than most maintenance or high-fiber diets, many renal diets still contain added dl-methionine. Most renal diets are low in calcium, so its decreased consumption should lead to a decrease in the amount of calcium absorbed (4).

Remember, however, that renal diets are also restricted in phosphorus, which may lead to increased calcitriol (active vitamin D) synthesis by the kidney; the action of this increased serum calcitriol could offset the advantage of the decreased calcium absorption in cats with idiopathic hypercalcemia (5,16).

Overall, because these diets are lower in protein, renal diets are not my first choice — with time, cats with idiopathic hypercalcemia can become muscle wasted on these diets (14,15).

Diets for calcium oxalate urolithiasis
Canned diets developed to prevent calcium oxalate urolithiasis (e.g., Royal Canin Urinary SO, Purina UR Urinary St/Ox, Iams Urinary-O Plus Moderate pH/O, Hill’s c/d) may be beneficial in the treatment of cats with idiopathic hypercalcemia (5,6). These diets are restricted in calcium and tend to be less acidifying, resulting in a neutral urine pH in most cats. However, some still contain dl-methionine, which should definitely be avoided. Some of these diets are also restricted in oxalic acid, which may help prevent the calcium oxalate stones that develop in 10-15% of cats with idiopathic hypercalcemia.

However, I do not find any of these “calcium oxalate” diets to be very helpful in normalizing the high ionized calcium concentrations found in cats with idiopathic hypercalcemia. Therefore, I cannot strongly recommend these diets, especially if no calcium oxalate stones are present.

Diets That I Recommend

Canned commercial diets with a "natural" macronutrient composition
Feeding commercial canned diets with a composition similar to what cats would eat in the wild—i.e., 40-60% protein, 30-50% fat, and <15% carbohydrates (17-20)— will also be beneficial in lowering serum calcium concentrations in some cats, particularly those with mild forms of idiopathic hypercalcemia.

One can use the online “Protein/Fat/Carbs Chart” found at www.catinfo.org to select a canned cat food that will provide a nutritional composition similar to what cats would ingest in small prey (e.g., small rodents, birds, and insects). Although this diet composition will result in an acidic urine pH (normal for cats), a high-protein diet is preferable over added acidifiers for prevention of struvite crystal formation in cats (12,21) and is not associated with the same degree of metabolic acidosis.

In addition to the macronutrient composition, one should ensure that the canned food selected does not have any added acidifiers (e.g., dl-methionine, phosphoric acid, or ammonium chloride) and is not a magnesium-restricted diet. A diet with a relatively low vitamin D content (< 5 μg [< 200 IU]/1000 kcal) is recommended. Although feeding a low-calcium diet may be ideal, none of the available commercial cat foods are calcium-restricted.

Home-prepared diet restricted in both calcium and vitamin D
For more control over the exact macronutrient, mineral, and vitamin D content of the cats’ diet, feeding a specially formulated, home-prepared diet is recommended. Some cats, especially those with mild ionized hypercalcemia, will show a good response to a diet restricted in both calcium and Vitamin D (22). Such diets must be specially formulated, since none of the commercial cat food diets could be low in either calcium or vitamin D content and still meet AAFCO guidelines to be a “complete and balanced” diet (23).

Again, I recommend formulating this diet to have a macronutritional composition similar to what cats would eat in the wild (i.e., 40-60% protein, 30-50% fat, and < 10% carbohydrates). Products containing high concentrations of vitamin D, such as organ meats and fish oil, should be avoided (22). Calcium content should be kept restricted to 600 mg per 1000 kcal of diet (in contrast, the minimal adult maintenance requirement set by AAFCO is 1500 mg per 1000 kcal) (23). Magnesium should not be restricted, and acidifiers should never be added.

Ideally, this home-prepared diet is formulated under the guidance of a veterinary nutritionist to ensure that it is nutritionally adequate for the cat. If no response is detected after a month or two on this restricted calcium diet, alternative medical therapies (e.g., glucocorticoids, alendronate) should be considered.

My Bottom Line

In cats with idiopathic hypercalcemia, clinical signs and the associated degree of ionized hypercalcemia are usually mild, at least at diagnosis. In general, the severity of hypercalcemia in these cats tends to be slowly progressive.

Therefore, as the first step in management of these cats, I recommend changing their diet to a canned food that has a macronutrient composition closer to a cat’s carnivorous diet in the wild — in other words, high protein, moderate fat, very low carbs, not magnesium-restricted, and no added acidifiers (17-20). Remember that, at least as far as we know, cats eating this way for many hundreds of years did not develop idiopathic hypercalcemia, so I'm hoping that Mother Nature knows best when it comes down to what these cats should be fed.

One should monitor ionized calcium concentrations at 4 and 8 weeks during this initial dietary change. If hypercalcemia persists, the diet can be switched to a home-prepared, formulated calcium- and vitamin D-restricted diet (22). Again, I would still maintain a macronutrient composition that mimics a cat’s natural diet.

If nutritional management fails to normalized ionized calcium concentrations or hypercalcemia is severe, drug therapy with glucocorticoids (e.g., daily oral prednisolone) or bisphosphonates (e.g., weekly oral alendronate) can be initiated (5-8,24). However, both of these drugs can produce adverse side effects (i.e., diabetes mellitus and esophagitis, respectively), so I prefer to withhold drug therapy until absolutely needed (8,25).

Once drug therapy has been instituted, I would still maintain the feeding a low-carb, high-protein canned diet to these cats. The higher protein intake will help maintain lean body mass, whereas the lower carbohydrates may help mitigate the diabetic effects of the high doses of prednisolone that may be needed to control hypercalcemia.

But in some cats, we'll be lucky, and the hypercalcemia will resolve after a change in the cat's diet to one with a nutrient composition closer to the food they were designed to eat. And in a few of those cats, the ionized calcium concentrations will remain normal for months to years, without the need for drug therapy.

References

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