Internal Medicine Debra L. Zoran DVM, PhD, DACVIM-SAIM March 24, 2010

Transcription

1 Internal Medicine by Debra L. Zoran DVM, PhD, DACVIM-SAIM March 24, 2010 Event Sponsored by: 0

2 HOW I TREAT OBESITY IN DOGS: USING DIET, EXERCISE AND PHARMACOTHERAPY TO CONQUER THE BEAST Debra L. Zoran, DVM, PhD, Diplomate ACVIM-SAIM Texas A&M University, College Station, TX Obesity is the excessive accumulation of adipose tissue in body, and has been defined to occur when dogs or cats are >20% over their optimal body weight. In humans, criteria have been established for what defines overweight and obese, and these criteria have generally been based on the body mass index. However, no similar index for optimal body weight has been identified in dogs and cats, primarily because of the wide variation in body sizes and shapes, so the use of these classifications has not been rigorously studied. However, in general, dogs are considered to be overweight when their body weight is up to 20% over their optimal body weight or have a body condition score of 6 or 7, and obese when they are >20% over the optimum or have a body condition score of 8 or 9 (Figure 2). Using these criteria, the incidence of obesity in dogs and cats in the United States is reportedly between 30-40%. More alarming, however, is the suggestion that the incidence of obesity in our pet population is increasing despite the many attempts to control weight with a variety of diet and exercise programs. Recently, a new pharmacologic tool (Slentrol ) became available for use in the battle against canine obesity. The purpose of this talk is to provide an overview of this lecturer s experience with the drug in US clinical trials and provide a background for further discussion about this new pharmacologic tool for obesity management. The Causes of Obesity The primary reason for development of obesity in any animal is that they are consuming more calories (energy) than they are expending. This can occur when a dog has excessive dietary intake of calories (food and treats) or when there is a reduction in energy expenditure (reduced activity, illness or injury resulting in less exercise, etc). There are some medical conditions and drugs that are associated with obesity: endocrinopathies, such as hyperadrenocorticism and hypothyroidism, and drugs such as steroids and anticonvulsants. But the primary reason that weight gain occurs in dogs on steroids or with hypothyroidism is that they have either increased food intake or decreased energy expenditure (or in some cases, both). Nevertheless, in both instances, the primary reason for the development of obesity is still a positive energy balance. While genetic factors are also likely involved (e.g. Labrador retrievers have a higher incidence of obesity than is seen in other breeds of like size), the role of inheritance in canine obesity needs more study. In both dogs and cats, neutering is an important risk factor due to the hormonal changes that occur that result in changes in levels of leptin, progestins, and other hormones that result in increased appetite, and reduced energy metabolism and metabolic rate. The key factors for prevention of obesity in neutered animals appears to be careful control of intake immediately after neutering (no free choice feeding, reduction of intake by 25% to account for the hormonal changes resulting in reduced energy needs), and close monitoring of body weight and BCS to allow adjustments in intake if needed. In dogs, there are a number of dietary factors that are also associated with obesity including: the number of snacks fed, especially table scraps, and the number of meals. Dogs that were allowed to be near their owners at mealtime also had a greater tendency to be obese due to the increased likelihood of receiving table scraps and human food treats. In addition, because feeding dogs is a social interaction, feeding and food interaction with the dog can become a daily social interaction that can become a problem resulting in overfeeding and inappropriate food intake patterns. It has been shown that in households where the owners are health conscious (conscious of diet and nutrition, who exercise regularly, and watch their own weight) they tend not to have obese dogs. Thus, there are clearly human behavioral and food is love issues that have to be considered in the development of obesity in dogs, and these must be addressed for successful weight control to be achieved. And this is especially important to implement as part of an overall obesity management plan as drugs alone are not the answer to obesity management and long term control appropriate dietary and exercise plans must be developed to help sustain the weight losses that occur. The Importance of Obesity as a Disease Obese humans generally do not live as long as their lean counterparts, and are much more likely to suffer from obesity-related diseases such as type II diabetes, coronary artery disease, osteoarthritis, hypertension, and some cancers. Dogs and cats are susceptible to the same detrimental effects, 1

3 including decreased longevity, and development of a variety of disorders that are associated with being obese. In a recent study, dietary calorie restriction was clearly shown to increase longevity in a group of 24 Labrador retrievers. In that study, the dogs in the energy restricted group were fed 75% of their counterparts, and the dogs lived an average of two years longer and had a reduced incidence of hip dysplasia, osteoarthritis and glucose intolerance. Other problems that were found to be more common in obese dogs compared to the dogs that were of ideal body condition, include heat intolerance, increased anesthetic risk, increased difficulty with routine clinical procedures (catheter placement, palpation, imaging), and prolonged surgical procedures. In order to understand the role of obesity in disease development, it is necessary to first understand the role of adipose tissue in energy balance and metabolism. The expansion of adipose tissue was long thought to be simply a depot for the deposition of fatty acids (triglycerides) that occurred because of the excess energy intake. However, research in the past decade has revealed that adipose tissue is not just a storage site, but also is responsible for production of many key hormones (e.g. leptin) involved in energy balance and a variety of other processes. Leptin was first identified in 1994 and its discovery opened the door to a whole new world of understanding about white adipose tissue. Leptin is an inhibitor of food intake primarily through suppression of neuropeptide Y and orexin in the brain, and plays a role in the regulation energy expenditure. In obese mice that lack leptin or have leptin resistance, appetite suppression mechanisms are non-functional and energy metabolism abnormal. However, despite the importance of leptin in appetite suppression and energy expenditure, it is not the silver bullet of obesity management: simply replacing leptin does not result in weight loss or changes in the metabolism of obese animals. Further research in recent years has elucidated an entire list of adipokines secreted by fat cells (Figure 3). These adipokines are involved in a wide variety of metabolic and physiologic, as well as inflammatory changes that are implicated in the pathophysiology of obesity. Why did it take so long to understand the importance of fat cells in disease? The key reason is their apparent simplicity in histologic appearance as well as metabolically that belied their important role in energy metabolism and as an endocrine organ. Adipose tissue is a major secretory organ and does not just release fatty acids during fasting the tissue also releases a wide variety of lipid based moieties: cholesterol, retinol, steroid hormones and prostaglandins. However, fat cells also secrete many pro-inflammatory cytokines (e.g. tumor necrosis factor alpha was the first to be discovered), including interleukins (IL-1, IL-6, IL-10), chemokines (such as monocyte chemoattractant protein -1), proteins involved in hemostasis (platelet activator inhibitor -1) and blood pressure (angiotensinogen). What does this mean for the obese dog? Obesity is a metabolic disease that results in major changes in appetite control, energy expenditure, and induces a chronic, low-grade, pro-inflammatory state that may be responsible for many of the diseases associated with increased body weight. There are a number of diseases in dogs and cats are reported to be associated with obesity, including orthopedic diseases, diabetes, heart disease, abnormal circulating lipids, certain cancers, urethral sphincter mechanism incompetence, dyspnea due to compromised ability to breathe (e.g. laryngeal paralysis, brachycephalic syndrome, tracheal collapse etc), heat intolerance, decreased immune function, and dystocia to name just a few. Further, we do not have a complete understanding of the inflammatory role of obesity hormones in our pets, and this could lead to an even greater connection between obesity and disease. Finally, as we have previously shown from the prospective study of calorie restricted dogs, dogs that are obese also do not, on average, live as long as their leaner counterparts. The bottom line is that prevention of obesity in dogs can increase both the quality and quantity of their life. Dietary Therapy There are two important goals in establishing an appropriate dietary therapy regimen: 1. It must be tailored to the individual animal (diet needs for allergy, renal disease, GI issues, etc), and 2. Caloric restriction must occur without concurrent protein starvation to prevent loss of lean muscle tissue during weight loss. The first step in making a diet plan is to obtain a complete dietary history that gives an accurate accounting of all foods fed to a pet on a typical day. In some cases, it may be necessary to have the owners keep a diet log for a week, writing down the meals, the treats, the table foods, etc. consumed by 2

4 the dog during that time. This is especially helpful in households where the dog may receive foods from more than one individual (especially children). In addition, it should be noted if the dog has access to any other foods (other pets in the family, outside scavenging), if the pet received medications in foods, and if there are other food items available to the dog (chew treats, dental chews, etc). The next step in designing a diet plan is to decide upon a weight loss goal. The goal does not necessarily have to be that the pet achieves its ideal body weight this goal should be based on the pet, the owner s situation and goals, and the ability to reach the goal. It is important to set reasonable goals that can be achieved, rather than overly ambitious goals that are not likely to be achieved and result in the client becoming discouraged because their pet is not meeting the expected goal. A step down approach to weight loss is much more likely to result in success and continued owner persistence, than a goal that is too ambitious and results in the owner abandoning the process due to lack of progress. Once you have set the appropriate weight loss target for that pet, then you can calculate the energy restriction that will be required to achieve the goals you have set. Ideally, the best way to set the new energy intake is to reduce intake to 60-80% of the pet s current intake. If the pets intake is not known (or cannot be calculated accurately), then it is necessary to calculate an estimate of intake for the target weight. There are a number of different equations recommended for calculating maintenance energy requirements, and ones the most frequently used are given in Table 3. Finally, another way that you can calculate calorie reduction is to calculate the energy content of the amount of fat mass you wish the pet to lose (e.g. 1 kg adipose tissue = 7700 kcal). Take this number and divide by the number of days you plan to feed the weight reduction diet. That number is subtracted from the dog s current intake to achieve a new, lower number of calories for intake. This method is more cumbersome, but is based on a more precise estimate of fat loss. Nevertheless, no matter which approach is used, the key to success is first to have complete client cooperation, then to monitor the pet frequently (e.g. every 3-4 weeks), and finally to make adjustments in intake as needed based on the plan you have developed. To be sure of accuracy in the weight loss period, it is important to weigh the pet on the same scale. To provide safe, but efficient weight loss, the dog should not lose more than 1-2% of its body weight/week. In addition to reducing the energy intake of pets that are overweight, it is also possible to increase weight loss by increasing energy expenditure through increased exercise. In obese dogs, as in obese humans, it is important to start slow with an exercise program, and only very gradually and slowly increase the duration and intensity of the exercise. In some dogs, exercise may be impossible, due to severe joint problems or exercise intolerance or due to inability of the owners to exercise with their pet. In these dogs, very minimal activity, or low impact activity, such as a tread mill or water treadmill may be needed to allow safe, non-painful activity. Consultation with a veterinary physical rehabilitation specialist is often very helpful in determining appropriate activities for the dog. This can also be part of the overall diet and weight reduction plan, as the weigh-ins and evaluation of the pet s progress can occur in conjunction with the visits to the rehabilitation program. Many dogs become obese due to the social bonding that occurs with owners and their dogs during feeding. This human animal bond activity results in a strong behavioral component to the development of obesity that must be addressed. In order to achieve success in changing these behaviors, it is important to substitute low calorie treats, games, or grooming activities for table scraps or other high calorie treats. Begging for food is more of a behavioral problem than a hunger problem, and if this relationship is not considered in weight loss programs, the plan is doomed to fail. In some cases, consultation with a veterinary behaviorist is an important part of the overall plan for weight loss. Treatment of Obesity: From Diet to Drugs The management of obesity in dogs has long been focused on reducing energy consumption (dietary management) and increasing energy expenditure (exercise). And, while this approach is very effective when it is implemented completely and early, it can be quite difficult to overcome the behavioral, social, metabolic, and hormonal influences of obesity and achieve long term success. In humans, obesity management options include dietary management, exercise, behavior modification, pharmacologic therapy, and surgery. At this point, surgical therapy of obesity in dogs and cats is an ethically grey area. Unfortunately, until recently, there were no therapeutic options for weight loss in dogs or cats, and that has limited the options for therapy beyond dieting for veterinarians and pet owners. With the acceptance 3

5 of dirlotapide (Slentrol ) this past spring, veterinarians in the US and Europe now have a new tool for those obese canine patients that needed additional help in their battle to lose the excessive weight. The goal of this paper is to provide an overview our clinical experience with Slentrol to date. Clinical Experience with Slentrol : How Does it Work? Dirlotapide (Slentrol ) is a selective (intestinal) microsomal triglyceride transfer protein (MTP) inhibitor. What does this mean? Slentrol reduces the absorption of fat by slowing the packaging of fatty acids with protein to form chylomicrons, a process that occurs inside enterocytes using the enzyme MTP (Figure 1). As a result of this process, there is a reduction in fat absorption in the small intestine, but this is responsible for only a small fraction (approximately 10%) of the drugs effect. The end result is that steatorrhea and other side effects related to fat malabsorption are minimal. Furthermore, the reduction in fat absorption with Slentrol therapy does not significantly reduce circulating levels of fat soluble vitamins, cholesterol or triglycerides as has been shown in the safety and toxicity studies. While this reduction in fat absorption is responsible for a small percentage of the weight lost by dogs on the drug; it still of major importance to it s mechanism of action, as the presence of unabsorbed fat in the enterocyte appears to be the trigger that causes an increase in peptide YY. Peptide YY is a potent appetite suppressant that sends signals to the hypothalamus and other brain centers that control satiety. Ultimately, the primary effect of Slentrol in achieving weight reduction is that it reduces appetite and thus by controlling intake, the dogs lose weight. Most dogs in my trial had a reduction of 10% in their intake but there was a wide variation in responses, as some dogs left up to 20% of their food, while others only 5% or less. How Much Weight Loss Can Be Expected? There was a wide variation in response to the drug in the dogs on the clinical trial, but average weight loss was 10-11% over the 4 month weight loss phase. One dog in my trial only lost 0.5 kg, while another lost nearly 10 kg. There appears to be some individual variation in response to the drug, as would be expected with any drug. However, some of the weight loss response variability may have been due to the diets used in the trial. The amount of dietary fat may be important in the individual responsiveness to Slentrol therapy, simply because a slightly higher fat diet will result in a greater amount of fat in the enterocytes, that will then trigger Peptide YY release. In our studies, the type of commercial diet was not restricted, so dogs entering the trials were on a wide variety of diets, with a wide variation in fat levels. Post trial, the role of fat levels in the diets and their relationship to the amount of weight loss was investigated and there were not enough dogs on the ultra-low fat diets to make any conclusions. However, the data seemed to suggest that the amount of fat in the diet did influence the amount of drug needed to achieve weight loss, as well the rate of the loss in the dogs. Needless to say, because of the wide variations in diets it is difficult to make concrete recommendations without further study. What are the Most Important Client Talking Points? What can be expected during weight loss therapy with Slentrol? What is involved in a Slentrol weight loss program? What types of blood work or monitoring is needed? Can this be given to my fat cat? What are the Side Effects and Owner Expectations With Slentrol Therapy? It is very important to set expectations for this therapy: Slentrol is an appetite suppressant that will help your dog to lose weight, but without development of a weight loss program that includes attitude changes about feeding their dog, exercise programs, and monitoring (weigh-ins) the weight lost will be regained. It is also important to address the likely side effects that will be observed when dogs are receiving Slentrol: including vomiting, reduced appetite, soft feces or diarrhea, and lethargy. Vomiting was observed in 24% of US dogs in the final clinical trial. This was primarily observed at the outset of the trial, or after the first increase in dose but did not require medical intervention in any of the dogs in my trial (e.g. dogs that vomited more than 2 times in one day or on consecutive days were examined). A common concern among owners at the outset of the trial was the decrease in their dog s appetite. This was of particular note to owners of Labrador retrievers, who had dogs that were highly food-driven, that all of a sudden were now not eating all of their food or eating more slowly. In our trial, owners were instructed to make note of their dog s intake, and if the dogs ate less than ¾ of their food, they were to bring them in for an examination. Over time, the reduction in appetite, was seen as normal and owners were less 4

6 concerned about it and came to recognize that their dogs were now eating the appropriate amount of food for them to achieve weight loss. What Monitoring is Needed with Slentrol Therapy? Slentrol is an inducer of hepatic transaminases (AST, ALT) and as such it is important to be sure that the dog has normal liver values prior to starting therapy. Studies evaluating high doses of Slentrol on liver function (bile acids) and liver morphology (biopsy and necropsy) were all normal, suggesting that the drug does not cause liver damage associated with the enzyme increases. Further, the increases in the transaminases that were observed in the dogs on the clinical trials were not associated with any clinical signs, increases in alkaline phosphatase, or changes in any other indicators of liver function (cholesterol, bilirubin, albumin, BUN). Can Slentrol be Administered to Fat Cats? Slentrol should not be given to cats for any reason. There is no immediate toxic effect to a cat if it receives an accidental dose, but because Slentrol will decrease appetite, this is a high risk factor for induction of hepatic lipidosis in an obese cat. Induction of hepatic lipidosis was observed in cats given Slentrol in preliminary studies, and thus, its use in cats is to be discouraged. Summary Slentrol is most effectively used in combination with an overall plan of dietary therapy (management of calories) and exercise (increased energy expenditure will maintain energy needs at a stable plane) in obese dogs. In those obese dogs that are unable to effectively exercise or achieve the calorie restriction required to see measureable weight loss, Slentrol can be an effective tool that increases the likelihood of successful weight loss and ultimately, an improvement in the quality of the pet s life. Suggested Readings German AJ. The growing problem of obesity in dogs and cats. J Nutr 136: 1940S-1946S, Burkholder WJ. Precision and practicality of methods assessing body composition of dogs and cats. Comp Cont Ed 23:1-10, Mawby DI, Bartges JW, d Avignon A, et al. Comparison of various methods for estimating body fat in dogs. Am Anim Hosp Assoc 40: , Trayhum P, Bing C, Wood, IS. Adipose tissue and adipokines Energy regulation from the human perspective. J Nutr 136: 1935S-1939S, Armstrong PJ, Lund EM, Kirk CA, et al. Prevalence and risk factors for obesity in dogs and cats. Proc ACVIM 22: 6-7, Kealy RD, Lawler DF, Ballam JM, et al. Effects of diet restriction on life span and age related changes in dogs. J Am Vet Med Assoc 220: , Fascetti AJ. Obesity management in dogs and cats. Proc West Vet Conf VET-109, Michel KE. Designing an effective weight reduction program. Proc Atlantic Coast Vet Conf Yaissle JE, Holloway C, Buffington CAT. Evaluation of owner education as a component of obesity treatment programs for dogs. J Am Vet Med Assoc 224: ,

7 FEEDING CATS AND FELINE OBESITY Debra L. Zoran, DVM, PhD, Diplomate ACVIM-SAIM Texas A&M University, College Station, TX Feline Nutrition Cats are obligate carnivores. This statement is news to no one, and yet we often don t recognize the importance of that statement or feed them accordingly. While cats can use carbohydrates (CHO) as a source of metabolic energy, they have no requirement for them (nor do dogs for that matter). But, more importantly, because cats evolved consuming prey (e.g. high protein, low to moderate fat, minimal carbohydrate), they are metabolically adapted for higher protein metabolism and lower CHO utilization. What does that mean metabolically and nutritionally? There are a number of specific metabolic and biochemical differences in feline physiology that are important. For those who are interested in the specific details of these metabolic and physiologic differences in the nutritional biochemistry of cats, the reader is referred to several recent reviews on this subject. This paper will discuss several important medical problems in cats that may be directly linked to, or may be specifically managed by, dietary manipulation. Feline Obesity The primary reason for development of obesity in any animal is that they are consuming more energy than they are expending. This can occur when a cat has excessive dietary intake of calories (food or treats) or when there is a reduction in energy expenditure (reduced activity, illness or injury resulting in less exercise, etc). In indoor cats, reduced energy expenditure is a very important problem, and this is compounded by the fact that it is not easy to increase energy expenditure in cats like dogs with directed exercise. Additionally, because many cat owners prefer to feed free choice dry food, the risk of overfeeding, even in very small amounts is very high. In either case, the primary reason that weight gain occurs in cats is that they have a positive energy balance and this must be changed to affect weight loss. In both dogs and cats, neutering is an important risk factor due to the hormonal changes that occur that result in changes in levels of leptin, progestins, and other hormones that result in increased appetite, and reduced energy metabolism and metabolic rate. The key factors for prevention of obesity in neutered animals appears to be careful control of intake immediately after neutering (no free choice feeding, reduction of intake by 25% to account for the hormonal changes resulting in reduced energy needs), and close monitoring of body weight and BCS to allow adjustments in intake if needed. In addition, because feeding our cats is a social interaction, feeding and food interaction with the cat can become a daily social interaction that can become a problem resulting in overfeeding and inappropriate food intake patterns. It has been shown that in households where the owners are health conscious (conscious of diet and nutrition, who exercise regularly, and watch their own weight) they tend not to have obese pets (except where free choice feeding is used). Thus, there are clearly human behavioral and food is love issues that have to be considered in the development of obesity, and these must be addressed for successful weight control to be achieved. The Importance of Obesity as a Disease Obese humans generally do not live as long as their lean counterparts, and are much more likely to suffer from obesity-related diseases such as type II diabetes, coronary artery disease, osteoarthritis, hypertension, and some cancers. Dogs and cats are susceptible to the same detrimental effects, including decreased longevity, and development of a variety of disorders that are associated with being obese. In a recent study, dietary calorie restriction was clearly shown to increase longevity in a group of 24 Labrador retrievers. In that study, the dogs in the energy restricted group were fed 75% of their counterparts, and the dogs lived an average of two years longer and had a reduced incidence of hip dysplasia, osteoarthritis and glucose intolerance. A similar study has not been performed in cats, but there is a clear difference in morbidity in obese cats compared to their lean counterparts. In order to understand the role of obesity in disease development, it is necessary to first understand the role of adipose tissue in energy balance and metabolism. The expansion of adipose tissue was long thought to be simply a depot for the deposition of fatty acids (triglycerides) that occurred because of the excess energy intake. However, research in the past decade has revealed that adipose tissue is not just a 6

8 storage site, but also is responsible for production of many key hormones (e.g. leptin) involved in energy balance and a variety of other processes. Leptin was first identified in 1994 and its discovery opened the door to a whole new world of understanding about white adipose tissue that continues to this day. Leptin is an inhibitor of food intake primarily through suppression of neuropeptide Y and orexin in the brain, and plays a role in the regulation energy expenditure. In obese mice that lack leptin or have leptin resistance, appetite suppression mechanisms are non-functional and energy metabolism abnormal. However, despite the importance of leptin in appetite suppression and energy expenditure, it is not the silver bullet of obesity management: simply replacing leptin does not result in weight loss or changes in the metabolism of obese animals. Further research in recent years has elucidated an entire list of adipokines secreted by fat cells. These adipokines are involved in a wide variety of metabolic and physiologic, as well as inflammatory changes that are implicated in the pathophysiology of obesity. Why did it take so long to understand the importance of fat cells in disease? The key reason is their apparent simplicity in histologic appearance as well as metabolically that belied their important role in energy metabolism and as an endocrine organ. Adipose tissue is a major secretory organ and does not just release fatty acids during fasting the tissue also releases a wide variety of lipid based moieties: cholesterol, retinol, steroid hormones and prostaglandins. However, fat cells also secrete many proinflammatory cytokines (e.g. tumor necrosis factor alpha was the first to be discovered), including interleukins (IL-1, IL-6, IL-10), chemokines (such as monocyte chemoattractant protein -1), proteins involved in hemostasis (platelet activator inhibitor -1) and blood pressure (angiotensinogen). What does this mean for the obese cat? Obesity is a metabolic disease that results in major changes in appetite control, energy expenditure, and induces a chronic, low-grade, pro-inflammatory state that may be responsible for many of the diseases associated with increased body weight. The interested reader is directed to large number of recent reviews on this subject for additional details, as this area of research is rapidly changing as we seek to better understand obesity as a disease. There are a number of diseases in dogs and cats are reported to be associated with obesity, including orthopedic diseases, diabetes, heart disease, abnormal circulating lipids, certain cancers, urethral sphincter mechanism incompetence, dyspnea due to compromised ability to breathe (e.g. laryngeal paralysis, brachycephalic syndrome, tracheal collapse etc), heat intolerance, decreased immune function, and dystocia to name just a few. Further, we do not have a complete understanding of the inflammatory role of obesity hormones in our pets, and this could lead to an even greater connection between obesity and disease. Obesity and Diet While figures vary, recent studies indicate that greater than 35% of cats in the United States are obese. There are a large number of factors that contribute to this problem, including sex (intact vs. neutered, male vs. female), age, activity (indoor vs. outdoor), and feeding style (meal feeding vs free choice). Further, it is much harder to take it off, than it is to put it on as we are all very aware. One factor that is that is important to consider, both in the development of and treatment of obesity, is the role of CHO in diet. Because of the metabolic requirement for cats to utilize protein as an energy source, CHO in the diet that are not immediately used for energy (e.g. via exercise or other utilization for energy) will be stored as fat. Traditional weight loss plans include feeding an energy restricted (e.g. low fat, high CHO, high fiber) diet. However, while these diets may result in weight loss, they do so to the detriment of lean body mass especially in cats that use protein for energy even in the face of other energy sources in the diet. Successful weight loss requires loss of adipose tissue as well as maintenance of lean body mass, as lean body mass is the driver of basal energy metabolism (loss of lean body mass is a major contributor to weight regain as appetite is not reduced and satiety not reached). Several recent studies have evaluated use of a high protein, low CHO diet (protein 45% or higher) for weight loss in cats, and in those studies, all cats lost weight, but maintained lean body mass. Importantly, high protein, low carbohydrate diets not only result in sustained weight loss in these cats, but also in normalization of appetite (reduced urge to eat constantly because they are satiated). Because dry foods must be extruded (i.e. made into a biscuit), CHO are required in the cooking process, and thus, it is difficult to achieve a very low CHO diet that is dry. Further, many of the available high protein, low CHO dry foods are NOT low calorie, so it is extremely easy to feed too much. Too many calories, including too many protein calories, will also cause weight gain or failure to lose as well. At this time, the best commercial diets for achieving a high protein, low 7

9 CHO profile, along with controlled calories, are canned (both kitten and many adult foods are acceptable) foods. Calculating calories: Most indoor cats do not need more than their resting energy requirement (RER) to meet their daily nutritional requirements. Cats that are very obese may need to reduce their intake by 20-40% (or 60-80% of RER) to lose weight. In general, this means that most average sized cats (5 kg) do not need more than 200 kcal/day, and many need LESS than this to maintain normal body weight. For EXAMPLE: Hill s m/d = 165 kcal/can, while Hill s m/d dry = 485 kcal/cup thus, it is much more difficult to reduce calories using the dry food. The key point is this: set a target calorie intake, then weigh the cat monthly, and adjust the amount of food based on weight loss. The goal is for 1% weight loss per week or 3-4% per month and if this goal is not being achieved, a reduction in calories (10-20%) must be done to meet the weight loss goals. Key Points: The commercially available diets lowest in CHO are canned foods. It is important to remember that just because you are feeding a canned food, it does mean that you are feeding a high protein, low CHO diet (you must read the label) and it also doesn t mean you are feeding a high quality protein (low quality protein in foods can cause fecal odor and diarrhea due to poor digestibility). Most cats should be fed some (50% is a starting point) canned food as part of their diet throughout their life both to reduce the CHO in their diet, but also to better control calories (dry foods are very calorie dense), and to increase the amount of water consumed daily. Furthermore, eating canned food is a learned behavior if canned food is part of a kittens diet, they will more readily eat canned food as an adult (e.g. when they need canned food for urinary disease or renal disease later in life). An important follow up point to remember about all diets is that calories count. You cannot free choice feed most indoor cats even with high protein, low carb diets because if they consume too many calories (and the diabetes diets are very calorie dense) they will become or remain obese. Also, calorie control must be started when they are kittens as obesity starts in young adults due to the above mentioned issues with neutering and energy intake. The key point for obesity prevention (or correction) is balancing the energy intake / energy expenditure equation. In indoor cats, where exercise is reduced by the nature of the lifestyle, energy restriction becomes paramount to obesity prevention or correction. Energy restriction can be achieved by low fat high fiber diets, but many of these diets are not high enough in protein to preserve muscle and result in loss of muscle mass first, then eventually they will lose fat mass, resulting in an unhealthy weight loss and a strong tendency to regain weight (muscle mass loss will always increase the likelihood of yo-yo weight effects or failure of weight loss). High protein, low carb, low fat diets are ideal for weight loss in cats because they preserve muscle mass while restricting energy sources that will induce fat loss. However, portion control is ultimately the key to controlling energy intake and the easiest way to achieve portion control is to feed canned food. In cats that won t eat canned food, there are only a few high protein, low fat, low carb dry foods but these should be selected for use in weight loss programs if at all possible. Table 1. Cats and Nutrition: Some Key Nutritional Differences Cats have an obligate need for protein and amino acids in their daily diet because they are unable to down regulate their urea cycle or transaminases (protein conversion to energy) as other species can in times of starvation. Cats utilize protein for energy, even in the face of large amounts of CHO in the diet Taurine, arginine, methionine, cysteiine, and possibly carnitine requirements for cats are greater than non-carnivores Arachidonic acid is also an essential fatty acid in cats (it is not in dogs), and is found only in fats from animal tissue Cats require vitamin A and D to be present in the active form in their diet as they are unable to synthesize adequate amounts from other dietary precursors (e.g. carotenoids or vitamin D precursors in skin) Cats have an increased need for many B vitamins in their diet (e.g. thiamin, pyridoxine, niacin, pantothenic acid) as they have greater metabolic needs for these vitamins and cannot synthesize or get them from other sources. 8

10 Salivary amylase is absent in cats, and they have greatly reduced levels of intestinal and pancreatic amylases so CHO digestion is much less efficient. Cats have fewer disaccharidases and other brush border enzymes in their small intestine designed to digest and absorb starches. The small intestine of cats is much shorter than that of an equally sized omnivore longer GI tracts are necessary for handling of complex carbohydrates. Cats have greatly reduced activities of hepatic enzymes (e.g. glucokinase) designed to convert a post prandial glucose load to glycogen and thus are less able to handle this glucose load. There are no fructokinases in cats they are unable to utilize fructose and other simple sugars. 9

11 FELINE PANCREATITIS: THE MORE WE KNOW Debra L. Zoran, DVM, PhD, Diplomate ACVIM-SAIM Texas A&M University, College Station, TX Feline pancreatitis is a very difficult disease to definitively diagnose antemortem (especially chronic cases or in cats that do not have persistent signs) and treatment remains symptomatic and supportive. The problems of diagnosis and treatment are due to the lack of specific clinical signs in cats, as well as the lack of a rapidly available test for diagnosis of the disease and in cats with chronic pancreatitis, testing is still very difficult. This talk will review the salient features of both acute and chronic pancreatitis in cats and discuss the treatment of cats with pancreatitis. Diagnosis The clinical signs of feline pancreatitis are quite different from those in dogs. Two forms of pancreatitis appear to occur in cats: acute necrotizing pancreatitis(anp) (a disease similar in appearance, if not cause, to canine acute pancreatitis), and lymphoplasmacytic pancreatitis (which can present as an acute or chronic disease). In a recent histologic review of pancreas from cats that were submitted to postmortem for any cause (not just pancreatitis), the percentage of cats with ANP was less than 15%, while 65% of cats had LP changes. This illustrates that the feline disease is quite different from that recognized in the dog. The acute pancreatitis that is frequently encountered in obese dogs fed a high fat diet is not reported in cats. Cats with acute necrotizing pancreatitis are more likely to be underweight, and high fat diets do not appear to be an important predisposing factor. In lymphocytic (LP) pancreatitis, cats of all ages, sexes and breeds are affected, although Siamese cats are reported to have pancreatitis more frequently. Finally the clinical signs of LP pancreatitis in cats are vague, with the most common signs being lethargy (reported in 100% of cats in one study), anorexia, dehydration and abnormal body temperature (either fever or hypothermia can be observed). This is especially true for cats with chronic or mild forms of LP pancreatitis. Vomiting and anterior abdominal pain, which are common clinical signs in dogs with acute pancreatitis, are reported to occur in only 35% and 25% of cats with LP pancreatitis, respectively, but are common in cats with ANP. However, cranial abdominal pain may be more common than is reported, as detection of abdominal pain may be difficult in obese cats or cats with very focal disease. Cats with the most severe forms of pancreatitis, such as acute necrotizing pancreatitis, may be icteric or in shock and the prognosis for these cats is significantly more guarded. Other conditions that may occur concurrently with pancreatitis in cats include hepatic lipidosis, cholangiohepatitis, inflammatory bowel disease, interstitial nephritis, diabetes mellitus or vitamin K responsive coagulopathy. Thus, the clinical signs may be quite variable, and this must be taken into consideration with each patient. In addition, with increases in liver enzymes and bilirubin, the signs and abnormalities can easily be attributed to liver dysfunction, which further delays the diagnosis. Routine evaluation of cats with suspected pancreatitis may include hematology, a serum biochemistry profile, urinalysis, abdominal radiography and/or ultrasound, and serum assays of pancreatic function (e.g. feline trypsin like immunoreactivity ftli, or feline pancreatic lipase immunoreactivity fpli). Hematologic findings in cats with pancreatitis are nonspecific, but may include a nonregenerative anemia, leukocytosis or leukopenia (less common). In a recent study, cats with pancreatitis consistently had an elevated WBC (20,300 cell/ul) and mild decreases in platelets (mean = 180,000 platelets/ul). Reported changes in the serum chemistry profile include elevated serum alanine aminotransferase (ALT), elevated serum alkaline phosphatase (ALP), hyperbilirubinemia, hyper- or hypoholesterolemia, hyperglycemia, azotemia, and hypokalemia. In a recent study, the most common abnormalities in cats with severe pancreatitis were hyperglycemia (180 mg/dl), hyperbilirubinemia (2.5 mg/dl), hypocholesterolemia (130 mg/dl), and hypoalbuminemia (1.8 g/dl). Liver enzyme elevations were more common in cats with mild pancreatitis (determined by surgical biopsy), and GGT ALP, and ALT were all moderately elevated in these cats. Hypocalcemia is less commonly observed, but when present may be a poor prognostic sign seen in cats with severe pancreatitis or multiple organ dysfunction. Serum lipase may be increased early in acute pancreatitis, but in a recent study amylase and lipase were found to be of little diagnostic value in distinguishing normal cats from those with pancreatitis. There are no changes in the urinalysis consistently observed or specific for pancreatitis in cats. 10

12 The ftli was developed years ago as the definitive test for diagnosis of exocrine pancreatic insufficiency, and the data and follow up have confirmed its utility for this condition. In recent years, others have evaluated the ftli as a diagnostic test for acute pancreatitis working on the premise than an elevation in serum concentrations were consistent with pancreatic leakage or inflammation. While an increase in ftli can be found in cats with acute pancreatitis, a normal ftli does not rule out pancreatitis. This is because the leakage of enzymes tends to decrease or is controlled by the body s peptidases (macroglobulin, etc) within12-24 hours following an acute insult. Further, in chronic or low grade pancreatitis, the leakage is not great enough to be detected by this assay. Thus, while an increase in ftli is specific for pancreatic enzyme leakage, it is not sensitive enough to be a definitive test for pancreatitis. More recently, an ELISA for pancreatic specific lipase (feline pancreatic lipase immunoreactivity fpli) was developed by the GI lab at Texas A&M University. The assay is species specific, has been used to detect elevations in pancreatic lipase in clinical cases, and appeared to be more specific and sensitive for diagnosis of pancreatitis in cats than ftli. The sensitivity in mild pancreatitis was found to be 65-80% while the specificity in healthy cats 75%. However, in severe pancreatitis (determined by pancreatic biopsy) the sensitivity and specificity were both 100%. These findings underscore the utility of this test in cats with acute pancreatitis; however, there still is a problem with detection of low grade or chronic pancreatic inflammation in cats with this assay. This is especially a problem in cats with chronic pancreatitis that have pancreatic atrophy and a reduction in enzyme production or release. Further, there appears to be an influence on this enzyme by other local factors such as intestinal inflammation (IBD) that may affect the diagnostic interpretation. In cats with chronic pancreatitis, enzyme levels can be quite variable, and thus it will still be necessary to evaluate the combined historical, physical exam, lab data and imaging information along with the fpli when making a diagnosis. Imaging studies are frequently used to help identify cats with acute pancreatitis; however, the changes are not consistent and can be particularly subject to interpretation and operator expertise. The most common radiographic abnormalities include a generalized or focal (upper right quadrant) loss of peritoneal detail (suggesting peritonitis or peritoneal effusion), presence of a mass in the area of the pancreas, hepatomegaly, dilated intestinal loops, or a fluid-filled duodenum. However, these findings are not specific for pancreatitis, and the sensitivity of radiography for diagnosing pancreatitis is low in cats. Ultrasonography may reveal a hypoechoic pancreas, hyperechoic mesentery, a mass effect, a dilated common bile duct or it may be normal. In previous studies, the sensitivity of ultrasound for diagnosis of pancreatitis was reported to be 24%. In a recent study, mild pancreatitis was still shown to be difficult to diagnose via abdominal ultrasound. However, in that same study, ultrasound had 80% sensitivity and 88% specificity in cats with moderate to severe pancreatitis. In humans, the gold standard for a noninvasive diagnosis of pancreatitis is CT, but in this study, only 2 of the 10 cats showed evidence consistent with pancreatitis and there was large variability in the ability of this imaging technique to assess pancreatic size. Thus, the costs, availability, the difficulties in imaging the normal feline pancreas using CT, make this method less attractive and unrealistic for use in the diagnosis of feline pancreatitis. The most reliable method for making an accurate diagnosis of pancreatic disease remains confirmation of inflammation on histopathology. However, this can be expensive, increase the risk of complications (anesthesia/surgery), and in cases with focal lesions, the lesions may be missed on visual or histopathologic inspection. Thus, while biopsy is an important tool, it cannot be used in all cases, and if the biopsy reveals normal pancreas focal or chronic segmental pancreatitis cannot be ruled out. There are several primary histopathologic differences in cats between acute pancreatitis and chronic pancreatitis. Acute pancreatitis is characterized by neutrophilic or lymphoplasmacytic inflammation, with edema and fat necrosis. Chronic pancreatitis is characterized by the absence of inflammation, fibrosis of pancreatic tissue, and cystic degeneration with zymogen depletion. The lesions of chronic pancreatitis were more prominent in the left limb of cats with concurrent GI disease. The chronic form of pancreatitis in cats resembles the chronic form in humans, where pain management using opoids and stent placement are key aspects of therapy. Treatment of Acute Pancreatitis Acute necrotizing pancreatitis in cats can be a significant therapeutic challenge. As with the treatment of dogs, the therapy is supportive and aimed at restoring circulating blood volume while allowing the pancreas to rest. If an inciting cause can be identified, it should be corrected; however, greater than 90% of cases are idiopathic. The mainstay of treatment is aggressive fluid therapy, and if the cat is 11

13 vomiting, withholding food and water for 2-3 days. Colloid support can be obtained with hydroxyethyl starch (Hetastarch) or plasma if it is available. If the cat is unable to tolerate water or food after the 2-3 day period, alternative routes of nutritional support must be considered to prevent development of hepatic lipidosis or protein/calorie malnutrition and immunosuppression. If the cat is not vomiting, placement of an esophagostomy (E) or percutaneous endoscopic gastrostomy (PEG) tube are reasonable alternatives especially in cats with known or suspected hepatic lipidosis as a concurrent problem. In vomiting cats, either parenteral (IV) nutrition or placement of a jejunal feeding tube is optimal. The key point is this: you can t starve cats with pancreatitis. In cats with chronic, low grade pancreatitis this is even a more important aspect of long term management. Another important aspect of therapy that must be considered in cats with pancreatitis is pain management (whether or not they show overt pain this is important). Careful palpation in most cats will reveal cranial quandrant pain in cats with significant pancreatic inflammation. Pain relief can be achieved with buprenorphine ( mg/kg IV, or IM q 4-8 hr), meperidine (1-2 mg/kg IM q2-4 hr), or butophanol ( mg/kg IM q2-4 hr). In addition, low dose CRI ketamine or lidocaine infusions are effective in reducing somatic pain, and lidocaine at these low doses has prokinetic activity. Morphine should be avoided as it can cause pancreatic duct spasm. The other aspects of supportive therapy to consider are antibiotic therapy, control of vomiting, and anti-coagulants (for cats in DIC). Antibiotic therapy is generally indicated in all cats with severe pancreatitis, or in cats with systemic inflammatory response syndrome (SIRS) as the risk of bacterial translocation and secondary sepsis are considerable. In general, broad spectrum antibiotics that cover intestinal aerobes and anaerobes should be chosen. Cefotaxime at a dose of 50 mg/kg administered intramuscularly every eight hours prevents bacterial colonization of the pancreas. Chronic Pancreatitis Therapy of chronic pancreatitis is somewhat controversial because there are no evidence based studies yet available reporting specific therapeutic approaches that are beneficial. Many have advocated the use of steroid therapy, and in some cats with chronic pancreatitis this may be reasonable, where LP inflammation is the primary problem causing clinical signs. However, in end stage cats where fibrosis and pancreatic degeneration, not inflammation, is occurring, steroids would be expected to be counterproductive. At this time, appetite stimulation (using cyproheptadine) and pain control (buprenorphine) are the most commonly recommended therapeutic approaches. Pancreatic biopsy is the most effective means of providing the information needed to determine the best course of therapy in these cats. At this time, fluid therapy to maintain hydration, appetite stimulation and a highly digestible or hypoallergenic diet, pain control, and judicious use of steroids are the mainstay of therapy. Further work on the underlying causes of this disease is needed to better define therapy. Nutritional Therapy of Pancreatitis The diet chosen should be highly digestible and palatable, but the concept of low fat diet to reduce stimulation of pancreatic secretions is not recognized as an important aspect of therapy (as it is in dogs) due to the different causes and histologic types (LP) pancreatitis. Ultimately, the goal is to find an appropriate diet for the cat that is highly digestible, commercially available and acceptable to the cat. An important point about feeding cats during this period is to avoid force feeding not only because it is very difficult to achieve the appropriate level of caloric intake by this method, but also because it can induce food aversion. References Steiner, J. Feline Pancreatitis. Vet Clin N Am, Washabau, R. Feline Pancreatitis. August s Consultations in Feline Internal Medicine,