Blood Glucose Curves and the Fractious Diabetic Cat

My problem patient is a 12-year old, DSH, female spayed cat with a 2-year history of insulin-dependent diabetes mellitus. She has been treated with glargine insulin at a variable dose, but typically between 1-3 units, BID. This cat will not eat canned food so we are feeding higher protein, lower carb dry foods (Hill's MD and Purina DM).

Six months ago, the cat was diagnosed with immune-mediated hemolytic anemia (IMHA) and was treated successfully with prednisolone and cyclosporine (Atopica). This led to development of insulin resistance and loss of diabetic control, but the cat did relatively well after raising the insulin dose to 6 units while on prednisolone. After a long and slow taper, the cat is now off all glucocorticoids for the last month, and the insulin dose is back down to 2 U, twice daily. The cat remains on Atopica, probably for life.

We have periodically done in-house blood glucose curves to adjust her insulin dose, but she becomes extremely fractious when hospitalized, and we can't really handle her (she bites, scratches, cries, and screams louder than any other cat I've ever had!). The owner does not care to check blood glucose at home, and given the cat's nature, I doubt if they could even do it. Since weaning her off the prednisolone, we have seen a couple of hypoglycemic readings on spot blood glucose checks so we are now worried that the current insulin dose may be too high.

Therefore a week ago, we performed a serial glucose curve on 2 units glargine, BID. The results were as follows:

• 6 am = Insulin given
• 8 am = 317 mg/dl
• 10 am = 376 mg/dl
• 12 noon = 352 mg/dl
• 2 pm = 299 mg/dl
• 4 pm = 229 mg/dl

We were a bit surprised by the high glucose concentrations during the day on this curve, but we increased glargine from 2 to 3 units BID based on the severe and persistent hyperglycemia. However, when I checked a spot afternoon blood glucose value yesterday, it was low-normal at 69 mg/dl. I rechecked another blood glucose reading 30 minutes later, and it was even lower at 57 mg/dl. Right or wrong, I put her back down to 2 units glargine BID and pm spot check in 1 week.

My main question is this: could this cat's in-hospital curve be leading us astray because she is so fractious? I am aware that spot checks aren't ideal. However, this cat is relatively easy to handle during a quick exam and single spot check, but she become so angry when hospitalized throughout the day.

What would you do? How do I adjust the insulin dosage in this cat? We've been trying to get the cat into remission but it's not looking good!

My Response:

Well, first the bad news: I can almost guarantee that this cat's diabetes will not go into remission, given the fact that she has been diabetic for 2 years. A number of studies have reported that diabetic remission, when it does occur, will generally happen within the first 6 months of diagnosis (1,2). In addition, the fact that she has concurrent disease and has been treated with glucocorticoids certainly hasn't increased her chances for remission.

The good news is that once we decide that diabetic remission is no longer our goal, then we can be more lax with our glucose regulation. Our goal for diabetic cats should then be 3-fold:

1. Control clinical signs of diabetes (e.g., weight loss, polyuria, polydispsia)
2. Prevent diabetic ketoacidosis
3. Avoid hypoglycemia

To do this, it's not really necessary to do the tight glucose regulation and frequent blood glucose monitoring that we would ideally do if we are trying to increase the odds for diabetic remission (3-5).

In fractious diabetic cats, I would never recommend doing serial blood glucoses to determine the best insulin dose. The release of catecholamines during this excitable state can absolutely increase the glucose readings during the curve (commonly referred to as stress hyperglycemia) (6). Overall, this means that all of the serial blood glucose curves you have done in this cat are most likely next to meaningless and that such testing should be stopped.

Spot glucose checks can't hurt, but as you say, they can be hard to interpret and may be misleading. If the blood glucose reading is low, you might want to decrease the insulin dose, but if the blood glucose is in the ideal range or high, you could still be overdosing the insulin.

In cats like this, I'd recommend that you adjust the insulin dose based on the presence or absence of clinical signs, including body weight and water intake (7).  If the owners can measure water intake at home, that can be a very sensitive way to help determine if more insulin is needed. If there are no clinical signs of diabetes and the weight is stable, the cat is probably adequately controlled. Monitoring an occasional serum fructosamine level can also help (8,9), as well as home measurement of urine glucose, if the owner can do it (7,19,11). A weekly check for urinary ketones can also be used to monitor for pending ketoacidosis, and become extremely important if anorexia, vomiting, or any other signs of illness develop.

Bottom Line:
In fractious cats, I would not recommend in-hospital blood glucose curves for monitoring. Stress hyperglycemia will give you results that are meaningless, and one could easily be misled into giving higher doses of insulin than are actually needed. This is especially true in cats with long-term diabetes that are unlikely to ever develop remission.

In cats like this case, I use a combination of clinical signs and blood/urine values, looking at the overall trend in results rather than the specific or individual values. For example, I don't use serum fructosamine concentration as the sole means of judging control, but I still think it is helpful as one piece of the puzzle. If it is high, that suggests that the insulin dosage may have to be increased; if the fructosamine value is low to low-normal, this may indicate overdosage and hypoglycemia.

Believe me, both your hospital staff and the fractious diabetic cat will all be better off with this approach!

References:

1. Gottlieb S, Rand JS. Remission in cats: including predictors and risk factors. Vet Clinics North America 2013: 43: 245-249
2. 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.
3. Roomp K, Rand J. Intensive blood glucose control is safe and effective in diabetic cats using home monitoring and treatment with glargine. J Feline Med Surg 2009;11:668-682.
4. 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.
5. Nack R, DeClue AE. In cats with newly diagnosed diabetes mellitus, use of a near-euglycemic management paradigm improves remission rate over a traditional paradigm. Vet Q 2014; 34:132-136.
6. Rand JS, Kinnaird E, Baglioni A, et al. Acute stress hyperglycemia in cats is associated with struggling and increased concentrations of lactate and norepinephrine. J Vet Intern Med 2002;16:123-132. 
7. Miller E. Long-term monitoring of the diabetic dog and cat. Clinical signs, serial blood glucose determinations, urine glucose, and glycated blood proteins. Vet Clin North Am Small Anim Pract 1995;25:571-584. 
8. Crenshaw KL, Peterson ME, Heeb LA, et al. Serum fructosamine concentration as an index of glycemia in cats with diabetes mellitus and stress hyperglycemia. J Vet Intern Med 1996;10:360-364. 
9. Thoresen SI, Bredal WP. Clinical usefulness of fructosamine measurements in diagnosing and monitoring feline diabetes mellitus. J Small Anim Pract 1996;37:64-68. 
10. Bennett N. Monitoring techniques for diabetes mellitus in the dog and the cat. Clin Tech Small Anim Pract 2002;17:65-69. 
11. Cook AK. Monitoring methods for dogs and cats with diabetes mellitus. J Diabetes Sci Technol 2012;6:491-495. 

Top Endocrine Publications of 2013: Feline Diabetes Mellitus

In my ninth compilation of the canine and feline endocrine publications of 2013, I’m moving on to disorders of the feline endocrine pancreas. I covered the canine diabetic publications in a blog post last spring. Click this link to review my list of 2013 research papers that pertain to diabetes in dogs.

Listed below are 29 papers published in 2013 that deal with a variety of diabetic topics of clinical importance for diabetic cats.

These topics range from a study of survival time and prognostic factors in cats with newly diagnosed diabetes (2) to studies involving pathogenesis or risk factors for development of diabetes (6,15,20,21,24); from the relationship between diabetes and kidney disease and pancreatits (1,3) to a review of what we know about diabetic remission (10); and, from reviews of insulin treatment of diabetic cats (4,16,26) to the use of oral hypoglycemia agent or incretin hormonal therapy in cats (22,25).

Other studies range from investigations of diet management of obese and diabetic cats (5,7,17,29) to studies of insulin antibodies in cats (28); from reviews of secondary diabetes, including acromegaly and hyperadrenocorticism (18,19) to ketoacidosis (16,23); and finally, from the use of routine home glucose monitoring (9) to continuous glucose monitoring in cats (11,27).

References:

1. Bloom CA, Rand JS. Diabetes and the kidney in human and veterinary medicine. Vet Clin North Am Small Anim Pract 2013;43:351-365. 
2. Callegari C, Mercuriali E, Hafner M, et al. Survival time and prognostic factors in cats with newly diagnosed diabetes mellitus: 114 cases (2000-2009). J Am Vet Med Assoc 2013;243:91-95. 
3. Caney SM. Pancreatitis and diabetes in cats. Vet Clin North Am Small Anim Pract 2013;43:303-317. 
4. Caney SM. Management of cats on Lente insulin: tips and traps. Vet Clin North Am Small Anim Pract 2013;43:267-282. 
5. Coradini M, Rand JS, Morton JM, et al. Fat mass, and not diet, has a large effect on postprandial leptin but not on adiponectin concentrations in cats. Domest Anim Endocrinol 2013;45:79-88. 
6. Dirtu AC, Niessen SJ, Jorens PG, et al. Organohalogenated contaminants in domestic cats' plasma in relation to spontaneous acromegaly and type 2 diabetes mellitus: A clue for endocrine disruption in humans? Environ Int 2013;57-58:60-67. 
7. 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. 
8. Fleischhacker SN, Bauersachs S, Wehner A, et al. Differential expression of circulating microRNAs in diabetic and healthy lean cats. Vet J 2013;197:688-693. 
9. Ford SL, Lynch H. Practical use of home blood glucose monitoring in feline diabetics. Vet Clin North Am Small Anim Pract 2013;43:283-301. 
10. Gottlieb S, Rand JS. Remission in cats: including predictors and risk factors. Vet Clin North Am Small Anim Pract 2013;43:245-249. 
11. Hafner M, Lutz TA, Reusch CE, et al. Evaluation of sensor sites for continuous glucose monitoring in cats with diabetes mellitus. J Feline Med Surg 2013;5:117-123. 
12. Hoenig M, Pach N, Thomaseth K, et al. Cats differ from other species in their cytokine and antioxidant enzyme response when developing obesity. Obesity (Silver Spring) 2013;21:E407-414. 
13. Hoenig M, Traas AM, Schaeffer DJ. Evaluation of routine hematology profile results and fructosamine, thyroxine, insulin, and proinsulin concentrations in lean, overweight, obese, and diabetic cats. J Am Vet Med Assoc 2013;243:1302-1309. 
14. Leal RO, Gil S, Brito MT, et al. The use of oral recombinant feline interferon omega in two cats with type II diabetes mellitus and concurrent feline chronic gingivostomatitis syndrome. Ir Vet J 2013;66:19. 
15. Link KR, Allio I, Rand JS, et al. The effect of experimentally induced chronic hyperglycaemia on serum and pancreatic insulin, pancreatic islet IGF-I and plasma and urinary ketones in the domestic cat (Felis felis). Gen Comp Endocrinol 2013;188:269-281. 
16. Marshall RD, Rand JS, Gunew MN, et al. Intramuscular glargine with or without concurrent subcutaneous administration for treatment of feline diabetic ketoacidosis. J Vet Emerg Crit Care (San Antonio) 2013;23:286-290.
17. Mimura K, Mori A, Lee P, et al. Impact of commercially available diabetic prescription diets on short-term postprandial serum glucose, insulin, triglyceride and free fatty acid concentrations of obese cats. J Vet Med Sci 2013;75:929-937. 
18. Niessen SJ. Update on feline acromegaly. In Practice 2013;35:2-6. 
19. Niessen SJ, Church DB, Forcada Y. Hypersomatotropism, acromegaly, and hyperadrenocorticism and feline diabetes mellitus. Vet Clin North Am Small Anim Pract 2013;43:319-350. 
20. O'Leary CA, Duffy DL, Gething MA, et al. Investigation of diabetes mellitus in Burmese cats as an inherited trait: a preliminary study. N Z Vet J 2013;61:354-358. 
21. Osto M, Zini E, Reusch CE, et al. Diabetes from humans to cats. Gen Comp Endocrinol 2013;182:48-53. 
22. Palm CA, Feldman EC. Oral hypoglycemics in cats with diabetes mellitus. Vet Clin North Am Small Anim Pract 2013;43:407-415. 
23. Rand JS. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in cats. Vet Clin North Am Small Anim Pract 2013;43:367-379. 
24. Rand JS. Pathogenesis of feline diabetes. Vet Clin North Am Small Anim Pract 2013;43:221-231. 
25. Reusch CE, Padrutt I. New incretin hormonal therapies in humans relevant to diabetic cats. Vet Clin North Am Small Anim Pract 2013;43:417-433. 
26. Roomp K, Rand JS. Management of diabetic cats with long-acting insulin. Vet Clin North Am Small Anim Pract 2013;43:251-266. 
27. Surman S, Fleeman L. Continuous glucose monitoring in small animals. Vet Clin North Am Small Anim Pract 2013;43:381-406. 
28. Takashima S, Nishii N, Hachisu T, et al. Natural anti-insulin autoantibodies in cats: enzyme-linked immunosorbent assay for the determination of plasma anti-insulin IgG and its concentrations in domestic cats. Res Vet Sci 2013;95:886-890. 
29. 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. 

Top Endocrine Publications of 2012: Feline Diabetes Mellitus

In my 10th compilation of the canine and feline endocrine publications of 2012, I’m moving on to the theme of feline diabetes mellitus.  I covered the canine diabetic publications in a blog post about 2 months ago. Click this link to review my list of of 2012 research papers that pertain to diabetes in dogs.

Listed below are 23 research papers written in 2012 that deal with a variety of topics and issues mainly related to the diagnosis, monitoring, and treatment of diabetes mellitus in cats.

These range from a review of pancreatitis and its relationship to diabetes in cats (1,22) to reports of the insulin resistance associated with acromegaly and Cushing's disease in some cats (5,7,8); from use of portable hand-held meters to measure blood ketones in cats (21,23) to an evaluation of serum concentrations of beta-hydroxybutyric acid as a diagnostic tool (2,20); and from a review of monitoring methods for cats with diabetes (4) to the use of glucagon for management of insulin-induced hypoglycemia (12).

Other studies include an evaluation of methods used to measure IGF-1 levels in diabetic cats (17) to the effects of diet and obesity on feline glucose metabolism and diabetic control (6,10,18,19); and finally, from studies of the use of insulin detemir to induce remission in diabetic cats (13) to a careful evaluation and comparison of a commercially manufactured protamine zinc insulin product (ProZinc) to compounded PZI products (14).

2012 Papers on Feline Diabetes Mellitus:

1. Armstrong PJ, Williams DA. Pancreatitis in cats. Top Companion Anim Med 2012;27:140-147. 
2. Aroch I, Shechter-Polak M, Segev G. A retrospective study of serum beta-hydroxybutyric acid in 215 ill cats: clinical signs, laboratory findings and diagnoses. Vet J 2012;191:240-245. 
3. Clark MH, Hoenig M, Ferguson DC, et al. Pharmacokinetics of pioglitazone in lean and obese cats. J Vet Pharmacol Ther 2012;35:428-436. 
4. Cook AK. Monitoring methods for dogs and cats with diabetes mellitus. J Diabetes Sci Technol 2012;6:491-495. 
5. Cross E, Moreland R, Wallack S. Feline pituitary-dependent hyperadrenocorticism and insulin resistance due to a plurihormonal adenoma. Top Companion Anim Med 2012;27:8-20. 
6. 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. 
7. Fischetti AJ, Gisselman K, Peterson ME. CT and MRI evaluation of skull bones and soft tissues in six cats with presumed acromegaly versus 12 unaffected cats. Vet Radiol Ultrasound 2012;53:535-539. 
8. Greco DS. Feline acromegaly. Top Companion Anim Med 2012;27:31-35. 
9. Haring T, Haase B, Zini E, et al. Overweight and impaired insulin sensitivity present in growing cats. J Anim Physiol Anim Nutr (Berl) 2012. 
10. Hoenig M. The cat as a model for human obesity and diabetes. J Diabetes Sci Technol 2012;6:525-533.
11. Hoenig M, Pach N, Thomaseth K, et al. Evaluation of long-term glucose homeostasis in lean and obese cats by use of continuous glucose monitoring. Am J Vet Res 2012;73:1100-1106. 
12. Niessen SJ. Glucagon: are we missing a (life-saving) trick? J Vet Emerg Crit Care (San Antonio) 2012;22:523-525. 
13. 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. 
14. Scott-Moncrieff JC, Moore GE, Coe J, et al. Characteristics of commercially manufactured and compounded protamine zinc insulin. J Am Vet Med Assoc 2012;240:600-605. 
15. Smith JR, Vrono Z, Rapoport GS, et al. A survey of southeastern United States veterinarians' preferences for managing cats with diabetes mellitus. J Feline Med Surg 2012;14:716-722. 
16. Steiner JM. Exocrine pancreatic insufficiency in the cat. Top Companion Anim Med 2012;27:113-116. 
17. Tschuor F, Zini E, Schellenberg S, et al. Evaluation of four methods used to measure plasma insulin-like growth factor 1 concentrations in healthy cats and cats with diabetes mellitus or other diseases. Am J Vet Res 2012;73:1925-1931.
18. 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. 
19. 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. 
20. Weingart C, Lotz F, Kohn B. Measurement of beta-hydroxybutyrate in cats with nonketotic diabetes mellitus, diabetic ketosis, and diabetic ketoacidosis. J Vet Diagn Invest 2012;24:295-300. 
21. Weingart C, Lotz F, Kohn B. Validation of a portable hand-held whole-blood ketone meter for use in cats. Vet Clin Pathol 2012;41:114-118. 
22. Xenoulis PG, Steiner JM. Canine and feline pancreatic lipase immunoreactivity. Vet Clin Pathol 2012;41:312-324. 
23. Zeugswetter FK, Rebuzzi L. Point-of-care beta-hydroxybutyrate measurement for the diagnosis of feline diabetic ketoacidaemia. J Small Anim Pract 2012;53:328-331. 

Top 10 Clinical Endocrinology Research Abstracts Presented at the 2013 ACVIM Meeting

Last month, I spent a week in Seattle, Washington attending the the 2013 American College of Veterinary Internal Medicine Forum.  As part of that meeting, a number of research abstracts were presented (oral and poster presentations) that dealt with various aspects of canine and feline endocrinology. I plan to spend the next three blogs discussing some of the newest and best research findings featured at the ACVIM meeting.

Of all of the excellent endocrine research abstracts presented, I've selected a "top 10 list" of the ones that have the most potential to change what I do in my clinical practice.  To do this, I've enlisted the help of Dr. Rhett Nichols, a well-known expert in endocrinology and internal medicine whose day-job is senor member of the veterinarian consulting service for Antech Diagnostics, the world's largest laboratory dedicated to animal health.  However, since Rhett also serves as a consultant for the Animal Endocrine Clinic (my practice), it was not that difficult to get him involved in this project!

In this post, we will review 4 of these top 10 abstracts, followed by the remaining 6 in the upcoming 2 posts. We hope you agree with our selections, but if you don't, remember that you can always post a comment and add your opinion.

Niessen S, Scudder C, Forcada Y, et al. Pasireotide (SOM230) opens doors to medical management of feline hypersomatotropism. J Vet Intern Med 2013:685.

Feline hypersomatotropism (HS) appears to be a significant cause of feline diabetes mellitus. However, successful treatment of HS is currently challenging. Radiotherapy and hypophysectomy seem the only effective therapeutic modalities, yet come with significant disadvantages. Medical options would be desirable although somatostatin (sst) analogues and dopamine agonists have thus far proven largely ineffective. Pasireotide (SOM230), a novel multi-receptor ligand sst analogue with high binding affinity for sst receptor subtypes 1, 2, 3 and 5 has been shown to suppress growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in rodents as well as humans suðering from HS. Additionally, direct and indirect anti-tumor activity has been observed in vitro including sst receptor-mediated apoptosis and anti-angiogenesis. The current study aimed to assess the potential of SOM230 as a treatment modality for naturally occurring feline HS. Feline HS was diagnosed in eight diabetic cats by documenting serum IGF-1 concentration >1000 ng/ml (radioimmunoassay) and presence of a pituitary enlargement (computed tomography). On day 1 and 5, serum IGF-1 concentration was established and glycemic control assessed using a 12-hour blood glucose (BG) curve, measuring BG every 2 hours. On day 2, 3 and 4, the cats were injected with 0.03 mg/kg SOM230 s.c. BID. The initial insulin dose was dictated by the choice of the attending clinician, although was reduced according to regular BG measurements during the treatment period to avoid hypoglycemia. Pre- and post-treatment IGF-1, average 12-hour BG and insulin dose were compared using a paired t-test (significance at P < 0.05). All eight cats showed a significant decrease in serum IGF-1 (mean+/-SD day 1: 1884 + /-218 ng/ml; day 5: 1169 + /-395 ng/ ml, p = 0.001) and average 12-hour BG (day 1: 20 + /-5 mmol/l; day 5: 13 + /-4 mmol/l; p = 0.002). A significant insulin dose reduction was necessary in all cats (day 1: 10.8 + /-6 iu/injection; day 5: 3.1 + /-2 iu/injection; p = 0.015). No side effects were noticed during or after the 3 day treatment period, apart from hypoglycemia in one cat, which resolved after provision of food and reduction of insulin dose. The current study indicates that SOM230 is able to rapidly decrease GH and IGF-1 concentrations in feline HS. This, therefore, suggests that sst receptors are present in most feline somatotrophinomas, which has previously been unclear given the disappointing results during somatostatins and sst analogue therapy attempts. A return of insulin sensitivity was seen, enabling improved glycemic control to be established with reduced doses of exogenous insulin in all cats. In light of these results, a clinical trial with a longer-acting formulation of SOM230 is currently being conducted to establish long-term effects and potential for diabetic remission. 

Comments— Pasireotide (SOM230, trade name Signofor, Novartis) is an orphan drug approved for the treatment of Cushing’s disease in adult human patients when surgery has failed or is not an option (1). The drug is a somatostatin analog that targets multiple somatostatin receptors with high affinity. The result is apoptosis of those cells that produce ACTH, with significant lowering of plasma ACTH levels (2,3).

In addition, pasireotide has been shown to suppress GH and IGF -1 in rodents and human patients with acromegaly (4). Moreover, recent results of a phase III study of human patients with acromegaly treated with a long-acting release form of pasireotide show that this novel form of therapy is significantly more effective than the current standard therapy with octreotide (5).

This study by Niessen et al indicates that pasireotide is able to rapidly decrease GH and IGF-1 concentrations in feline acromegaly and suggests that somatostain receptors are present in most cats with pituitary tumors that produce excessive GH. In light of these results, a clinical trial with the long-acting release form of pasireotide is currently being conducted to establish long-term effects and potential for diabetic remission in cats with acromegaly.

The Bottom Line—It is great to finally have a medical treatment that may actually work for cats with acromegaly. Unfortunately, administration of pasireotide SC twice daily may not be a practical or affordable therapeutic option for many of our cat owners.

References:

1. Signifor Official Site - Signifor® (pasireotide) Injection. Signifor.US‎. 
2. Colao A, Petersenn S, Newell-Price J, et al. A 12-month phase 3 study of pasireotide in Cushing's disease. N Engl J Med 2012;366:914-924. 
3. McKeage K. Pasireotide: a review of its use in Cushing's disease. Drugs 2013;73:563-574. 
4. Petersenn S, Farrall AJ, Block C, et al. Long-term efficacy and safety of subcutaneous pasireotide in acromegaly: results from an open-ended, multicenter, Phase II extension study. Pituitary 2013. DOI 10.1007/s11102-013-0478-0 
5. Colao A, Bronstein M, Freda P, et al. Pasireotide LAR is significantly more effective than octreotide LAR at inducing biochemical control in patients with acromegaly: Results of a 12-month randomized, double-blind, multicenter, Phase III study. Joint 15th International Congress of Endocrinology and 14th European Congress of Endocrinology. Abstract #OC1.1. 2012 

De Marco V, Noronha KSM, Casado TC, et al. Therapy of canine hyperlipidemia with bezafibrate. J Vet Intern Med2013;27:694.

The primary and secondary hyperlipidemia are common in dogs and its treatment is necessary to prevent clinical complications such as pancreatitis, seizures, liver disease and diabetes. The therapy of mild hyperlipidemia comprising a fat restricted diet, but in more severe cases pharmacological treatment is necessary. Bezafibrate (BZF) is effective in the treatment of hypertriglyceridemia in humans, however there are no clinical studies in dogs. The objectives of this study were to assess the efficacy of BZF in reducing serum triglyceride (TG) and cholesterol (CHO) in hyperlipidemic dogs, identify a therapeutic protocol for this drug and assess possible side eðects such as muscle pain, emesis, diarrhea and elevated CK and TGP levels. Only animals with moderate to severe hypertriglyceridemia (TG> 350 mg/dL) were treated with BZF every 24 hours for 30 days before introduction of any other therapy according to the protocol: tablet 200 mg for dogs weighting less than 12 kg, tablet 200 mg for dogs weighing between 13 and 25 kg, 1 tablet 200 mg for dogs weighing over 25 kg. We studied 46 dogs (26 females and 20 males) with a mean age of 9 years. Fifteen dogs (32.6%) had primary hyperlipidemia and 31 (67.4%) secondary hyperlipidemia, which included hyperadrenocorticism (41.3%), hypothyroidism (15.2%) and chronic corticoideterapia (10.8%). All 46 (100%) dogs had hypertriglyceridaemia and 33 (71.7%) had both hypertriglyceridaemia and hypercholesterolemia. After 30 days using BZF, normalization of serum TG (TG <150 mg/dL) was observed in 91.3% of cases (n = 42/46) and of CHO (CHO < 270 mg/dL) in 66 7% (n = 22/33) of cases. Means and standard deviations of serum TG and COL before (752 ± 663 mg/dL and 428 ± 217 mg/dL) and after therapy (110 ± 82 and 244 ± 71 mg /dL) were significantly lower (p < 0.005, paired Student t test). The bezafibrate dose most used with a 95% confidence interval was 5.3 to 6.1 mg/kg (range: 4–10 mg/kg). No side effects were observed, and there was no statistical difference between the values of ALT and CK before and after therapy. It can be concluded that bezafibrate is a safe and effective drug for the canine hyperlipidemia therapy.
  

Comments—Bezafibrate is a fibrate drug used for the treatment of hyperlipidemia (1-3). In people, fibrates are used as an accessory drug in many forms of hypercholesterolemia, usually along with statins. Bezafibrate helps lower cholesterol and triglycerides in the blood and increase high density lipoproteins (HDL). The main toxicity is hepatic, myopathy, and rarely rhabomyolysis.

Hyperlipidemia is a relatively commonly recognized disorder in dogs but management can be frustrating (4). In this study, 46 dogs with primary or secondary hyperlipidemia (diabetes mellitus, Cushing’s syndrome. hypothyroidism) were treated with bezafibrate once a day over a 30-day period; triglycerides and cholesterol were significantly lowered in the majority of dogs. In addition, there was no evidence of untoward side effects (e.g., no clinical issues and ALT and CK levels were not altered).

There are 2 preparations of bezafibrate available: 200 mg tablets and 400 mg sustained-release tablets. The sustained-release preparation is taken once a day; the non-sustained release tablets are taken with each meal. For dogs, the average dose used in this study was 5 to 6 mg/kg once a day. The dosing protocol was ¼ of a 200 mg tablet for dogs < 12 kg, ½ of a 200 mg tablet for dogs weighing between 12 and 25 kg, and one 200 mg tablet for dogs > 25 kg.

The Bottom Line—Bezafibrate given once a day appears to be a safe and effective drug for the treatment of hyperlipidemia in the dog.

References:

1. Goa KL, Barradell LB, Plosker GL. Bezafibrate. An update of its pharmacology and use in the management of dyslipidaemia. Drugs 1996;52:725-753.  
2. Goldenberg I, Benderly M, Goldbourt U. Update on the use of fibrates: focus on bezafibrate. Vasc Health Risk Manag 2008;4:131-141.  
3. Teramoto T, Shirai K, Daida H, et al. Effects of bezafibrate on lipid and glucose metabolism in dyslipidemic patients with diabetes: the J-BENEFIT study. Cardiovasc Diabetol 2012;11:29. 
4. Xenoulis PG, Steiner JM. Lipid metabolism and hyperlipidemia in dogs. Vet J 2010;183:12-21.

Salesov E, Boretti FS, Sieber-Ruckstuhl NS, et al. Urinary and plasma catecholamine and metanephrine in dogs with pheochromocytoma, hyperadrenocorticism and in healthy dogs. J Vet Intern Med 2013 27:688-689.

Pheochromocytoma (PHEO) is a rare malignant catecholamine-secreting tumor of the adrenal medulla. Catecholamines and metanephrines in plasma and in 24-h urine are approved biomarkers for the detection of the disease in humans, however, the question which of the tests is best is controversial. We previously demonstrated that measurement of urinary catecholamine and metanephrine to creatinine ratios is helpful for the diagnosis of PHEO in dogs and that urinary normetanephrine to creatinine ratio may be the best test to discriminate between PHEO and hypercortisolism (HC). Knowledge on plasma catecholamines and metanephrines in dogs is scarce and no comparison between urinary and plasma parameters has been performed. The objective of the study was to measure urinary as well as plasma catecholamines and metanephrines in dogs with PHEO, HC and in healthy dogs and to determine the test with the least overlap between the group. Six dogs with PHEO, 9 dogs with HC (6 with ATH, 3 with PDH) and 10 healthy dogs were included. Urine samples were collected into HCL containing tubes to ensure a pH 2, blood samples were collected on ice, centrifuged at 4°C and immediately snap frozen in liquid nitrogen. All samples were stored at – 80°C. Urinary epinephrine (U-Epi), norepinephrine (U-Norepi), metanephrine (U-Meta) and normetanephrine (U-Normeta), and epinephrine (P-Epi), norepinephrine (P-Norepi), free and total metanephrine (PF-Meta and PT-Meta) and free and total normetanephrine (PF-Normeta and PT-Meta) were analysed by HPLC. Urinary catecholamines and metanephrines were expressed as ratios to urine creatinine concentrations. Data were analysed by non-parametric tests (P < 0,05). Similar to our previous findings U-Epi, U-Norepi, U-Meta and U-Normeta were significantly higher in dogs with PHEO and U-Norepi and U-Normeta were significantly higher in dogs with HC compared to healthy dogs. Comparison between dogs with HC and dogs with PHEO revealed significantly higher U-Meta and U-Normeta in the latter group. U-Normeta was the only parameter with no overlap. In dogs with PHEO P-Norepi, PF-Meta, PT-Meta, PF-Normeta, PT-Normeta were significantly higher and in dogs with HC P-Norepi, PF- Normeta and PT-Normeta were significantly higher than in healthy dogs. Comparison between dogs with HC and dogs with PHEO showed significant higher PF-Meta, PT-Meta, PF- Normeta, PT-Normeta in the PHEO group. Overlap was present with all 4 parameters, but was least with PF-Normeta and PT-Normeta. According to our results U-Normeta, PF- Normeta and PT-Normeta are valuable parameters for the diagnosis of PHEO, so far U-Normeta performed better than the plasma parameters. 

Comments—In some recent studies, up to one in five adrenal tumors has been a pheochromocytoma. In the past, a presumptive diagnosis of a pheochromocytoma was based on history which was often a vague, sometimes episodic description of illness, documentation of hypertension, an adrenal mass noted on abdominal ultrasound, and ruling out adrenal-dependent Cushing’s syndrome with an endogenous ACTH level or the results of dexamethasone suppression testing. This current research adds additional data to the idea that measurement of urinary and plasma catecholamine and metanephrine can also be used to aid in diagnosis.

The Bottom Line—Currently, a urine normetaphrine/creatinine level, appears to be the most sensitive and specific test to document a pheochromocytoma.  This test requires that the urine sample is acidified at the time of collection and a control urine sample from a normal dog (also acidified) is submitted. A urine normetaphrine/creatinine level at least 4-times the control is consistent with pheochromocytoma.

In the US, the test for urine normetaphrine/creatinine can be performed at Marshfield Labs (www.marshfieldlabs.com). Acid pellets for urinary acidification are available from the laboratory.

References:

1. Quante S, Boretti FS, Kook PH, et al. Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs. J Vet Intern Med 2010;24:1093-1097. 
2. Kook PH, Grest P, Quante S, et al. Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a phaeochromocytoma. Vet Rec2010;166:169-174. 
3. Kook PH, Boretti FS, Hersberger M, et al. Urinary catecholamine and metanephrine to creatinine ratios in healthy dogs at home and in a hospital environment and in 2 dogs with pheochromocytoma. J Vet Intern Med2007;21:388-393. 

Sangster K, Panciera JL, Abbott A, et al. Cardiac biomarkers in hyperthyroid cats. J Vet Intern Med 2013:637. 

Differentiation of hyperthyroid heart disease from primary myocardial disease is challenging. The cardiac biomarkers NT- proBNP and troponin I (cTNI) have proven useful in identifying cats with myocardial disease and may provide a method by which hypertrophic cardiomyopathy (HCM) and hyperthyroid heart disease can be discriminated. The primary purpose of this study was to compare plasma concentrations of NT-proBNP and cTNI in three groups of cats: cats with naturally occurring hyperthyroidism, cats with primary cardiomyopathy, and healthy older cats to determine if biomarkers differ between groups and if bio-marker concentrations in hyperthyroid cats change after resolution of the thyroid disease. We prospectively evaluated 61 client-owned cats: 23 hyperthyroid cats, 19 cats with HCM without congestive heart failure, and 19 euthyroid, normotensive healthy cats eight years of age or older. Fourteen of the hyperthyroid cats were re-evaluated three months after administration of I-131. A complete history, physical examination, CBC, serum biochemistries, urinalysis, blood pressure measurement, serum T4 concentration, plasma concentrations of NT-proBNP and cardiac troponin I, and echocardiography was obtained for each cat. Hyperthyroid and HCM cats had plasma NT-proBNP and cTNI concentrations that were significantly greater than healthy older cats, but there was no significant difference between hyperthyroid and HCM cats with respect to concentration of either biomarker. Plasma NT-proBNP and cTNI concentrations decreased in each cat that was examined three months after I-131 treatment. Plasma cTNI was within the reference interval for all cats at the three month recheck. Severely thickened myocardium persisted in one formerly hyperthyroid cat at the three month recheck, and this cat’s plasma NT-proBNP remained elevated. Although there may be a role for NT-proBNP in monitoring the cardiac response to treatment of hyperthyroidism, neither NT-proBNP nor cTNI can be used to distinguish hyperthyroid cats from cats with HCM. Therefore, the thyroid status of older cats should be ascertained prior to interpreting results of cardiac biomarker testing.
  

 Comments—Although it is well established that hyperthyroid cats will commonly develop secondary heart disease (1), it can sometimes be difficult to distinguish thyroid-induced cardiac disease from primary myocardial disease (cardiomyopathy). Over the last few years, a number of studies have confirmed the usefulness of plasma cardiac biomarkers (especially N-terminal pro-brain natriuretic peptide or NT-proBNP) to help detect hypertrophic cardiomyopathy in cats and to distinguish primary cardiac from non-cardiac causes of dyspnea in cats (2-5). Previous studies have found that hyperthyroid cats can have high circulaing levels of either troponin I or NT-proBNP; both biomarkers fall after successful treatment of the hyperthyroid state (6,7).

This research study confirmed that hyperthyroid cats can have high plasma NT-proBNP and troponin I (cTNI) concentrations, which decreased after I-131 treatment. However, there was no significant difference between hyperthyroid and HCM cats with respect to concentration of either biomarker.

The Bottom Line— Although hyperthyroid cats can have high plasma NT-proBNP and cTNI concentrations, there was no significant difference between hyperthyroid and HCM cats with respect to concentration of either biomarker. Therefore, neither of these cardiac biomarkers can be used to distinguish hyperthyroid cats from cats with HCM. Since hyperthyroidism can result in high levels of both biomarkers (6,7), the thyroid status of older cats should always be ascertained prior to interpreting results of cardiac biomarker testing.

References:

1. Syme HM. Cardiovascular and renal manifestations of hyperthyroidism. Vet Clin North Am Small Anim Pract 2007;37:723-743, vi. 
2. Wells SM, Sleeper M. Cardiac troponins. J Vet Emerg Crit Care 2008;18:235–245. 
3. Boswood A. Biomarkers in cardiovascular disease: beyond natriuretic peptides. J Vet Cardiol 2009;11 Suppl 1:S23-32. 
4. Fox PR, Oyama MA, Reynolds C, et al. Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to distinguish between congestive heart failure and non-cardiac causes of acute dyspnea in cats. J Vet Cardiol 2009;11 Suppl 1:S51-61. 
5. Wess G, Daisenberger P, Mahling M, et al. Utility of measuring plasma N-terminal pro-brain natriuretic peptide in detecting hypertrophic cardiomyopathy and differentiating grades of severity in cats. Vet Clin Pathol 2011;40:237-244. 
6. Connolly DJ, Guitian J, Boswood A, et al. Serum troponin I levels in hyperthyroid cats before and after treatment with radioactive iodine. J Feline Med Surg 2005;7:289-300. 
7. Menaut P, Connolly DJ, Volk A, et al. Circulating natriuretic peptide concentrations in hyperthyroid cats. J Small Anim Pract 2012;53:673-678.  

Top Endocrine Publications of 2012: Canine Diabetes Mellitus

In my second compilation of the canine and feline endocrine publications of 2012, I’m moving on to the theme of canine diabetes mellitus.

Listed below are 31 research papers written in 2012 that deal with a variety of topics and issues related to the diagnosis, monitoring, and treatment of diabetes mellitus in dogs. I've already reviewed a few of these papers and, if so, I've included a link to that paper's review.

These range from the studies of the alternative sampling sites for home glucose testing (1) to a review of monitoring methods for dogs with diabetes (5); from studies of the use of long-acting insulin preparations (i.e., PZI, glargine, or detemir) in dogs (4,8,15,17) to evaluation of a quality-of-life tool for diabetic dogs (21); and from the investigation of insulin resistance in dogs associated with estrus, glucocorticoid excess, or  infection (6,9,10,11,14,16,22,23) to evaluation of "low" carbohydrate diets in the management of dogs with diabetes (7).

Other studies include an evaluation of the sodium-retaining effect of insulin in diabetic dogs (2) to the use of glucagon for management of insulin-induced hypoglycemia (19,31); and finally, from studies of a short-acting insulin analogue for treatment of ketoacidosis in dogs (24) to the investigations on the use of gene therapy as a potential cure for canine diabetes (20).

2012 Papers on Diabetes Mellitus in the Dog:

1. Borin-Crivellenti S, Crivellenti LZ, Tinucci-Costa M. The carpal pad as an alternative sampling site for blood glucose testing in dogs. J Small Anim Pract 2012;53:684-686. 
2. Brands MW, Manhiani MM. Sodium-retaining effect of insulin in diabetes. Am J Physiol Regul, Integr Comp Physiol 2012;303:R1101-1109. 
3. Clark L, Leece EA, Brearley JC. Diabetes mellitus affects the duration of action of vecuronium in dogs. Vet Anaesth Analg 2012;39:472-479.
4. Clark M, Thomaseth K, Heit M, et al. Pharmacokinetics and pharmacodynamics of protamine zinc recombinant human insulin in healthy dogs. J Vet Pharmacol Ther 2012;35:342-350. 
5. Cook AK. Monitoring methods for dogs and cats with diabetes mellitus. J Diabetes Sci Technol 2012;6:491-495. 
6. Declue AE, Nickell J, Chang CH, et al. Upregulation of proinflammatory cytokine production in response to bacterial pathogen-associated molecular patterns in dogs with diabetes mellitus undergoing insulin therapy. J Diabetes Sci Technol 2012;6:496-502. 
7. 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. 
8. Fracassi F, Boretti FS, Sieber-Ruckstuhl NS, et al. Use of insulin glargine in dogs with diabetes mellitus. Vet Rec 2012;170:52. Click here to see my review of this paper. 
9. Fukuta H, Mori A, Urumuhan N, et al. Characterization and comparison of insulin resistance induced by Cushing Syndrome or diestrus against healthy control dogs as determined by euglycemic- hyperinsulinemic glucose clamp profile glucose infusion rate using an artificial pancreas apparatus. J Vet Med Sci 2012;74:1527-1530. 
10. Gomes Poppl A, Costa Valle S, Hilario Diaz Gonzalez F, et al. Estrus cycle effect on muscle tyrosine kinase activity in bitches. Vet Res Commun 2012;36:81-84. 
11. Hofer-Inteeworn N, Panciera DL, Monroe WE, et al. Effect of hypothyroidism on insulin sensitivity and glucose tolerance in dogs. Am J Vet Res 2012;73:529-538.  Click here to see my review of this paper.
12. Hugler S. Diabetic alert dogs: A good nose for hypoglycemia. Dtsch Med Wochenschr 2012;137:p25. 
13. Jeong YW, Lee GS, Kim JJ, et al. Establishment of a canine model of human type 2 diabetes mellitus by overexpressing phosphoenolypyruvate carboxykinase. Int J Mol Med 2012;30:321-329. 
14. Kovalik M, Thoday KL, Evans H, et al. Prednisolone is associated with an increase in serum insulin but not serum fructosamine concentrations in dogs with atopic dermatitis. Vet J 2012;192:212-216. 
15. Maggiore AD, Nelson RW, Dennis J, et al. Efficacy of protamine zinc recombinant human insulin for controlling hyperglycemia in dogs with diabetes mellitus. J Vet Intern Med 2012;26:109-115. Click here to see my review of this paper.  
16. Mared M, Catchpole B, Kampe O, et al. Evaluation of circulating concentrations of glucose homeostasis biomarkers, progesterone, and growth hormone in healthy Elkhounds during anestrus and diestrus. Am J Vet Res 2012;73:242-247. 
17. Miceli DD, Gallelli MF, Cabrera Blatter MF, et al. Low dose of insulin detemir controls glycaemia, insulinemia and prevents diabetes mellitus progression in the dog with pituitary-dependent hyperadrenocorticism. Res Vet Sci 2012;93:114-120. 
18. Murai A, Nishii N, Morita T, et al. GH-producing mammary tumors in two dogs with acromegaly. J Vet Med Sci 2012;74:771-774.
19. Niessen SJ. Glucagon: are we missing a (life-saving) trick? J Vet Emerg Crit Care (San Antonio) 2012;22:523-525. 
20. Niessen SJ, Fernandez-Fuente M, Mahmoud A, et al. Novel diabetes mellitus treatment: mature canine insulin production by canine striated muscle through gene therapy. Domest Anim Endocrinol 2012;43:16-25. 
21. Niessen SJ, Powney S, Guitian J, et al. Evaluation of a quality-of-life tool for dogs with diabetes mellitus. J Vet Intern Med 2012;26:953-961.
22. O'Neill S, Drobatz K, Satyaraj E, et al. Evaluation of cytokines and hormones in dogs before and after treatment of diabetic ketoacidosis and in uncomplicated diabetes mellitus. Vet Immunol Immunopathol 2012;148:276-283.
23. Poppl AG, Mottin TS, Gonzalez FH. Diabetes mellitus remission after resolution of inflammatory and progesterone-related conditions in bitches. Res Vet Sci 2012. 
24. Sears KW, Drobatz KJ, Hess RS. Use of lispro insulin for treatment of diabetic ketoacidosis in dogs. J Vet Emerg Crit Care (San Antonio) 2012;22:211-218. Click here to see my review of this paper. 
25. Tvarijonaviciute A, Ceron JJ, Caldin M. Serum butyrylcholinesterase activity in dogs with diabetes mellitus. Vet J 2012;192:494-497.
26. 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. 
27. 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. 
28. 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. 
29. Watson P. Chronic pancreatitis in dogs. Top Companion Anim Med 2012;27:133-139. 
30. Xenoulis PG, Steiner JM. Canine and feline pancreatic lipase immunoreactivity. Vet Clin Pathol 2012;41:312-324. 
31. Zeugswetter FK, Schornsteiner E, Haimel G, et al. Metabolic and hormonal responses to subcutaneous glucagon in healthy beagles. J Vet Emerg Crit Care (San Antonio) 2012;22:558-563. 

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: 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. 

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.