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Feline DiabetesFeline Diabetes

PathophysiologyPathophysiology andandManagementManagement

CorettaCoretta C. Patterson DVMC. Patterson DVM

DACVIMDACVIMMichigan State UniversityMichigan State University


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Diabetes is defined as a chronicDiabetes is defined as a chronicsyndrome of impaired carbohydrate,syndrome of impaired carbohydrate,

protein and fat metabolism owing toprotein and fat metabolism owing toinsufficient secretion of insulin or toinsufficient secretion of insulin or totarget tissue insulin resistance.target tissue insulin resistance.


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The cause of type 2 diabetes is stillThe cause of type 2 diabetes is stilllargely unknown in both cats andlargely unknown in both cats andhumanshumans

The hallmarks of type 2 diabetes inThe hallmarks of type 2 diabetes in

humans are impaired insulin secretion,humans are impaired insulin secretion,insulin resistance andinsulin resistance and amyloidamyloiddeposition in the isletsdeposition in the islets


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Secondary diabetes may also resultSecondary diabetes may also resultfrom chronically elevated levels offrom chronically elevated levels of

hormones which oppose insulin action,hormones which oppose insulin action,

causing insulin resistancecausing insulin resistance


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Feline diabetes is characterized by:Feline diabetes is characterized by: Decreased insulin secretionDecreased insulin secretion

AmyloidAmyloid deposition in the pancreatic isletsdeposition in the pancreatic islets

Insulin resistanceInsulin resistance


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The characteristicThe characteristic histologichistologic finding infinding infeline and human type 2 diabetes is thefeline and human type 2 diabetes is the

deposition ofdeposition of amyloidamyloid in the pancreaticin the pancreatic

islets. These deposits are found in upislets. These deposits are found in upto 90% of human type 2 diabeticto 90% of human type 2 diabetic

humanshumans


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AmyolidAmyolid deposition increases with agedeposition increases with age

in cats, in cats seven years or older, itin cats, in cats seven years or older, it

frequently comprised more than 50% offrequently comprised more than 50% of

islet volumeislet volume


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IsletIslet amyloidamyloid depositondepositon is thought tois thought tocontribute to beta cell dysfunction andcontribute to beta cell dysfunction and

degeneration both directly anddegeneration both directly and

indirectlyindirectly

IsletIslet amyloidamyloid surrounds the beta cells,surrounds the beta cells,

isolating them from adjacent pancreaticisolating them from adjacent pancreatictissue and blood capillariestissue and blood capillaries


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IntracellularIntracellular amyloidamyloid formation andformation and

contact ofcontact of amyloidamyloid fibrils with cellfibrils with cell

membranes has also been shown tomembranes has also been shown to

impair beta cell function and to causeimpair beta cell function and to cause

beta cell deathbeta cell death


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In cats,In cats, amyloidamyloid deposition starts in thedeposition starts in the

islet periphery and extends to theislet periphery and extends to the

center of the islet with the increasingcenter of the islet with the increasing

depositiondeposition


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The major constituent of cat and humanThe major constituent of cat and human

isletislet amyloidamyloid is the pancreatic hormoneis the pancreatic hormone

isletislet amyloidamyloid polypeptide(IAPP), alsopolypeptide(IAPP), also

calledcalled amylinamylin


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For isletFor islet amyloidamyloid deposition to occur,deposition to occur,

two prerequisites must be fulfilled;two prerequisites must be fulfilled;

there must be a specific amino acidthere must be a specific amino acid

sequence ofsequence of amylinamylin and an increasedand an increased

locallocal amylinamylin concentrationconcentration


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Exercise increases insulin sensitivity inExercise increases insulin sensitivity innormal and diabetic humans andnormal and diabetic humans and

reduces requirements in diabeticsreduces requirements in diabetics

Physical inactivity increases the risk ofPhysical inactivity increases the risk of

diabetes directly via decreased insulindiabetes directly via decreased insulin

sensitivity(insulin resistance)sensitivity(insulin resistance)


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Glucose toxicity is an important featureGlucose toxicity is an important featureof feline diabetesof feline diabetes

Defined as impaired insulin secretionDefined as impaired insulin secretion

from beta cells as a result of prolongedfrom beta cells as a result of prolonged

hyperglycemiahyperglycemia

Initially this glucose mediated change isInitially this glucose mediated change isfunctional and reversiblefunctional and reversible--later structurallater structural

changes occur in beta cellschanges occur in beta cells


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Suppression of insulin secretion bySuppression of insulin secretion byglucose toxicity is postulated to be theglucose toxicity is postulated to be the

reason that measuring insulinreason that measuring insulin

concentration in cats prior to initiatingconcentration in cats prior to initiatingtherapy is not useful for predictingtherapy is not useful for predicting

which cats will respond to oralwhich cats will respond to oralhypoglycemicshypoglycemics and which will requireand which will require

insulininsulin


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What is impaired glucose tolerance?What is impaired glucose tolerance?

Cats with impaired glucose toleranceCats with impaired glucose tolerancehave a normal or slightly increasedhave a normal or slightly increased

fasting blood glucose and an increasedfasting blood glucose and an increased

glucose concentration or glucose halfglucose concentration or glucose halflife after a glucose tolerance testlife after a glucose tolerance test


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Insulin resistance developed in peopleInsulin resistance developed in peopleand cats as a mechanism for dealingand cats as a mechanism for dealing

with shortages of dietary glucosewith shortages of dietary glucose


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In cats, age is the most significant riskIn cats, age is the most significant riskfactor for the development of diabetesfactor for the development of diabetes

An Australian study of 45 diabetic catsAn Australian study of 45 diabetic cats

found that 90% were 7 years or olderfound that 90% were 7 years or older

and 66% were over 10 years of age. Inand 66% were over 10 years of age. In

North America, of 333 diabetic cats,North America, of 333 diabetic cats,72% were 7 years or older72% were 7 years or older


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Diet inarguable plays a role in theDiet inarguable plays a role in thedevelopment of feline diabetesdevelopment of feline diabetes


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Cats given the opportunity would eat 5Cats given the opportunity would eat 5--1212times per daytimes per day

Dr. RandDr. Rands group in Australia looked ats group in Australia looked at

the amount of food consumed andthe amount of food consumed and

frequency of consumption of diabeticfrequency of consumption of diabetic

versus normal cats over 24 hoursversus normal cats over 24 hours


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Cats should be fed ad libCats should be fed ad libAmount of per feeding should beAmount of per feeding should bedetermined by energy requirements anddetermined by energy requirements and

the cats body condition.the cats body condition.Remember the equationRemember the equation

BW kg x 70+30 = BER (existence energy)BW kg x 70+30 = BER (existence energy)Multiplier of 1.2 used for neutered healthyMultiplier of 1.2 used for neutered healthy

catcat


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Obese diabetics can be fed 75% of theirObese diabetics can be fed 75% of theircalculated needscalculated needs

Underweight diabetics should be fed atUnderweight diabetics should be fed at

least the calculated requirement*least the calculated requirement*


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Genetics is thought to play a role inGenetics is thought to play a role inhuman diabeteshuman diabetes

It is unknown at this point what roleIt is unknown at this point what role

genetics plays in feline diabetesgenetics plays in feline diabetes

In Australia, there is a very high incidenceIn Australia, there is a very high incidence

of diabetes in Burmese catsof diabetes in Burmese cats


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Treatment of diabetesTreatment of diabetesDietary changesDietary changes

ExerciseExercise

MedicationsMedications


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Types of insulinTypes of insulinRegularRegular

NPH(neutralNPH(neutral

protamineprotamine

HagedornHagedorn

))

PZI(protaminePZI(protamine zinc insulin)zinc insulin)

Glargine(LantusGlargine(Lantus))


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Dosage of insulin depends on which type ofDosage of insulin depends on which type of

insulin is selectedinsulin is selected

Longer actingLonger acting insulinsinsulins tend to be less potenttend to be less potent

IntermediateIntermediate insulins(e.ginsulins(e.g., NPH) tend to be., NPH) tend to bemoremore bioavailablebioavailable than longer actingthan longer acting insulinsinsulins;;

thus an injection of NPH achieves a higherthus an injection of NPH achieves a higher

serum insulin concentration more rapidly andserum insulin concentration more rapidly andthe starting dose is lowerthe starting dose is lower


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Changes in insulin dosage should beChanges in insulin dosage should bemade cautiously with multiple pieces ofmade cautiously with multiple pieces of

information contributinginformation contributing

Urine volumes and sugarUrine volumes and sugar

Blood glucose curve(s)Blood glucose curve(s)

FructosamineFructosamine oror GlycosylatedGlycosylated HBHB


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OralOral hypoglycemicshypoglycemicsIn general oralIn general oral antidiabeticantidiabetic drugs act bydrugs act by

stimulating insulin secretion, decreasingstimulating insulin secretion, decreasing

hepatichepatic gluconeogenesisgluconeogenesis or improvingor improvingmuscle and adipose sensitivity to insulinmuscle and adipose sensitivity to insulin


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SulfonylureasSulfonylureasThe most studied in cats isThe most studied in cats is GlipizideGlipizide

It is really the only oralIt is really the only oral

antidiabeticantidiabetic

drugdrug

that has been evaluated in cats to datethat has been evaluated in cats to date

Feldman looked at 50 cats takingFeldman looked at 50 cats taking

glipizideglipizide in 1997in 1997


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Incidence of side effects to the drugIncidence of side effects to the drugwas 16% in the 1997 studywas 16% in the 1997 study

Side effects reported include; elevatedSide effects reported include; elevated

liver enzymes,liver enzymes, hepatotoxicityhepatotoxicity, anorexia, anorexiaand vomitingand vomiting


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BiguanidesBiguanidesThe active component,The active component, guanideguanide is foundis found

naturally in animal and plant materialnaturally in animal and plant material

and explains the medieval Europeanand explains the medieval Europeanpractice of administering components ofpractice of administering components of

the French lilac flower to diabeticthe French lilac flower to diabeticpatientspatients


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MetforminMetformin has been evaluated in catshas been evaluated in cats

It acts by improving insulin sensitivity inIt acts by improving insulin sensitivity inperipheral tissuesperipheral tissues

In humans the hypoglycemic effects ofIn humans the hypoglycemic effects ofmetforminmetformin are additive to those ofare additive to those ofglipizideglipizide

Used to treat five diabetic cats and oneUsed to treat five diabetic cats and oneacromegalicacromegalic catcat


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--GlucosidaseGlucosidase inhibitorsinhibitors

This class of drug delays glucose absorptionThis class of drug delays glucose absorptionfrom the GI tractfrom the GI tract

AcarboseAcarbose inhibits theinhibits the

--glucosidasesglucosidases, which, whichinclude enzymes produced in the brushinclude enzymes produced in the brushborder of the small intestineborder of the small intestine

The end result of the action ofThe end result of the action of acarboseacarbose is ais ablunted entry of glucose into the systemicblunted entry of glucose into the systemiccirculationcirculation


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OralOral antidiabeticantidiabetic therapy is appropriate totherapy is appropriate toinitially in the newly diabetic stableinitially in the newly diabetic stable

feline patient attemptfeline patient attempt

Monitor frequently and carefullyMonitor frequently and carefully

Make changes if indicatedMake changes if indicated

Look out for more information on otherLook out for more information on otherdrugsdrugs

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