Feline diabetes mellitus_diagnosis treatment

*A companion article on patho-genesis, risk factors, and the dis-tinction between insulin-dependentand non–insulin-dependent dia-betes mellitus is available atCompendiumVet.com.aDr. Ward discloses that she hasreceived financial support fromMorris Animal Foundation andNestlé Purina PetCare Company.

iabetes mellitus is a frequently encoun-tered disease in small animal practice.Both dogs and cats appear to be

affected by the disease at similar frequencies.However, cats, more commonly than dogs,experience a form of diabetes most closelyrelated to type 2 diabetes mellitus in humans.In addition, some cats may not need insulintherapy to regulate their blood glucose.This hasled to the use of the terms insulin-dependentdiabetes mellitus and non–insulin-dependent dia-betes mellitus to describe the clinical entities andtreatment modalities needed in these patients.However, when diagnosing and treating dia-

betic cats, it is important for practicing cliniciansto be aware of the pathogenesis and not simplythe clinical response to insulin therapy, as therationale for various treatment strategies is basedon the type and extent of disease.*

DIAGNOSISA diagnosis of diabetes mellitus is establishedthrough demonstration of appropriate clinicalsigns, persistent hyperglycemia, and glucosuria.When cats with suspected diabetes are evaluated,a thorough history, careful physical examination,complete blood count, serum biochemistry, uri-nalysis (preferably by cystocentesis), and urineculture are part of a minimum database. Giventhat most cats suspected of having diabetes aremiddle aged or older, the serum thyroxine con-centration is also part of the initial diagnosticworkup. Abdominal ultrasonography may beuseful in evaluating diabetic cats because of theprevalence of concurrent pancreatitis. Felinepancreatic lipase immunoreactivity concentra-

COMPENDIUM 626 December 2008

Feline Diabetes Mellitus:Diagnosis,Treatment, andMonitoring*Lori Rios, DVM, PhD,DACVIMVeterinary Referral and Critical CareManakin-Sabot, Virginia

Cynthia Ward, VMD, PhD,DACVIMa

The University of Georgia

D

ABSTRACT: As the prevalence of diabetes mellitus increases in humans, dogs, and cats, advances in

monitoring and treating human disease are being applied to veterinary medicine.This article reviews

the diagnosis and treatment of feline diabetes and discusses the latest developments in treating and

monitoring this disease. New technology is increasing the accuracy of glucose control and assessment

of insulin response, thereby improving the opportunities to achieve diabetic remission in many cats.

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December 2008 COMPENDIUM

Feline Diabetes Mellitus 627CE

tion has also been shown to be a sensitive and specific indicator of felinepancreatitis.1

Clinical SignsThe most common clinical signs of feline diabetes mellitus are polyuria,polydipsia, polyphagia, muscle wasting, and weight loss, although cats mayalso be obese.2 Unkempt haircoat, lethargy, and progressive weakness arealso typical presentations. The polyphagia that is seen in diabetic cats isincompletely understood. Murine models have implicated decreased circu-lating levels of insulin and leptin and increased release of ghrelin as triggersfor diabetic polyphagia.3,4Diabetic neuropathy occurs in approximately 10% of diabetic cats.2 The eti-ology is unknown but may involve alteration in the sorbitol metabolic path-way. Cats display a range of neurologic signs, of which a plantigrade stance ismost evident.The hocks touch the ground when walking, and jumping abilityis often impaired.Hindlimb weakness and muscle atrophy may also be identi-fied. Although the hindlimbs are affected first, signs can progress to the tho-racic limbs. Results of electrophysiologic assessment and analysis of nerve andmuscle biopsy samples reveal decreased motor and sensory nerve conduction

velocity, pervasive Schwann cell injury with myelin deficits, and axonal degen-eration. The severity of clinical signs is correlated with the severity ofhistopathologic lesions.5 There is no specific treatment for diabetic neuropa-thy, but strict glycemic control may improve clinical signs in diabetic cats.6Cataract formation, an important complication of diabetes mellitus indogs, is comparably rare in cats.7

Laboratory FindingsComplete Blood CountResults of the complete blood count in a cat with uncomplicated diabetesare typically within normal limits. Dehydration may lead to a slight increasein hematocrit; conversely, a mild nonregenerative anemia may reflect anemiaof chronic disease. A stress leukogram, characterized by a mature neu-trophilia and mild lymphopenia, may also be present but is not specific forthe diagnosis of diabetes. Concurrent infection or inflammation may also besuspected based on an elevated white blood cell count.

Serum BiochemistrySerum biochemistry abnormalities vary in diabetic cats. Nondiabetic,unstressed cats typically have blood glucose levels less than 171 mg/dL.8 Asingle blood glucose value above the reference range is not sufficient for adiagnosis of diabetes. Persistent hyperglycemia can be difficult to ascertain incats because of their tendency to develop stress hyperglycemia. It has beendemonstrated that healthy cats subjected to a brief stressful event (a bath)

A combination of appropriate insulin therapy and a low-carbohydrate diet may induce diabetic remission in many cats.

COMPENDIUM December 2008

Feline Diabetes Mellitus628 CE

had significant changes in blood glucose, with a meanrise of 79 mg/dL and individual increases as high as 194mg/dL.9 Some of the cats continued to have blood glu-cose values over 200 mg/dL for at least 90 minutes afterthe event. Hyperglycemia as a result of venipuncture canpersist throughout an entire day, invalidating results of anin-hospital blood glucose curve.2If stress hyperglycemia is suspected, keeping the cat inthe hospital in a quiet, stress-free area for several hoursbefore rechecking the blood glucose level may be help-ful. The owner can also be sent home with strips tomonitor urine glucose to document glucosuria. Addi-tionally, a serum fructosamine level can be obtained.Fructosamine is a glycosylated protein that results froman irreversible, nonenzymatic reaction that binds glucoseto amino acid residues, especially albumin, in circula-tion. The concentration of fructosamine in serum is areflection of mean blood glucose level over the preced-ing 1 to 3 weeks. The reliability of the fructosamineassay has been documented in numerous studies.10,11Values above the reference range help confirm the diag-

nosis of diabetes. The normal reference range used atThe University of Georgia Veterinary Medical TeachingHospital is 175 to 400 µmol/L in cats, but referenceintervals vary between laboratories, and each laboratoryshould establish its own reference interval. Hypopro-teinemia and hyperthyroidism have been demonstratedto decrease fructosamine levels in cats.12In addition to hyperglycemia, the most common bio-chemical abnormalities are increases in alanine aminotrans-ferase and alkaline phosphatase and hypercholesterolemia.

UrinalysisGlucosuria is invariably present in diabetic cats.Ketonuria may be present and signals a need to carefullyevaluate for diabetic ketoacidosis. Refractometry resultsmay reflect moderately concentrated urine despitepolyuria because glucose increases urine specific gravityas measured by refractometer. Proteinuria may indicatebacterial infection or damage to the glomerular mem-brane as a consequence of diabetes.2 Red or white bloodcells may also be present. A recent study found that 13%

of diabetic cats had urinary tract infections, with femalecats having an increased risk of infection.13 More thanhalf of culture-positive cats had no clinical signs asreported by their owners. Periodic monitoring with uri-nalysis or urine culture is advisable in diabetic cats.13

TREATMENTOnce the diagnosis is confirmed, veterinarians face a myr-iad of choices for treating and monitoring a diabetic cat.Owner education and compliance are essential for effectivetreatment as well as to minimize the risk of life-threaten-ing complications. Fortunately, most owners are aware ofdiabetes because of its prevalence in humans. Unfortu-nately, personal or anecdotal experience of the disease inhumans can make owners wary of undertaking the chal-lenge of treating their cat. It is a delicate balance for theveterinarian to fully inform clients of the dedication andsurveillance necessary to treat this disease while not undulyfrightening them or making them feel unable to attempthome medical care. Given the time necessary to help own-ers learn to manage this disease, we recommend having a

checklist for the veterinarian to go over to make sure alldetails are covered. Handouts explaining the disease;instructions for drugs, diet, and insulin therapy; urine andblood glucose monitoring instructions; details on emer-gency treatment of hypoglycemia; and emergency numbersfor owners to call should be part of a diabetes packet.The goals of treatment for all diabetic cats are to mini-mize or eliminate clinical signs of the disease, preventhyperosmolality or diabetic ketoacidosis, and decrease theoccurrence of secondary or concurrent diseases such as dia-betic neuropathy, recurrent infections, chronic pancreatitis,and glomerulonephropathy. The most common long-termcomplications in diabetic cats are diabetic neuropathy anddiabetic ketoacidosis.2 In addition, awareness of the risk ofhypoglycemia and the need to carefully adjust treatmentprotocols is essential in monitoring diabetic cats. Ideally, forcats with non–insulin-dependent diabetes mellitus, treat-ment should be designed to reverse glucose toxicity, slow orhalt progressive destruction of β cells, and reverse insulinresistance at the peripheral level so that reduction or elimi-nation of insulin therapy is possible.

Close monitoring is essential to determine which cats may achieve diabeticremission after diet change with or without insulin.


Insulin therapy is frequently the initial starting choicefor treatment and is often necessary and appropriate forlong-term management as well. However, new researchon dietary manipulation and the impact of dietary man-agement may enable more cats to be treated successfullywithout insulin therapy.

Dietary ManagementA decision to begin treatment in diabetic cats withdietary management alone must be carefully based onclinical signs, level of blood glucose dysregulation, andexcellent client compliance. Similarly, initiating insulintherapy and dietary management simultaneously necessi-tates close monitoring because research clearly indicatesthat many cats have a reduction in insulin requirementjust from response to diet change. Cats that do notrespond to dietary management alone may have perma-nently lost significant β-cell function.Dietary manipulation has been a mainstay of diabetictreatment for humans, cats, and dogs. Historically,dietary recommendations for cats have been similar tothose for humans and dogs. In humans and dogs, high-fiber diets are recommended because they have been

demonstrated to decrease postprandial hyperglycemia.Increased levels of fiber decrease intestinal carbohydrateabsorption. One study of the use of a high-fiber dietdemonstrated improved glycemic control in cats com-pared with low-fiber diets.14 However, many of thehigh-fiber diets formulated for cats also contained highlevels of carbohydrates, and there is evidence that catsare not well equipped to handle high carbohydrateloads. Cats, being obligate carnivores, have a differentmetabolism from dogs and humans.In the wild, cats typically eat 10 to 20 small, high-pro-tein meals (e.g., mice) throughout the day. The felinegastrointestinal tract is therefore geared away from car-bohydrate metabolism. Disaccharidase activity in catscannot up-regulate on demand and is only 40% of theactivity in dogs. In dogs, hexokinase and glucokinase areresponsible for glucose phosphorylation in the liver,trapping glucose inside hepatocytes and setting thestage for glucose oxidation. Cats have no hepatic glu-cokinase activity, which minimizes their ability tometabolize large glucose loads.15However, cats, like other animals, need glucose as asubstrate for metabolic activity. Their natural high-pro-



tein diet provides a supply of amino acids that serve asbuilding blocks for gluconeogenesis. In cats, amino acidsare powerful insulin secretagogues, and thus cats contin-uously produce glucose as a way to maintain adequateblood glucose levels. Because cats produce glucose con-tinuously, they do not experience postprandial hyper-glycemia under natural feeding conditions, nor do theyexperience drops in blood glucose when deprived offood over a period of several days.16 However, whenexposed to a high carbohydrate load, they are less able toadapt to the postprandial glucose surge and experiencesignificant increases in blood glucose concentration.Current recommendations support the use of a high-protein, low-carbohydrate diet for management of felinediabetes. Several studies have demonstrated an improve-ment in blood glucose levels and a decreased need forinsulin therapy after implementation of such a diet.17–19In a recent study,20 although both a moderate-carbohy-drate, high-fiber diet and a low-carbohydrate, low-fiberdiet were found to revert cats to a non–insulin-depen-

dent state, the cats fed a low-carbohydrate, low-fiber dietwere significantly more likely to revert (68% versus 41%of cats). There are several excellent low-carbohydratecommercial diets available for cats with diabetes mellitus,and owners should be encouraged to try available choicesif an initial choice is not palatable to their cat.Weight loss is also an essential component of diabeticmanagement. Initial goals of treatment should be animprovement in glycemic control and clinical signs ofdisease. Cats should be given some time to adjust to adiet change and the addition of insulin therapy. Ownersshould then be encouraged to implement a weight-lossprogram developed by their veterinarian. Weight lossshould be at a rate of 1% to 2% of total body weight perweek. Owners should be encouraged to precisely mea-sure the food they give and weigh their cats on a babyscale weekly. As the cat ’s weight decreases, insulinrequirements will probably also decrease; therefore, thesecats should be closely monitored.

Oral Hypoglycemic AgentsOral hypoglycemic agents are a mainstay of treatmentfor type 2 diabetes in humans. Hypoglycemic agents

work by decreasing intestinal absorption of glucose,improving peripheral sensitivity to insulin, inhibitinghepatic glucose output, or increasing insulin secretionfrom the pancreas. Their use in veterinary medicine hasbeen limited for a number of reasons. First, many catsare difficult to pill. In addition, for most cats, adequatediabetic control cannot be achieved with oral hypo-glycemic agents alone. There is also evidence that use ofthese medications to treat diabetes mellitus may worsenpancreatic amyloidosis in cats.21Glipizide, an oral sulfonylurea, is the main hypo-glycemic agent studied in cats. This drug directly stimu-lates the pancreas to secrete insulin; therefore, it is onlyhelpful in cats that retain some ability to secrete insulin.Overall, approximately 30% of cats appear to have a pos-itive response to glipizide, which probably depends onthe percentage of functional β cells.22 Adverse reactionsinclude vomiting shortly after drug administration,hypoglycemia, and elevated levels of liver enzymes.Mon-itoring of liver enzymes is recommended if glipizide is

used. Hypoglycemia and liver enzyme elevation resolve ifthe drug is discontinued. Additionally, glipizide mayexacerbate formation of amyloid deposits and thus con-tribute to destruction of β cells.21 The role of glipizide istherefore unclear; however, glipizide may be helpful forowners who cannot give insulin injections to their catand for whom an oral agent is the only option. Glipizideis typically given at 2.5 mg PO bid with a meal. Thisdose is increased to 5.0 mg PO bid if adverse effects donot occur. Careful monitoring of clinical signs, bloodglucose regulation, and liver enzymes dictates future doseadjustments.2Other oral hypoglycemic agents that have been usedin cats include α-glucosidase inhibitors (e.g., acarbose),biguanides (e.g., metformin), and the trace elementschromium and vanadium.2 Acarbose competitivelyinhibits α-glucosidase and α-amylase in the small intes-tine, thereby delaying digestion of carbohydrates andglucose absorption. Metformin reduces hepatic gluco-neogenesis and glycogenolysis and enhances insulin-stimulated uptake of glucose by muscle and adiposecells.23 The mechanisms of action of chromium andvanadium are not completely understood, but chromium

Stress hyperglycemia makes in-hospital monitoring of diabetic cats difficult; thus, encouragingowners to do as much home monitoring as possible will greatly facilitate glycemic control.

exerts its effects by increasing insulin sensitivity, andvanadium acts at postreceptor sites to stimulate glucosemetabolism.24,25 There are limited studies demonstratingthe efficacy of oral hypoglycemic agents in cats.

Insulin TherapyDespite the positive impact of dietary management inreverting cats to a non–insulin-dependent state, mostdiabetic cats still need insulin therapy, whether tem-porarily or long term. Several available insulins havedemonstrated a good response in cats (Table 1).

GlargineGlargine is a long-acting human recombinant insulindesigned for human use. It is marketed to give 24-hourbasal control of insulin circulation. In humans, glargineis often used in a basal-bolus pattern with injection ofanother insulin preparation at mealtimes. This isdesigned to most closely recreate the human body’s nat-ural pattern of insulin release. Glargine has no pro-nounced peak of activity in humans, which means it isreleased into the bloodstream at a relatively constantrate. In cats, glargine has been demonstrated to havepeak activity at about 16 hours and to effectively sup-press blood glucose levels for 24 hours, although twice-daily dosing seemed to be most effective in one study.26In our experience, this peak does not require differentmonitoring from other insulins. A recent study demon-strated that diabetic cats treated with glargine had lowerserum fructosamine levels and achieved diabetic remis-sion earlier than cats treated with protamine zinc insulin

(PZI) or lente insulin.27 Initial dosing should be startedat 0.25 to 0.5 U/kg bid. Given that cats appear torespond well to glargine and that normoglycemia anddiabetic remission are real possibilities, it may be pru-dent to begin treatment at the low end of the dosagerange to minimize the risk of hypoglycemia. Additionaladvantages of glargine are that it is available at anyhuman pharmacy and at a concentration of 100 U/mL,which is compatible with easily available U-100 insulinsyringes.

Protamine Zinc InsulinProtamine zinc insulin (PZI) is insulin combined withzinc and protamine (a protein extracted from salmontestes). PZI contains more protamine than NPH, whichgives it a longer duration of action than NPH. Untilrecently, the product used most commonly for cats wasmade from 90% bovine and 10% porcine insulin (PZIVet, Idexx Pharmaceuticals), although PZI can also beformulated from human recombinant insulin or frombovine insulin only. Feline insulin differs from bovineinsulin by one amino acid and from porcine insulin bythree amino acids. PZI can be formulated at a concen-tration of 40 or 100 U/mL.PZI was originally thought of as a long-acting insulinin cats; however, most cats need twice-daily dosing toattain good glycemic control. One study demonstratedthat PZI was effective in reducing blood glucose levelsand clinical signs of diabetes within 45 days of initiatingtreatment.28 However, clinical signs of hypoglycemiadeveloped in 7% of the cats, and there was considerable



Table 1. Long-Term Insulin Options for Cats

Number ofAminoAcids

Insulin Recommended Syringe Different fromProduct Manufacturer Source Duration Dose Concentration Type Feline Insulin

Glargine Sanofi Recombinant Long acting 0.25–0.5 U/kg 100 IU/mL U-100 4Aventis human bid

PZI Several Varies Long acting Consult product Varies Varies 1 (bovine),information 3 (porcine)

NPH Several Recombinant Intermediate 0.25–0.5 U/kg 100 IU/mL U-100 4human acting bid

Vetsulin Intervet Porcine Intermediate 0.25–0.5 U/kg 40 IU/mL U-40 3acting bid

overlap between the dosages that caused hypoglycemia,glycemic control, and lack of control after 45 days oftreatment. Although variable, the blood glucose nadiroccurred between 5 and 7 hours after administration inmany cats; thus, twice-daily dosing is more appropriateto achieve glycemic control. Use of PZI Vet is limited tothe existing supply; in April 2008, the manufacturerannounced that following the sale of existing inventory,it will no longer manufacture or sell animal-basedinsulin. A bovine insulin product (BCP PZI, BCP Vet-erinary Pharmacy, Houston) is still available.

VetsulinVetsulin (Intervet/Schering-Plough Animal Health) is aporcine zinc insulin suspension that is the only insulin fordogs and cats approved by the US Food and DrugAdministration (FDA). It is identical to canine insulinbut differs from feline insulin by three amino acids. Vet-sulin is also formulated at a concentration of 40 U/mL.Its pharmacologic properties have been demonstrated tobe suitable for twice-daily administration in cats,29 inwhich it appears to have a shorter peak onset and dura-

tion of action than PZI or glargine. The peak effect ofVetsulin in cats has been shown to be about 4 hours afteradministration.29

Neutral Protamine HagedornNeutral protamine Hagedorn (NPH) insulin is pro-duced by recombinant DNA technology and is consid-ered an intermediate-acting insulin. It is distributed byseveral manufacturers under names such as Humulin N(Eli Lilly) and Novolin N (Novo Nordisk). It is a crys-talline suspension of human recombinant insulin withprotamine and zinc added. The concentration of NPHis 100 U/mL. Short duration of action is a commonproblem with NPH, and thus cats can remain hyper-glycemic for significant portions of the day.2

MONITORING RESPONSETOTREATMENTFor most newly diagnosed diabetic cats, treatmentbegins with the initiation of dietary modification alongwith conservative insulin therapy. If the cat is stable andhas a blood glucose <350 mg/dL, therapy can be startedwith diet alone. Sometimes this can bring about remis-

sion without further medical treatment. Clients must beaware that this is the first step in diabetic managementand that careful follow-up for life will be necessary. Noconsensus dictates the appropriate follow-up for diabeticcats. An ideal plan consists of a combination of in-hos-pital monitoring, periodic measurement of fructosaminelevels, owner awareness of clinical signs, and a degree ofin-home monitoring.

In-Hospital MonitoringWhen initially reevaluating a newly treated diabetic cat,it is important to increase insulin dosages slowly. It cantake several weeks on a particular insulin regimen forglycemic control to improve. Perhaps more importantly,initial rechecks help to identify hypoglycemia or theSomogyi phenomenon. Ideally, cats should be reevalu-ated every 1 to 2 weeks for the first month or two oftreatment. In reality, this can be difficult for owners interms of expense or time involved. Therefore, it isimportant for the veterinarian and the owner to comeup with a protocol that allows close monitoring but doesnot make owner compliance impossible.

Serial in-hospital blood glucose curves have been amainstay of diabetic management. They are essential inidentifying critical events such as the Somogyi phenom-enon and periods of hypoglycemia, and they aid in iden-tifying the duration and efficacy of insulin action andglucose nadir. However, the accuracy of data generatedfrom in-hospital curves is questionable in cats becausestress hyperglycemia and in-hospital anorexia are com-mon. Although stress hyperglycemia is sometimes diffi-cult to identify, clearly stressed cats should be monitoredby a combination of other methods, and data generatedin “calm” cats must be evaluated with the awareness thatstress may raise blood glucose levels.Even if a serial blood glucose curve cannot beobtained, recheck examinations are imperative forobtaining owner reports of clinical signs, evaluating clin-ical manifestations of disease (hydration status, weightgain or loss, evidence of diabetic neuropathy), and meas-uring fructosamine levels. However, there are importantlimitations to fructosamine interpretation. First, highlevels indicate that the mean blood glucose level over thepast several weeks has been elevated but not why. One



Continuous interstitial glucose monitoring is a valuable tool for diabetes monitoring in cats.

possibility is that the insulin dosage may not be suffi-cient; others are extreme glucose fluctuations, as wouldbe seen in the Somogyi phenomenon, and problems withowner insulin administration. If the Somogyi phenome-non is suspected or if there is a question about ownercompliance, a blood glucose curve may be helpful to fur-ther assess the cat’s level of glycemic control. Second,while normal serum levels of fructosamine may indicategood glycemic control, they do not reflect episodes ofhypoglycemia.

Home MonitoringHome monitoring is imperative for all diabetic cats.Theextent of home monitoring can range from ownerobservations of clinical signs to urine glucose andketone monitoring to in-home blood glucose monitor-ing. In all cases, owners must be told that adjustments ininsulin cannot be based on their judgments or percep-tions alone, but only in consultation with their veterinar-ian. They should be encouraged to keep a log assessingwater intake, frequency and quantity of urine output,appetite, and overall energy level. They should also be

advised to watch for clinical signs of hypoglycemia suchas lethargy, weakness, ataxia, and seizures. Urine glucoseand ketone strips can be used once or twice weekly tocheck for uncontrolled hyperglycemia or negative urineglucose. Negative glucose dipstick findings may indicatediabetic remission or impending hypoglycemia and are asign that reassessment via blood glucose curve is neces-sary. Likewise, elevated levels of glucosuria may indicateinsulin resistance or the Somogyi phenomenon. Ideally,well-regulated, stable cats have urine glucose levelsbetween a trace value and 1+. A series of values outsidethis range should prompt the owner to call the veteri-narian and schedule further assessment after the initialinsulin adjustment period.

Portable Blood Glucose MetersPortable blood glucose meters (PBGMs) are now avail-able. When used in the home setting, they are invalu-able for reducing artifactual increases in blood glucose as

a result of hospital-induced stress hyperglycemia.Results from several studies30,31 have demonstrated thatblood glucose concentration measurements obtainedfrom PBGMs are sufficiently accurate compared withresults obtained from automated chemistry analyzers,although some meters tend to be more accurate thanothers. Owners interested in obtaining in-home bloodglucose curves should be encouraged to receive trainingfrom the veterinary staff and try monitoring at home.The success of home blood glucose monitoringappears to depend on the temperament of the cat andthe skills of the owner. A recent retrospective study32involving 26 cats over a 3-year period found that homemonitoring appeared to be a feasible option and thatmost owners used home monitoring on a regular basisto generate blood glucose curves for their cat. In addi-tion, owners who were successful at home monitoringfelt they had become more confident in their ability tomanage their pet’s disease. Therefore, it appears that forinterested owners and compliant cats, home monitoringof diabetic cats can be an important adjunct to treat-ment. However, owners need clear and thorough

instruction in the use of monitoring devices, and theveterinary staff must be committed to helping ownersgain competence and confidence.Blood for use in a PBGM is obtained from a capillaryin the inner pinna using a lancing device. Differentdevices are available; some create negative pressure tofacilitate blood collection. The user holds the cat’s ear inone hand, keeping the outer pinna flat. The user thenplaces the lancet on the ear, being careful to not applytoo much pressure to the device against the ear. After thedevice is depressed and blood is visible, the test strip isplaced next to the ear to allow the blood to fill the strip.In several studies evaluating home blood glucose moni-toring, owner and cat compliance appeared to be good,with one study reporting 17 of 26 cat owners using theprocedure on a regular basis.32 Prospective studies areneeded to determine if cats undergoing home blood glu-cose monitoring have better glycemic control than catsmonitored with more conventional methods.



Fructosamine levels are a helpful tool to monitor diabetic cats,but clinical signs, physical examination findings, and results of home monitoring

should be considered when evaluating the efficacy of insulin therapy.



Continuous Glucose Monitoring SystemsContinuous glucose monitoring systems (CGMSs), whichmonitor interstitial glucose levels via a subcutaneouslyplaced sensor, are the latest devices to help diabetic humanpatients improve glycemic control. This technology repre-sents a significant advancement in the way veterinarianswill be able to monitor their diabetic patients. Variousmodels are available, but to date, the only FDA-approveddevices are from Medtronic. Measurements of interstitialglucose concentrations avoid the need for repeated periph-eral blood sampling either through numerous venipunc-tures or placement of an indwelling catheter. In addition,the technology may allow the patient to go home for theduration of the monitoring period. Several studies inhumans and animals have demonstrated good correlationbetween interstitial glucose concentration and blood glu-cose concentration.

A first-generation CGMS called the MiniMed(Medtronic) consists of a subcutaneously placed sensor,transmitter, and pager-sized monitor. The sensor andtransmitter are connected by a cable, which is secured tothe patient’s back or side (Figures 1 and 2).The transmit-ter relays data to the monitor, which must be placedwithin several feet of the transmitter (e.g., hung on thepatient’s cage). Glucose in interstitial fluid passes through

a semipermeable membrane and interacts with glucoseoxidase on the sensor electrode. This reaction generatesan electrical current that is proportional to the glucoseconcentration. The current is sampled by the monitorevery 10 seconds, and a mean reading is recorded every 5minutes in milligrams per deciliter. Therefore, in a 24-hour period, 288 readings are recorded. The device canrecord for a total of 72 hours. For placement in dogs andcats, a small area on the thorax, either over the spine orthe lateral thorax, is shaved and surgically prepared. Thesensor is inserted and taped into place, and the transmit-ter is attached to a harness or wrapped in bandage mate-rial (Figure 3). After an hour, the monitoring device needsto be calibrated. A blood glucose reading is obtained andentered into the recording device for calibration. Themanufacturer recommends three calibrations within a 24-hour period; however, after the initial calibration, one cal-ibration every 12 hours is adequate. At the end of themonitoring period, data are downloaded and displayed ona spreadsheet.The MiniMed CGMS has been demonstrated to bevalid for cats, with good correlation between interstitialglucose concentration and blood glucose in the cats

Figure 1. Components of the MiniMed.The radiofrequencytransmitter (left) is attached to the sensor (middle), which isplaced subcutaneously and measures interstitial glucose levels.The transmitter allows wireless communication with the monitor(right) within a distance of 6 ft.The monitor displays an updatedglucose reading every 5 minutes.

Figure 2. Close-up of the interstitial glucose monitor.The interstitial sensor appears on the right, and the transmitter ison the patient’s left side. Shaving of the fur is essential to allowadhesive taping of the unit to the skin.



tested.33 The device appears to be well tolerated by cats,and it did not appear to disrupt normal movement andfeeding behavior in a study of hospitalized subjects.33,34The advantages of this device are the ability to generatea continuous blood glucose curve without patient han-dling and the ability to adapt the system for at-homeuse. The sensor can record for up to 72 hours, whichmay be advantageous for some patients because glucosecurves can vary from day to day and longer samplingperiods give a more accurate indication of trends. The

limitations of the CGMS include potential undetectedinterruptions in sensing. In addition, the need for cali-bration every 12 hours requires the owner to either use aPBGM at home or bring the patient back to the hospi-tal. For cats, the stress involved in returning to the hos-pital may invalidate results, as for a traditional bloodglucose curve. In one study of 14 cats, one cat removedthe sensor, and two cats kinked it.34 Finally, the sensorrecords interstitial glucose readings only between 40 to400 mg/dL. A flat line at the 400 level is displayedwhen values are above this level.

The latest generation of CGMS is Medtronic’sGuardian RT (Figure 4). This system displays anupdated real-time interstitial glucose value every 5 min-utes and has an alarm to monitor high or low glucoselevels. The difference between the MiniMed and theGuardian RT is that the former was designed as a 72-hour diagnostic tool and the latter is designed to providehuman patients with instant information about theirown glycemic control. Similar to the MiniMed, theGuardian RT uses a subcutaneous sensor. However, italso includes a small radiotransmitter that is placed onthe skin and communicates wirelessly with the monitor-ing device (Figures 5, 6, and 7). The patient and themonitor need to be within 6 ft for transmission. The

Figure 3. Glucose monitoring with the MiniMed.Placement of the interstitial glucose monitoring system allows thecat to sit and move comfortably.The cat in this picture movedfreely about its cage and ate and slept normally. Figure 4. Components of the Guardian RT. Top row:The

ComLink (left) takes data from the monitor and uploads it to acomputer.The monitor (right) displays real-time glucose readings.Bottom row:The Sen-serter (left) aids insertion of the glucosesensor (not shown).The charger (middle) is needed to charge thetransmitter (right), which collects glucose information from thesensor and sends it to the monitor. (Scalpel handle shown for scale.)

Figure 5. Close-up of the sensor for the Guardian RT,which has been inserted subcutaneously into the back ofthe cat.



device is calibrated 2 hours after placement and 8 to 12hours later. The results are downloaded into a softwareprogram, and a glucose curve is generated.In humans, the technology has progressed to integrat-ing insulin pumps with CGMSs to allow patients to pro-gram delivery of one to 12 different basal rates of insulinper 24 hours. One potential advantage of the GuardianRT system for use in feline patients is elimination of theneed to wear the bulky cable-attached transmitter device.Although most cats evaluated appeared to accept wear-ing the radiotransmitter, it is unlikely to be as well toler-ated by cats as it is by dogs. Cats in our hospital havetolerated the smaller Guardian RT well, with no adverseevents to date. One disadvantage of the Guardian RT isthe need to be within 6 ft of the monitor.Therefore, a catat home would need to be placed in a crate or smallroom for the readings to be successfully transmitted.At The University of Georgia, we have successfullyused both the older MiniMed and the Guardian RT incats; however, we currently use the Guardian RT. Themajor limitation of each device thus far has been briefperiods in which the device did not record glucose read-ings. We are actively evaluating the Guardian RT toeliminate technical difficulties as well as to further assessthe clinical utility of this type of monitoring. Overall,the many advantages of this type of glucose monitoringsystem will likely make CGMSs a standard of care fordiabetic monitoring in the near future.

CONCLUSIONThe treatment of diabetes mellitus in cats continues to beboth rewarding and challenging. It is important for practi-

tioners to be aware of species-specific differences whentreating feline and canine patients. The availability of newinsulin therapies and advancements in nutritional recom-mendations hold much promise for effective managementof this disease. Client education and participation in treat-ment can greatly improve diabetic control in feline patients,as can advances in monitoring equipment. Great advancesare being made in the understanding and treatment of dia-betes in human medicine, and it is anticipated that theseadvances will aid in the treatment of feline patients.

REFERENCES1. Forman MA, Marks SL, DeCock HE, et al. Evaluation of serum feline pan-creatic lipase immunoreactivity and helical computed tomography versus con-ventional testing for the diagnosis of feline pancreatitis. J Vet Intern Med2004;18(6):807-815.

2. Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction.St. Louis: Saunders; 2004.

3. Sindelar DK, Havel PJ, Seeley RJ, et al. Low plasma leptin levels contributeto diabetic hyperphagia in rats.Diabetes 1999;48:1275-1280.

4. Dong J, Peeters L, De Smet B, et al. Role of endogenous ghrelin in thehyperphagia of mice with streptozotocin-induced diabetes. Endocrinology2006;147(6):2634-2642.

5. Mizisin AP, Shelton GD, Burger ML, et al. Neurological complications asso-ciated with spontaneously occurring feline diabetes mellitus. J NeuropatholExp Neurol 2002;61(10):872-884.

6. Kennedy WR, Navarro X, Goetz FC, et al. Effects of pancreatic transplanta-tion on diabetic neuropathy.N Engl J Med 1990;322(15):1031-1037.

7. Salgado D, Reusch C, Speiss B. Diabetic cataracts: different incidencebetween dogs and cats. Schweiz Arch Tierheilkd 2000;142(6):349-353.

8. Link KRJ, Rand JS. Reference values for glucose tolerance and glucose statusin cats. JAVMA 1998;231(4):492-496.

9. Rand JS, Kinnaird E, Baglioni A, et al. Acute stress hyperglycemia in cats isassociated with struggling and increased concentrations of lactate and norepi-

Figure 7. The Guardian RT sensor and transmitter on acat.Note the compact nature of the device compared with theMiniMed in Figure 3.

Figure 6. Close-up of the transmitter portion of theGuardian RT.The transmitter is directly attached to the sensor.

nephrine. J Vet Intern Med 2002;16:123-132.10. Crenshaw KL, Peterson ME,Heeb LA, et al. Serum fructosamine concentra-

tion as an index of glycemia in cats with diabetes mellitus and stress hyper-glycemia. J Vet Intern Med 1996;10(6):360-364.

11. Elliott DA, Nelson RW, Reusch CE, et al. Comparison of serum fruc-tosamine and blood glycosylated hemoglobin concentrations for assessmentof glycemic control in cats with diabetes mellitus. JAVMA 1999; 214(12):1794-1798.

12. Reusch CE, Haberer B. Evaluation of fructosamine in dogs and cats withhypo- or hyperproteinaemia, azotaemia, hyperlipidaemia and hyperbilirubi-naemia. Vet Rec 2001;148(12):370-376.

13. Bailiff NL, Nelson RW, Feldman JL, et al. Frequency and risk factors for uri-nary tract infection in cats with diabetes mellitus. J Vet Intern Med2006;20:850-855.

14. Nelson RW, Scott-Moncrieff C, Feldman EC, et al. Effect of dietary insolu-ble fiber on control of glycemia in cats with naturally acquired diabetes melli-tus. JAVMA 2000;216(7):1082-1088.

15. Tanaka A, Inoue A,Takeguchi A, et al. Comparison of expression of glucoki-nase gene and activities of enzymes related to glucose metabolism in liversbetween dog and cat.Vet Res Commun 2005;29:477-485.

16. Martin GJW, Rand JS. Food intake and blood glucose in normal and diabeticcats fed ad libitum. J Feline Med Surg 1999;1:241-251.

17. Frank G, Anderson W, Pazak K, et al. Use of a high-protein diet in the man-agement of feline diabetes mellitus. Vet Ther 2002;2(3):238-246.

18. Bennett N. Comparison of a low carbohydrate versus high fiber diet in catswith diabetes mellitus (abstract). J Vet Intern Med 2001;15:297.

19. Mazzaferro EM, Greco DS, Turner AS, et al. Treatment of feline diabetesmellitus using an alpha-glucosidase inhibitor and a low-carbohydrate diet. JFeline Med Surg 2003;5:183-189.

20. Bennett N, Greco D, Peterson M, et al. Comparison of a low carbohydrate-low fiber diet and a moderate carbohydrate-high fiber diet in the manage-ment of feline diabetes mellitus. J Feline Med Surg 2006;8:73-84.

21. Hoenig M, Hall G, Ferguson D, et al. A feline model of experimentallyinduced islet amyloidosis.Am J Pathol 2000;157:2143-2150.

22. Feldman EC, Nelson RW, Feldman MS. Intensive 50-week evaluation ofglipizide administration in 50 cats with previously untreated diabetes melli-tus. JAVMA 1997;210(6):772-777.

23. Bailey CJ,Turner RC.Metformin.N Engl J Med 1996;332(9):574-579.24. Brichard SM, Henquin J. The role of vanadium in the management of dia-

betes. Trends Pharmacol Sci 1995;16:265.25. Striffler JS, Law JS, Polansky MM, et al. Chromium improves insulin

response to glucose in rats.Metabolism 1995;44(10):1314-1320.26. Marshall R, Rand J. Comparison of the pharmacokinetics and pharmacody-

namics of glargine, protamine zinc and porcine lente insulins in normal cats(abstract). J Vet Intern Med 2002;16(3):358.

27. Marshall RD, Rand JS. Treatment with glargine results in higher remissionrates than lente or protamine zinc insulins in newly diagnosed diabetic cats(abstract). J Vet Intern Med 2005;19(3):425.

28. Nelson RW, Lynn RC, Wagner-Mann CC, et al. Efficacy of protamine zincinsulin for treatment of diabetes mellitus in cats. JAVMA 2001;218(1):38-42.

29. Martin GJ, Rand JS. Pharmacology of a 40 IU/ml porcine lente insulinpreparation in diabetic cats: findings during the week and after 5 or 9 weeksof therapy. J Feline Med Surg 2001;3:23-30.

30. Wess G, Reusch C. Capillary blood sampling from the ear of dogs and catsand use of portable meters to measure glucose concentration. J Small AnimPract 2000;41(2):60-66.

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32. Kley S, Casella M, Reusch C. Evaluation of long-term home monitoring ofblood glucose concentrations in cats with diabetes mellitus: 26 cases (1999-2002). JAVMA 2004;225(2):261-266.

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ARTICLE #1 CETESTThe Auburn University College of Veterinary Medicineapproves this article for 3 contact hours of continuingeducation credit.Subscribers may take individual CEtests or sign up for our annual CE program. Those whowish to apply this credit to fulfill state relicensure requirementsshould consult their respective state authorities regarding theapplicability of this program. CE subscribers can take CE testsonline and get real-time scores at CompendiumVet.com.

CE

1. Diabetic neuropathy in catsa. is rare, seen in less than 5% of feline diabetic patients.b. leads to an increase in motor and sensory nerve con-

duction velocities.c. appears to be due to alterations in the sorbitol meta-

bolic pathway.d. is typically identified by forelimb weakness that pro-

gresses to the hindlimbs.

2. Cats differ from dogs in glucose metabolism inthat theya. can handle a carbohydrate load better than dogs.b. can up-regulate disaccharidase activity when faced

with increased intestinal glucose.c. do not need glucose as a substrate for metabolic

activity.d. lack the hepatic enzyme glucokinase, which minimizes

their ability to metabolize large glucose loads.

3. When assessing a newly diagnosed diabetic cat,which of the following is true?a. The complete blood count invariably demonstrates a

decreased hematocrit as a reflection of anemia ofchronic disease.

b. Dilute urine is typically noted due to the polyuriaexperienced by most diabetic cats.

c. Urinary tract infection is a common finding, despitethe lack of clinical signs reported by owners.

d. Fructosamine levels are not affected by the presenceof other disease conditions.

4. Which statement regarding the long-term effectsof diabetes mellitus in cats is true?a. Cataract formation is an important complication, as

in dogs.

b. Control of glucose regulation will completely reversesigns of diabetic neuropathy in most cats.

c. Nephropathy and vasculopathy are common long-term complications, as they are in humans.

d. Diabetic neuropathy is the most common long-termcomplication of diabetes mellitus in cats.

5. Which statement is false regarding current re-search findings on the role of diet in the manage-ment of feline diabetes?a. Increased dietary fiber levels negatively affect glycemic

control in cats.b. Moderate-carbohydrate, high-fiber diets and low-car-

bohydrate, low-fiber diets have both been shown tobe of benefit in cats with diabetes mellitus.

c. Low-carbohydrate, low-fiber diets appear to be supe-rior to moderate-carbohydrate, high-fiber diets inhelping cats achieve diabetic remission

d. Cats are less adapted than dogs to deal with high car-bohydrate loads due to decreased glucokinase activ-ity in the liver.

6. Which statement best characterizes the use oforal hypoglycemic agents in cats?a. Oral hypoglycemic agents have a greater role in the

treatment of canine diabetes than in feline diabetes.b. They can be used alone to achieve diabetic control in

most cats.c. Glipizide works best in patients that have lost insulin-

secreting ability.d. The use of glipizide may lead to an increase in amyloid

deposits.

7. Which statement best represents current infor-mation about the use of glargine in cats?a. Glargine is unique among insulins in that it is consid-

ered a peakless insulin in cats.b. The use of glargine has been shown to help induce dia-

betic remission earlier than PZI or lente insulin insome cats.

c. Glargine is similar to Vetsulin in that it is formulatedat a concentration of 40 U/mL.

d. Due to its long duration of action, glargine shouldonly be used once a day in cats.

8. Which statement regarding current insulin ther-apy for cats is true?a. No insulin currently on the market has been

approved by the FDA for use in cats.b. Several available insulins have demonstrated a good

response in cats.c. NPH has a long duration of action and, therefore,

may be an excellent choice for use in cats.d. All available insulins are administered with the same

syringe.

9. Owners of diabetic cats should not attempt to__________ by themselves at home.a. monitor blood glucoseb. generate a blood glucose curvec. monitor urine glucosed. adjust the insulin dose

10. Continuous glucose monitoring systemsa. have not been validated for use in small animals;

therefore, results from these devices must be evalu-ated with caution.

b. need to be calibrated every 6 hours; therefore, theyare most useful in a hospital setting.

c. are not tolerated by cats.d. record only interstitial glucose levels between 40 and

400 mg/dL.



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