Journal of Feline Medicine and Surgery (2000) 2, 317

e

cly

emian

orts

glipizide is well establiswhich have residual be

tssuatsedThis is the second of a two-part review ondiabetes in cats. Part I (Rand 1999) dis-cussed the pathogenesis and diagnosis ofdiabetes in cats. Knowledge of pathogenesis isimportant for understanding treatment issues.

Sick ketotic diabetic catsDiabetic cats that present with diabetic ketosisor ketoacidosis (DKA) may be severely ill, andtheir treatment is a medical emergency. In twoseparate studies, each of 104 diabetic cats,there were 12 cats (11.5%) and 38 cats (36.5%)diagnosed with DKA on the basis of ketosisand metabolic acidosis (Crenshaw & Peterson1996, Goossens et al 1998). In Goossens study,eight of 12 cats with DKA died or were eutha-nased in the initial hospitalisation period(Goossens et al 1998). Acute necrotising pan-creatitis was a frequent concomitant problemin these cats. The treatment of DKA involvesaddressing underlying disease processes

Depressed, dehydrated, hypothermic, orpyrexic cats require hospitalisation. In dehy-drated diabetic cats, fluids are as important asinsulin therapy. For most dehydrated diabeticcats, the type of fluid is not as important as thefluid itself, and a balanced electrolyte solution,preferably with lactate, is a good initial choice.Generally, fluid administration rates of 100 to150 ml/kg/24 h are appropriate for dehydrateddiabetic cats. For severely hyperglycaemic(>32 mmol/l) dehydrated cats, half strengthsodium chloride (0.45% NaCl) may be the pre-ferred choice of fluid for the first few hours,because these cats are markedly hyperosmotic.However, it should be used with carefulmonitoring of blood glucose and electrolytes.Bicarbonate supplementation is rarely indicatedbecause acidosis improves rapidly with fluid andinsulin therapy.

Ketoacidotic cats may initially be hyperkalae-mic. Acidosis causes intracellular potassium tobe exchanged with extracellular hydrogen ions,Date accepted: 29 October 1999

such as vanadium salsome diabetic cats. Inmajority of diabetic ctreatment are discussREVIEWCurrent understanding of fPart 2, treatmentG Martin, J Rand

Companion Animal Sciences,School of Veterinary Science andAnimal Production, TheUniversity of Queensland,Australia 4072

When treating diabeticausing clinical hypogof attaining diabetic rchronic hyperglycaemimportant for compliafed with the aim of nnon-obese diabetic capresent, correcting fluid, electrolyte, and acid-base imbalances, and lowering blood glucose(Macintire 1995).

1098-612X/00/010003+15 $35.00/0line diabetes:

cats, the primary aim is to control clinical signs withoutcaemia. Secondary goals are to maximise the chancesission and to minimise the risk of complications due to

. A treatment plan that is convenient for the owner isce. Underweight or overweight diabetic cats should bemalising bodyweight. Current evidence suggests thatcan be fed ad libitum. The oral hypoglycaemic drughed as a treatment for about a third of diabetic cats,

ta cell function. Preliminary studies on other oral agents, metformin, and troglitazone indicate a potential use inlin treatment remains the treatment of choice for the. Choice of insulin, dose rates and monitoring of.

2000 European Society of Feline Medicinewhich may result in hyperkalaemia. Extracellularpotassium concentration falls quickly as potass-ium moves intracellularly with insulin and fluid

2000 European Society of Feline Medicine

therapy, and as acidosis is corrected. Whole body doses may have to be increased to 0.2 iu/kg/h

severe forms of diabetes mellitus in cats, thereader is referred to reviews on this specificdisorder and its clinical management (Macintire

4 G Martin and J Randpotassium depletion occurs when glucose andfluid induced diuresis causes renal potassiumloss (Dow et al 1987, Feldman & Nelson 1996).Hypokalaemia may occur within 1224 h in catsthat were hyperkalaemic on admission. Hypo-kalaemic myopathy and weakness can occurwith plasma potassium concentrations less than3.5 mmol/l, and levels below 2 mmol/l shouldbe considered an emergency because of thepossibility of death from respiratory paralysis(Dow et al 1987). Potassium therapy shouldcommence immediately in normokalaemicacidotic cats, and within 1224 h after com-mencement of fluid therapy in initially hyper-kalaemic cats. If possible, potassium therapyshould consist of both oral and intravenoustherapy. Potassium chloride should be added tofluids at between 40 and 80 mmol/l, and potass-ium gluconate given at 23 mmol/cat per os, oneto three times per day. Potassium concen-trations need to be monitored carefully in thefirst few days of fluid therapy to avoid hypo- orhyperkalaemia.

Often ketoacidotic cats become hypophospho-taemic within 1224 h after commencement ofinsulin therapy (Feldman & Nelson 1996). Meta-bolic acidosis causes cellular and whole bodyloss of phosphorus, similar to potassium (Willardet al 1987). Signs of hypophosphataemia(

hyperglycaemia such as retinopathy, but this

insoluble fibre) was found to be beneficial insome diabetic cats, in comparison to a very low

content (eg, 5%). The benefit of increased fibre,

have reduced or no appetite. This may require

weight diabetic cats, as obesity in cats reversibly

Current understanding of feline diabetes: treatment 5fibre diet (1%) (Nelson et al 1994). However,varying carbohydrate contents of the diets con-founded the results of this study, as the low fibrediet had substantially more carbohydrate. Thereare no studies in diabetic cats showing an advan-tage of a high-fibre diet over a good qualitycommercial cat food with a moderate fibreand increase peripheral insulin sensitivity(Anderson & Akanji 1991). A high fibre diet (12%High fibre diets are recommended in diabetichumans to blunt post-prandial hyperglycaemialeads to an increase in the frequency ofclinical hypoglycaemic episodes (Reichard 1994).Because of the risk of hypoglycaemia in insulin-treated diabetic cats (Whitley et al 1997) and thelack of life-threatening complications associatedwith moderate hyperglycaemia, pursuing tightglycaemic control is not advised.

Treatment modalities

Diet

General considerations. Unlike humans and dogs,normal cats fed ad libitum will eat 12-20 mealsspread throughout the day and night, and tra-ditionally the major energy source is proteinrather than carbohydrate (Morris & Rogers 1983,Houpt 1991). Another important species differ-ence is that post-prandial hyperglycaemia doesnot occur in cats fed typical cat foods (Kienzle1994, Martin & Rand 1997). Therefore there doesnot seem any need to match the timing of theinsulin dose to meals, which is important in thecontrol of blood glucose in human diabetics(Eaton et al 1978). Diabetic cats can be fed adlibitum and allowed to follow a normal feedingpattern of multiple small meals (Kane 1989,Martin & Rand 1997). Feeding multiple kilojoule-restricted meals may also be advantageous forweight loss in obese diabetic cats (Hand et al1989).

Diabetics have energy loss via glucose inthe urine, and may have maldigestion/malabsorption due to previous pancreatitis ordiabetic enteropathy (Diehl 1995), thereforemaintenance energy requirements may be higherthan in normal cats. Polyphagic diabetic catsshould not have their food intake restrictedunless as part of a planned weight loss programfor obesity.decreases glucose tolerance (Nelson et al 1990,Biourge et al 1997). Calorie restriction should beconservative, and matched to the individual catby ongoing monitoring of food intake and body-weight (Sloth 1992). Cats should be fed approxi-mately 70% of their maintenance energyrequirements for their target weights (Sloth1992). Severe calorie restriction or starvationshould not be used for weight loss becausediabetic cats have an increased risk of hepaticlipidosis (Bruskiewicz et al 1997). It is importantthe initiation of assisted feeding, such as handfeeding of highly aromatic, palatable food(Laflamme et al 1993). Once eating normally,diabetic cats with a normal bodyweight shouldbe fed a good quality feline diet ad libitum,and have their bodyweight monitored. As thediabetes is stabilised with therapy, bodyweightoften increases. If the cat starts to become over-weight, it should be changed to a moderatelycalorie-restricted diet, such as a geriatric diet, ora diet for less active cats. Most high fibre dietsare calorie-restricted, and these diets may beunsatisfactory for some non-obese diabetic cats.Some normal weight diabetic cats lose weight,and underweight cats may fail to achieve normalbodyweight, despite polyphagia when fed thistype of diet. The increased stool volume mayalso be unacceptable to the owner.

When diabetic cats are underweight, energydense foods such as conditioning or growth dietsshould be used. As weight approaches normal,cats can be switched to maintenance cat foods.The best combination of protein, fat, and carbo-hydrate for diabetic cats is currently unknown.

Obese diabetics. Weight loss and attainment ofnormal bodyweight is a treatment goal of over-isolated from changes in dietary carbohydrate,may be less in cats than in humans because ofthe absence of post-prandial hyperglycaemia incats.

Although only foods containing substantialamounts (36.1% w/w) of glucose (and not othercarbohydrates) led to post-prandial hyperglycae-mia in a study of normal cats (Kienzle 1994), fordiabetic cats it is probably advisable to avoiddiets that are unusually high in carbohydrate,and to avoid glucose-containing treats.

Feeding recommendations for diabetic cats. Dia-betic cats, particularly soon after diagnosis, may

to ensure that the cat will eat the diet when

particularly in those cats whose hyperglycaemiais mild (1215 mmol/l), or those which are

control has been reported in about 3540% of

6 G Martin and J Randattaining diabetic remission (Nelson et al 1993,Feldman et al 1997).

Glipizide stimulates beta cells to produceinsulin and is only effective in diabetics whichhave functional beta cells (Zimmerman 1997),which were about 40% of diabetic cats reportedin a recent study (Feldman et al 1997). Gooda change is made to a weight reducing diet.To avoid excessively rapid weight loss, slowintroduction of a diet over 2 weeks may be moresuccessful in getting the cat to eat a new diet thanabrupt dietary changes. Once the estimatedtarget weight is reached, re-evaluation of thecats body condition should be made.

Oral hypoglycaemicsApproximately one-third of diabetic cats achievegood clinical control with oral hypoglycaemicdrugs. However, in the majority of cats, thecontrol of diabetes is not as good with oralhypoglycaemics as with insulin, and in some catsit may be more difficult for the owners to admin-ister oral medication than insulin injections.When owners are unwilling to use insulin, oralagents may be lifesaving for a cat that wouldotherwise be euthanased. Insulin treatment canbe started if oral treatment is unsuccessful, whichis usually evident within 46 weeks. By this time,owners may be more amenable to the use ofinsulin (Feldman et al 1997). Oral hypoglycaemicagents are generally not recommended in sickketotic or anorexic diabetic cats, which should betreated with insulin (Nelson et al 1993). Treat-ment for these cats may be subsequently at-tempted using oral drugs, once their conditionhas improved with insulin and supportive care.

The oral sulphonylurea hypoglycaemic drugglipizide has been used successfully in the treat-ment of diabetic cats (Miller et al 1992, Nelson etal 1993, Feldman et al 1997). The usual dose ofglipizide is 5 mg bid, regardless of the body-weight of the cat, though lower doses (1.252.5 mg bid) may initially be used to acclimatisethe cat to the drug and reduce side-effects (Milleret al 1992, Nelson et al 1993, Feldman et al 1997).Glipizide requires less intensive clinical monitor-ing than insulin treatment, due to a lower risk ofclinical hypoglycaemia, and may create sufficientglycaemic control to lead to diabetic remission(Nelson et al 1993, Feldman et al 1997). Hypogly-caemia may still occur in cats given glipizide,diabetic cats treated with glipizide (Feldman et al1997), although the success rate depends on thepopulation of cats studied and criteria for goodcontrol. As glipizide may cause transient elev-ation of liver enzymes and in some cases icterus,monitoring hepatic enzymes is recommendedduring glipizide treatment, which adds to treat-ment costs (Miller et al 1992, Nelson et al 1993,Feldman et al 1997). Oral hypoglycaemic drugsfail to function adequately in some humanpatients over time, as the number of functionalbeta cells decreases (Chow et al 1995), and thismay also occur in some cats on glipizide treat-ment (Feldman et al 1997). Of concern withdrugs which stimulate insulin and amylin secre-tion, such as glipizide, is that amyloid depositionmay be accelerated and lead to further loss ofbeta cells (Hoenig & OBrien 1998, Rachman et al1998). This may lead to insulin-dependence andpoorer control of blood glucose than if othertypes of drugs, including insulin, had been usedinitially.

There are a variety of other oral agents that areused in humans for the treatment of diabetes.Preliminary studies in cats have been performedwith vanadium, which increases insulin receptorsensitivity. However, as a sole agent it was onlyuseful early in the pathogenesis of diabetes whenblood glucose was relatively low (Greco 1997).By the time a diagnosis of diabetes is made,vanadium is unlikely to be effective by itself. Afurther preliminary report of a comparativestudy using PZI insulin with and without con-current vanadium administration (45 mg orallyonce daily), showed that vanadium may reducethe required dosage of insulin (Fondacaro et al1999). However, the biologically available formsof vanadium, such as di- and tripicolinate orbismaltolatooxo, may not be readily obtainableby practitioners.

Chromium, a compound next to vanadium onthe periodic table and with similar properties,has been shown to have small but significanteffects on blood glucose in some normal cats,although there are no reports of its efficacy indiabetic cats (Appleton et al 1999). It has a widesafety margin and if useful, it could be used asan adjunctive dietary additive for diabetic cats.The biologically available tripicolinate form isusually used.

There are anecdotal reports of the use in dia-betic cats of acarbose, an agent which blocksglucose absorption from the gastrointestinal tract(Greco 1999), but there are no studies document-

ing its effectiveness. The lack of post-prandial

1999). An anecdotal report of its use in diabetic

injectable insulin. The types of insulin availableand the rationale for their use in cats has been

The antigenicity of an injected insulin is pro-

Current understanding of feline diabetes: treatment 7the subject of several papers and reviews (Moise& Riemers 1983, Schaer 1983, McMillan &Feldman 1986, Nelson et al 1992b, Bertoy et al1995, Broussard & Wallace 1995, Dowling 1995,Goossens et al 1998) (see Table 1). The followingdiscussion concentrates on some aspects ofinsulin treatment, treatment monitoring, andmaking insulin dose rate adjustments.

Choice of insulin. The choice of insulin for dia-betic cats centres around minimising the numberof injections required each day, while still achiev-ing adequate diabetic control. Insulins used formaintenance are those classified as either inter-mediate duration (lente or NPH [Isophane]), orlong acting (ultralente or protamine zinc insulin[PZI]) (Greco et al 1995). The species of origin ofthe insulin effects the duration of insulin action,with beef insulin being longer acting than pork,and human insulin the shortest in duration(Brange et al 1990). Despite the variation ininsulin types used, no correlation was foundbetween the type of insulin and diabetic control(Goossens et al 1998).cats at a dose of 200 mg once daily suggests itsefficacy may be limited (Greco 1999).

In summary, glipizide is the only oral hypo-glycaemic drug that has well documented ef-fectiveness in diabetic cats. A preliminarystudy suggests vanadium may be a useful ad-junct to insulin treatment to improve insulinsensitivity.

Insulin

The mainstay of treatment in diabetic cats ishypoglycaemia in cats may reduce the usefulnessof acarbose in diabetic cats, but it may have a rolein combination with other agents (Greco 1999).

One drug which has potential to be usefulin the treatment of feline diabetes is met-formin, which enhances peripheral insulinsensitivity and reduces hepatic glucose output(Schernthaner 1985). To date, the only studyreported describes the pharmacokinetics ofmetformin in normal cats (Michels et al1999). Studies on metformin in diabetic cats arecurrently in progress.

The pharmacokinetics of the insulin-resistancereducing drug troglitazone have been reportedfor normal cats in a recent study (Boudinot et alportional to the difference in its amino acidsequence to the amino acid sequence of theanimals native insulin (Neubauer & Schone1978, Schernthaner 1993). Cat insulin is mostsimilar to beef insulin (one amino acid differ-ence), less so to pork (three amino acids dif-ference), and least similar to human (four aminoacids difference) (Hallden et al 1986). Unfortu-nately in many countries, the withdrawal ofanimal insulins for human use, and insulin con-taining the amino acid protamine (PZI), hasdecreased the range of suitable insulins for thetreatment of diabetes in cats.

Human insulin has been found to be effectivein the treatment of feline diabetics (Nelson et al1992b, Bertoy et al 1995). Although most differentfrom feline insulin, it has not been found to beassociated with substantial antibody production.Human insulins are sold as 100 iu/ml concen-tration or greater in most countries, which maycause difficulties in dosing cats, as doses of lessthan 2 iu cannot be measured accurately in aU-100 syringe (Casella et al 1993). Dilution ofinsulin may significantly shorten its durationof action (Binder 1969, Chantelau et al 1985,Heinemann et al 1992).

The long-acting insulin PZI insulin wasparticularly favoured for the treatment of catsuntil it became unavailable as a human product,forcing a change to shorter-acting insulins, whichhave subsequently been found to give as good,and in some cats better glycaemic control. PZIinsulin is now available as a veterinary productin the USA as a 40 iu/ml 90% beef10% porksuspension (PZI insulin; Blue Ridge Pharmacy)and in the UK as a 100 iu/ml beef suspension(Insuvet Protamine Zinc, Schering-Plough Ani-mal Health). PZI can be used once daily in 50%of cats (Moise & Riemers 1983, Goossens et al1998), but is noted for its unpredictable onsetand duration of action (Moise & Riemers 1983).Prolonged marked hypoglycaemia may occurin some cats on PZI and, in some cats, gly-cemic control is poor, possibly because of in-adequate absorption. PZI is particularly usefulfor cats in which the duration of action oflente insulin is too short to give adequate gly-caemic control, and when owners are unwillingto give twice-daily injections. Many cats havegood to excellent clinical control with PZI, butcats which do not achieve good control should betried on a shorter acting insulin such as lente,before the poor control is attributed to insulinresistance.

8 G Martin and J RandTabl

e1.

Exam

ples

ofi

nsul

ins

ford

iabe

ticca

ts

Insu

linA

dva

ntag

esD

isad

vant

ages

Trad

ena

mes

Lon

gac

tin

gPZ

IC

anbe

give

non

ce-d

aily

inm

any

cats

May

have

anun

pred

icta

ble

onse

tan

dd

urat

ion

ofac

tion

.24

-hbl

ood

gluc

ose

curv

essh

ould

bepe

rfor

med

toen

sure

noct

urna

lhy

pogl

ycae

mia

isno

toc

curr

ing.

Acc

urat

ed

osin

gw

ith

100

iu/

ml

prep

arat

ion

may

bea

prob

lem

.Pro

long

edhy

pogl

ycae

mia

may

occu

r

PZI

insu

lin,4

0iu

/m

l*In

suve

t,10

0iu

/m

l(E

urop

e)

Hum

anor

porc

ine

ultr

alen

teC

anbe

used

succ

essf

ully

once

-dai

lyin

som

eca

tsA

sfo

rPZ

I,bu

tfe

wer

cats

can

bem

anag

edon

once

dai

lyul

tral

ente

than

PZI.

The

maj

orit

yof

cats

will

requ

ire

twic

ed

aily

dos

ing.

Som

eca

tsw

illha

vebe

tter

cont

rol

wit

hle

nte

insu

lin.A

ccur

ate

dos

ing

wit

h10

0iu

/m

lpr

epar

atio

nm

aybe

apr

oble

m

Ult

rata

rdor

Ult

rata

rdM

C(p

orci

ne)

100

iu/

ml

Hum

ulin

UL

**10

0iu

/m

l

Bov

ine

ultr

alen

teC

anbe

give

non

ce-d

aily

inm

any

cats

As

for

PZI,

but

may

beso

poor

lyab

sorb

edin

som

eca

tsth

atve

ryhi

ghd

oses

are

need

edto

adeq

uate

lylo

wer

bloo

dgl

ucos

e.A

ccur

ate

dos

ing

wit

h10

0iu

/m

lpr

epar

atio

nm

aybe

apr

oble

m.A

vaila

bilit

yis

apr

oble

min

man

yco

untr

ies

Inte

rmed

iate

acti

ng

NPH

(hum

anor

porc

ine)

Mor

epr

edic

tabl

eon

set

and

dur

atio

nof

acti

onth

anlo

ng-a

ctin

gin

sulin

s.12

-hbl

ood

gluc

ose

curv

esta

ken

dur

ing

the

day

shou

ldgi

vean

ind

icat

ion

ofbl

ood

gluc

ose

stat

usd

urin

gth

eni

ght

asw

ell

asth

ed

ay

Req

uire

stw

ice-

dai

lyd

osag

e.In

man

yca

ts,d

urat

ion

ofac

tion

may

beto

osh

ort

(20 mmol/l) on 0.5 iu/kg insulin when usingporcine lente, and to start cats with lesspronounced hyperglycaemia (blood glucose

Inter-day variability of the insulin response. The Day-to-day variation in insulin sensitivity

2 or more weeks to occur, hence a period of

10 G Martin and J Randresponsiveness of diabetic cats to insulin can befrustratingly variable, both from day to day andover longer periods. For example, we have seendifferences in the nadir (lowest) blood glucose ofgreater than 5 mmol/l on consecutive days. Thereasons for inter-day variability may come fromvariations in the amount of insulin administered,in the concentration of insulin per batch, in theabsorption of insulin, the availability of insulinin the plasma to the insulin receptors, and themagnitude of the responsiveness of the periph-eral tissues (peripheral insulin sensitivity).Because of inter-day variation in insulin effects,the serial blood glucose results should be inter-preted conservatively for the purpose of makingdose rate adjustments.

The rate of insulin absorption may be affectedby the type of insulin, its species of origin,concentration, dose, and handling (Gallowayet al 1981, Hildebrandt 1991, Home & Alberti1992). Practitioners should re-evaluate the bloodglucose response if the insulin type is changed,the insulin dose is changed, or the insulin con-centration is changed. Although U-100 and U-40have a similar time action profile of bloodglucose in humans (Chantelau et al 1985,Heinemann et al 1992), dilutions of insulin by afactor of five or greater may significantly shorteninsulin absorption and the blood glucoseresponse (Binder 1969, Chantelau et al 1985,Heinemann et al 1992). Clients should be advisedcarefully on the appropriate methods of storing,handling, and drawing up of insulin (Greco et al1995). If U-100 syringes are being used with aU-40 insulin, it is important to ensure that thecorrect dose rate is calculated.

Variability in insulin absorption is suspected toaccount for some of the day-to-day variability inthe response to a consistent insulin dose inhumans; factors include: blood flow at the injec-tion site, anatomical location of the injection site,circulating epinephrine, ketoacidosis, amount offat at the injection site, exercise or local massage,injection technique (subcutaneous versus intra-muscular), ambient temperature, scarring andlipodystrophy at the injection site, and/or anti-insulin antibodies causing local degradation ofthe insulin at the injection site (Galloway et al1981, Binder et al 1984, Skyler 1988). The varia-bility in insulin absorption has not been studiedin diabetic cats, but based on the findings inhumans it is advisable to use a consistent injec-tion site and to minimise stress at the time ofinjection to avoid circulating epinephrine release.24 weeks between insulin dose increases isrecommended (Garvey et al 1985, Nijs et al 1989,Link & Rand 1996). This effect is probably dueto the reversal of one or more of the threemajor metabolic lesions of type 2 diabetes:glucose toxicity, decreased insulin sensitivity,and increased hepatic glucose output, asis thought to be a significant cause of inter-dayvariation in normal (Steil et al 1994) and dia-betic (Ziel et al 1988) humans. Studies in nor-mal cats have shown inter-day variation ininsulin sensitivity to be marked (Feldhahn et al1998), and this may also be the case in diabeticcats.

Longer term variability in insulin response. Inhumans, the clinical term brittle diabetes isused to refer to patients whose blood glucoseresponds in an unpredictable fashion to insulininjections, particularly where hypoglycaemiaoccurs (Schade & Burge 1995). One specific causeof brittle diabetes in humans is the loss of thenormal counter-regulatory glucagon response tohypoglycaemia, which may lead to hypoglycae-mia or post-hypoglycaemic hyperglycaemiathrough activated counter-regulation (theSomogyi effect) (Gerich 1988). Cats may exhibitthe features of brittle diabetes, and the Somogyiphenomenon has been previously reportedin insulin-treated diabetic cats (McMillan &Feldman 1986). Although the existence of theSomogyi phenomenon has been subsequentlyquestioned in human diabetology (Kidson 1993),a reduction in the insulin dose may improvecontrol in cats in which either hypoglycaemiaand/or hyperglycaemia is recurrent. Hypo-glycaemia is more common in dogs when inter-mediate acting insulin is given once daily, and inhumans, when long-acting insulin is given twicedaily. If glycaemic control is poor in an indi-vidual cat, especially if insulin seems to havelittle effect when previously it caused substantiallowering of glucose, it is safer to first try lower-ing the dose of insulin to 0.30.5 iu/kg (lenteinsulin) for 23 weeks and see if blood glucoseor water intake improve. Poor control andapparent insulin resistance with persistenthyperglycaemia may result from excessiveinsulin dose.

As the hyperglycaemia of diabetes is reducedby insulin treatment over time, the insulinrequirement of the cat may decrease (Garveyet al 1985, Link & Rand 1996). This effect requires

hyper glycaemia is diminished (Garvey et al

every 3060 min until the blood glucose rises, to

Stress resulting in struggling can acutely

glucose curve to allow them to settle into a

methods for measuring blood glucose are under

Current understanding of feline diabetes: treatment 11determine if glucose should be administered.Typically, blood glucose is measured every 2 h,from immediately prior to one insulin dose toimmediately prior to the subsequent insulindose. If insulin is given once daily, ideally theblood glucose should be followed for 24 h, asnocturnal hypoglycaemia may occur even if theblood glucose is normal or elevated during theday. If the insulin is given twice daily, 12 hshould be suitable, although it is uncertain if theovernight blood glucose curve will exactly matchthe daytime curve. When Caninsulin was used,the median nadir was found to be statisticallyhigher during the night than during the day(Martin & Rand, unpublished data).

Pocket glucometers are sufficiently accurate touse to perform serial blood glucose curves in aclinical setting (Link et al 1997). The limitationsof such meters, such as the maximum bloodglucose measurable and the tendency to befalsely low at the lower end of the range, shouldbe considered when interpreting results (Linket al 1997).1985). The insulin requirement may increase insome cats after several months of therapy asfurther loss of beta cells occurs.

In cats where some functional islet cellsremain, resumption of beta-cell function mayoccur after at least 12 weeks of good glycaemiccontrol, which may lead to cessation of thediabetes within 13 months (Link & Rand 1996).If the loss of beta cells is too great for diabeticremission to occur, the cat may remain insulin-dependent but with reduced insulin doses beingrequired. Sudden or gradual reductions of morethan 50% in the required insulin dose may occureven after several months of insulin therapy incats, possibly through this mechanism (Martin &Rand, unpublished data).

A recent study found that diabetic control wasnot correlated with anti-insulin antibody titre indiabetic cats (Harb-Hauser et al 1998). Furtherstudies are needed to determine if insulin anti-bodies affect diabetic control in certain felinediabetics with, for example, high insulin require-ments or repeated episodes of hypoglycaemia.

Serial blood glucose curves. Serial blood glucosecurves are essential for establishing and monitor-ing the blood glucose response to insulin, and formaking insulin dose rate adjustments (Miller1995, Zerbe 1999). When a low blood glucose(

nadir gives an indication of how rapidly the cat despite the mean blood glucose remaining high

poorly controlled diabetics, and untreated dia-

12 G Martin and J Randis responding to the insulin injection. The nadirof blood glucose determines whether the insulindose should be increased or decreased.

In practice the most important value to deter-mine is the nadir blood glucose, as this indicatesthe maximum dose of insulin which can betolerated by the cat. The dose should not beincreased to the point where hypoglycaemicepisodes are likely (

was found that normal cats infused with glucose

fructosamine is probably most useful for monitor-

as a measure of diabetic control. If significant

better information. For PZI, glucose should bemeasured for at least 6, 8, 12, and 14 h after

Current understanding of feline diabetes: treatment 13ing change in an individual diabetic cat over time.There are no studies that demonstrate convincinglythat glycated proteins are better, or even as usefulas clinical parameters and blood glucose measure-ment for monitoring diabetic control in cats.

Urine glucose measurements are an inexpen-sive and simple method for monitoring of dia-betic status by the owner, and can be measuredfrom urine soaked cat litter if necessary (Schaer1994). However, urine glucose also does not giveinformation about how an insulin dose should bechanged, and is most useful for indicating orpredicting diabetic remission. We get owners tomeasure urine glucose once or twice weekly ifpossible, particularly in the first 36 months oftherapy. If the cat becomes aglycosuric, this mayindicate that diabetic remission has occurred,and the insulin can be discontinued for severaldays while the urine glucose is monitored daily.If glycosuria recurs, it may be necessary to per-form a serial blood glucose curve to determinethe subsequent insulin dose. Substantial worsen-ing of glycosuria in a diabetic cat indicates thatthe cat should be re-evaluated using blood glu-cose measurements to determine the direction ofadjustment of insulin dose.

Owner initiated dose rate changes and home moni-toring. As the blood glucose response to insulinis so variable, and individual blood glucosemeasurements may be easily influenced bystress, owner monitoring of blood glucose maygive a better indication of true glycaemic control,especially if curves are performed frequently, forexample weekly. However, owner-initiated insu-lin dose rate changes are not recommended andinsulin dose rate adjustments should follow dis-cussion with the veterinarian managing the case.

We advise owners to monitor urine glucose,bodyweight, and the cats food and water intaketo create hyperglycaemia of around 20 mmol/ldid not have fructosamine levels above thereference range (Link & Rand 1995).

High fructosamine levels (>500 mol/l) indicatea problem, but not necessarily whether the insulindose needs to be increased or decreased. Makinginsulin dose rate changes on the basis of fructos-amine measurements should be done with caution,as the fructosamine level does not give an indi-cation of the nadir blood glucose. However,fructosamine may be a useful marker where stressor fractiousness makes an accurate serial bloodglucose curve unobtainable. As with water intake,administration. However, better information isgained by including 0, 2 and 4 h measurements.

Concomitant diseaseSeveral diseases which cause insulin resistancemay underlie or complicate the treatment ofdiabetes; in particular hyperthyroidism, hyper-adrenocorticism, acromegaly, infections, pancrea-titis, and uraemia from renal failure (Ihle &Nelson 1991, Peterson 1995). Bacterial cystitis,which occurs with a high incidence in diabetic catsespecially if polyuria is present (Crenshaw &Peterson 1996, Kirsch 1998), should be treated withappropriate antibiotics. Although there have beenno detailed studies, anecdotal reports indicate thatdiabetic cats commonly have dental disease andchronic gingivitis (Diehl 1995). The authors haveencountered insulin-treated diabetic cats in whichdiabetic control improved markedly when thedental disease was treated. It has been recorded inother species that chronic inflammatory diseasemay lead to a chronic hypercortisolaemia (Ley et al1994), which may reduce insulin sensitivity andtherefore in diabetics decrease insulin responsive-ness. Although treatment of concurrent diseasewill not improve glycaemic control in some cats(Goossens et al 1998), it is recommended thatchanges occur, or if markedly abnormal valuespersist, a serial blood glucose curve should beperformed before insulin dose rate changes aremade. Cats may have marked polydipsia andglycosuria while having a low blood glucosenadir, so increasing the insulin dose withoutperforming serial blood glucose measurementsrisks a hypoglycaemic episode. If blood glucoseis only measured in the afternoon when usingtwice daily insulin, especially lente or NPH insu-lin, the nadir glucose may be missed. This maylead to inappropriate dose increases and a risk ofhypoglycaemia. If only a few blood glucosemeasurements are performed for cost reasons,the best information is gained from glucosemeasurements around the time of, and includingthe glucose nadir. With lente insulin, the nadiroccurs approximately 4 h after insulin admin-istration. With PZI insulin, the time of nadirglucose is very variable. For lente insulin, glu-cose measurements at 2, 4, and 6 h may besufficient to make an informed adjustment ofinsulin dose, but measurements every 2 h from 0to 8 or 12 h after insulin administration gives

chronic disorders of this type are addressed as part

acidosis at diagnosis, poor glycaemic control,and the presence of concurrent disease (princi-

ful treatment requires an understanding of theadvantages and limitations of different treatment

performing blood glucose curves in a clinic orhome setting.

v Measure blood glucose immediately before

concentration at nadir, time to reach nadir ofblood glucose, and the mean blood glucose.

and more than 12 mmol/l by 12 h after injec-tion, or (2) the blood glucose level drops to a

14 G Martin and J Randv Feed as usual.modalities, and the rationale for clinical decisionmaking and therapeutic monitoring.

Summary: blood glucose curvesand changing the insulin doseMeasuringv Ensure that stress and struggling are mini-

mised.v Use venous catheters or vacuum assisted

lances to obtain multiple samples atraumati-cally.

v Pocket blood glucose meters are suitable forpally renal failure) (Kraus et al 1997, Goossenset al 1998).

Concluding remarksThrough an understanding of the pathophysiol-ogy of feline diabetes, cats can be treated moreeasily and successfully. Studies demonstratingthe lack of post-prandial hypoglycaemia in catshave highlighted an important species difference,that shows ad libitum feeding is suitable fordiabetic cats. Glipizide remains the only oralagent that has been studied in detail in diabeticcats. Preliminary studies have been performedon other agents, but further clinical studies indiabetic cats are necessary to determine theefficiency of these drugs. Currently, insulin pro-vides the most successful clinical and glycaemiccontrol for the majority of diabetic cats. Success-nosed with diabetes survive less than 12 months(Kraus et al 1997, Goossens et al 1998). Factorsreducing survival time included diabetic keto-of the diabetes treatment regime.

SurvivalIn one study of 92 diabetic cats, average survivaltime was 17 months (Goossens et al 1998). Thesurvival of diabetic cats is affected by old ageand concurrent disease, as the diabetic cats inthis study had a mean age of 12 years (Goossenset al 1998). A significant proportion of cats diag-distinct nadir then rises back above 15 mmol/lby 12 h after injection

v If the nadir of blood glucose is occurringwithin 2 or 3 h of injection, a longer actinginsulin should be considered.

v Insulin dose rate changes should be madeconservatively. Where indicated, dose increasesshould be made at 24 week intervals and1 unit at a time.The difference between baseline and nadirmay be measured, as well as the time takenfor the blood glucose to return to baselineconcentration.

v The nadir of blood glucose concentration is themost important parameter for determininginsulin dose rate changes, as it determineswhether the dose can be safely increased, or ifthe dose needs to be reduced.

v The time taken to reach blood glucose nadirand the time taken to return to baseline bloodglucose concentration are used to determinethe dose frequency and the insulin type.

v The difference between baseline and nadir ofblood glucose concentration can be used todetermine how responsive the cat is to givendoses of insulin.

v The mean blood glucose gives a measure of theoverall diabetic control.

Insulin and dose changesv Twice-daily administration is indicated if

either: (1) the blood glucose drops to a nadirand returns to within 6070% of the baselineinsulin is given, then every 2 h.v Preferably follow the blood glucose through to

the next insulin dose (12 or 24 h later).v If this is not possible, follow the blood glucose

until it comes back close to baseline.v If the blood glucose drops below 3.0 mmol/l,

take more frequent samples to ensure hypo-glycaemia is avoided. Administer oral orparenteral glucose as needed.

Interpretingv Parameters that can be determined from the

serial blood glucose curve include baselineblood glucose concentration, blood glucose

v The target for treatment is to achieve a blood

Bruskiewicz KA, Nelson RW, Feldman EC, Griffey SM (1997)Diabetic ketosis and ketoacidosis in cats: 42 cases (1980

human and porcine insulin in different concentrations.

Current understanding of feline diabetes: treatment 151995). Journal of the American Veterinary Medical Association211, 188192

Burrows CF (1973) Techniques and complications of intra-venous and intraarterial catheterization in dogs and cats.Journal of the American Veterinary Medical Association 163,13571363

Casella SJ, Mongilio MK, Plotnick LP, Hesterberg MP, LongCA (1993) Accuracy and precision of low-dose insulinadministration. Pediatrics 91, 11551157

Chantelau E, Sonneberg GE, Rajab A, Romisch J, Berger M(1985) Absorption of subcutaneously administered regularglucose concentration of 5.09.0 mmol/l atnadir. If the nadir blood glucose is greaterthan 9.0 mmol/l, the insulin dose should beincreased by 1 iu.

v Daily changes in insulin dose based on foodintake are not recommended. If the cat shows areduced or lack of appetite for more than1224 h at home, the veterinarian shouldexamine the cat.

ReferencesAnderson JW, Akanji AO (1991) Dietary fiberan overview.

Diabetes Care 14, 11261131Appleton DJ, Rand JS, Priest J, Sunvold GD (1999) Reference

values for glucose tolerance, insulin tolerance, and insulinsensitivity tests in normal cats (Abstract). Proceedings ofthe 17th ACVIM Forum, Chicago, IL, USA, p. 375

Arnold MA (1996) Non-invasive glucose monitoring. CurrentOpinion in Biotechnology 7, 4649

Bertoy EH, Nelson RW, Feldman EC (1995) Effect of lenteinsulin for treatment of diabetes mellitus in 12 cats. Jour-nal of the American Veterinary Medical Association 206,17291731

Binder C (1969) Absorption of injected insulin: a clinical-pharmacological study (Thesis). Acta Pharmacologica etToxicologica 27 (Suppl 2), 187

Binder C, Lauritzen T, Faber O, Pramming S (1984) Insulinpharmacokinetics. Diabetes Care 7, 188199

Biourge V, Nelson RW, Feldman EC, Willits NH, Morris JG,Rogers QR (1997) Effect of weight gain and subsequentweight loss on glucose tolerance and insulin response inhealthy cats. Journal of Veterinary Internal Medicine 11,8691

Boudinot FD, Ferguson DC, Hoenig M (1999) Pharmaco-kinetics of troglitazone, an insulin-senstitising agent, inhealthy cats (Abstract). Proceedings of the 17th ACVIMForum, Chicago, IL, USA, p. 708

Brange J, Owens DR, Kang S, Volund A (1990) Monomericinsulins and their experimental and clinical implications.Diabetes Care 13, 923954

Broussard JD, Peterson ME (1994) Comparison of two ultra-lente insulin preparations with protamine zinc insulinin clinically normal cats. American Journal of VeterinaryResearch 55, 127131

Broussard JD, Wallace MS (1995) Insulin treatment ofdiabetes mellitus in the dog and cat. In: Kirks CurrentVeterinary Therapy Bonagura J (ed). Philadelphia, USA, WBSaunders, pp. 393398Diabete et Metabolisme 11, 106110Chow C-C, Tsang LWW, Sorenson J-P, Cockram CC (1995)

Comparison of insulin with or without continuation oforal hypoglycemic agents in the treatment of secondaryfailure in NIDDM patients. Diabetes Care 18, 307314

Crenshaw KL, Peterson ME (1996) Pretreatment clinical andlaboratory evaluation of cats with diabetes mellitus:104 cases (19921994). Journal of the American VeterinaryMedical Association 209, 943949

Crenshaw KL, Peterson ME, Heeb LA, Moroff SD, Nichols R(1996) Serum fructosamine concentration as an indexof glycemia in cats with diabetes mellitus and stresshyperglycemia. Journal of Veterinary Internal Medicine 10,360364

Diehl KJ (1995) Long-term complications of diabetesmellitus, part II: gastrointestinal and infectious. Veterin-ary Clinics of North America. Small Animal Practice 25,731752

Dow SW, Lecouteur RA, Fettman MJ, Spurgeon TL (1987)Potassium depletion in cats. Journal of the AmericanVeterinary Medical Association 191, 15631568

Dowling PM (1995) Insulin therapy for dogs and cats.Canadian Veterinary Journal 36, 577579

Eaton RP, Spencer W, Schade DS, Shafer BD, Corbett W(1978) Diabetic glucose control: matching plasma insulinconcentration to dietary and stress hyperglycemia.Diabetes Care 1, 4044

Elliott DA, Nelson RW, Feldman EC, Neal LA (1997)Glycosylated hemoglobin concentration for assessment ofglycemic control in diabetic cats. Journal of VeterinaryInternal Medicine 11, 161165

Feldhahn JR, Rand JS, Martin GJ (1998) Insulin sensitivity innormal and diabetic cats, and normal cats under stress(Abstract). 16th Annual Veterinary Medical Forum of theAmerican College of Veterinary Internal Medicine, SanDiego, CA, USA

Feldman EC, Nelson RW, Feldman MS (1997) Inten-sive 50-week evaluation of glipizide administration in50 cats with previously untreated diabetes mellitus.Journal of the American Veterinary Medical Association 210,772777

Feldman EC Nelson RW, (1996) Canine and Feline Endo-crinology and Reproduction (2nd edn). W.B. Saunders,Philadelphia

Fondacaro JV, Greco DS, Crans DC (1999) Treatment of felinediabetes mellitus with protamine zinc alanine insulinalone compared with PZI and oral vanadium salts(Abstract). Proceedings of the 17th ACVIM Forum,Chicago, IL, USA, p. 710

Forrester SD, Moreland KJ (1989) Hypophosphatemia.Causes and clinical consequences. Journal of VeterinaryInternal Medicine 3, 149159

Galloway JA, Spradlin CT, Nelson RL, Wentworth SM,Davidson JA, Swarner JL (1981) Factors influencing theabsorption, serum insulin concentration, and blood glu-cose after injections of regular insulin and various insulinmixtures. Diabetes Care 4, 366376

Garvey WT, Olefsky JM, Griffin J, Hamman RF, KoltermanOG (1985) The effect of insulin treatment on insulinsecretion and action in type 2 diabetes mellitus. Diabetes34, 222234

Gerich JE (1988) Lilly lecture 1988. Glucose counterregu-lation and its impact on diabetes mellitus. Diabetes 37,16081617

Goossens MMC, Nelson RW, Feldman EC, Griffey SM (1998) Kraus MS, Calvert CA, Jacobs GJ, Brown J (1997) Feline

16 G Martin and J RandResponse to treatment and survival in 104 cats withdiabetes mellitus (1985-1995). Journal of Veterinary InternalMedicine 12, 16

Greco DS (1997) Treatment of non-insulin dependentdiabetes mellitus with oral hypoglycemic agents. 15thAnnual Forum of the American College of VeterinaryInternal Medicine, Lake Buena Vista, Florida, USA,pp. 252254

Greco DS (1999) Oral hypoglycemic therapy in cats. Proceed-ings of the 17th ACVIM Forum, Chicago, IL, USA,pp. 647649

Greco DS, Broussard JD, Peterson ME (1995) Insulin therapy.Veterinary Clinics of North America. Small Animal Practice25, 677690

Hallden G, Gafvelin G, Mutt V, Jornvall H (1986) Charac-terization of cat insulin. Archives of Biochemistry andBiophysics 247, 2027

Hand MS, Armstrong PJ, Allen TA (1989) Obesity: occur-rence, treatment, and prevention. Veterinary Clinics ofNorth America. Small Animal Practice 19, 447474

Harb-Hauser M, Nelson R, Gershwin L, Neal L (1998)Prevalence of insulin antibodies in diabetic cats (Abstract).16th Annual Forum of the American College of VeterinaryInternal Medicine, San Diego, USA, p. 735

Heinemann L, Chanteleau EA, Starke AAR (1992) Pharmaco-kinetics and pharmacodynamics of subcutaneouslyadministered U40 and U100 formulations of regularhuman insulin. Diabete et Metabolisme 18, 2124

Hildebrandt P (1991) Subcutaneous absorption of insulinin insulin-dependent diabetic patients. Danish MedicalBulletin 38, 337346

Hoenig M, OBrien TD (1998) Glipizide leads to amyloidosisin a cat model of type 2 diabetes (Abstract). Diabetologia(Suppl. 1), A648

Home PD, Alberti KGGM (1992) Insulin therapy. In: Inter-national Textbook of Diabetes Mellitus, Alberti KGGM,DeFronzo RA, Keen H, Zimmet P (eds.), Vol. 1. John Wileyand Sons, Chichester, NY, pp. 831863

Houpt KA (1991) Ingestive behaviour: food and waterintake. In: Domestic Animal Behavior for Veterinarians andAnimal Scientists, Houpt KA (ed.). Iowa State UniversityPress, Ames, Iowa, USA, 270306

Ihle SL, Nelson RW (1991) Insulin resistance and diabetesmellitus. Compendium on Continuing Education for thePracticing Veterinarian 13, 197203

Kane E (1989) Feeding behaviour of the cat. In: Nutritionof the Dog and Cat. Waltham Symposium 7, Kronfeld DS,Adkins TO, Downey R, Burger IH, Rivers JP (eds.).Cambridge University Press, Cambridge, UK, pp. 147158

Kidson W (1993) The Somogyi effect. Has it ever existed andwhat harm has it caused? Medical Journal of Australia 159,480482

Kienzle E (1994) Blood sugar levels and renal sugar excretionafter the intake of high carbohydrate diets in cats. Journalof Nutrition 124, 2563S2567S

Kinnaird ER, Rand JS, Baglioni Jr AJ, Blackshaw J (1998)Stress hyperglycaemia in cats (Abstract). 16th AnnualVeterinary Medical Forum of the American College ofVeterinary Internal Medicine, San Diego, USA, p. 703

Kirsch M (1998) [Incidence of bacterial cystitis in diabeticdogs and cats at the time of diagnosis. Retrospective studyfor the period 19901996]. Tierarztliche Praxis Ausgabe K(Klientiere und Heimtiere) 26, 3236diabetes mellitus: a retrospective mortality study of 55cats (1982-1994). Journal of the American Animal HospitalAssociation 33, 107111

Laflamme DP, Cornelius LM, Roberts HE (1993) Enteralnutrition as an adjunct to the management of a compli-cated case of diabetes mellitus in a cat. Journal of theAmerican Animal Hospital Association 29, 264266

Ley SJ, Waterman AE, Livingston A, Parkinson TJ (1994)Effect of chronic pain associated with lameness on plasmacortisol concentrations in sheep: a field study. Research inVeterinary Science 57, 332335

Link KRJ, Rand JS (1995) Changes in fructosamine concen-tration in cats with induction and resolution of chronichyperglycemia (abstract). Journal of Veterinary InternalMedicine 9, 180

Link KRJ, Rand JS (1996) Glucose toxicity in cats (abstract).Journal of Veterinary Internal Medicine 10, 185

Link KRJ, Rand JS, Hendrikz JK (1997) Evaluation of asimplified intravenous glucose tolerance test and a reflect-ance glucose meter for use in cats. Veterinary Record 140,253256

Macintire DK (1995) Emergency therapy of diabetic crises:insulin overdose, diabetic acidosis, and hyperosmolarcoma. Veterinary Clinics of North America. Small AnimalPractice 25, 639650

Martin GJ, Rand JS (1997) Lack of correlation betweenfeeding and blood glucose in diabetic cats (Abstract). 15thAnnual Forum of the American College of VeterinaryInternal Medicine, Orlando, Florida, USA

Martin GJW, Rand JS (1999a) Correlations between monitor-ing parameters for insulin-treated diabetic cats (Abstract).Proceedings of the 17th ACVIM Forum, Chicago, IL, USA,p. 735

Martin GJW, Rand JS (1999b) Evaluation of a poly-urethane jugular catheter in cats placed using a modifiedSeldinger technique. Australian Veterinary Journal 77, 250254

McMillan FD, Feldman EC (1986) Rebound hypoglycemiafollowing overdosing of insulin in cats with diabetesmellitus. Journal of the American Veterinary MedicalAssociation 188, 14261431

Michels GM, Boudinot FD, Ferguson DC, Hoenig M (1999)Pharmacokinetics of the antihyperglycemic drug met-formin in cats. Journal of Veterinary Internal Medicine 60,738742

Miller E (1995) Long-term monitoring of the diabetic dogand cat: clinical signs, serial blood glucose deter-minations, urine glucose, and glycated blood proteins.Veterinary Clinics of North America. Small Animal Practice25, 571584

Miller AB, Nelson RW, Kirk CA, Neal N, Feldman EC (1992)Effect of glipizide on serum insulin and glucose concen-trations in healthy cats. Research in Veterinary Science 52,177181

Moise NS, Riemers TJ (1983) Insulin therapy in cats withdiabetes mellitus. Journal of the American Veterinary MedicalAssociation 182, 158164

Morris JG, Rogers QR (1983) Nutritional implications ofsome metabolic anomalies of the cat. Proceedings of the50th Annual Meeting of the American Animal HospitalAssociation, USA, pp. 325331

Munana K (1995) Long-term complications of diabetesmellitus, part I: retinopathy, nephropathy, neuropathy.

Veterinary Clinics of North America. Small Animal Practice25, 715730

Nelson R, Feldman E, Ford S, Kirk C (1992a) Transientdiabetes mellitus in the cat (Abstract). Journal of VeterinaryInternal Medicine 6, 111

Nelson R, Scott-Montcrief C, DeVries S, Davenport D, Neal L(1994) Dietary insoluble fiber and glycemic control ofdiabetic cats (Abstract). Proceedings of the 12th ACVIMForum, San Francisco, CA, USA, p. 996

Nelson RW, Feldman EC, DeVries SE (1992b) Use ofultralente insulin in cats with diabetes mellitus. Journalof the American Veterinary Medical Association 200, 18281829

Schade DS, Burge MR (1995) Brittle diabetes: etiology andtreatment. Advances in Endocrinology and Metabolism 6,289319

Schaer M (1983) Insulin treatment for the diabetic dog andcat. Compendium on Continuing Education for the PracticingVeterinarian 5, 579588

Schaer M (1994) A method for detecting glycosuria in urinesoaked cat litter. Feline Practice 22, 69

Schernthaner G (1985) Improvement of insulin action is animportant part of the antidiabetic effect of metformin.Hormone and Metabolic Research. Supplement 15, 116120

Schernthaner G (1993) Immunogenicity and allergic

Current understanding of feline diabetes: treatment 17Nelson RW, Feldman EC, Ford SL, Roemer OP (1993) Effectof an orally administered sulphonylurea, glipizide, fortreatment of diabetes mellitus in cats. Journal of theAmerican Veterinary Medical Association 203, 821827

Nelson RW, Himsel CA, Feldman EC, Bottoms GD (1990)Glucose tolerance and insulin response in normal weightand obese cats. American Journal of Veterinary Research 51,13571362

Neubauer HP, Schone HH (1978) The immunogenicity ofdifferent insulins in several animal species. Diabetes 27,815

Nicholls R, Crenshaw KL (1995a) Complications and concur-rent disease associated with diabetic ketoacidosis andother severe forms of diabetes mellitus. In: Kirks CurrentVeterinary Therapy, Bonagura J (ed.). Philadelphia, USA,WB Saunders, pp. 384387

Nicholls R, Crenshaw KL (1995b) Complications and concur-rent disease associated with diabetic ketoacidosis andother severe forms of diabetes mellitus. Veterinary Clinicsof North America. Small Animal Practice 25, 617624

Nijs HGT, Radder JK, Frolich M, Krans HMJ (1989) Thecourse and determinants of insulin action in type 1(insulin-dependent) diabetes mellitus. Diabetologia 32,2027

Peterson ME (1995) Diagnosis and management of insulinresistance in dogs and cats with diabetes mellitus.Veterinary Clinics of North America. Small Animal Practice25, 691714

Rachman J, Payne MJ, Levy JC, Barrow BA, Holman RR,Turner RC (1998) Changes in amylin and amylin-likepeptide concentrations and beta-cell function in responseto sulfonylurea or insulin therapy in NIDDM. DiabetesCare 21, 810816

Rand JS (1997) Management of feline diabetes. AustralianVeterinary Practitioner 27, 6878

Rand JS (1999) Current understanding of feline diabetes:Part 1, pathogenesis. Journal of feline Medicine and Surgery1, 143153

Reichard P (1994) A risk-benefit assessment of conven-tional versus intensive insulin therapy. Drug Safety 10,196202potential of animal and human insulins. Diabetes Care 16(Suppl 3), 155165

Skyler JS (1988) Insulin pharmacology. Medical Clinics ofNorth America 72, 13371354

Sloth C (1992) The practical management of obesity incats and dogs. Journal of Small Animal Practice 33, 178182

Steil GM, Murray J, Bergman RN, Buchanan TA (1994)Repeatability of insulin sensitivity and glucose effective-ness from the minimal model. Implications for studydesign. Diabetes 43, 13651371

Thoresen SI, Bredal WP (1996) Clinical usefulness of fructo-samine measurements in diagnosing and monitoringfeline diabetes mellitus. Journal of Small Animal Practice 37,6488

Tunbridge FKE, Newens A, Home PD, Davis SN, MurphyM, Burrin JM, Alberti KGGM, Jensen I (1989) A compari-son of human ultralente- and lente-based twice-dailyinjection regimens. Diabetic Medicine 6, 496501

Wess G, Reusch C (1999) New methods for simplifiedglucose measurements by capillary blood sampling(Abstract). Proceedings of the 17th ACVIM Forum,Chicago, IL, USA, p. 734

Whitley NT, Drobatz KJ, Panciera DL (1997) Insulin over-dose in dogs and cats: 28 cases (19861993). Journal of theAmerican Veterinary Medical Association 211, 326330

Willard MD, Zerbe CA, Schall WD, Johnson C, Crow CE,Jones R (1987) Severe hypophosphatemia associatedwith diabetes mellitus in six dogs and one cat. Journalof the American Veterinary Medical Association 190, 10071010

Zerbe CA (1999) The glucose curve: what is it and howshould we use it? Proceedings of the 17th ACVIM Forum,Chicago, IL, USA, pp. 436437

Ziel FH, Davidson MB, Harris MD, Rosenberg CS (1988) Thevariability in the action of unmodified insulin is moredependent on changes in tissue sensitivity than on insulinabsorption. Diabetic Medicine 5, 662666

Zimmerman BR (1997) Sulfonylureas. Endocrinology andMetabolism Clinics of North America 26, 511522

Current understanding of feline diabetes: Part 2, treatmentSick ketotic diabetic catsTherapeutic goals for otherwise healthy diabetic catsTreatment modalitiesDietGeneral considerationsFeeding recommendations for diabetic catsObese diabetics

Oral hypoglycaemicsInsulinChoice of insulin

Table 1Starting dose of insulinInter-day variability of the insulin responseLonger term variability in insulin responseSerial blood glucose curvesBlood collectionInsulin dose adjustmentsMonitoring diabeticsOwner initiated dose rate changes and home monitoring

Concomitant diseaseSurvivalConcluding remarksSummary: Blood glucose curves and changing the insulin doseMeasuringInterpretingInsulin and dose changes

References