Canine-nutritional Management Of Diabetic Dogs

20TH ANNIVERSARY

Vol. 21, No. 8 August 1999

CE

Refereed Peer Review

FOCAL POINT ★ Managing canine diabetes mellitus requires a consistent feeding plan and food that minimizes postprandial fluctuations in blood glucose concentrations.

KEY FACTS ■ Dietary modification, in conjunction with insulin therapy, is an effective adjunct in the control of diabetes mellitus in dogs. ■ The single most effective dietary change is to include moderate amounts of insoluble and/or soluble dietary fiber. ■ For most dogs, feeding at the daily energy requirement for ideal body weight in conjunction with adequate pharmacologic control of diabetes mellitus will maintain a desired body weight. ■ For obese animals, a conservative weight-loss protocol should be instituted after primary medical problems have been stabilized.

Nutritional Management of Diabetic Dogs Angell Memorial Animal Hospital, Boston, Massachusetts

Rebecca L. Remillard, PhD, DVM ABSTRACT: The goals of nutritional therapy in the management of diabetes mellitus are to approach physiologic blood glucose levels, match postprandial glucose absorption with insulin therapy, attain and maintain optimal body weight, reduce the likelihood of diabetic complications, and address other concurrent disease conditions amenable to dietary therapy. Managing diabetes mellitus requires a consistent feeding plan and food that minimizes postprandial fluctuations in blood glucose concentrations. Because fiber modulates blood glucose levels and favors optimum body weight maintenance, the single most effective dietary tool in the medical management of diabetic dogs is feeding a diet containing insoluble or soluble fiber at 8% to 18% on a dry-matter basis.

D

iabetes mellitus (DM) in dogs is a complex disorder caused by a multitude of factors; it is characterized by an insulin deficiency or dysfunction that results in hyperglycemia and abnormal lipid and protein metabolism. In 1985, a revised classification system divided diabetes in humans into four categories: insulin-dependent diabetes mellitus (IDDM or type 1), non– insulin-dependent diabetes mellitus (NIDDM or type 2), gestational diabetes, and secondary diabetes.1 DM in dogs is broadly classified as IDDM or NIDDM based on the need for insulin.1 –3 When approximately 75% of pancreatic beta cells have been destroyed in patients, the ability to maintain normal blood glucose level is decreased.4 IDDM is characterized by low blood insulin levels, and therefore the patient is dependent on an exogenous insulin source. Immune-mediated insulitis may play a role in development of IDDM in dogs because beta-cell–specific antibodies have been identified in approximately 50% of diabetic dogs studied.5 Non–insulin-dependent DM is classically characterized by insulin resistance in peripheral tissues and/or dysfunctional beta cells.6 NIDDM is less common in dogs than in cats and not well described but still accounts for approximately one in five cases of diabetes.7,8 NIDDM has been referred to as a relative insulin deficiency because blood insulin levels may be increased, decreased, or normal. Patients with NIDDM are not completely dependent on administration of exogenous insulin to maintain glucose homeostasis. The number and intrinsic activity of glucose transporters are decreased in humans and rats with NIDDM.9 The pathophysiologic defect in NIDDM more likely involves depletion of glucose

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transporters and/or a dysfunctional receptor/postreceptor intracellular signaling event resulting from translational suppression of the transporter genes.10–12 In dogs, NIDDM appears to be associated with obesity and possibly a subsequent down-regulation of peripheral insulin receptors similar to that noted in humans.13 Some authors consider the pathogenesis and clinical picture of IDDM and NIDDM to be different,1 whereas others report that patients may initially appear to have one type but either progress to the other type or alternate between the two through the course of the disease.3 The cause is probably multifactorial; genetics, immune-mediated disease, obesity, inflammatory/infectious conditions, exogenous drugs, concurrent disease, and pancreatic beta-cell degeneration have been suggested. Regardless of pathophysiology, most diabetic dogs should be considered to have IDDM and treated with insulin and dietary management unless there is a strong indication that the diabetes is secondary.3 Dietary recommendations cannot be made based on research alone because of the paucity of well-designed studies using diabetic dogs. Therefore the state of the art in making dietary recommendations is based on research in normal and diabetic dogs, extrapolations from other species, and simple clinical experience.

PATIENT ASSESSMENT Dogs diagnosed with DM may be of any age and sex but are more commonly 4 to 14 years of age; females are affected twice as often as are males. Breeds apparently at higher risk include the keeshond, puli, cairn terrier, miniature pinscher, and poodle.14 Obese dogs have been shown to be glucose intolerant and hyperinsulinemic.15 Regardless of the etiology, therapy must be directed at eliminating the clinical signs of hyperglycemia and preventing the development of chronic secondary complications. Dogs with DM are usually presented for examination because of polyuria, polydipsia, polyphagia, weight loss, and diminished activity and thus have fasting hyperglycemia and glycosuria.3 Weight loss in the face of polyphagia, the hallmark of DM, occurs as the disease progresses. Weight loss is not always synonymous with being underweight; an obese dog could have a history of losing weight but still be overweight at the time of presentation, which is true for most diabetic dogs. Additional physical findings may include lethargy, hepatomegaly, cataracts, and dehydration.16 Other disease conditions (e.g., infection, hypokalemia, hypomagnesemia, renal failure, pancreatitis) or concurrent use of drugs that decrease insulin secretion or cause insulin resistance may precipitate a diabetic ketoacidotic state.17 The clinical expression of DM may not be apparent to

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an owner until the patient becomes ketoacidotic. Body condition scores (BCSs) for diabetic dogs range from emaciated (BCS = 1) to obese (BCS = 9) depending on the severity and duration of disease; most diabetic dogs, however, have a BCS greater than 5.18 BCSs provide estimates of total body fat composition (r2 = .90a) via the palpation of subcutaneous fat stores at specific anatomic sites; thus this method is still useful when patients have diseases associated with muscle wasting.19 Many diabetic dogs are obese, and therefore attainment of an ideal weight (BCS = 5) is an early goal. Studies in obese dogs suggest that obesity causes insulin resistance that may be resolved with weight loss.15,20,21 As a dog loses weight, insulin requirements may decrease.22 A small number of diabetic patients with a history of maintaining optimal weight or being overweight will have lost weight as the disease progressed and could be underweight at the time of diagnosis. Underweight diabetic dogs may regain weight with insulin therapy as cells, once again in the presence of insulin, metabolize serum glucose and fat (through improved lipoprotein lipase activity). The feeding plan for underweight dogs should include increased caloric intake in the form of fat as well as increased fiber. Adding vegetable oil or cooked animal fatb to the diet and feeding meals frequently may improve body weight (BW) in addition to providing better glycemic control. In clinical experience at Angell Memorial Animal Hospital, however, most of these underweight dogs do not attain normal weight; continue to be difficult to control; and have some other complication, usually one that includes the pancreas (exocrine insufficiency and/or cancer).

KEY NUTRITIONAL FACTORS Key nutritional factors emphasize food-related issues that markedly affect the management of a disease. The consequences of an absolute or relative insulin deficiency are a constant catabolic state with increased hepatic glucose output; decreased tissue utilization of glucose; and concurrent increases in glycogenolysis, lipolysis, and proteolysis. Therefore key nutritional factors for managing diabetic pets include specific dietary nutrients (nutrients of concern), food type and digestibility, and a feeding schedule (see Current Feeding Recommendations and Diet Characteristics Helpful in Managing Diabetic Dogs). These factors help to successfully aThis

indicates that 90% of the variation in BCSs can be explained by differences in total body fat content. bOne tablespoon of fat is approximately 150 kcal; feeding a dog 1 tbsp of fat per 30 lb BW per day increases caloric intake by approximately 15%. The added fat should be divided among the meals fed.

AT-RISK BREEDS ■ PRESENTING SIGNS ■ BODY CONDITION SCORES ■ OBESITY

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manage diabetic dogs when the primary disease is controlled with insulin or other pharmacologic treatments. The goals of nutritional therapy are to approach physiologic blood glucose levels, match postprandial glucose absorption with insulin therapy, attain and maintain optimal BW, reduce the likelihood of diabetic complications, and address other concurrent disease conditions that are amenable to dietary therapy. Caloric intake, nutrient composition of the diet, form of the food, feeding schedule, and control of concurrent disease must be considered in planning the dietary management of diabetes.2 3

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Current Feeding Recommendations and Diet Characteristics Helpful in Managing Diabetic Dogs Nutrients of Concern Water Available ad libitum Carbohydrate

Referred to as nitrogen-free extract; approximately 50% (DMB)

Fiber

8%–18% crude fiber (DMB; insoluble and/or soluble fiber)

Energy intake

A reasonable initial estimate of daily energy intake is 1.6 × RER for neutered dogs and 1.8 × RER for intact dogs; RER is approximately 15 kcal per lb BW

Fat

6%–10% (DMB) when dog is at optimal weight or needs to lose weight; fat contents of 10%–20% can be used if weight gain is indicated; no recommendations can be made at this time concerning omega-3 fatty acid content

Nutrients of Concern Nutrients of concern, in decreasing order of importance, are water, carbohydrate (sugar, fiber), energy, fat, protein, and micronutrients (minerals and vitamins). A diabetic dog’s current diet should be evaluated in terms of these nutrients and then compared with recommendations for diabetic dogs. If key nutrients in the current food(s) do not match the recommended levels, changing to a more appropriate food is indicated.

Protein

18%–25% (DMB) with a protein digestibility >85%

Minerals

Foods formulated as complete and balanced according to AAFCO recommendations for adult maintenance provide an adequate supply of macro- and microminerals

Vitamins

Foods designed as complete and balanced according to AAFCO recommendations for adult maintenance provide an adequate supply of fat- and water-soluble vitamins; antioxidant formulations of vitamin C, α-tocopherol, and beta-carotene may be given

Water When glucose is present in the urine, an osmotic diuresis occurs and water loss via urination increases. Ad libitum potable water is recommended and is usually accomplished by providing ad libitum access to water (e.g., having several water bowls in different places available at all times).

Formulation

Fixed; products designed to be sold through veterinarians usually have fixed formulations (i.e., the ingredient formulation does not vary from unit to unit)

Digestibility

Diets containing dry-matter digestibility coefficients of 70%–80% are desirable; highly digestible (i.e., >90%) and poorly digestible (i.e., <70%) diets should be avoided unless warranted in dogs that have difficulty maintaining optimal body weight

Carbohydrate Sugar. Commonly used sources of carbohydrate in dog foods include barley, corn, rice, wheat, oats, and sorghum. These ingre-

Feeding schedule

Most owners can feed two equal-sized meals daily: one at the time of insulin injection and the other 8–10 hr later

Food Type Form

A dry diet is preferred over a canned diet, and a canned diet over soft–moist foods

AAFCO = Association of American Feed Control Officials; BW = body weight; DMB = drymatter basis; RER = resting energy requirement.

GOALS OF NUTRITIONAL THERAPY ■ OSMOTIC DIURESIS ■ DIETARY GUIDELINES

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dients are primarily composed of starch (more than 60% starch), although they differ in their nutrient analysis and availability of protein, fat, minerals, and vitamins. Glucose from dietary starch digestion is the most potent secretagogue of insulin; diets that result in more manageable postprandial blood glucose increases are recommended for diabetics. In humans, glycemic index and dietary carbohydrate concentrations explain almost 90% of blood glucose and insulin responses to a meal.24,25 Glycemic index classifies foods based on their blood glucose–raising potential; this valid and potentially useful concept is also deceptively complex.2 6 There are a number of unresolved problems and unanswered questions (particularly of a mixed-carbohydrate meal). Predicting glycemic response is no longer based on the difference between a simple versus a complex carbohydrate but depends on a variety of such factors as the carbohydrate type, the matrix in which the carbohydrate is found, type of processing the carbohydrate has undergone, and total amount of carbohydrate consumed.2 7 For example, extrusion is the process of cooking a grain to gelatinize the starches, which increases digestibility. In one study, dog foods containing 67% extruded corn, rice, barley, or oats had small intestinal and total gastrointestinal tract starch digestibility coefficients above 98%.28 When these grains were fed whole to dogs, however, their dry-matter digestibilities were lower and differed according to the level of fiber in the grain (rice is the most digestible, oats are the least). The glycemic and insulin responses of normal dogs to diets containing the same amount of different carbohydrate types (corn, wheat, barley, rice, and sorghum) have been investigated.29 Sorghum produced the lowest postprandial glucose response; however, there was an unexplained, disproportionate response between glucose and insulin levels (i.e., sorghum produced the lowest blood glucose levels but did not produce the lowest insulin levels). Starches that resist intestinal hydrolysis, called resistant starches, have resulted in significant reductions in postprandial glycemia and insulinemia in humans and may prove useful in diabetic pets.30,31 Dietary carbohydrate content is not commonly reported; it is referred to as nitrogen-free extract and is a calculated, not a determined, value. The dog foods successfully used in managing canine diabetes contain 45% to 55% nitrogen-free extracton a dry-matter basis (DMB). Fiber. The amount of crude fiber in the various types of commercial dog food ranges from 0.4% to 25% on a DMB; estimates of crude fiber in grocery-brand dog foods (i.e., foods generally available in grocery or pet stores as opposed to therapeutic diets) average 3.7% for dry (range, 1.5% to 10.9%) and 1.5% for canned

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(range, 0.1% to 4.2%) products. However, the analytic crude fiber method required by the Association of American Feed Control Officials (AAFCO)32 excludes variable fractions of insoluble (hemicellulose, cellulose, lignin) and soluble (pectins, gums, resistance starches) fibers and therefore underestimates the fiber content. Total dietary fiber as described for human foods is probably a more meaningful estimate when comparing different fiber levels across foods, but this information is rarely available for pet foods.33 Fiber types are differentiated by their physiologic characteristics and in vivo systemic effects. Soluble fibers (pectins and gums) are soluble in water and increase the viscosity of the intestinal contents, thereby delaying gastric emptying and slowing intestinal transit times. The increased viscosity is also thought to slow glucose absorption.34 Viscosity markedly affects the extent of intraluminal mixing of digesta and digestive enzymes, which can shift absorption sites and subsequently the rate of nutrients entering the bloodstream.35 Soluble fibers are fermented in the colon to short-chain fatty acids (SCFAs; acetic, propionic, and butyric acid). Butyrate appears to be used by colonocytes, whereas propionic and acetic acid are absorbed. These properties result in an acidic colonic pH and increased colonic bacterial numbers, colonic mucosal mass, fecal dry matter, and water content.36 Soluble fiber incorporated into foods at 5%, 10%, or 13% DMB did decrease postprandial blood glucose and insulin levels in normal dogs.37,38 The clinical significance of feeding soluble fiber to diabetic patients may be limited to a particular type because only some gums—not all soluble fiber types—have been reported to lower fasting and postprandial blood glucose levels. Insoluble fiber is primarily composed of cellulose and structural polysaccharides, which are relatively resistant to digestion, ferment slowly, and increase intestinal residue and transit times.39–41 Insoluble fibers reportedly have less of an effect on gastric emptying, lowering of blood glucose, or colonic microflora compared with soluble fibers.34 However, there is evidence to support the hypothesis that feeding foods with moderate amounts of insoluble fiber substituted for starch has a positive effect on glycemic control in dogs. Diabetic dogs eating foods with more than 50% digestible carbohydrate and 10% to 15% DMB cellulose had significantly better glycemic control than did dogs fed the same food without the insoluble fiber.42,43 Fiber helps modulate postprandial blood glucose levels by several plausible mechanisms: delaying gastric emptying, slowing carbohydrate digestion and monosaccharide absorption from the small bowel, altering gastrointestinal hormones (which in turn affects nutrient metabolism), and producing SCFAs that may

GLYCEMIC INDEX ■ NITROGEN-FREE EXTRACT ■ SOLUBLE VS. INSOLUBLE FIBER

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directly affect hepatic glucose metabolism. 44–47 Although the mechanism is not precisely known, longterm consumption of guar gum has been shown to increase plasma insulin levels and improve glucose homeostasis in humans.48,49 In vitro, propionate has been shown to inhibit hepatic glucose production and stimulate glucose utilization via glycolysis.48 SCFAs administered parenterally to rats (and possibly those absorbed from the large bowel) increase the concentration of plasma proglucagon-derived peptides (GLP-1).50,51 GLP-1 is a potent insulin secretagogue and an inhibitor of glucagon secretion and gastric acid secretion and emptying.52,53 Normal dogs fed a highly fermentable fiber (8% DMB) for 14 days had significantly lower blood glucose but greater GLP-1 and insulin concentrations compared with dogs fed the same concentration of a less fermentable fiber source.54 An ideal fiber content and type have not yet been established; based on a limited number of published canine studies and personal clinical experience, a moderate amount (8% to 18% crude fiber DMB) of insoluble fiber evidently improves glucose management in diabetic dogs. Results of some published studies in dogs and other species indicate that the same level of soluble fiber may be equally effective.54,55

Energy Before making feeding recommendations to owners, it is important to emphasize that a diabetic animal’s clinical response to dietary manipulation depends on the level of control achieved over the primary disease process as well as the presence or absence of concurrent disease.17 For example, ideal BW may not be achieved if there is poor control of the diabetes or if such complications as hypothyroidism or hyperadrenocorticism are present. Owner education and consistent reevaluations are important tools in adjusting the food, dose, and feeding plan. Basal metabolic rate may actually be decreased in unregulated diabetic patients because of decreased triiodothyronine (T3) levels. The thyroxine (T4)-deiodinase system that converts T4 to T3 is directly responsive to blood insulin levels (i.e., as blood insulin levels decrease, T3 levels decrease). Basal metabolic rate is directly responsive to T3 concentrations and therefore balances energy expenditure, presumably with energy (glucose) intake. T4 levels may be decreased, and caution should be taken not to interpret a low T4 level at this time as being diagnostic of hypothyroidism (euthyroid sick syndrome). For most animals within the ideal BCS range (4 to 6), feeding at the daily maintenance energy requirement (DER) in conjunction with adequate control of

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DM should effectively maintain a desired BW. It is best to initially calculate DER as a multiple of resting energy requirement (RER) based on the standard formulas for normal animals. A reasonable initial estimate of DER is 1.6 × RER for neutered dogs and 1.8 × RER for intact dogs (RER is 70 × [BW in kg]0.75, or 15 kcal/lb BW).56 Patients should be reevaluated monthly and food amounts adjusted as indicated by body condition and weight. After medical problems have been stabilized, a conservative weight-loss protocol may need to be instituted for overweight animals. Frequent monitoring and readjustment should be the norm rather than the exception in weight-loss programs for animals with such concurrent diseases as DM. A weekly loss of 1% to 4% of weight is considered safe, although it may take several months to a year to achieve an ideal weight in severely obese animals.57,58

Fat In diabetic dogs, abnormalities in lipid metabolism are manifested as increased serum concentrations of triglycerides, cholesterol, lipoproteins, chylomicrons, and free fatty acids. Lipid derangements can occur for several reasons but appear to be related to decreased insulin levels; most serum lipid values improve with insulin and dietary therapy (decreased fat, increased fiber).3 Cardiovascular disease accounts for the majority of deaths in humans with diabetes; canine patients, however, are more likely to suffer from pancreatitis associated with persistent hyperlipidemia.59–61 Although diets high in fiber (10% to 25% DMB) have decreased overall dry-matter digestibilities, fat digestibility remains above 90% when the fiber source is powdered cellulose.39,62 Therefore feeding a lower-fat (12% or less DMB), high-fiber diet is recommended to minimize the risk of pancreatitis, control some aspects of hyperlipidemia (chylomicrons), and reduce overall caloric intake to favor weight loss or maintenance. Major initial benefits reported with omega-3 fatty acid supplementation in humans with DM included markedly lower serum triglycerides; moderately decreased levels of cholesterol; a general increase in highdensity lipoprotein concentrations; and reduced blood pressure, viscosity, and platelet aggregation. In addition, all of these benefits potentially reduce the risk of atherosclerosis, coronary heart disease, and stroke.34 However, some diabetic patients that consume omega-3 fatty acids have increased levels of blood glucose, glycohemoglobin, low-density lipoprotein, and cholesterol.63 Because there is little cardiovascular risk associated with canine diabetes, the use of omega-3 fatty acids may not be warranted given the potential loss of glycemic control.

GLP-1 ■ BASAL METABOLIC RATE ■ LIPID DERANGEMENTS ■ OMEGA-3 FATTY ACIDS

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Protein When insulin levels are low or ineffective, the body “assumes” that blood glucose is low and begins to catabolize heart and skeletal muscle to supply amino acids to gluconeogenesis as a substrate for the production of “new glucose.” As insulin levels fall, serum glucagon increases. Glucagon decreases protein synthesis and increases amino acid membrane transport, protein catabolism, and amino acid conversion into glucose via gluconeogenesis. Studies completed in humans, rats, and dogs demonstrate that the catabolism of skeletal muscle is directly proportional to serum levels of amino acids, insulin, and glucagon. It is therefore important to provide protein of a quality and in a quantity that will meet the amino acid requirements of the diabetic animal, which may have increased skeletal catabolism and urinary losses of amino acids during periods of low insulin/high glucagon blood levels. Protein quality is the quantity and ratio of the essential and nonessential amino acids and digestibility and metabolizability of dietary protein. Food for diabetic dogs should contain approximately 18% to 25% protein DMB, preferably from an animal source and with a true protein digestibility above 85%. Dietary protein has been implicated in the pathogenesis of canine diabetic renal disease, and restricting protein has been recommended to retard the progression of the nephropathy; however, there is currently very little scientific data upon which to modify protein recommendations for human or canine diabetics.64 Micronutrients Although high-fiber (approximately 10% DMB) diets do decrease overall diet dry-matter digestibility and have been reported to inhibit the absorption of some ingested minerals, instances of clinically important deficiencies of vitamins or minerals induced by dietary fiber have not been found in humans or dogs. In general, when a complete and balanced diet is consumed in quantities sufficient to maintain optimum BW, there is no need for additional vitamin or mineral supplementation. However, patients with uncontrolled diabetes, on weight-loss programs, or with other concurrent diseases are at greater risk of developing a micronutrient imbalance when consuming home-cooked foods (hamburger and rice) or single-item diets (e.g., eating just baby food or just chicken). Patients with poor appetites should be fed a specifically formulated homemade recipe using ingredients that dogs will consistently consume and be given a vitamin–mineral supplement known to be in proper balance with the recipe (Table I). Macrominerals. Increased urine output associated with DM may increase obligatory loss of such elec-

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TABLE I Balanced Generic Homemade Diet (1000 kcal/day) for a 40-lb Adult Dog with Diabetesa As-Fed Formulation Ingredient

Amount (g/day)b

Rice (long-grain, white, cooked) 332 Chicken (dark meat, cooked) 202 Fiber (Fiber One Cereal®, General Mills, Inc, Minneapolis, MN)c 53 d Vitamin/mineral supplement 16 (1.5 tablets) Bonemeal 16 ® Salt (Morton’s Light Salt, 6 Morton International, a subsidiary of Rohm and Haas, Philadelphia, PA) Fat (corn oil) 5 Daily total 630 Dry-Matter Analysis Compared with AAFCO Allowances for Adult Dogs Nutrient AAFCO Homemade diet Dry matter (%) Energy (kcal/100 g) Protein (%) Fat (%) Fiber (%) Calcium (%) Phosphorus (%)

≥12 350 18 5 None 0.60–2.5 0.50–1.6

aFormulated

43 366 25 10 10 1.6 1.1

using Mixit-Win, version 2.34, 1999, Agricultural Software Consultants, Inc., San Diego, CA, and Food Processor® Plus, Diet Analysis Software, version 5.03, 1990, ESHA Research, Inc., Salem, OR. bApproximate conversions between grams and dry volumes: 1 tsp = 5 g, 1 tbsp = 15 g, 1 cup = 250 g. Owners should be encouraged to use a dietary gram scale to weigh these foods consistently. All items should be mixed together in a blender to prevent dogs from picking out single food items. When a homemade diet is fed, the patient should be examined by a veterinarian regularly. Vitamin/mineral supplements should not be cooked, heated, or stored with the food; instead, they should be kept separate from the food and administered just before, during, or after a meal to ensure proper dosing. Overall digestibility and availability of the vitamin and mineral supplements are improved when using a United States Pharmacopoeia (USP)–labeled product and when the product is in the small intestine along with a meal composed of proteins, fats, and carbohydrates. c To increase fiber content, Post® 100% Bran™ (Kraft Foods Inc, Northfield, IL) can be used; to decrease fiber content, Kellogg’s® All Bran® (Kellogg Company, Battle Creek, MI) can be used. d Theragran M ® (Mead Johnson and Co., Evansville, IN) adult vitamin/mineral tablet. AAFCO = Association of American Feed Control Officials.

GLUCONEOGENESIS ■ AMINO ACIDS ■ PROTEIN QUALITY AND DIGESTIBILITY

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trolytes as sodium, potassium, chloride, calcium, and phosphorus. A ketoacidotic diabetic may have wholebody potassium and/or phosphorus deficits despite normal or near-normal serum concentrations. The ketoacidotic state hastens the urinary loss of cations and moves intracellular potassium into extracellular spaces. Correction of acidosis with fluid, glucose, and insulin can cause a precipitous decline in serum potassium.65 When serum calcium, potassium, or phosphate concentrations are difficult to maintain, measuring serum magnesium and/or giving a loading dose of magnesium and then providing supplemental magnesium should be considered.66,67 Body magnesium stores are depleted via an osmotic diuresis when hyperglycemia is poorly controlled.68,69 In a magnesium-deficient patient, insulin sensitivity may improve with supplementation but the clinical signs of diabetes are not expected to resolve with dietary repletion of magnesium alone. In general, treatment of DM that results in glycemic control will also correct macromineral deficiencies if the patient is fed an adult maintenance food; however, excess dietary phosphorus should be avoided in dogs with renal impairment. Foods that meet AAFCO recommendations for adult maintenance should supply adequate amounts of macrominerals to compensate for the increased ongoing losses in controlled diabetic dogs. Microminerals. Changes in micromineral nutrition status associated with DM have been evaluated in many species. Zinc plays a clear role in the synthesis, storage, and secretion of insulin as well as the conformational integrity of insulin. Whole-body stores of zinc are usually low in diabetic humans and rats, which affects the ability of islet cells to produce and secrete insulin and compounds the problem.70,71Diabetic complications in humans are postulated to be related to increased intracellular oxidants and free radical production associated with decreases in intracellular zinc and zinc-dependent antioxidant enzymes.72 The relationship among diabetes, insulin, and zinc is complex with no clear cause and effect. The exact mechanisms underlying altered zinc metabolism in diabetes have not been adequately identified to make specific recommendations. Chromium (Cr) is an essential nutrient involved in normal carbohydrate and lipid metabolism; requirements are postulated to increase with increased glucose intolerance and diabetes. Cr supplementation improves the glucose–insulin system in humans with hypoglycemia, hyperglycemia, diabetes, and hyperlipemia.73 Cr improves insulin binding, insulin receptor numbers, insulin internalization, beta-cell sensitivity, and insulin receptor enzymes with overall increases in insulin sensitivity.74 Cr has no known enzymatic cofactor function,

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but it may exist as a complex with nicotinic acid and amino acids to form a “glucose tolerance factor” that may aid insulin action. Chinese subjects with NIDDM receiving 500 µg of Cr twice daily for 2 and 4 months had improved fasting and 2-hour insulin values.75 However, these beneficial effects were associated with Cr intakes higher than the upper limit regarded as safe and adequate in the United States.76 Because investigations evaluating Cr supplementation in canine diabetics have not been done, Cr supplementation is at best intriguing based on information from other species and from normal dogs. Substantiation of micromineral benefits in diabetics has been confounding in most species.77 Improvement may occur in malnourished patients receiving supplementation, but no micromineral has been implicated in the pathogenesis of DM. For example, manganese deficiency has also been associated with alterations in insulin secretion, carbohydrate and lipid metabolism, and impaired glucose utilization; repletion of manganese in deficient animals restores normal glucose tolerance and improves insulin secretion, yet treatment of diabetic subjects with manganese supplements had no impact on glycemic control.78 Iron overload can cause glucose intolerance due to pancreatic damage secondary to hemochromatosis; however, iron status does not seem to play a role in the pathogenesis of DM.79 Selenium deficiency has also been associated with changes in glucose tolerance or insulinlike activity but does not appear to play a role in the development or manifestation of DM.68 In general, until proven otherwise, providing a food with microminerals supplied according to AAFCO recommendations for an adult maintenance diet should suffice for most patients with DM. For clients interested in antioxidant supplementation, an over-the-counter human antioxidant formulationc (1 tablet/dog/day) containing zinc, selenium, copper, and manganese is well within the AAFCO allowances. Vitamins. DM may increase or decrease vitamin balance, and, conversely, vitamin status may affect the development and manifestations of DM. Much of the investigative work in this area is controversial and needs clarification but probably involves protecting diabetics cAntioxidant vitamin and mineral supplement containing 5000 IU vitamin A (as beta-carotene), 250 mg vitamin C, 200 IU vitamin E (as α-tocopherol), 7.5 mg zinc, 15 µg selenium, 1 mg copper, and 1.5 mg manganese per tablet and that carries a United States Pharmacopoeia (USP) label (Spring Valey Antioxidant Vitamins, Pharmavite Corp., Mission Hill, CA). When recommending supplements, it is advisable to use products that carry the USP label, which indicates a standardized formulation and ensures product disintegration, weight, purity, and potency.

KETOACIDOSIS ■ MAGNESIUM ■ ZINC ■ CHROMIUM

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from oxidative and free radical damage.80–82 Supplementation of vitamins C and E in humans at a rate of two to 10 times the recommended daily allowance has been suggested based on reported benefits in a few small trials and because these supplements are generally regarded as safe and affordable.83 For clients interested in antioxidant supplementation, an over-the-counter human antioxidant formulationc (1 tablet/dog/day) containing beta-carotene, vitamin C, and α-tocopherol is well within the AAFCO allowances. In diabetic patients requiring intravenous fluid therapy to correct polyuria/polydipsia, water-soluble B-vitamin supplements should be administered until hyperglycemia is controlled. Based on the daily vitamin recommendations for adult dogs and the vitamin concentrations available in most solutions,d a recommended dose of 1 ml of B vitamins per 100 kcal DER will meet, and in some cases exceed, a dog’s daily B-vitamin (except for B12) requirements by severalfold. Most formerly healthy pets and humans, however, have hepatic stores of B12 that are sufficient for 3 to 5 years.

Food Type and Digestibility Soft–moist canine foods contain increased amounts of humectants (e.g., corn syrup, sucrose, dextrose, cane molasses, propylene glycol) to control water activity or microbial growth and thus tend to have a hyperglycemic effect compared with canned or dry foods.84,85 Fructose in the form of sucrose (or high-fructose corn syrup) may also be used as a humectant in commercial semimoist foods. The potential effects of fructose in foods for dogs with DM have not been evaluated. Soft–moist foods also have the highest digestible energy content because highly digestible carbohydrate sources are used. Canned and dry foods tend to have lower drymatter and energy digestibilities and thus are preferred for diabetic pets. Dry foods may have a slight advantage over canned foods in controlling postprandial blood glucose levels because dry foods empty from the stomach more slowly than do canned foods; this is because stomach contents must have a high water content before passing into the duodenum. A fixed-, as opposed to an open-, formula diet is also important in the overall successful management of diabetic dogs (Table II). “Open-formula diets” are typical of those purchased from the grocery or pet store; the exact ingredient formulation varies with market prices. Hence glycemic index and postprandial glucose response will vary as the formulation varies over time (e.g., unit to dProduct

containing 50 mg thiamin, 2 mg riboflavin, 100 mg niacin, 2 mg pyridoxine, 10 mg pantothenic acid, and 0.4 µg vitamin B12 per ml (B-Vitamin Complex, Butler Co., Columbus, OH).

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unit). A consistent “fixed” dietary formula eliminates this source of variables and need not be examined when glycemic control is poor or weight begins to change. Highly digestible foods (i.e., those for which more than 90% of dry matter is digested) make it more difficult to control serum glucose and should be avoided. Diets containing 8% to 18% crude fiber (DMB) typically have dry-matter digestibility coefficients between 70% and 80%. Diets with less than 70% dry-matter digestibility and low fat concentrations may not adequately maintain optimal BW. Dogs with difficult appetites that are fed homemade diets, table food, vegetarian diets, or single-food items are at greater risk of developing subclinical nutritional imbalances. Foods designed, formulated, or prepared by owners are rarely nutritionally complete, balanced, or consistent. These patients may not only have protein–calorie malnutrition but are more likely to have several vitamin and mineral imbalances concurrently (e.g., calcium and tracemineral deficiencies if no supplements are used and/or subclinical vitamin A and D toxicities if liver is fed). A well-formulated homemade diet (Table I) composed of a meat and carbohydrate source readily consumed by the patient is preferable to unpredictable consumption of various pet foods or single food items. Once a homemade recipe is determined to be successful (i.e., consistently made by the owner and consumed by the dog), insulin dosage can be determined and adjusted.

Feeding Schedule Because insulin is usually administered in conjunction with meals, feeding methods must complement pharmacologic protocols. Feeding must be coordinated with administration of exogenous insulin. The goal is to have glucose slowly absorbed when insulin levels are adequate, thereby minimizing postprandial hyperglycemia. Ideally, small meals fed at the time of insulin administration and at regular intervals throughout the day result in minimal hyperglycemia.24,86 Most owners can feed two equal-sized meals daily: one at the time of insulin injection and the other 8 to 10 hours later.22 For animals with poor glycemic control, feeding should be divided into three or more smaller meals to help maintain serum glucose concentrations within an acceptable range.1,24,87 For example, patients receiving two insulin injections daily and fed four equal small meals are fed a meal with each insulin injection; the other two meals are spaced equally throughout the day. REASSESSMENT Diabetes mellitus can be frustrating to manage. The long-term side effects of poor glycemic control seen in humans are uncommon in dogs.88 Clinical signs of im-

B-VITAMIN SUPPLEMENTS ■ HUMECTANTS ■ POSTPRANDIAL HYPERGLYCEMIA

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20TH ANNIVERSARY

Compendium August 1999

TABLE II Approximate Nutrient Profiles of Foods Marketed for Canine Diabetics versus Average Grocery or Pet Store Brands Diet Type

Calories a (kcal)

Fat (DMB)

Protein) (DMB)

NFE b (DMB)

Crude Fiber (DMB)

Fiber Type

Dry Canned

223 347

6.9 12.0

16.7 16.5

55.2 53.9

16.8 13.5

Insoluble Insoluble

Eukanuba Veterinary Diets® Nutritional Weight Maintenance Formula™ GlucoseControl™ (The IAMS Company, Dayton, OH)

Dry

253

8.0

29

48.3

2.9

Soluble

CNM OM-Formula® Canine Diet (Pro-Visions, Pet Specialty Enterprises, a division of Ralston Purina Company, St. Louis, MO)

Dry Canned

276 204

6.0 8.4

22.8 44.1

48.6 21.7

15.2 19.2

Mixedc Mixedc

IVD™ Select Care™ Canine Hifactor Formula (Innovative Veterinary Diets, Newport, KY)

Dry Canned

278 282

9.8 7.9

23.7 24.7

43.9 47.6

15.8 15.9

Mixedc Mixedc

Dry

223

7.5

20.0

48.8

4.5

Mixedc

Dry Canned

350 450

11.8 27.4

23.6 41.9

52.8 18.4

3.7 1.5

Mixedc Mixedc

Product Name Hill’s Prescription Diet® Canine w/d® (Hill’s Pet Nutrition, Topeka, KS)

Waltham® Veterinary Diet Canine High Fiber (Waltham Company, Vernon, CA) Grocery or pet store brands (n = 33) aCalories

per 8 oz of dry food or 14 oz of canned food. as a measure of carbohydrates. cA mixture of soluble and insoluble types. Proper ratio for diabetics is unknown. DMB = dry-matter basis; NFE = nitrogen-free extract. bNFE

provement are indicated by decreased water intake, urination, and food intake; achievement of weight goals; and a generalized increased thriftiness. Conversely, persistent polyuria, polydipsia, polyphagia, urinary tract infections, and inability to achieve weight goals indicate poor glycemic control. Response to treatment can be assessed through careful questioning of the owner, by performing a 12- to 24-hour blood glucose curve, and by measuring glycosylated hemoglobin.89 Exercise should be consistent from day to day because large variations in activity level may affect glycemic control. Dietary changes (e.g., increasing or decreasing fiber

levels) or weight changes (intentional or unintentional) may require adjustments in the insulin dosage to maintain glycemic control. It is also important to monitor and control concurrent disease processes commonly associated with diabetes. Reassessment may take place every 3 to 4 months if the animal is stable and reportedly doing well; if the patient should become symptomatic, however, reassessment may be necessary every 1 to 2 weeks until control has been reestablished. Regardless of how frequent the recheck visits occur, the owner should always be asked to describe the diet being consumed by the dog and the feeding schedule.

EVALUATING TREATMENT RESPONSES ■ REASSESSMENT SCHEDULES

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About the Author Dr. Remillard is the staff nutritionist at the Angell Memorial Animal Hospital, Boston, Massachusetts. She is a Diplomate of the American College of Veterinary Nutrition.