VETERINARY PRACTICE GUIDELINES 2018 AAHA Diabetes Management Guidelines .

2018 AAHA Diabetes Management Guidelines for Dogs and CatsClinical signs of DM will typically be present when there is persistent hyperglycemia and glucosuria. Clinical signs are usuallystance. If ketosis is present, a sweet odor may be noticed on thebreath of the pet.absent with glucose levels ranging between the upper reference levelsLaboratory evaluation includes a basic minimum databaseand the renal threshold values noted above. Blood glucose concentra-(CBC, chemistry with electrolytes, urine analysis with culture, trigly-tions in these ranges may occur for a variety of reasons, includingcerides, UPC, BP, and T4 level in cats). Typical findings includestress hyperglycemia in cats, corticosteroid administration, the pres-hyperglycemia, glucosuria, and stress leukogram, as well as increasedence of concurrent insulin-resistant disease (hyperadrenocorticism,cholesterol and triglycerides. Dogs frequently show increased levelsobesity), or as part of the early stage of developing DM.of alkaline phosphatase (ALP) and alanine aminotransferase. Cats,Dogs and cats in the early stages of nonclinical DM appearhowever, show more variability in the presence of a stress leukogramhealthy, have a stable weight, and are usually identified as a result ofand elevated ALP. Elevated liver enzymes in a cat may warrant fur-routine laboratory evaluation. They do not have clinical signs of DM.ther evaluation for concurrent liver disease.10 Pancreatitis is a com-Stress hyperglycemia needs to be ruled out, as well as correction ofmon comorbidity and may need to be addressed.10any insulin-resistant disorders and discontinuation of drugs associatedCats and dogs with diabetic ketoacidosis may show very ele-with impaired insulin release or sensitivity. Reassessing BG or moni-vated BG concentrations, azotemia, and decreased total CO2 second-toring urine glucose (UG) levels once the patient is no longer stressedary to metabolic acidosis, osmotic diuresis, dehydration, and, in theat home or measuring serum fructosamine concentrations may helpcase of profound hyperosmolarity, coma.differentiate between stress hyperglycemia and DM and determine iffurther action should be taken.Urinalysis will reveal the presence of glucose. It may also showthe presence of protein, ketones, bacteria, and/or casts. Because a uri-Clinical DM is diagnosed based on persistent glucosuria, persis-nary tract infection cannot be ruled out by the absence of an activetent hyperglycemia, and presence of characteristic clinical signs.urine sediment, a urine culture should always be performed in gluco-Documentation of an elevated serum fructosamine concentrationsuric animals, because infection is commonly present.may be necessary to confirm the diagnosis in cats.9 Fructosamine lev-If thyroid disease is suspected in a dog, it is best to perform thy-els may be only mildly elevated with lower levels of persistent hyper-roid testing after DM is stabilized because of the likelihood of euthy-glycemia and should be interpreted as part of a complete evaluation.9roid sick syndrome. Cats over 7 yr of age with weight loss and PPAnimals with clinical DM will present with PU, PD, PP, andweight loss. Some may present with lethargy, weakness, and poorshould be tested for hyperthyroidism because DM and hyperthyroidism cause similar clinical signs and can occur concurrently.body condition. Dogs may have cataracts, and cats may present witha complaint of impaired jumping and abnormal gait. Some patientswill present with systemic signs of illness due to diabetic ketosis/ketoacidosis, such as anorexia, vomiting, dehydration, and depression.The initial evaluation of the diabetic dog and cat should: Assess the overall health of the pet (history including diet and concurrent medications, and a complete physical exam). Identify any complications that may be associated with the disease(e.g., cataracts in dogs, peripheral neuropathy in cats). Identify any concurrent problems often associated with the disease(e.g., urinary tract infections, pancreatitis). Identify any conditions that may interfere with the patient’s response totreatment (e.g., hyperthyroidism, renal disease, hyperadrenocorticism). Evaluate for risk factors such as obesity, pancreatitis, insulinresistant disease, diabetogenic medications, and diestrus in femaledogs.TreatmentThe mainstay of treatment for clinical DM in dogs and cats is insulinalong with dietary modification. Goals include controlling BG belowthe renal threshold for as much of a 24 hr period as possible, whichwill improve clinical signs of DM, and avoiding clinically significanthypoglycemia.Treatment for CatsIn cats, diabetic remission is a reasonable goal.4 Successful management of DM in cats consists of minimal or no clinical signs, ownerperception of good quality of life and favorable treatment response,avoidance or improvement of DM complications, (specifically, diabetic ketoacidosis and peripheral neuropathy), and avoidance ofPhysical exam results of the diabetic cat or dog can be relativelyhypoglycemia. Predictors of diabetic remission in cats includenormal early in the course of the disease. As the disease persists with-achieving excellent glycemic control within 6 mo of diagnosis, usingout treatment, the physical exam may reveal weight loss, dehydra-intensive home monitoring, discontinuation of insulin-antagonizingtion, poor hair coat, abdominal pain if concurrent pancreatitis ismedications, and use of insulin glargine (Lantus) or detemir (Leve-present, or cataracts. Some cats with longstanding hyperglycemia canmir) along with a low-carbohydrate diet.4 A clinically sick, diabetic,develop peripheral neuropathy, which manifests as a plantigradeketotic cat should be hospitalized to initiate aggressive therapy. If 24JAAHA.ORG3

hr care is not feasible, the patient should be referred to an emergencyprogression to clinical DM. Subclinical DM is not commonly identi-or specialty hospital. Adjunct therapy for diabetic cats should includefied in the dog. Most dogs in the early stages of naturally acquiredenvironmental enrichment using creative feeding tools such as fooddiabetes (i.e., not induced by insulin resistance) quickly progress topuzzles, particularly for obese cats. Oral hypoglycemic drugs are nei-clinical DM and should be managed using insulin.ther recommended nor considered appropriate for long-term use.Veterinarians use a variety of insulin products, but only two areTheir use is considered temporary and only if combined with dietarypresently approved by the FDA for use in dogs and cats. A porcinemodification if the owner refuses insulin therapy or is consideringlente product (porcine zinc insulin suspension, Vetsulin) is approvedeuthanasia for the pet.for both species. Human recombinant protamine zinc insulin, orThe initial approach to management of the diabetic cat is to ini-PZI (ProZinc) insulin, is also FDA approved for both cats (as oftiate insulin therapy with glargine (Lantus) or protamine zinc insulin2009) and dogs (as of 2019). It is considered by clinicians as a(PZI; ProZinc) at a starting dose of 1–2 units (U) per cat q 12 hr.long-acting insulin. Because of limited controlled, comparative studies,The decision to monitor BG on the first day of insulin treatment ismost experts’ recommendations are based on a combination of clini-at the discretion of the veterinarian. The goal of first-day monitoringcal and anecdotal experience. The guidelines Task Force strives tois solely to identify hypoglycemia. The insulin dose should not bemake evidence-based recommendations when data are available.increased based on first-day BG evaluation. If monitoring is elected,However, the ability to make specific recommendations based on dif-measure BG q 2–4 hr for cats on PZI and q 4 hr for those on glargineferences and preferences between veterinary insulin products is lim-for 10–12 hr following insulin administration. Decrease the insulinited. Members of the Task Force most commonly use porcine lentedose by 50% if BG is ,150 mg/dL any time during the day. Treatinsulin (Vetsulin) in dogs and glargine (Lantus) in cats as their firstthe diabetic cat as an outpatient after the first day of monitoring, ifchoice, recognizing that other acceptable options used by many clini-elected, and plan to reevaluate in 7–14 days regardless of whethercians include Neutral Protamine Hagedorn (NPH; Humulin N, Novo-BG values are monitored on the first day. Immediately re-evaluate iflin N) in dogs and PZI (ProZinc) in cats and dogs.clinical signs suggest hypoglycemia or if lethargy, anorexia, or vomit-Although compounded insulin is available, its use is not recom-ing is noted. See Algorithm 2, “Monitoring blood glucose levels inmended because of concerns about production methods, diluents,diabetic dogs and cats,” and Table 1, “Insulin Products,” for moresterility, and insulin concentration consistency between lots. A studyinformation on monitoring and dosing.comparing commercially available insulin with its compoundedcounterparts showed that the manufactured insulin met all US Phar-Treatment for Dogsmacopeia requirements and only 1 of 12 compounders met US Phar-Treatment of clinical DM in the dog always requires exogenous insulinmacopeia specifications at all time points. The variability betweentherapy. U-40 pork lente (porcine zinc insulin suspension; Vetsulin) iscompounded insulins was also significant enough to have clinicalthe Task Force’s first-choice recommendation for dogs using a startingconsequences.11 It is also not recommended to dilute insulin becausedose of 0.25 U/kg q 12 hr, rounded to the nearest whole U. The dura-dilution can produce unpredictable results, alter insulin efficacy, andtion of action is close to 12 hr in most dogs, and the amorphous com-result in bacterial contamination.5,12ponent of the insulin helps to minimize postprandial hyperglycemia.As with cats, a clinically sick, diabetic, ketotic dog should be admittedfor 24 hr care for aggressive therapy of the ketosis and other underlying illnesses. A critical initial goal of treatment is avoidance of symptomatic hypoglycemia, which may occur if the insulin dose isincreased too aggressively. Feed equal-sized meals twice daily at thetime of each insulin injection. In contrast to cats, diabetic remissionoccurs only rarely in dogs with naturally acquired DM. Performing anovariohysterectomy in intact diabetic dogs will support remission,regardless of the underlying cause of the diabetes.In dogs with subclinical DM, investigate and address causes ofinsulin resistance, including obesity, medications, hyperadrenocorticism and diestrus in intact females. Initiate dietary therapy to limitpostprandial hyperglycemia (see “Dietary Therapy Goals and Management” for additional information.) Evaluate the dog closely for4JAAHA 54:1 Jan/Feb 2018Insulin Products (see Table 1)1. Lente (U-40 porcine zinc insulin suspension; Vetsulin, Merck Animal Health) is an intermediate-acting insulin commonly used bythe Task Force in dogs. It is FDA approved for use in dogs and cats.It has a close to 12 hr duration of action in most dogs and is usefulfor minimizing postprandial hyperglycemia.2. Glargine (U-100 human recombinant; Lantus, Sanofi) is alonger-acting insulin commonly used by the Task Force in catsbecause it has an adequate duration of action in most diabetic cats.Several studies have demonstrated that glargine is effective for controlling blood sugar levels in diabetic cats and achieving high remission rates.12 Glargine can also be used in dogs. It is a human analoginsulin with modifications that provide variable solubility at different pHs. Glargine is soluble at a pH of 4.0, the pH at which it issupplied and stored, but in the neutral pH of the body’s blood orsubcutaneous tissues it forms microprecipitates, facilitating slowabsorption after injection. This results in rapid onset and long duration of action. Glargine is sometimes described as a “peakless”

JAAHA.ORGinsulinorigin humanRecombinant DNAinsulinLevemir (Novo Nordisk)Humulin (Lilly)Novolin (Novo Nordisk)Health)insulinRecombinant humanIngelheim AnimalProZinc (Boehringerorigin humanRecombinant DNANeitherNeitherCats, dogsDuration 12–24 hr.Nadir 12–14 hr.CatsU-100higher end for a small dog.short duration of activity.0.10 U/kg q 12 hr.Dogsq 12 hr if BG , 360 mg/dL.used in dogs and cats; suitable forVery potent in dogs (caution required);dogs in which NPH and lente haveU-100starting dose for a large dog andConsider using the lower end of thecats due to short duration of effect.Option for dogs; rarely recommended forapproved by the FDA.Once-daily dosing in dogs is nowBG . 360 mg/dL, and 0.25 U/kg0.5 U/kg q 12 hr ifCats0.25–0.5 U/kg q 12 hr.14Nadir 0.5–8.5 hr.14Duration 4–10 hr.DogsDogs0.5 U/kg q 12 hr should be reservedfor potentially challenging diabetics.0.25 U/kg q 12 hr is appropriate andthat for dogs, a starting dose ofused in dogs. Some clinicians believeCommonly used in cats; not commonlydogs(U-300 available); potential option inCommonly used in cats; use only U-1000.5 U/kg q 24 hr.recommends a starting dose ofNOTE: In dogs, the manufacturerinsulin bottle is required.available for dogs and cats. Shakingeither 0.5 U or 1 U increments)Commonly used in dogs; injection pens (inComments0.5–1 U/kg q 24 hr.150.25–0.5 U/kg q 12 hr.DogsNadir 8–12 hr.23DogsDuration 8–24 hr.14U-40U-100, U-300U-40Concentration231–2 U per cat q 12 hr.Nadir 5–7 hr.Cats0.3 U/kg q 12 hr.Duration 12–20 hr.CatsDogs12 hr if BG , 360 mg/dL.DogsNadir 6–10 hr.22BG . 360 mg/dL and 0.25 U/kg q0.5 U/kg q 12 hr ifCatsDuration 12–24 hr.CatsNadir 12–14 hr.Not approved0.25–0.5 U/kg q 12 hr.Nadir 1–10 hr.21Duration 10–24 hr.21Dogs(not to exceed 3 U per cat).50.25–0.5 U/kg q 12 hrCatsStarting DoseDogsDuration 8–14 hr.20Nadir 2–8 hr.CatsPeak Action (Nadir) andDuration of EffectinsulinLantus (Sanofi)Dogs, catsVeterinary FDAApproval Statusorigin humanRecombinant DNAHealth)Vetsulin (Merck AnimalBrand Name(Manufacturer)Abbreviations: BG, blood glucose; NPH, Neutral Protamine Hagedorn; PZI, protamine zinc insulin; U, units.Detemir (long-acting)acting)NPH (intermediate-PZI (long-acting)Glargine (long-acting)suspensionPorcine zinc insulinLente (intermediate-acting)Product DescriptionInsulin ProductInsulin Products Commonly Used in Dogs and CatsTABLE 12018 AAHA Diabetes Management Guidelines for Dogs and Cats5

insulin, although peakless does not mean an absence of a nadir incats but rather refers to glucose utilization rates.4 In dogs, a flatblood glucose curve (BGC) may be seen, so glargine can be referredto as a peakless insulin in that species.133. PZI (U-40 human recombinant protamine zinc insulin; ProZinc,Boehringer Ingelheim Animal Health) is considered by clinicians asa long-acting insulin, and is FDA approved for use in cats and dogs.In field studies in cats, mean time of the BG nadir was between 5and 7 hr and the duration of action was 8–24 hr, which was deemedan appropriate duration of action by the FDA.14 The results suggested that ProZinc should be administered twice daily in most diabetic cats to maintain control of glycemia.14 This insulin is used inboth cats and dogs, although it is less commonly used in dogs. Protamine zinc insulin can have a prolonged duration of action in dogsand may be tried on once-daily dosing schedule to minimize thechances of clinically significant hypoglycemia and/or the Somogyiphenomenon.154. NPH (U-100 human recombinant; Neutral Protamine HagedornHumulin N, Lilly or Novulin N, Novo Nordisk) is anintermediate-acting insulin that is used in dogs. The Task Forcedoes not recommend use of this insulin in cats due to its shortduration of action. The duration of action of NPH in dogs is often,12 hr. Some dogs can have postprandial hyperglycemia whentreated with this insulin.16 A combination form of NPH plus regularinsulin (70 NPH/30 Regular) is available that may be suitable if thedog has an appropriate duration of action (8–12 hr) with an earlynadir or postprandial BG spike. Some clinicians use this product indogs who develop postprandial hyperglycemia when being treatedwith NPH.5. Detemir (U-100 human recombinant; Levemir, Novo Nordisk) is along-acting insulin that can be used in both dogs and cats. Detemiris a human analog insulin engineered with modifications that allowit to bind albumin with high affinity in the subcutaneous and intravascular spaces, prolonging the insulin’s absorption.4,17 This prolonged absorption gives detemir a long and steady duration ofaction and less variability in biological activity.4 Detemir has a verysimilar profile to glargine (Lantus) in cats in terms of BG controland remission rates.12 However, cats receiving detemir require alower median maximal dose than cats receiving glargine (1.75 U percat for detemir versus 2.5 U per cat of glargine).18 Dogs are verysensitive to the higher potency of this insulin and require lowerstarting doses (0.1 U/kg).19 Particular caution must be used in smalldogs because they are more likely to have more frequent hypoglycemic excursions.19estimated ideal body weight of the cat and BG levels (0.5 U/kg q 12hr if BG . 360 mg/dL and 0.25 U/kg q 12 hr if BG , 360 mg/dL).This equates to 1 U q 12 hr in the average cat. Even in a very largecat, the starting dose of insulin should not exceed 2 U per cat q 12hr. Most cats are well regulated on insulin at an average dose of 0.5U/kg q 12 hr, with a range of 0.2–0.8 U/kg. With PZI (ProZinc), atypical starting dose is 1–2 U per cat.In diabetic dogs, the Task Force recommends a starting dose of0.25 U/kg of lente (Vetsulin) q 12 hr, rounded to the nearest wholeU. Most dogs are well controlled on insulin at an average dose of0.5 U/kg q 12 hr with a range of 0.2–1.0 U/kg.See Table 1 for more detailed information on alternative dosingand insulin selections for both dogs and cats.It should be noted that product pharmacokinetics vary depending on insulin type, product formulation, and the individual patient’sresponse. One should employ reasonable dosing flexibility based onindividual patient response and the owner’s compliance limitations.For example, a 12 6 2-hour window on each side of the dosinginterval and occasional missed doses are considered acceptable bymost practitioners. Other insulin types and other therapeutics can beused in dogs and cats based on the patient’s response to first-lineinsulin therapy and associated recommendations, as discussed in the“Monitoring” section of the guidelines.Although none of the insulin products available for use in dogsand cats have canine- or feline-specific amino acid sequences, antiinsulin antibodies do not appear to cause a significant clinical problem.Insulin manufacturers generally recommend discarding openedand used bottles of insulin after 4–6 wk or until the date of expiration listed by the manufacturer. However, if handled carefully andstored in the refrigerator, the Task Force is comfortable using insulins beyond the date of expiration (up to 3–6 mo) as long as they arenot discolored, flocculent, or have any change in consistency. Insulinmust be discarded if these changes occur. If a lack of BG regulationis noted 3–6 mo after using a

the American Animal Hospital Association. This document is intended as a guideline only, not an AAHA standard of care. These guidelines and recommendations should not be construed as dictating an exclusive pro-tocol, course of treatment, or procedure. Variations in practice may be warranted based on the needs of the individual patient .