Top Endocrine Publications of 2013: The Feline Thyroid Gland

In my eighth compilation of the canine and feline endocrine publications of 2013, I’m moving on to disorders of the feline thyroid gland.

Listed below are 26 papers published in 2013 that deal with a variety of thyroid gland topics of issues of clinical importance in cats.

These range from from studies of the duration of serum T4 suppression in cats treated with methimazole (1) to the results of a long-term follow-up study of cats treated with transdermal methimazole (2); and from case reports of methimazole or carbimazole-induced toxicity in cats (3,6,19) to the results of an online survey to determine owner experiences and opinions on the management of their hyperthyroid cats using oral anti-thyroid medications (5).

Other studies report the variability in iodine concentrations found in commercial cats foods in the USA (7) to investigation of the radioactivity in the excreta of hyperthyroid cats treated with radioiodine (8); from a comparison of computed tomography and scintigraphy for thyroid imaging in hyperthyroid cats (9) to a review of the clinical usefulness of an assay for measurement of circulating B-type natriuretic peptide (BNP) concentration in hyperthyroid cats (11); and from an overview of the diagnostic tests useful for confirming feline hyperthyroidism (4,12,13,15,17) and hypothyroidism (14) to a study of the effects of an iodine-restricted diet for management of cats with hyperthyroidism (22); from investigations of the pathophysiological mechanism for altered calcium homeostasis in hyperthyroid cats (24) to studies of the renin-angiotensin-aldosterone system activity in hyperthyroid cats with and without hypertension (25).

References:

1. Boretti FS, Sieber-Ruckstuhl NS, Schafer S, et al. Duration of T4 suppression in hyperthyroid cats treated once and twice daily with transdermal methimazole. J Vet Intern Med 2013;27:377-381. 
2. Boretti FS, Sieber-Ruckstuhl NS, Schafer S, et al. Transdermal application of methimazole in hyperthyroid cats: a long-term follow-up study. J Feline Med Surg 2013;16:453-459. 
3. Bowlt K, Cattin I, Stewart J. Carbimazole-associated hypersensitivity vasculitis in a cat. J Small Anim Pract 2013; doi: 10.1111/jsap.12154. 
4. Bruyette D. Feline hyperthyroidism: Diagnosis and therapeutic modalities. Today's Veterinary Practice 2013;3:25-30.
5. Caney SM. An online survey to determine owner experiences and opinions on the management of their hyperthyroid cats using oral anti-thyroid medications. J Feline Med Surg 2013;15:494-502. 
6. Castro Lopez J, Lloret A, Ravera I, et al. Pyogranulomatous mural folliculitis in a cat treated with methimazole. J Feline Med Surg 2013;16:527-531. 
7. Edinboro CH, Pearce EN, Pino S, et al. Iodine concentration in commercial cat foods from three regions of the USA, 2008-2009. J Feline Med Surg 2013;15:717-724. 
8. Lamb V, Gray J, Parkin T, et al. Measurement of the radioactivity in the excreta of cats treated with iodine-131 for hyperthyroidism. Vet Rec 2013;172:45. 
9. Lautenschlaeger IE, Hartmann A, Sicken J, et al. Comparison between computed tomography and Tc-Pertechnetate scintigraphy characteristics of the thyroid gland in cats with hyperthyroidism. Vet Radiol Ultrasound 2013;54:666-673. 
10. North DL. Uptake of 131-I in households of thyroid cancer patients. Health Phys 2013;104:434-436. 
11. Oyama MA, Boswood A, Connolly DJ, et al. Clinical usefulness of an assay for measurement of circulating N-terminal pro-B-type natriuretic peptide concentration in dogs and cats with heart disease. J Am Vet Med Assoc 2013;243:71-82. 
12. Paepe D, Verjans G, Duchateau L, et al. Routine health screening: findings in apparently healthy middle-aged and old cats. J Feline Med Surg 2013;15:8-19. 
13. Peterson ME. More than just T4: Diagnostic testing for hyperthyroidism in cats. J Feline Med Surg 2013;15:765-777. 
14. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism. Compend Contin Educ Vet 2013;35:E4. 
15. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: hyperthyroidism. Compend Contin Educ Vet 2013;35:E3. 
16. Ramoo S, Bradbury L, Anderson G, et al. Sedation of hyperthyroid cats with subcutaneous administration of a combination of alfaxalone and butorphanol. Aust Vet J 2013;91:131-136. 
17. Rasmussen SH, Andersen HH, Kjelgaard-Hansen M. Combined assessment of serum free and total T4 in a general clinical setting seemingly has limited potential in improving diagnostic accuracy of thyroid dysfunction in dogs and cats (Letter). Vet Clin Pathol 2014;43:1-3. 
18. Sabatino BR, Rohrbach BW, Armstrong PJ, et al. Amino acid, iodine, selenium, and coat color status among hyperthyroid, Siamese, and age-matched control cats. J Vet Intern Med 2013;27:1049-1055. 
19. Snead E, Kerr M, Macdonald V. Cutaneous lymphoid hyperplasia mimicking cutaneous lymphoma in a hyperthyroid cat. Can Vet J 2013;54:974-978. 
20. Sparkes A. Health screening of cats: some timely justification. J Feline Med Surg 2013;15:5. 
21. Taylor BE, Leibman NF, Luong R, et al. Detection of carcinoma micrometastases in bone marrow of dogs and cats using conventional and cell block cytology. Vet Clin Pathol 2013;42:85-91.
22. van der Kooij M, Becvarova I, Meyer HP, et al. Effects of an iodine-restricted food on client-owned cats with hyperthyroidism. J Feline Med Surg 2013;14:491-498. 
23. Whitehouse-Tedd KM, Cave NJ, Ugarte CE, et al. Isoflavone metabolism in domestic cats (Felis catus): Comparison of plasma metabolites detected after ingestion of two different dietary forms of genistein and daidzein. J Anim Sci 2013;91:1295-1306. 
24. Williams TL, Elliott J, Berry J, et al. Investigation of the pathophysiological mechanism for altered calcium homeostasis in hyperthyroid cats. J Small Anim Pract 2013;54:367-373. 
25. Williams TL, Elliott J, Syme HM. Renin-angiotensin-aldosterone system activity in hyperthyroid cats with and without concurrent hypertension. J Vet Intern Med 2013;27:522-529. 
26. Wongbandue G, Jewgenow K, Chatdarong K. Effects of thyroxin (T4) and activin A on in vitro growth of preantral follicles in domestic cats. Theriogenology 2013;79:824-832. 

Diet Recommendations for Dogs with Metastatic Insulinoma

My patient is “Ben,” a 10-year old, male Lab weighing 35 kg that presented with a 2-month history of having strange episodes, which included signs of disorientation and ataxia lasting from 10 minutes to 2 hours. The episodes were initially intermittent, but became much more frequent (2-3 times per day), so that the owner (finally) brought him in for an evaluation.

On physical exam, the dog was clinically normal. On our routine chemistry profile, the serum glucose value was very low (28 mg/dl; 1.56 mmol/l). We collected another blood sample for paired serum insulin and glucose concentrations. These test results showed an extremely low serum glucose concentration (25 ng/dl; 1.39 mmol/l) with a high serum insulin value (439 pmol/l; reference interval, 36-287 pmol/l).

An abdominal ultrasound showed a solitary 7-9 mm hypoechoic nodule on the pancreatic body between the pyloris and the proximal duodenal flexure. Unfortunately, multiple, small, very discrete solitary hypoechoic masses or nodules were also found throughout the liver, suggesting metastatic disease.

Based upon the hypoglycemia, hyperinsulinemia, and ultrasound findings, my presumptive diagnosis is insulinoma with metastasis to the liver. His owners have declined surgical exploration or biopsy.

We started Ben on oral prednisone (5 mg three times daily), and the owners have been feeding him small frequent meals. His improvement has been dramatic— no further episodes of disorientation or ataxia have been noted. I'm planning on keeping Ben on long-term, daily prednisone, but have some questions about the best diet to feed.

My understanding is that these dogs do best when fed frequent meals with high complex carbohydrates and low simple carbohydrates. I’ve also read that puppy diets are best, whereas others have said that a diabetic diet is better. But I was also concerned that a lower carbohydrate diet may not keep the blood glucose high enough. Which diets do you recommend?

My Response:

Unfortunately, there are no published studies to help us decide which is the best nutritional approach for management of dogs with insulinoma. This is not a very common endocrine tumor (1,2), so it’s difficult to do randomized trials that would evaluate the glucose response to different diets in dogs with insulinoma.

In my experience, there is not a single type of diet that will work well in all dogs. This is likely related to what stimulates that dog’s insulinoma to secrete insulin. In most dogs, hypoglycemia occurs most often during periods of fasting or exercise, whereas other dogs appear to develop the most severe signs of hypoglycemia after feeding (1,2).

Low carbohydrate, high protein diets?
Dogs with insulinomas should be fed every 4 to 8 hours, with a diet containing moderate to high levels of protein and fat and low amounts of simple carbohydrates (3). By avoiding simple sugars, an appropriate diet can dramatically reduce the stimulus for tumor insulin release, thereby controlling the clinical signs of hypoglycemia. The only exception is when a dog is actively exhibiting signs of hypoglycemia. In those cases, a rapidly absorbed source of sugar (such as honey, corn syrup, or maple syrup) may be administered orally at home pending further veterinary consultation (1,2).

Some dogs do well on a low-carbohydrate, high-protein diet, similar to what is commonly recommended for the diabetic cat. Most “young dog diets" fit reasonably well into this category. Since these diets are higher in fat, however, they can lead to weight gain in some dogs. Again, such low-carb diets reduce the stimulus for insulin secretion since these diets lessen postprandial hyperglycemia. During the metabolism of protein to glucose, glucose is liberated slowly into the blood stream, thus avoiding excessive production of insulin but providing a source of glucose over a prolonged period of time (4,5).

High-fiber, complex carbohydrate diet?
If a higher carbohydrate diet is fed, one containing complex carbohydrate and/or high fiber is ideal, since the digestion and absorption of carbohydrates should be slower and the rise in blood glucose more sustained over time (2). However, as opposed to the lower carbohydrate, higher fat diets, these high fiber diets tend to be low in energy density; therefore, if the dog is underweight or starts to lose weight, this type of diet might not be the best choice.

Bottom line
A number of different types of diets can be used to help manage the signs of hypoglycemia in dogs with insulinoma. Some dogs will do best on low carb diets, whereas others may respond better to a higher fiber diet. Whatever type of diet is chosen, multiple small feedings a day are indicated.

But remember: diet therapy generally plays only a minor role in management of dogs with insulinoma. Surgical resection of gross pancreatic disease is the treatment of choice and should always be considered, even in dogs with known metastatic disease. If surgery is not possible or it fails to control hypoglycemia, glucocorticoids (prednisone) and diazoxide are two drugs commonly used in conjunction with diet for the long-term management of dogs with insulinoma (1,2,6,7).

Overall, the combination of surgical and medical therapy, together with proper dietary management, offers the greatest chance to control clinical signs and prolong survival time (8,9) in dogs with this malignant islet-cell pancreatic tumor.

References:

1. Kintzer PP. Insulinoma and other gastrointestinal tract tumours. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association; 2012:148-155.
2. Goutal CM, Brugmann BL, Ryan KA. Insulinoma in dogs: a review. J Am Anim Hosp Assoc 2012;48:151-163.
3. Bell SJ, Forse RA. Nutritional management of hypoglycemia. Diabetes Educ 1999;25:41-47.
4. Conn JW. The advantage of a high protein diet in the treatment of spontaneous hypoglycemia. Preliminary report J Clin Invest 1936;15:673-678.
5. Blumberg S. Should hypoglycemia patients be prescribed a high-protein diet? J Am Diet Assoc 2005;105:196-197.
6. Meleo KA, Peterson ME. Treatment of insulinoma in the dog, cat, and ferret In: Bonagura JD,Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2013.
7. Leifer CE, Peterson ME, Matus RE. Insulin-secreting tumor: diagnosis and medical and surgical management in 55 dogs. J Am Vet Med Assoc 1986;188:60-64.
8. Rychel J, Worley DR, Hardy CS, et al. Prolonged survival in an aged labrador retriever with a metastatic insulinoma. J Am Anim Hosp Assoc 2013;49:224-229.
9. Polton GA, White RN, Brearley MJ, et al. Improved survival in a retrospective cohort of 28 dogs with insulinoma. J Small Anim Pract 2007;48:151-156.

How to Calculate the Carbohydrate and Protein Content of Cat Foods

After reading your last 2 posts on how to feed cats with diabetes, I realize that I don’t really understand how to determine the carbohydrate or protein content of cat (or dog) foods. I have looked on the packaging of a few diets and can only find listing for crude protein (listed as a minimum), without any listing for carbohydrates. Is fiber the same as the carbohydrate content?

For example, when I go onto the Fancy Feast website for the nutritional information for the Classic Chopped Grill Feast, the nutritional information is listed like this:

• Crude Protein (Min) 10.0%
• Crude Fat (Min) 6.0%
• Crude Fiber (Max) 1.5%
• Moisture (Max) 78.0%
• Ash (Max) 3.3%
• Taurine (Min) 0.05%

So how in the world do I calculate the percent protein content (as the % of calories ingested) from this information? Again, carbohydrates aren't even listed so how do I calculate that figure? Obviously, I need a need a crash course on how to determine the the protein and carbohydrate content of fed foods so I can recommend the best diets to feed.

My Response:

That is actually a great question, as it is not intuitive. The pet food companies are only required to provide a "Guaranteed Analysis" on the pet food label, as well as a list of ingredients (1,2). They never list the carbohydrate content on the label. Carbohydrate must be calculated by subtracting all of the other ingredients from the diet (see below); it is not determined directly in pet food.

The other confusing thing about pet foods is that, although the label lists the breakdown as Guaranteed Analysis, this is not a very accurate way to express the protein or carb content of a diet. It is much more accurate to express the composition of the food on a dry matter basis (DMB) or even better, as the metabolizable energy (ME) or calorie basis, but that information will never be found on the label.

What does Guaranteed Analysis tell us?
As you pointed out in your question, the guaranteed analysis lists the minimum levels of crude protein and fat and the maximum levels of crude fiber and moisture. The term “crude” signifies that all sources of protein, fat, and fiber are included—not just digestible sources. Guaranteed analysis should always be evaluated in conjunction with the ingredient list to help us determine the adequacy of the diet.

Looking at these percentage values by themselves is of little value in evaluating or comparing the carbohydrate, protein, or fat content of different cat foods. Also, the information on guaranteed analyses listed on pet food labels can never be totally accurate since the label only requires minimums and maximums, not exact measurements.

Converting the Guaranteed Analysis to percentage values on a dry matter or calorie basis
If we are going to use the guaranteed analysis at all, it is best to convert the protein, fat, and carb listing to % values on a dry matter basis (DMB) or metabolizable energy (ME)/calorie basis.

To convert the guaranteed analysis into a dry matter profile, this is what we can do. Begin at 100%, subtract the values for % moisture as listed on the label. The remaining percentage gives us the actual amount of dry matter in the pet food product. Next, take the listed percentage of one of the main nutrients (protein or fat), and divide that number by the percentage of dry matter. This will give us the actual dry matter percentage of the nutrient in the food.

So for your example Fancy Feast food (above), the water content is listed on the label as 78% (max moisture), and the crude protein content analysis is guaranteed to be a minimum of 10%. Subtracting the 78% water content from 100% leaves us with 22% dry matter in the cat food product. Then dividing that 10% protein value by the 22% dry matter calculates out to give us a protein content of 45.5% (DMB).  For the 6% fat figure, this calculates out to give a a fat content of 27.3% (DMB). As you can see, the percentages aren't even close to those we started with on the label.

But what about the carbs? As you stated in your question, they aren't listed on the guaranteed analysis! To estimate the carbohydrate content from the percentage figures on the label, we must first add up everything else listed within guaranteed analysis and subtract that total amount from 100%. So again, we need to add up the protein, fat, fiber, moisture, and ash percentages, and then subtract from 100 to get a % carbs portion on a dry matter basis. So in this example food, the total adds up to 98.8%, leaving on 1.2% carbs.

Next step: Converting the percentage from dry matter basis to metabolizable energy/calorie basis
When analyzing a diet, I like to examine or calculate the amount of the calories each nutrient (i.e., protein, fat or carbohydrates) provides — this is called the “metabolizable energy,” abbreviated ME. This measure disregards any part of the food that does not provide any energy (kcal) such as water, ash, or fiber. It only considers the 3 nutrients that provide the needed calories and nothing else.

It's these ME percent values I am referring to when I recommend that diabetic cats be fed a diet containing less than 12% carbs and more than 40% protein.

To convert the nutrient composition from a DMB to a ME basis, we must remember that protein and carbohydrate both provide approximately 3.5 kcal/g of food, whereas fat provides much more — approximately 8.5 kcal/g of food. Thus, in this diet, the energy provided by protein is 45.5% times 3.5 kcal/g, or 159 kcal, and the energy provided by fat and carbohydrate are 232 kcal and 4 kcal, respectively, for a total of 395 kcal. The percentage of metabolizable energy that is provided from protein, fat, and carb is then calculated (by dividing the 159, 232, and 4 kcal each by 395 kcal and multiplying by 100), which gives us a protein, fat, and carb content (ME) of approximately 40.3%. 58.7%, and 1.0%, respectively.

Too Complicated? Here's 2 Simpler Ways to Get the Same Information

Instead of going through all of these calculations, one should remember that some pet food companies list the composition of their diets on a DMB or as a percent of calorie (ME basis) on their website. If you call any reputable pet food company, they can certainly provided that information for us. But for those who don't have time to call pet food companies, here are two easy ways to get the information.

First way: Go to the BalanceIT website and use the Guaranteed Analysis Converter (3). Once on this web page, simply enter the values for crude protein, crude fat, moisture, fiber, and ash (see Figure below). This converter will calculate the percent of calories that food provides as protein, fat, and carbs (ME basis). This does all of the calculations for you!

Guaranteed Analysis Converter available on the BalanceIT website.

Again, we must remember that the information provided with the guaranteed analysis will never be 100% accurate since the pet food label only requires minimums and maximums, not exact measurements. But these calculations still should provide a pretty good estimate of the diet composition.

Second way: Go to CatInfo.org website and open the link to the Protein/Fat/Carbs chart on the right panel of the home page (4). This gives a list of many different kinds and brands of canned cat foods, providing the composition of each diet (protein, fats, and carbs) both as a percentage of calorie provided (ME basis) as well as on a dry matter percentage.

This is the most up-to-date list of canned cat food available.  Unfortunately, some pet food companies change their products and formulations often, making at least some of the information on any compiled list rapidly go out-of-date. As Dr. Pierson has told me, it can be very difficult to pry these numbers from some companies (they act as if this is top secret information); therefore, keeping any list completely current would be a monumental task.  That all said, I find this information to be an extremely useful guide when selecting the best cat food diet(s) to feed my diabetic patients.

References:

1. AAFCO web site. Nutritional Labeling. 
2. U.S. Food & Drug Administration Center for Veterinary Medicine web site. Pet food labels— general. 
3. BalanceIT website
4. CatInfo.org website

How to Feed Cats with Diabetes: Part 2— Protein

Evolutionary events shaped the cat’s core metabolism such that their systems are uniquely set up to metabolize a diet which is high in moisture, high in protein, and very low in carbohydrates. Because this is the diet cats have relied upon for tens of thousands of years, they depend more on protein intake than omnivores (e.g., dogs and man) (1-3).

As I discussed in my last blog post (How to Feed Cats with Diabetes), cats do not have the ability to process carbohydrates very efficiently and show relative carbohydrate intolerance. This becomes extremely important when selecting a diet for cats with diabetes, and what is fed can play a key role in the successful management of the diabetic cat.

Weight Loss, Obesity, Muscle Wasting, and Sarcopenia— Common Features of Diabetes
At time of diagnosis of diabetes, weight loss is reported in about 70% of cats. However, cats are more often overweight or obese (40%) than of normal weight or underweight. In addition, muscle wasting and poor muscle condition scores are reported in about half of cats with diabetes.

One contributing factor for the muscle wasting seen in the diabetic cats is their age. The typical diabetic cat is a senior, with about 70% older than 10 years of age at time of diagnosis (4,5). Therefore, since most of these cats are older, they are also prone to develop sarcopenia (from the Greek meaning "poverty of flesh") which is commonly associated with aging. 

In human patients, Type 2 diabetes is associated with an increased risk of concurrent sarcopenia (8). In addition, because skeletal muscle is a primary site for insulin-mediated glucose uptake and deposition, sarcopenia (and especially sarcopenic obesity) (9) may promote insulin resistance, predisposing patients to development of type 2 diabetes and making existing diabetes more difficult to control (10,11).

We do not know if the loss of muscle mass alone (sarcopenia) or combined with weight gain (i.e., sarcopenic obesity) also contributes to the insulin resistance and hyperglycemia associated with the feline disorder. However, given that both obesity and some degree of muscle wasting are common in diabetic cats, it seems reasonable to assume that sarcopenia and sarcopenic obesity may indeed contribute to worsening of feline diabetes, as it does in man (8-11).

Management Goals of Feline Diabetes
In cats with diabetes, a primary goal of therapy is to feed a diet that will lessen postprandial hyperglycemia, reduce marked fluctuations of blood glucose concentrations, minimize the demand on beta cells to produce insulin, and improve insulin sensitivity (6,7,12). By doing this, we decrease the effect of “glucose toxicity” and hopefully allow the pancreatic islet cell to partially recover. In about half of newly diagnosed diabetic cats, this will lead to remission of the diabetic state (13-15). As I discussed last week, we can do this in our diabetic cats by feeding a diet low in carbohydrates.

A secondary goal of therapy is to provide a diet that will help normalize body weight and maintain and/or restore lost muscle mass (16,17), as discussed below.

Recommendations for Diabetic Cats: Higher Dietary Protein:
Because diabetes is a catabolic state, loss of muscle mass is common in cats with diabetes, even if their body condition score indicates overweight or obesity. In these cats, high-protein diets are essential to ensure replacement of any lost muscle mass. In addition, higher protein diets will help prevent the hepatic lipidosis from developing during induction of weight loss (needed in many diabetic cats), and are essential to increasing metabolism to help promote fat burning and normal insulin function (16-19).

Protein is the primary macronutrient responsible for maintenance of muscle mass (20,21). Restoring and preserving any remaining muscle tissue in diabetic cats, an obligate carnivore, depends upon the cat consuming a diet with sufficient amounts of high-quality protein (greater than 40% ME; greater than 10 g/100kcal). This higher than average protein level also helps restore and maintain lost muscle mass, since many diabetic cats will develop “sarcopenia” as they age.

Although it is important to implement a low-carbohydrate/high protein diet in the management of cats with diabetes as soon as possible, there are circumstances where this should be delayed or may be inappropriate (18). For example, in cats with advanced (IRIS stage 3-4) chronic kidney disease (CKD) requiring phosphorus restriction and a reduction in dietary protein, high-protein/low-carbohydrate diabetic diets may not be appropriate (19,22,23).

In cats with earlier stages of CKD, phosphorus should be restricted using other methods than changing to a protein-restricted/higher carb diet (if possible), because feeding higher amounts of carbohydrates would reduce the probability of remission. It is important to remember that over-the-counter low carbohydrate cat foods often contain predominantly fish or meat and tend to have substantially higher phosphate levels than some of the veterinary prescription diets designed for diabetes.

References:

1. MacDonald ML, Rogers QR, Morris JG. Nutrition of the domestic cat, a mammalian carnivore. Annu Rev Nutr 1984;4:521-562. 
2. Zoran DL. The carnivore connection to nutrition in cats. J Am Vet Med Assoc 2002;221:1559-1567. 
3. Eisert R. Hypercarnivory and the brain: protein requirements of cats reconsidered. J Comp Physiol B 2011;181:1-17. 
4. Farrow H, Rand JS, Morton JM, et al. Postprandial glycemia in cats fed a moderate carbohydrate meal persists for a median of 12 hours -- female cats have higher peak glucose concentrations. J Feline Med Surg 2012;14:706-715. 
5. Farrow HA, Rand JS, Morton JM, et al. Effect of dietary carbohydrate, fat, and protein on postprandial glycemia and energy intake in cats. J Vet Intern Med 2013;27:1121-1135. 
6. Rand JS. Feline diabetes mellitus In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;133-147.
7. Baral RM, Little SE. Endocrine pancreatic disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;547-571.
8. Kim TN, Park MS, Yang SJ, et al. Prevalence and determinant factors of sarcopenia in patients with type 2 diabetes: the Korean Sarcopenic Obesity Study (KSOS). Diabetes Care 2010;33:1497-1499. 
9. Stenholm S, Harris TB, Rantanen T, et al. Sarcopenic obesity: definition, cause and consequences. Curr Opin Clin Nutr Metab Care 2008;11:693-700. 
10. Srikanthan P, Hevener AL, Karlamangla AS. Sarcopenia exacerbates obesity-associated insulin resistance and dysglycemia: findings from the National Health and Nutrition Examination Survey III. PLoS One 2010;5:e10805. 
11. Moon SS. Low skeletal muscle mass is associated with insulin resistance, diabetes, and metabolic syndrome in the Korean population: The Korea National Health and Nutrition Examination Survey (KNHANES) 2009-2010. Endocr J 2013. 
12. Zini E, Osto M, Franchini M, et al. Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat. Diabetologia 2009;52:336-346. 
13. Zini E, Hafner M, Osto M, et al. Predictors of clinical remission in cats with diabetes mellitus. J Vet Intern Med 2010;24:1314-1321. 
14. Reusch CE, Hafner M, Tschuor F, et al. Diabetes remission in cats: a review. Schweiz Arch Tierheilkd 2011;153:495-500. 
15. Gottlieb S, Rand JS. Remission in cats: including predictors and risk factors. Vet Clin North Am Small Anim Pract 2013;43:245-249. 
16. Nguyen P, Leray V, Dumon H, et al. High protein intake affects lean body mass but not energy expenditure in nonobese neutered cats. J Nutr 2004;134:2084S-2086S. 
17. Keller U. Dietary proteins in obesity and in diabetes. Int J Vitam Nutr Res 2011;81:125-133. 
18. Zoran DL, Rand JS. The role of diet in the prevention and management of feline diabetes. Vet Clin North Am Small Anim Pract 2013;43:233-243. 
19. Frank G, Anderson W, Pazak H, et al. Use of a high-protein diet in the management of feline diabetes mellitus. Vet Ther 2001;2:238-246. 
20. Paddon-Jones D, Short KR, Campbell WW, et al. Role of dietary protein in the sarcopenia of aging. Am J Clin Nutr 2008;87:1562S-1566S. 
21. Wakshlag JJ. Dietary protein consumption in the healthy aging companion animal. Proceedings of the Nestlé Purina Companion Animal Nutrition Summit: Focus on Gerontology 2010;32-39.
22. Kidder AC, Chew D. Treatment options for hyperphosphatemia in feline CKD: what's out there? J Feline Med Surg 2009;11:913-924. 
23. Ross SJ, Osborne CA, Kirk CA, et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats. J Am Vet Med Assoc 2006;229:949-957. 

How to Feed Cats with Diabetes

Diet plays a key role in the successful management of the diabetic cat. Because cats are obligate carnivores (1-3), diabetic cats are relatively carbohydrate intolerant and respond best to a low carbohydrate diet. This differs from dogs, which are omnivores and are quite tolerant of a moderate to high carbohydrate meal, even when diabetic (4,5).

Evolutionary events shaped the cat’s core metabolism such that their systems are uniquely set up to metabolize a diet which is high in moisture, high in protein, and very low in carbohydrates. Because this is the diet they have relied upon for tens of thousands of years, they do not have the ability to process carbohydrates very efficiently and show relative carbohydrate intolerance (1-3). This becomes extremely important when selecting a diet for cats with diabetes.

Postprandial Glycemia in Man, Dogs, and Cats
As a result of these differences, plasma glucose clearance rates are longer in cats compared to dogs or humans after feeding a moderate to high carbohydrate meal — in other words, even normal cats have much more prolonged postprandial period of hyperglycemia than might be expected. In healthy humans and dogs, postprandial hyperglycemia normally persists for 2 to 6 hours (4,6).

In contrast, recent studies of healthy cats found that both serum glucose and insulin concentrations remained significantly increased for a median time of 12 hours following ingestion of a moderate carbohydrate meal (25% of calories), and that both glucose and insulin concentrations remained above baseline values for 24 hours in approximately 20% of the cats (7,8). Most feline diets contain even higher amounts of carbohydrate (greater than 25%) and, therefore, would be expected to result in more severe postprandial hyperglycemia and a longer time to return to baseline.

Management Goals of Feline Diabetes
In cats with diabetes, a primary goal of therapy is to feed a diet that will lessen postprandial hyperglycemia, reduce marked fluctuations of blood glucose concentrations, minimize the demand on beta cells to produce insulin, and improve insulin sensitivity (9-11). By doing this, we decrease the effect of “glucose toxicity” and hopefully allow the pancreatic islet cell to partially recover. In about half of newly diagnosed diabetic cats, this will lead to remission of the diabetic state (12-14).

A secondary goal of therapy is to provide a diet that will help normalize body weight and maintain and/or restore lost muscle mass (15,16). I'll be covering the reason why higher protein diets are also important for diabetes in my post next week.

Recommendations for Diabetic Cats: Low Dietary Carbohydrates:
It is well accepted dogma, at least by most practicing veterinarians who specialize in feline medicine, that feeding a low-carbohydrate diet is the mainstay in the treatment of diabetes mellitus, especially if remission of the diabetic state is the goal. In accord with that, there is strong clinical and research evidence that a diet containing very low concentrations of carbohydrate (e.g., carbohydrates less than 12% of calories) is the most effective means for achieving our nutritional goals for cats with diabetes (5,9,17-19).

Feeding a low carbohydrate diet will improve insulin sensitivity, help stabilize glucose metabolism, and can reduce or eliminate the need for exogenous insulin in these cats (5,20,13,14).  The likely mechanism for these observations is relatively simple —decreasing dietary carbohydrate load reduces the postprandial blood glucose elevation, which in cats is prolonged, sometimes lasting for over 12 hours (7,8).

In some diabetic cats, decreasing carbohydrate content to a level significantly less than 12% of the daily calories may help increase their rate of remission. In accord with that, the highest remission rates (greater than 80%) have been reported feeding diets with approximately 6% of energy from carbohydrate (21).

If a change in feeding to a low-carbohydrate diet is made in a diabetic cat already stabilized on insulin, it is extremely important to realize that this will result in a lowered daily insulin dosage — often significantly (9.20). If not closely monitored—ideally with home glucose testing— severe hypoglycemia can develop in these cats because they become more sensitive to insulin after the diet composition is changed.

Therefore, when changing from a higher-carbohydrate to a low-carbohydrate diet, we recommend initially reducing the insulin dose by 30% to 50% to help avoid hypoglycemia. If the diabetic cat goes into remission (no more insulin needed to maintain euglycemia), we recommend maintaining the low-carbohydrate diet for life to help prevent relapse of the diabetic state.

References:

1. MacDonald ML, Rogers QR, Morris JG. Nutrition of the domestic cat, a mammalian carnivore. Annu Rev Nutr 1984;4:521-562. 
2. Zoran DL. The carnivore connection to nutrition in cats. J Am Vet Med Assoc 2002;221:1559-1567. 
3. Eisert R. Hypercarnivory and the brain: protein requirements of cats reconsidered. J Comp Physiol B 2011;181:1-17. 
4. Elliott KF, Rand JS, Fleeman LM, et al. A diet lower in digestible carbohydrate results in lower postprandial glucose concentrations compared with a traditional canine diabetes diet and an adult maintenance diet in healthy dogs. Res Vet Sci 2011;93. 
5. Rucinsky R, Cook A, Haley S, et al. AAHA diabetes management guidelines. J Am Anim Hosp Assoc 2010;46:215-224. 
6. American Diabetes Association. Postprandial blood glucose. Diabetes Care 2001;24:775-778. 
7. Farrow H, Rand JS, Morton JM, et al. Postprandial glycemia in cats fed a moderate carbohydrate meal persists for a median of 12 hours -- female cats have higher peak glucose concentrations. J Feline Med Surg 2012;14:706-715. 
8. Farrow HA, Rand JS, Morton JM, et al. Effect of dietary carbohydrate, fat, and protein on postprandial glycemia and energy intake in cats. J Vet Intern Med 2013;27:1121-1135. 
9. Rand JS. Feline diabetes mellitus In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;133-147.
10. Rand JS. Pathogenesis of feline diabetes. Vet Clin North Am Small Anim Pract 2013;43:221-231. 
11. Zini E, Osto M, Franchini M, et al. Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat. Diabetologia 2009;52:336-346. 
12.  Zini E, Hafner M, Osto M, et al. Predictors of clinical remission in cats with diabetes mellitus. J Vet Intern Med 2010;24:1314-1321. 
13. Reusch CE, Hafner M, Tschuor F, et al. Diabetes remission in cats: a review. Schweiz Arch Tierheilkd 2011;153:495-500. 
14. Gottlieb S, Rand JS. Remission in cats: including predictors and risk factors. Vet Clin North Am Small Anim Pract 2013;43:245-249. 
15. Nguyen P, Leray V, Dumon H, et al. High protein intake affects lean body mass but not energy expenditure in nonobese neutered cats. J Nutr 2004;134:2084S-2086S. 
16. Keller U. Dietary proteins in obesity and in diabetes. Int J Vitam Nutr Res 2011;81:125-133. 
17. Baral RM, Little SE. Endocrine pancreatic disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;547-571.
18. Bennett N, Greco DS, Peterson ME, et al. Comparison of a low carbohydrate-low fiber diet and a moderate carbohydrate-high fiber diet in the management of feline diabetes mellitus. J Feline Med Surg 2006;8:73-84. 
19. Boari A, Aste G, Rocconi F, et al. Glargine insulin and high-protein-low-carbohydrate diet in cats with diabetes mellitus. Vet Res Commun 2008;32 Suppl 1:S243-245. 
20. Zoran DL, Rand JS. The role of diet in the prevention and management of feline diabetes. Vet Clin North Am Small Anim Pract 2013;43:233-243. 
21. 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. 

Top Endocrine Publications of 2012: Canine and Feline Endocrine Nutrition

In my 11th and last compilation of canine and feline endocrine publications of 2012, I’m finishing up with endocrine nutrition and treatment of obesity in dogs and cats. Starting in February of 2014, I'm planning to start posting the endocrine publications for 2013. I'm only waiting for the final papers published in December to come out so they can be included in my lists and reviews.

Listed below are 31 research papers written in 2012 that deal with a variety of topics concerning endocrine nutrition or obesity in the dog and cat. Remember that adipose tissue is the largest endocrine gland in the body, making a number of hormones, including leptin, adiponectin, and resistin. These hormones generally influence energy metabolism, which is of great interest to the understanding and treatment of type 2 diabetes and obesity.

These papers range from the studies of the effects of calcium deficiency in growing and adult dogs (1) to studies of the effect of dietary fat intake on circulating lipids in cats (2); from cause, prevalence, and management of obesity in dogs and cats (3,4,12-16,21,25-27,30) to the effect of nutrition on calcium oxalate and calcium excretion in cats (7,8); and from the effects on dietary L-carnitine supplementation on metabolism in cats (4) to the changes in fat-free mass and leptin in hyperthyroid cats before and after treatment (11,18).

Other research studies include the influence of dietary composition on the circulating glucose and insulin response to feeding (9,10) to factors that regulate serum leptin and adiponectin concentrations in dogs and cats (12,20,21,23) and studies of the role of dietary selenium and iodine on nutrition and metabolism (22,31). Finally, this lists also includes a excellent paper on dietary hyperthyroidism in dogs (19) — where we are reminded that not all dogs with thyrotoxicosis have a hyperfunctioning thyroid carcinoma!

2012 Papers on Endocrine Nutrition and Obesity:

1. Becker N, Kienzle E, Dobenecker B. Calcium deficiency: a problem in growing and adult dogs: two case reports. Tierarztl Prax Ausg K Kleintiere Heimtiere 2012;40:135-139. 
2. Butterwick RF, Salt C, Watson TD. Effects of increases in dietary fat intake on plasma lipid and lipoprotein cholesterol concentrations and associated enzyme activities in cats. Am J Vet Res 2012;73:62-67. 
3. Cave NJ, Allan FJ, Schokkenbroek SL, et al. A cross-sectional study to compare changes in the prevalence and risk factors for feline obesity between 1993 and 2007 in New Zealand. Prev Vet Med 2012;107:121-133. 
4. Center SA, Warner KL, Randolph JF, et al. Influence of dietary supplementation with l-carnitine on metabolic rate, fatty acid oxidation, body condition, and weight loss in overweight cats. Am J Vet Res 2012;73:1002-1015. 
5. Clark MH, Hoenig M, Ferguson DC, et al. Pharmacokinetics of pioglitazone in lean and obese cats. J Vet Pharmacol Ther 2012;35:428-436. 
6. Corbee RJ, Tryfonidou MA, Meij BP, et al. Vitamin D status before and after hypophysectomy in dogs with pituitary-dependent hypercortisolism. Domest Anim Endocrinol 2012;42:43-49. 
7. Dijcker JC, Hagen-Plantinga EA, Everts H, et al. Dietary and animal-related factors associated with the rate of urinary oxalate and calcium excretion in dogs and cats. Vet Rec 2012;171:46. 
8. Dijcker JC, Kummeling A, Hagen-Plantinga EA, et al. Urinary oxalate and calcium excretion by dogs and cats diagnosed with calcium oxalate urolithiasis. Vet Rec 2012;171:646. 
9. Elliott KF, Rand JS, Fleeman LM, et al. A diet lower in digestible carbohydrate results in lower postprandial glucose concentrations compared with a traditional canine diabetes diet and an adult maintenance diet in healthy dogs. Res Vet Sci 2012;93:288-295. 
10. Farrow H, Rand JS, Morton JM, et al. Postprandial glycemia in cats fed a moderate carbohydrate meal persists for a median of 12 hours -- female cats have higher peak glucose concentrations. J Feline Med Surg 2012;14:706-705. 
11. Finch NC, Welsh CP, Hibbert A. Changes in fat-free mass (FFM) in cats undergoing radioactive iodine therapy. J Feline Med Surg 2012;14:652-653.
12. German AJ. Barking up the wrong tree: what's the deal with obesity, adiponectin and inflammation in dogs? Vet J 2012;194:272-273.
13. German AJ, Holden SL, Morris PJ, et al. Long-term follow-up after weight management in obese dogs: the role of diet in preventing regain. Vet J 2012;192:65-70. 
14. German AJ, Holden SL, Wiseman-Orr ML, et al. Quality of life is reduced in obese dogs but improves after successful weight loss. Vet J 2012;192:428-434. 
15. Haring T, Haase B, Zini E, et al. Overweight and impaired insulin sensitivity present in growing cats. J Anim Physiol Anim Nutr (Berl) 2012; doi: 10.1111/j.1439-0396.2012.01322.x. 
16. Hoenig M. The cat as a model for human obesity and diabetes. J Diabetes Sci Technol 2012;6:525-533. 
17. Hutchinson D, Freeman LM, McCarthy R, et al. Seizures and severe nutrient deficiencies in a puppy fed a homemade diet. J Am Vet Med Assoc 2012;241:477-483. 
18. Jaillardon L, Burger M, Siliart B. Leptin levels in hyperthyroid cats before and after treatment. Vet Rec 2012;170:155. 
19. Köhler B, Stengel D, Neiger R. Dietary hyperthyroidism in dogs. J Small Anim Pract 2012;53:182-184. 
20. Mazaki-Tovi M, Abood SK, Schenck PA. Effect of omega-3 polyunsaturated fatty acids and body condition on serum concentrations of adipokines in healthy dogs. Am J Vet Res 2012;73:1273-1281. 
21. Ricci R, Bevilacqua F. The potential role of leptin and adiponectin in obesity: a comparative review. Vet J 2012;191:292-298. 
22. Todd SE, Thomas DG, Bosch G, et al. Selenium status in adult cats and dogs fed high levels of dietary inorganic and organic selenium. J Anim Sci 2012;90:2549-2555. 
23. Tvarijonaviciute A, Ceron JJ, Martinez-Subiela S, et al. Serum and urinary adiponectin in dogs with renal disease from leishmaniasis. Vet Rec 2012;171:297. 
24. Tvarijonaviciute A, German AJ, Martinez-Subiela S, et al. Analytical performance of commercially-available assays for feline insulin-like growth factor 1 (IGF-1), adiponectin and ghrelin measurements. J Feline Med Surg 2012;14:138-146. 
25. Tvarijonaviciute A, Ceron JJ, Holden SL, et al. Obesity-related metabolic dysfunction in dogs: a comparison with human metabolic syndrome. BMC Vet Res 2012;8:147. h
26. Tvarijonaviciute A, Tecles F, Martinez-Subiela S, et al. Effect of weight loss on inflammatory biomarkers in obese dogs. Vet J 2012;193570-572. 
27. Tvarijonaviciute A, Ceron JJ, Holden SL, et al. Effects of weight loss in obese cats on biochemical analytes related to inflammation and glucose homeostasis. Domest Anim Endocrinol 2012;42:129-141. 
28. Verbrugghe A, Hesta M, Daminet S, et al. Nutritional modulation of insulin resistance in the true carnivorous cat: a review. Crit Rev Food Sci Nutr 2012;52:172-182. 
29. Verkest KR, Fleeman LM, Morton JM, et al. Association of postprandial serum triglyceride concentration and serum canine pancreatic lipase immunoreactivity in overweight and obese dogs. J Vet Intern Med 2012;26:46-53. 
30. Verkest KR, Rand JS, Fleeman LM, et al. Spontaneously obese dogs exhibit greater postprandial glucose, triglyceride, and insulin concentrations than lean dogs. Domest Anim Endocrinol 2012;42:103-112.
31. Zicker S, B. S. Focus on nutrition: the role of iodine in nutrition and metabolism. Compendium 2012;34:E1-E4. 

Obesity Epidemic Expanding in Dogs and Cats

The rates of overweight and obesity in dogs and cats in the U.S. continued to increase in 2012, with the number of overweight cats reaching an all-time high.

Results of the sixth annual National Pet Obesity Awareness Day Survey, conducted by the Association for Pet Obesity Prevention (APOP), revealed that 52.5% of dogs and 58.3% of cats were overweight or obese (Figure 1). That equals approximately 80 million U.S. dogs and cats at increased risk for weight-related disorders such as diabetes, osteoarthritis, hypertension, and many cancers.

Figure 1. Incidence of overweight and obesity in cats and dogs (from APOP website).

As Dr. Ernie Ward, APOP’s founder and lead veterinarian for the survey states. “Pet obesity remains the leading health threat to our nation’s pets. We continue to see an escalation in the number of overweight cats and an explosion in the number of type 2 diabetes cases.”

And veterinary endocrinologist and APOP board member Dr. Mark Peterson agrees: “The soaring rate of feline and canine obesity is taking a terrible toll on our animals’ health. There is a vast population of overweight cats and dogs facing an epidemic of diabetes. The best preventive measure a pet owner can make is to keep their dog or cat at a healthy weight. Diabetes is far easier to prevent than treat, especially when twice daily insulin injections are needed.”

For more information about the 2012 National Pet Obesity survey results or the Association for Pet Obesity Prevention in general, please visit their website at www.petobesityprevention.com.

Feeding the Cat with Diabetes Mellitus

Evolutionary events shaped the cat’s core metabolism such that their systems are uniquely set up to metabolize a diet which is high in moisture, high in protein, and very low in carbohydrates. Because this is the diet they have relied upon for tens of thousands of years, they do not have the ability to process carbohydrates very efficiently (1-4). This becomes extremely important when selecting a diet for cats with diabetes, as I’ll discuss below.

Normal Glucose Metabolism and Postprandial Glycemia in Cats

So what are these specific feline adaptive mechanisms that have developed to meet the requirements of a carnivorous diet?

• First, cat’s gluconeogenic pathway provides an almost continuous source of carbon skeletons for glucose or energy production.
• Secondly, glucokinase concentrations are markedly reduced or absent, whereas hexokinase activity is increased. This is in marked contrast to the liver of omnivores (dogs, man), which contains both glycolytic enzymes that act to catalyze the phosphorylation of glucose during glycolysis.
• Finally, cats have reduced amylase and disaccarharide activity in the small intestine, reduced and delayed insulin secretion, and delayed gastric emptying (1-4).

As a result of these differences, plasma glucose clearance rates are longer in cats compared to dogs or humans after feeding a moderate to high carbohydrate meal — in other words, even normal cats have much more prolonged postprandial period of hyperglycemia than might be expected.

In healthy humans and dogs, postprandial hyperglycemia normally persists for 2 to 5 hours (5-6). In contrast, a recent study of healthy cats found that both serum glucose and insulin concentrations remained significantly increased for a median time of 12 hours following ingestion of a moderate carbohydrate meal (25% ME), and that both glucose and insulin concentrations remained above baseline values for 24 hours in approximately 20% of the cats (7).  Most feline diets (especially dry foods) contain ever higher amounts of carbohydrate and therefore would be expected to result in more severe postprandial hyperglycemia and a longer time to return to baseline.

Dietary Management of Cats with Diabetes Mellitus: Key Part of Treatment!

In cats with diabetes, a primary goal of therapy is to minimize the degree of hyperglycemia that develops after feeding in order to lessen the subsequent demand on beta-cells to secrete insulin. By doing this, we decrease the effect of “glucose toxicity” and allow the pancreatic islet cell to hopefully recover (8,9).

But how do we do this? It has long been known and is a well accepted “dogma” by most practicing veterinarians who specialize in feline medicine that feeding a low-carbohydrate diet is the mainstay in the treatment of diabetes mellitus, especially if remission of the diabetic state is the goal. Feeding a low carbohydrate diet will improve insulin sensitivity, reduce or eliminate the need for exogenous insulin, and help stabilize glucose metabolism in these cats (9-12). Again, one major way a low-carb diet improves the diabetic state is by helping to prevent severe and prolonged postprandial hyperglycemia.

The sooner one starts the diabetic cat on a low-carbohydrate diet, the better. By “low-carb,” I mean a diet that provides less than 10% of the calories as carbohydrate. Some cats will do fine on a slightly higher-carb diet (12-14%) whereas others do best on a diet containing less than 7% carbohydrate.

To achieve these low carbohydrate levels, we must formulate a homemade diet or feed a canned food. I'd recommend that one go to Dr. Lisa Pierson's website at www.catinfo.org. Once there, you should review the “Protein/Fat/Carbs Chart” on the sidebar of the homepage to select an appropriate low-carb diet.

None of the available dry cat foods are very low in carbohydrates and most are too low in protein. 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.

When we reduce the content of carb in a cat food, we must raise the content of either protein or fat, or both. I like to do both, feeding my diabetic cats a diet that mimics the composition of their prey in the wild: about 40-60% of protein with the remaining amount in fat. This higher than average protein level also helps restore and maintain lost muscle mass, since many diabetic cats will develop muscle wasting or “sarcopenia” as they age (13-17).

Dietary Management of Diabetic Cats and Remission

Another plus for feeding low-carb, hi-protein diets in cats with relatively early diabetes is that this diet composition (together with insulin treatment) greatly improves the diabetic remission rate (18-20). If the diabetic cat goes into remission (no more insulin needed to maintain euglycemia), we recommend maintaining a restricted carbohydrate diet for life to help prevent relapse of the diabetic state.

References:

1. Zoran DL. The unique nutritional needs of the cat In: Ettinger SJ,Feldman EC, eds. Textbook of Veterinary Internal Medicine. 7th ed: Saunders Elsevier, 2010;652-659.
2. Eisert R. Hypercarnivory and the brain: protein requirements of cats reconsidered. J Comp Physiol B 2011;181:1-17.
3. MacDonald ML, Rogers QR, Morris JG. Nutrition of the domestic cat, a mammalian carnivore. Annu Rev Nutr 1984;4:521-562.
4. Verbrugghe A, Hesta M, Daminet S, et al. Nutritional modulation of insulin resistance in the true carnivorous cat: a review. Crit Rev Food Sci Nutr 2012;52:172-182.
5. American Diabetes Association. Postprandial blood glucose. Diabetes Care 2001;24:775-778. 
6. Elliott KF, Rand JS, Fleeman LM, et al. A diet lower indigestible carbohydrate results in lower postprandial glucose concentrationscompared with a traditional canine diabetes diet and an adult maintenance dietin healthy dogs. Res Vet Sci 2012;93:288-295.
7. Farrow H, Rand JS, Morton JM, et al. Postprandial glycemia in cats fed a moderate carbohydrate meal persists for a median of 12 hours — female cats have higher peak glucose concentrations. J Feline Med Surg 2012; 14:706-715.
8. Zini E, Osto M, Franchini M, et al. Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat. Diabetologia 2009;52:336-346.
9. Rucinsky R, Cook A, Haley S, et al.  AAHA diabetes management guidelines for dogs and cats. Journal of the American Animal Hospital Association 2010;46:215-224.
10. Frank G, Anderson W, Pazak H, et al. Use of a high-protein diet in the management of feline diabetes mellitus. Vet Ther 2001;2:238-246
11. Bennett N, Greco DS, Peterson ME, et al. Comparison of a low carbohydrate-low fiber diet and a moderate carbohydrate-high fiber diet in the management of feline diabetes mellitus. J Feline Med Surg 2006;8:73-84.
12. 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 2003;5:183-189.
13. Little S: Evaluation of the senior cat with weight loss, In: Little, S. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders, in press.
14. Perez-Camargo G: Cat nutrition: What is new in the old? Compendium for Continuing Education for the Practicing Veterinarian 2004;26 (Suppl 2A):5-10.
15. Patil AR, Cupp C, Pérez-Camargo G. Incidence of impaired nutrient digestibility in aging cats. Nestlé Purina Nutrition Forum Proceedings. 2003;26,2(A):72.
16. Wakshlag JJ. Dietary protein consumption in the healthy aging companion animal. Proceedings of the Nestlé Purina Companion Animal Nutrition Summit: Focus on Gerontology. St. Louis, MO. 2010, pp. 32-39.
17. Sparkes AH. Feeding old cats— An update on new nutritional therapies. Topics in Companion Animal Medicine 2011;26:37-42.
18. Boari A, Aste G, Rocconi F, et al. Glargine insulin andhigh-protein-low-carbohydrate diet in cats with diabetes mellitus. Vet Res Commun 2008;32 Suppl 1:S243-245.
19. Roomp K, Rand J. Evaluation of detemir in diabetic catsmanaged with a protocol for intensive blood glucose control. J Feline Med Surg 2012;14:566-572. 
20. Reusch CE, Hafner M, Tschuor F, et al. Diabetes remission incats: a review. Schweiz Arch Tierheilkd 2011;153:495-500. 

Top Endocrine Publications of 2011: Canine and Feline Endocrine Nutrition

In my 10th and last compilation of the canine and feline endocrine publications of 2011, I’m finishing up with endocrine nutrition and treatment of obesity in dogs and cats. Starting in February of the New Year, I'm planning to start posting the endocrine publications for 2012. I'm only waiting for the final papers published in December to come out so they can be included in my lists and reviews.

Listed below are 27 research papers written in 2011 that deal with a variety of topics of clinical importance concerning endocrine nutrition or obesity in the dog and cat. Remember that adipose tissue is the largest endocrine gland in the body, making a number of hormones, including leptin, adiponectin, and resistin. These hormones generally influence energy metabolism, which is of great interest to the understanding and treatment of type 2 diabetes and obesity.

These papers range from the studies of the effects of neutering on body weight and body composition in cats (1,2) to studies of the glucose intolerance and insulin resistance associated with obesity (3, 20-22); from the cause, prevalence, and management of obesity in dogs and cats (5,8-10,25,26) to the effect of nutrition and dietary water on calcium oxalate and stuvite in cats (4,7).

Other research studies include the influence of dietary composition on the circulating glucose and insulin response to feeding (6,11-13) to factors that regulate serum leptin and adiponectin concentrations in dogs and cats (16-18,22-24). Finally, this lists also includes two excellent review papers on feline nutrition (15,27) — where we are reminded that cats are true carnivores and need higher amounts of protein, and not carbs!

References:

1. Alexander LG, Salt C, Thomas G, et al. Effects of neuteringon food intake, body weight and body composition in growing female kittens. Br J Nutr 2011;106 Suppl 1:S19-23. 
2. Backus R. Plasma oestrogen changes in adult male cats afterorchiectomy, body-weight gain and low-dosage oestradiol administration. Br J Nutr 2011;106 Suppl 1:S15-18. 
3. 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. 
4. Buckley CM, Hawthorne A, Colyer A, et al. Effect of dietary water intake on urinary output, specific gravity and relative supersaturation for calcium oxalate and struvite in the cat. Br J Nutr 2011;106 Suppl 1:S128-130. 
5. Chauvet A, Laclair J, Elliott DA, et al. Incorporation of exercise, using an underwater treadmill, and active client education into a weight management program for obese dogs. Can Vet J 2011;52:491-496. 
6. Coradini M, Rand JS, Morton JM, et al. Effects of twocommercially available feline diets on glucose and insulin concentrations,insulin sensitivity and energetic efficiency of weight gain. Br J Nutr 2011;106 Suppl 1:S64-77. 
7. Dijcker JC, Plantinga EA, van Baal J, et al. Influence ofnutrition on feline calcium oxalate urolithiasis with emphasis on endogenousoxalate synthesis. Nutr Res Rev 2011:1-15. 
8. German AJ. Canine obesity--weighing on the mind of the owner? J Small Anim Pract 2011;52:619-620. 
9. German AJ, Holden SL, Gernon LJ, et al. Do feeding practices of obese dogs, before weight loss, affect the success of weight management? Br J Nutr 2011;106 Suppl 1:S97-100. 
10. German AJ, Holden SL, Mather NJ, et al. Low-maintenance energy requirements of obese dogs after weight loss. Br J Nutr 2011;106 Suppl 1:S93-96. 
11. Hewson-Hughes AK, Gilham MS, Upton S, et al. Postprandialglucose and insulin profiles following a glucose-loaded meal in cats and dogs. Br J Nutr 2011;106 Suppl 1:S101-104. 
12. Hewson-Hughes AK, Gilham MS, Upton S, et al. The effect ofdietary starch level on postprandial glucose and insulin concentrations in catsand dogs. Br J Nutr 2011;106 Suppl 1:S105-109.
13. 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. 
14. Ryan VH, Trayhurn P, Hunter L, et al. 11-Hydroxy-beta-steroid dehydrogenase gene expression in canine adipose tissue and adipocytes: stimulation by lipopolysaccharide and tumor necrosis factor alpha. Domest Anim Endocrinol 2011;41:150-161. 
15. Sparkes AH. Feeding old cats—an update on new nutritional therapies. Top Companion Anim Med 2011;26:37-42. 
16. Tan HY, Rand JS, Morton JM, et al. Adiponectin profiles areaffected by chronic and acute changes in carbohydrate intake in healthy cats. General & Comparative Endocrinology 2011;172:468-474. 
17.  Tvarijonaviciute A, Ceron JJ, Martinez-Subiela S. Assessment of five ELISAs for measurement of leptin concentrations in dogs. Am J Vet Res 2011;72:169-173. 
18. Tvarijonaviciute A, Eralp O, Kocaturk M, et al. Adiponectin and IGF-1 are negative acute phase proteins in a dog model of acute endotoxaemia. Vet Immunol Immunopathol 2011;140:147-151. 
19. Tvarijonaviciute A, Tecles F, Carillo JM, et al. Serum insulin-like growth factor-1 measurements in dogs: performance characteristics of an automated assay and study of some sources of variation. Can J Vet Res 2011;75:312-316. 
20. 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. 
21. 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. 
22. 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. 
23. Verkest KR, Rose FJ, Fleeman LM, et al. Adiposity and adiponectin in dogs: investigation of causes of discrepant results between two studies. Domest Anim Endocrinol 2011;41:35-41. 
24. Wakshlag JJ, Struble AM, Levine CB, et al. The effects of weight loss on adipokines and markers of inflammation in dogs. Br J Nutr 2011;106 Suppl 1:S11-14. 
25. Warren BS, Wakshlag JJ, Maley M, et al. Use of pedometers to measure the relationship of dog walking to body condition score in obese and non-obese dogs. Br J Nutr 2011;106 Suppl 1:S85-89. 
26. White GA, Hobson-West P, Cobb K, et al. Canine obesity: is there a difference between veterinarian and owner perception? J Small Anim Pract 2011;52:622-626. 
27. 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. 

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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23. AAFCO (Association of American Feed Control Officials). Official Publication, 2012.
24. Whitney JL, Barrs VR, Wilkinson MR, et al. Use of bisphosphonates to treat severe idiopathic hypercalcaemia in a young Ragdoll cat. J Fel Med Surg 2011;13:129-134.
25. Lowe AD, Graves TK, Campbell KL, et al. Apilot study comparing the diabetogenic effects of dexamethasone andprednisolone in cats. J Am Anim Hosp Assoc 2009;45:215-224.