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S P E C I A L A R T I C L E
Journal of Feline Medicine and Surgery (2015) 17 , 235–250
Andrew H SparkesBVetMed PhD DipECVIM
MANZCVS MRCVS Veterinary Director, ISFM1
Panel Chair*
Martha CannonBA VetMB DSAM(Fel) MRCVS2
David ChurchBVSc PhD MANZCVS MRCVS3
Linda FleemanBVSc PhD MANZCVS4
Andrea HarveyBVSc DSAM(Fel) DipECVIM
MANZCVS MRCVS5
Margarethe HoenigDrMedVet PhD6
Mark E PetersonDVM DipACVIM7
Claudia E ReuschDVM DipECVIM8
Samantha TaylorBVetMed(Hons) CertSAM
DipECVIM MRCVSInternational Cat Care Distance
Education Coordinator 1
Dan RosenbergDVM PhD9
1International Cat Care/ISFM,Tisbury, Wiltshire SP3 6LD, UK
2Oxford Cat Clinic,Oxford OX2 9JU, UK
3Professor, Small Animal Medicineand Surgery Group,
The Royal Veterinary College,North Mymms, Hatfield,
Hertfordshire AL9 7TA, UK4 Animal Diabetes Australia,
Rowville Veterinary Clinic, Rowville, VIC 3178, Australia
5Small Animal Specialist Hospital,North Ryde, NSW 2113, Australia
6Professor, Department of Veterinary Clinical Medicine,University of Illinois College
of Veterinary Medicine,Urbana-Champaign, Illinois, USA
7 Animal Endocrine Clinic,21 West 100th Street, New York,
NY 10025, USA 8Professor & Director, Clinic forSmall Animal Internal Medicine, Vetsuisse Faculty, University ofZurich, Winterthurerstrasse 260,
8057 Zurich, Switzerland9Micen Vet Centre, 58 Rue Auguste
Perret, Parc Technologique,Europarc, 9400 Créteil, France
*Correspondence:[email protected]
ISFM Consensus Guidelines
on the Practical Management
of Diabetes Mellitus in Cats
JFMS CLINICAL PRACTICE 235Doi: 10.1177/1098612X15571880© iSFM and AAFP 2015
Practical relevance: Diabetes mellitus (DM) is a common endocrinopathy in cats that
appears to be increasing in prevalence. The prognosis for affected cats can be good when
the disease is well managed, but clinical management presents challenges, both for the
veterinary team and for the owner. These ISFM Guidelines have been developed by an
independent, international expert panel of clinicians and academics to provide practical advice
on the management of routine (uncomplicated) diabetic cats.
Clinical challenges: Although the diagnosis of diabetes is usually straightforward, optimal management
can be challenging. Clinical goals should be to limit or eliminate clinical signs of the disease using atreatment regimen suitable for the owner, and to avoid insulin-induced hypoglycaemia or other
complications. Optimising bodyweight, feeding an appropriate diet and using a longer acting insulin
preparation (eg, protamine zinc insulin, insulin glargine or insulin detemir) are all factors that are likely to
result in improved glycaemic control in the majority of cats. There is also some evidence that improved
glycaemic control and reversal of glucose toxicity may promote the chances of diabetic remission. Owner
considerations and owner involvement are an important aspect of management. Provided adequate support
is given, and owners are able to take an active role in monitoring blood glucose concentrations in the home
environment, glycaemic control may be improved. Monitoring of other parameters is also vitally important
in assessing the response to insulin. Insulin adjustments should always be made cautiously and not too
frequently – unless hypoglycaemia is encountered.
Evidence base: The Panel has produced these Guidelines after careful review of the existing literature
and of the quality of the published studies. They represent a consensus view on practical management of
cats with DM based on available clinical data and experience. However, in many areas, substantial data arelacking and there is a need for better studies in the future to help inform and refine recommendations for
the clinical management of this common disease.
Introduction
Dabetes melltus (DM) s a cmmn dseasen cats, wth sme estmates suggestng aprevalence n frst pnn practce f arund1:100–1:500.1–3 There s als evdence that theprevalence f felne DM has been ncreasng,pssbly at least partly due t the rse nprevalence f besty.4
Managng DM n cats represents a challengefr bth wners and the veternary healthcareteam, and cnsderable supprt s needed frwners as they cntnue t care fr cats nthe hme envrnment. Studes have shwnmedan survval tmes n cats wth DM f
between 13 and 29 mnths, wth lnger sur-vval tmes n better stablsed cats, and wthmany cats dyng f dseases ther than DM.5–7The prgnss fr cats wth DM s thus gdwhen the dsease s well managed.
These Gudelnes have been develped byan ndependent, nternatnal expert panel f clncans and academcs wth the am fprducng practcal advce fr dealng wththe rutne dabetc cat, based n currentlyavalable best evdence. The Gudelnes arent ntended t be a cmprehensve resurcen all aspects f management f DM, andreferences t ther resurces are prvdedwhere relevant.
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Epidemiology, pathogenesisand diagnosis
The majrty f cats wth DM appear t havea dsease bearng smlartes t human type 2DM,8–11 resultng frm β-cell dysfunctn andnsuln resstance; type 1 DM (mmune-med-ated) s rare n cats.12 in cats wth DM, the
β-cell dysfunctn usually results n nsulndefcency and s lkely t be caused by anumber f factrs ncludng slet amylddepstn, glucse txcty and pssblydamage frm reactve xygen speces and/rnflammatry cytknes.13 Many factrs maycntrbute t nsuln resstance – besty sa cmmn cause, but thers nclude cn-cmtant endcrnpathes (eg, acrmegaly,hyperadrencrtcsm), drug-nduced da-
betes (eg, crtcsterds, prgestagens) andpancreatts. imprtantly, f nsuln resstancecan be reduced and β-cell functn mprved,n sme cats dabetc remssn may beacheved; n ther wrds, exgenus nsulntherapy may n lnger be needed, althughthe remssn may nly be temprary n smecases.14
Clinical signs and risk factorsClassc clncal sgns f DM nclude plyuraand plydpsa (PU/PD), lethargy, weght lssand plyphaga. Less cmmnly, weakness,plantgrade stance, depressn and anrexamay be seen (the last especally wth ket-acdss).
Numerus studes have dentfed rsk
factrs fr the develpment f felne DM,althugh the presence f undentfed cn-cmtant dsease (eg, acrmegaly) may havenfluenced the results btaned. Majr reprt-ed rsk factrs nclude: Obesity Ths reduces nsuln senstvtyand bese cats are up t fur tmes mrelkely t develp DM than ptmal-weghtcats.2–4,8,15–19 Increasing age Cats ver 7 years ld areat greatest rsk.2,4,18 Breed Burmese cats have been reprted thave a hgher rsk n studes frm Australa,New Zealand and Eurpe.2,20,21 Physical inactivity indr and nactvecats are at ncreased rsk.2,3,20,22 Gender Male cats and neutered cats areat hgher rsk.2–4,18,20,21,23 Drug treatment Gluccrtcds andprgestagens may cause nsuln resstanceand predspse cats t DM.2,24,25
236 JFMS CLINICAL PRACTICE
DiagnosisDabetes s usually dagnsed by dcument-ng persstent hyperglycaema and glucsura,wth cnsstent clncal sgns. Stress hyper-glycaema (and glucsura) must be excludedprr t ntatng therapy – stress uncmmn-ly causes hyperglycaema >16 mml/l (288mg/dl) (althugh ccasnally bld glucse
[BG] can be very hgh) and generally treslves wthn a few hurs. Repeat bld andurne mntrng wll cnfrm persstenthyperglycaema wth DM, and hme mntr-ng f these parameters may be useful wherethe dagnss s n dubt.
Serum fructsamne s ndcatve f theaverage BG durng apprxmately the preced-ng week,26 and may nt be affected by shrt-term stress hyperglycaema (dependng n tsmagntude and duratn). its measurementcan be helpful n cnfrmng a dagnss f DM and n mntrng glycaemc cntrl(see page 245), althugh t may nt bencreased n cats wth recent-nset and/rmld DM.23,26–28
Evaluation of the diabetic cat
Evaluatn f a cat wth suspected DM shuldnclude: Thrugh hstry and physcalexamnatn. Rutne serum bchemstry. Cmplete urnalyss, deally wth culture(especally f there s an actve sedment).
ideally, evaluatn wuld als nclude:
Cmplete bld cunt (CBC). Serum fructsamne (althugh nt alwaysrequred fr dagnss and mntrng). Serum thyrxne n lder cats t excludehyperthyrdsm.
Because f the hgh prevalence f cncur-rent dseases, ncludng pancreatts, abdm-nal ultrasngraphy and/r determnatn f serum pancreatc lpase mmunreactvtymay be ndcated (especally n cats that aredepressed r nt eatng well), althughnterpretatn f these tests may nt bestraghtfrward.29
Dabetc ketacdss (DKA) develps n aprprtn f untreated dabetc cats, andshuld be suspected when cats are depressed,anrexc, vmtng, weak, cllapsed r mr-
bund. Dagnss requres these clncal sgnsplus cnfrmatn f hgh bld r urneketne cncentratns and metablc acdss,n cnjunctn wth persstent hyperglycaema.
Clncans shuld be vglant and mntrpatents fr the develpment f dabetc cm-plcatns (eg, hypglycaema, DKA, dabetcneurpathy) r the presence f cncmtantdsease, partcularly f treatment respnse spr r erratc.
SPEC IAL ART ICLE / ISFM guidelines on diabetes mellitus
The majorityof diabetic cats
appear to
have a disease
bearing
similarities to
human type 2
diabetes,
resulting from β-cell
dysfunction
and insulin
resistance.
Stress hyperglycaemia (and glucosuria)
must be excluded prior to initiating therapy.
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JFMS CLINICAL PRACTICE 237
SPEC IAL ART ICLE / ISFM guidelines on diabetes mellitus
Overall goals in managingdiabetic cats
Despte the favurable prgnss fr well-managed cats, euthanasa s smetmes anutcme due t unmet wner expectatns rthe mpact f dsease management n wners’lves (see bx, rght). Thus, the man gals f
management are twfld:
on ccasn, achevng bth f these galscan be dffcult. Gven the negatve mpacthypglycaema can have n cats and the cn-cern ths causes wners,30 t s preferable, nthe Panel’s pnn, t prrtse avdnghypglycaema at the expense f allwngperds f hyperglycaema. That sad, nmany cats, t may be pssble t acheve gdglycaemc cntrl safely, partcularly wthgd hme mntrng by wners, and ths nturn may als mprve the prspects f da-
betc remssn (see belw).
Controlling hyperglycaemiaMantanng bld glucse belw the renal
threshld (~14 mml/l [252 mg/dl] n mstcats)31 avds smtc duress, may reducethe rsk f glucse txcty,32 and shuld helpmnmse metablc derangements asscatedwth DM, ncludng the rsk f DKA. Further,exgenus nsuln therapy and gd cntrlf glycaema may result n reduced endge-nus nsuln requrements and ‘restng’ f theβ-cells, whch may ncrease ther capacty tregan nsuln-secretng ablty and amelratethe effects f glucse txcty.
Dabetc remssn may ccur n a prpr-tn f treated cats, and appears mre cm-mn n cats wth better glycaemc cntrl.33–36
Early dagnss (eg, regular screenng f beseand lder cats), gd management andHMBG (see later) may all ptentally helpmprve glycaemc cntrl and the lng-termutcme.33–36
Avoiding hypoglycaemiaHypglycaema s defned as BG
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SPEC IAL ART ICLE / ISFM guidelines on diabetes mellitus
238 JFMS CLINICAL PRACTICE
Choosing an optimum diet for catswith DMimprved management f cats wth DM slkely wth restrcted detary carbhydrate(CHo). Tw randmsed cntrlled studessuggest a ptental beneft f lwer CHodets, wth hgher dabetc remssn rates45and mprved glycaemc cntrl46 beng
reprted; nte, hwever, that t s mpssblet adjust nly ne element (the CHo cntent)f a det. Althugh the ptmal detary CHocntent has nt been determned, dets wthrestrcted CHo cntent (⩽12% metablsableenergy [ME] r 3 g/100 kcal was suggested bythe majrty f the Panel)45 are apprpratependng further studes. Mst wet cat fdsand therapeutc dry cat fds frmulated frmanagement f DM are lw n CHo. othercat fds wth a hgher CHo cncentratn(ncludng mst dry fds) are nt recm-mended as frst-chce dets fr dabetc cats.
Studes suggest that bth the amunt andtype f CHo n the det are mprtant determ-nants f pstprandal nsuln and glucsecncentratns n cats; and, when t ccurs,pstprandal hyperglycaema may als be pr-lnged.47–54 Althugh lw CHo dets desgnedt manage DM are therefre the preferredptn, gd cntrl f DM can stll be achevedwth nsuln therapy and a hgher CHo det, salternatve dets may be used f clncally nd-cated (eg, due t cncmtant dsease).55
Recommended feeding regimen for catswith DMThe ptmal feedng regmen fr cats wth DMhas been prly nvestgated.54 Hwever,
based manly n studes n healthy cats, whenfeedng a lw CHo det (and ne wth cmplexCHos) t appears that the tmng f meals desnt need t be matched t nsuln njectns, as
clncally relevant pstprandal ncreases n BGare unlkely. in practce, as pstprandalchanges n glucse may be uncertan, and treduce pssble det-related ncreases n glu-cse, sme clncans prefer t ensure cats arefed at the same tme as they receve nsulnnjectns; fr sme wners, njectng the catwhle t s eatng may als be easer.
Frequency f feedng s lkewse nt crt-cal – cntnung the nrmal frequency fr thendvdual cat s generally advsed (assumnga mnmum f tw meals daly), as s man-tanng a daly rutne. Ad lbtum feedngmay be acceptable fr sme cats, but especal-ly wth bese cats daly fd allwancesshuld be accurately measured.
Where fd s wthheld (eg, vernght, prrt anaesthesa), and dependng n the detcnsumed, there may be n sgnfcant effectn the mrnng BG cncentratn.54 Never-theless, t s safer t admnster 50% f thenrmal nsuln dse and then mntr BG,supplementng wth addtnal nsuln rglucse as requred.
Action Examples Notes
Promotionof insulinsecretion fromthe pancreas
Sulfonylureas Glipizide Glyburide Glimepiride
Incretins GLP-1 (glucagon-like peptide 1) DPP-4 (dipeptidyl peptidase-4)
Oral glipizide has been used successfully in cats with DM, with benefits being reportedin >40% cats,57–59 but transdermal application is unreliable.60 Adverse effects includecholestasis, hypoglycaemia and vomiting.57,58 Glimepiride stimulates insulin secretion inhealthy cats,61 but has not yet been evaluated in diabetic cats. There is a concern that allthese agents may contribute to progression of pancreatic amyloidosis and the underlyingdisease62
GLP-1 and DPP-4 increase insulin secretion in healthy cats,63–65 but have not yet beenevaluated in diabetic cats
Inhibitionof intestinalglucose
absorption
α-glucosidase inhibitors Acarbose
Acarbose inhibits intestinal glucose production and reduces postprandial hyperglycaemiain healthy cats fed a high (but not low) CHO diet.66 The only published data in cats withDM was an uncontrolled study in cats fed a low CHO diet39
Inhibition ofhepatic glucoseproduction
Biguanides Metformin
Thiazolidinediones Troglitazone Darglitazone Pioglitazone
Metformin has limited value in diabetic cats.67 It should be avoided with concomitantkidney disease, and there may be dose-dependent gastrointestinal adverse effects67,68
Troglitazone has poor bioavailability in cats69 and is no longer used in humans.Darglitazone and pioglitazone improved insulin sensitivity and lipid metabolism in obesecats,70,71 but have not been evaluated in diabetic cats
Improvementof peripheralinsulin sensitivity
Thiazolidinediones
Transition metals Chromium Vanadium
See above
Chromium supplementation improved glucose tolerance in non-diabetic cats in onestudy,72 but not in another.73 In a small group of diabetic cats, those supplemented withvanadium apparently had lower insulin requirements.74 However, use of these metals islikely only to significantly benefit cats with chromium or vanadium deficiency
DM = diabetes mellitus; CHO = carbohydrate
Table 1 Use of oral hypoglycaemics in diabetic cats – summary of current knowledge
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SPEC IAL ART ICLE / ISFM guidelines on diabetes mellitus
JFMS CLINICAL PRACTICE 239
Role of oral hypoglycaemicagents
Whle ral hypglycaemcs are ften used ntype 2 dabetcs n human medcne, there sn gd evdence t supprt ther use npreference t nsuln therapy n cats. A recentrevew summarses current knwledge f
these agents n cats (Table 1).56
Recommendations on using oralhypoglycaemicsThe man ndcatn fr usng an ral hyp-glycaemc s when wners ntally refusensuln treatment. Currently, glpzde s thenly agent wth suffcent evdence t supprtts use as sle therapy n cats. it s gven at anntal dse f 2.5 mg Po q12h. if there are nadverse effects and glycaemc cntrl has nt
been acheved after 2 weeks, the dse can bencreased t 5 mg q12h. A clncal respnse, f seen, s usually apparent after 4–6 weeks. (SeeTable 1 fr ptental prblems wth glpzdeuse.)
owners frequently change t nsuln treat-ment when glpzde s fund t be neffectve.Ths transtn can ften be acheved wthna few weeks – earler beng valuable t avdmssng the ‘wndw f pprtunty’ frreversal f glucse txcty and achevngdabetc remssn.
Insulin choices
There are many nsuln frmulatns avalable
wrldwde, sme specfcally lcensed n cats,whch can be used t manage felne DM safely
and effectvely, especally when cmbnedwth an apprprate det. The chce f nsulnused by a clncan wll depend n avalablty,famlarty and the prpertes f the nsulntself. Addtnally, n sme cuntres, regula-tns may lmt the frst-lne chce t certanveternary regstered prducts.
insuln preparatns avalable wrldwde
and sutable fr lng-term use n cats wthDM fall nt three man grups (see bx belw). The pharmacknetcs f these nsulnpreparatns vares between nsuln type,ndvdual cats, and between dfferent frmu-latns f the same type. Addtnally, thepharmacknetcs are nfluenced by themethdlgy used n dfferent studes. Whlen avalable nsuln shares the same amnacd sequence as felne nsuln, prductn f ant-nsuln antbdes des nt appear t be asgnfcant clncal prblem n cats.12
Althugh n many pharmacdynamc stud-es f healthy cats, nsuln glargne and nsulndetemr have been shwn t have a duratnf actvty f ver 24 h,75,79 there s evdencefrm alternatve studes that ther true clncalduratn f actvty may be clser t 10–16 h,83,84whle cmparatve studes fr PZi have nt
been dne. Addtnally, whle a clear BGnadr s seen n sme cats wth these lngeractng nsuln analgues, a much smthercurve s seen n thers.84 insuln glargne,nsuln detemr and PZi last lnger n catsthan lente nsuln,79,83 and thus are lkely tprvde better cntrl f dabetes when usedtwce daly. Addtnally, lnger actng nsuln
preparatns may prduce a mre gradualdeclne n BG fllwng njectn n many cats.
I n s u l i n t y p e s a n d p r o p e r t i e s i n c a t s
Medium-acting insulins
Lente insulin or insulin zinc suspension; eg, veterinary licensed Caninsulin/Vetsulin (Merck/MSD
Animal Health).
Typical peak activity (anticipated glucose nadir) in cats: 2–8 h post-injection
Typical duration of effect in cats: 8–10 h75–77
Longer acting insulins
Protamine zinc insulin (PZI); eg, veterinary licensed ProZinc (Boehringer Ingelheim).
Typical peak activity (anticipated glucose nadir) in cats: 2–6 h post-injection
Typical duration of effect in cats: 13–24 h, although few studies have specifically evaluated the
veterinary licensed recombinant human product (ProZinc)78–82
Longer acting insulin analogues
Insulin glargine (Lantus; Sanofi) and insulin detemir (Levemir; Novo Nordisk).
Typical peak activity (anticipated glucose nadir) in cats: 12–14 h
Typical duration of effect in cats: 12 to >24 h75,79
The use of
longer-acting
insulin
preparations,
injected twicedaily, is
recommended
for optimal
diabetic
control.
While no
available insulin
shares the
same amino
acid sequence
as feline insulin,
production of
anti-insulin
antibodies does
not appear to
be a significant
clinical problem
in cats.
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Recommendations for insulin preparationand frequency of dosingAlthugh gd cntrl f DM can be achevedn cats wth bth ntermedate and lnger act-ng nsuln preparatns, and defntve cm-paratve studes n dabetc cats are lackng,gven current knwledge f the pharmac-dynamcs f nsuln preparatns n cats, the
Panel recmmends, whenever pssble, theuse f lnger actng nsuln preparatns (eg,glargne, detemr r PZi), njected twce daly,fr ptmal dabetc cntrl.
Rgd adherence t a 12 hurly njectnschedule, althugh deal, wll be unachevablefr many wners. Allwng flexblty wthdsng (12 h ± 2 h), and/r smply mssng annsuln njectn when wrk r scal cmmt-ments preclude dsng at the crrect tme, areacceptable cmprmses.
The prmary gal f therapy s t mnmseclncal sgns asscated wth DM. The mre spe-cfc ams f nsuln therapy can be defned as:
if cntrl wth twce daly admnstratn f nsuln s prvng dffcult, the pssblty f mre frequent nsuln dsng and/r use f adfferent preparatn shuld be cnsdered.
Many nsuln preparatns cntan 100U/ml, whle thers (such as Cannsuln/Vetsuln [Merck/MSD Anmal Health] andPrZnc [Behrnger ingelhem]) are frmulat-ed t 40 U/ml, whch can be helpful fraccuracy f dsng wth syrnges n cats. it sessental t ensure that nsuln syrnges r pensare used that are apprprate fr the nsulncncentratn beng used.
Manufacturers ften state that, nce pened,nsuln vals shuld be dscarded after 4–6weeks. Wth careful handlng and refrgeratedstrage, t has been suggested that at least smensuln preparatns can be safely used fr
between 3 and 6 mnths.85 Hwever, anydevatn frm manufacturers’ recmmenda-tns shuld be undertaken cautusly. if nsuln s ever stred and used fr lnger thanrecmmended, cnsderable care s needed asrepeated needle puncture renders the vals vul-nerable t cntamnatn and wners must beadvsed t dscard nsuln f t becmes ds-clured r mre cludy than usual.
240 JFMS CLINICAL PRACTICE
SPEC IAL ART ICLE / ISFM guidelines on diabetes mellitus
Initial management of thediabetic cat
The startng dse f an ntermedate rlnger actng nsuln preparatn n a nn-kettc cat s generally:
Because hyperglycaema tself causesnsuln resstance and β-cell dysfunctn,successful treatment may reduce nsulnrequrements after a varable perd f tme.Early mntrng f BG s thus amed manlyat dentfyng hypglycaema, whch mghtrequre a reductn n nsuln dse. increasesn nsuln dses (f requred) shuld be maden the bass f persstent clncal sgnssupprted by assessment f glycaema; frexample, seral BG estmates cllected etherat hme r n the clnc, startng apprx-mately 5–7 days after ntatng therapy.
Dses shuld generally nt be ncreasedmre frequently than every 5–7 days. Rapdescalatn n dse s a cmmn cause f hypglycaema, rebund hyperglycaema
and pr cntrl.
Insulin syringes and pens
The dose of insulin administered to most diabetic cats is small. Thus using
an insulin preparation with a concentration of 40 U/ml, rather than 100 U/ml,
along with an appropriate, calibrated, low-dose insulin syringe is likely to be
helpful.86 Insulin preparations should not be diluted to facilitate dosing
small volumes, as this interferes with
their physicochemical properties.
At least one insulin pen (VetPen;
Merck/MSD Animal Health) has been
produced for the veterinary market(Figure 1). This equipment may poten-
tially make administering insulin more
reproducible and accurate (especially
with lower doses),87 and many owners
find an insulin pen easier to use than a
syringe and needle.
Starting dose: 0.25–0.5 U/kg q12h The dose is rounded down to the nearest
unit, and is generally ⩽2 U/cat q12h
The higher dose of 0.5 U/kg may be
appropriate if BG is >20 mmol/l (360 mg/dl)
Obese and underweight cats should be
dosed according to their estimated ideal
weight, and not their current weight
Insulin preparations
should not be diluted
to facilitate dosing.
Aims of insulin treatment
To control BG to
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JFMS CLINICAL PRACTICE 241
SPEC IAL ART ICLE / ISFM guidelines on diabetes mellitus
Mst cats wth uncmplcated DM (e, cln-cally well, wth n DKA r ther majrcmplcatns) are best ntally managed athme wth nsuln and detary therapy. Smeveternarans and wners prefer t managethe cat n the clnc fr the frst few days, thelp ensure severe hypglycaema des ntdevelp and t assess the ntal respnse t
nsuln. Hwever, wners shuld be madeaware that stablsatn wuld nt beacheved wthn these frst few days.
in preparatn fr the cat’s dscharge frmthe clnc, the wner shuld be educated n thetechncal aspects f treatng a dabetc cat.Ths shuld nclude detaled nstructns anddemnstratns abut: Transtn t ptmal det and feedng. Usng nsuln syrnges and/r nsuln pens. Crrect handlng, strage and njectn f nsuln. Clncal sgns f hypglycaema, and hwt treat lw glucse cncentratns.
Wrtten nstructns fr the wner are nval-uable. Addtnal web-based wner resurcesare als avalable (see page 247).
Home (outpatient) stabilisation of thediabetic catThe fllwng gudelnes are ffered, butsme wll vary accrdng t the type f nsulnused as ndcated.
Five to 10 days post-discharge The cat shuld be re-examned n theclnc, ether after t has receved fd and
nsuln at hme, r befre the nsuln dse sdue f the cat eats well when hsptalsed. A thrugh physcal examnatn shuld
be perfrmed, the hstry f clncal respnseat hme, ncludng hme recrds f dalywater ntake, urne glucse testng, ands n, revewed, and labratry parametersre-evaluated as needed. A bld glucse curve (BGC) shuld beperfrmed, where pssble and apprprate(see bx n page 242). ideally, BG smeasured every 1–2 h (fr lentensuln) r every 2–3 h (fr lngeractng preparatns) fr at least12 h, bearng n mnd that BG canvary frm day t day wthnndvduals. As cats are prne t stresshyperglycaema, the accuracy f data generated frm n-hsptalcurves may be questnable. Serumfructsamne measurement and/rthe use f HMBG (see later) can,therefre, be helpful. Sme clncs use a cntnuusglucse mntrng (CGM) system tevaluate the respnse t nsuln (Fgure 2) –
ths can reduce the rsk f stresshyperglycaema nduced by repeat samplngfr BG, allw detectn f bref perds f hypglycaema and facltate vernght BGmntrng.88 CGM systems can als be usedn the hme, but wners must be able t take
bld frm the cat fr calbratn f themachne. The drsal neck may be the mstapprprate ste fr sensr placement.89 insuln adjustments are made accrdngt results f clncal mntrng, BGcncentratns and clncal sgns (Table 2).
Three weeks post-discharge (dependingon prior response)
The cat s re-evaluated as abve, wth aBGC perfrmed at hme r n the clnc. HMBG shuld, where pssble andapprprate, be dscussed wth the wnerand supprt materal prvded.
Home monitoring of blood glucoseThe Panel encurages the use f HMBG, asths helps prvde mre cntrl ver thedsease, ads n the dentfcatn f hypgly-caema and may prvde better glycaemc
cntrl.90,91 Althugh nt all wnersare able t perfrm HMBG,91 t can
be successfully undertaken by mst,wth suffcent supprt, and shulddeally be ntrduced early n themanagement f DM. Assstance(prvded by the veternaran and/r veternary nurse/techncan)shuld be readly avalable frwners.92,93
An experenced techncan r vet-ernaran shuld teach capllary rmargnal ear ven bld samplngusng a lancng devce and a prtable
glucse meter valdated fr use n cats, durngan extended cnsultatn (Fgure 3). Bld
Blood glucose Action
Nadir BG 14
mmol/l (252 mg/dl)
BG 4.5–14 mmol/l (80–252
mg/dl) on all samples measuredthroughout the day
Maintain therapy
Peak BG >14 mmol/l (252 mg/dl)and nadir BG 4.5–8.0 mmol/l(80–144 mg/dl)
Maintain therapy and retest after 1–2 weeks; or Change insulin (if using lente insulin) to a longer
acting insulin; or Increase dose by 0.5 U/cat q12h (depending on
peak and nadir BG)
Peak BG >14 mmol/l (252 mg/dl)and nadir BG >8.0 mmol/l(144 mg/dl), with signs ofongoing hyperglycaemia
Increase dose by 0.5–1.0 U/cat q12h
Table 2 Blood glucose (BG) concentrations and possiblealterations in insulin after first 5–10 days of therapy
Figure 3 Monitoring bloodglucose from the marginalear vein – a technique that
owners can use at home
Figure 2 Diabetic cat witha continuous blood glucosemonitor in place
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may be btaned nterchangeably frm thepnnae and metacarpal r metatarsal pads,and the prcedure s well tlerated by mstcats.94,95 Prnted and web-based resurcesshuld be made avalable t wners (see page247).
A hme BGC can be btaned by measurngBG befre the mrnng nsuln njectn, andevery 2–3 h fr 12 h (r hurly f hyp-glycaema s suspected). Hwever, wnersmust be cunselled nt t make decsnsregardng nsuln dsage wthut dscussnwth the veternaran.
Intensive management of feline DMintensve management f DM has beendescrbed usng regular HMBG (generally amnmum f three, and n average fve, BGsamples daly) and apprprate adjustments
f nsuln,35,36,85 wth the am f mantanngtghter cntrl f BG cncentratns and thuskeepng BG clser t the physlgcal range.
There s sme evdence frm tw smallstudes usng twce daly glargne njectns ndabetc cats that tghter cntrl f BG may bemre lkely t result n remssn f DM.33,34There s als sme evdence that the lngeractng nsuln analgues (glargne anddetemr) may be less lkely t prduce clncalhypglycaema when amng fr tghter cn-trl f BG,33,34,101 althugh gd cmparatvestudes are lackng.
Studes nvlvng ntensve management f DM have ften recmmended amng fr aBG cncentratn between a lw f 2.8–3.0mml/l (50–54 mg/dl) and a hgh f5.5–11.1 mml/l (99–200 mg/dl) thrughut a24 h perd.34–36,85
U s e o f b l o o d g l u c o s e c u r v e s
BGCs can be very useful in the assessment of feline DM (Figures
4 and 5), although they have limitations and there is considerable
day-to-day variation in results, especially in cats with poor
glycaemic control.96 Compared with home BGCs, those per-
formed in-clinic may either over- or underestimate glycaemic
control (Figure 4), perhaps reflecting natural daily variation but
also the influence of stress, variations in insulin dose and
possibly variable food intake.92 In-clinic BGCs should, therefore,
be interpreted with great caution and in the light of the clinical
data.
Initial BGCs should be used to identify hypoglycaemia rather
than fine-tune the treatment of DM. It may not be necessary to
complete a full 12 h BGC on each reassessment, as this would
not always add useful information (eg, where there are clinical
signs such as PU/PD indicating that the BG is consistently high).
The BG nadir, duration of insulin effect and pre-insulin BG are
the most important parameters on which to base adjustments in
insulin dose. Taking blood samples every 2–3 h (for a longer
acting insulin) is usually adequate but if hypoglycaemia is sus-
pected then hourly sampling may be indicated. In some cats,
with known and predictable responses to longer acting insulin
preparations, assessing BG every 4 h might be possible.
An ideal BGC has the shape of a shallow bowl, but this is not
always achieved. The highest value should ideally not exceed
14 mmol/l (252 mg/dl) and the lowest value should generally not
be
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Hwever, the Panel beleves that: Undertakng multple BG measurementsevery day s nt sutable fr mst wners f dabetc cats. Such an aggressve apprach and tghtcntrl f BG s unrealstc fr mst wnerst acheve safely. Whle ntensve mntrng f dabetes
may allw a target f lwer peak BG levels(eg, ⩽11 mml/l [198 mg/dl]), unless anduntl evdence emerges (thrugh use f randmsed cntrlled clncal studes)f a clear clncal beneft, amng fr a BGnadr
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– BG measurement prr t nsuln dsng asfrequently as practcal.
Tgether, sme r all f these measures may be useful fr wners wh fnd perfrmngrepeat BGCs dffcult r stressful. if BG smeasured prr t nsuln dsng, nsuln can
be wthheld r a lwer dse admnsteredwhenever a lw readng s btaned, helpng
t avd hypglycaema. Agan, wners must be advsed nt t adjust nsuln dsage wth-ut dscussn wth ther veternaran.
Monitoring in the clinicFrequent re-evaluatns are requred ntallyt slwly ttrate the nsuln dse, t detectdabetc remssn and t dentfy dffcult-t-stablse cats that requre further wrk-up.The frequency f clnc vsts wll dependmanly n the respnse t treatment and thewner’s ablty t perfrm HMBG.
Fr n-clnc mntrng a gude wuld beassessment at 1, 2–3, 6–8, 10–12 and 14–16 weeksafter ntatng treatment. The frequency f clncre-examnatns can then generally be reducedt apprxmately every 1–4 mnths dependngn hw stable the cat s and the cnscentus-ness/ablty f the wner wth regard t hmemntrng. if dabetc remssn seems lkely,mre frequent checks may be apprprate.
Each re-evaluatn wll vary accrdng tclncal needs but may nclude: owner dary (see abve). Bdy weght and bdy cndtn. Physcal examnatn. in-clnc BGC (eg, after the wner frst gves
nsuln and fd at hme); ths may be desr-able f HMBG s nt regularly perfrmed. Measurement f serum fructsamne (seepage 245).
Adjusting insulin therapy
Clncal sgns and BG measurements (at hmer n-clnc, takng nt accunt ther lmta-tns) are the mst mprtant parameters nwhch t base adjustments n nsuln dse.102if clncal sgns, such as PU/PD, have reslvedand bdy weght s stable, cats are usuallywell cntrlled (althugh sme may als beverdsed). Cnversely, persstent clncalsgns and weght lss suggest pr glycaemccntrl and/r cncmtant dsease.
if there s a dscrepancy between clncalsgns and results f a BGC, treatment dec-sns shuld err n the sde f cautn – fruc-tsamne cncentratns shuld be re-evaluat-ed, and a BGC may be repeated after a fewdays befre any treatment decsn s taken.
Durng the frst 3–4 mnths f therapy theveternaran shuld nterpret BGCs, and makedecsns n treatment adjustments (Table 3).Hwever, wth supprt frm the veternaryhealthcare team, durng lng-term manage-ment wners may gan suffcent experencet make (slght) nsuln adjustments n therwn, accrdng t wrtten gudelnes. Dse
adjustments shuld be made n mre ftenthan every 5–7 days, except n the case f hypglycaema, t allw tme fr equlbra-tn t a new nsuln dse.
Blood glucose Insulin adjustment
Nadir BG 8.0 mmol/l (144 mg/dl) Increase insulin by 0.5–1.0 U/cat q12h
Pre-insulin BG 8–10 mmol/l(144–180 mg/dl)
Consider reducing insulin by 0.5 U/cat q12h
Pre-insulin BG 4.5–7.9 mmol/l(80–142 mg/dl)
Reduce insulin by at least 0.5 U/cat q12h
Pre-insulin BG
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The prmary gal f management s defnedabve. Nte that: Durng ntal stablsatn the nsuln dse
shuld be ncreased gradually n steps f 0.5–1.0 U/cat q12h untl the glucse nadr s4.5–8.0 mml/l (80–144 mg/dl). if the glucse nadr s n the desred range –
but the duratn f nsuln effect s cnsstent-ly less than 8–10 h and there are clncal sgnsf nadequate glycaemc cntrl – the catshuld be swtched t a lnger actng nsulnpreparatn. ideally, a BGC shuld be perfrmed 5–7days after any adjustment n nsuln dse rchange n nsuln preparatn. Hwever, aBGC shuld be repeated sner (after 1–3days) where there s a hgher rsk f hyp-glycaema (eg, a glucse nadr
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Complications with themanagement of DM
Diabetic ketoacidosisNt all cats wth ketnaema and ketnurawll be sufferng frm DKA, but cats wthDKA wll have a lw bld pH and wll beunwell. A kettc nn-acdtc cat can be
managed n the same way as a nn-kettc cat, but f DKA s present mmedate hsptalsa-tn wth ntensve treatment and mntrngs requred. The man bjectves n treatmentare t: Crrect dehydratn and electrlytedefcts. Crrect acdss (usng bcarbnate nlyf apprprate flud therapy s nt suffcent). Prvde adequate amunts f nsuln tnrmalse ntermedary metablsm (e,gradually stp ketgeness and reducehyperglycaema). Prvde a parenteral CHo surce nvmtng anmals and when requred durngnsuln treatment. identfy precptatng factrs (eg, nfectn)n the dsease prcess.
Fr these cats, a shrt-actng nsuln prepa-ratn (eg, regular/sluble nsuln) s general-ly gven ether ntramuscularly (iM) r byntravenus nfusn.114 if regular/slublensuln s nt avalable, t has been suggestedthat glargne may als be gven iM r ntra-venusly (iV),115 althugh gd data n tseffcacy by these rutes s currently lackng.When the cat s stablsed, nsuln treatment s
changed t a lnger actng nsuln va thesubcutaneus rute and the cat managed as astable dabetc.
HypoglycaemiaHypglycaema (BG 6 U/cat,116 and requres n-clnc manage-ment wth parenteral glucse supplementa-tn. A 50% dextrse slutn shuld bedluted 1:2 and an ntal dse f 2–4 ml f the25% slutn (e, 0.5–1.0 g glucse) admns-tered slwly iV ver 5–10 mns. Bldglucse shuld be mntred and furtherdextrse admnstered t effect. Euglycaemashuld result n rapd clncal mprvement,
but treatment shuld stll be fllwed wtha 5% dextrse cnstant rate nfusn (CRi)adjusted t mantan euglycaema wth BG
beng clsely mntred. insuln antagnsts,such as crtcsterds, r a glucagn CRimay als be used.
if nsuln therapy needs t be re-nsttuted,ths shuld be dne cautusly, wth veryclse mntrng.
The unstable diabetic catWhle detaled dscussn f the unstabledabetc cat s utsde the scpe f theseGudelnes, clearly any unstable dabetcshuld underg further nvestgatn. Theprecse nature f ths may vary accrdng tthe prblems encuntered, and the presencef ther knwn r prevus cncurrentdseases.
investgatns t cnsder nclude: Checkng the wner’s nsuln strageand admnstratn. Revewng the dabetc hstry tassess:– Startng dse f nsuln.
– Type f nsuln, duratn f effectand BG nadr.– over what tme perd nsuln has
been ncreased and by hw much.– BGCs (hme vs n-clnc curves).– Fructsamne results.– Mntrng f clncal sgns, bdyweght change, detary hstry, and anyther medcatns that the cat srecevng. Further assessment fr cncurrentdsease, t nclude cnsderatn f:– Physcal examnatn, ncludng bdyweght and bdy cndtn.– Urnalyss and culture.– CBC and serum bchemstry.– Dagnstc magng (ncludngevaluatn f the pancreas).
– Felne pancreatc lpase assay (eg, DGGRr SpecfPL).117–119– Evaluatn fr acrmegaly (eg, nsuln-lkegrwth factr-1 assay, grwth hrmneassay).– Evaluatn f thyrd functn (eg, ttalT4).– Evaluatn f adrenal functn (eg, lwdse dexamethasne suppressn test).
A diabetic cat may be
considered unstable in
the following
scenarios:
High insulin requirement(>1.5 U/kg per dose)
Unexplained increase
in insulin requirements
in a previously stable
diabetic cat
Unexpected
hypoglycaemia during
stabilisation or in a
previously stable
diabetic cat
Difficulty monitoring
glycaemic response
where BG results are
inconsistent with the
cat’s clinical signs
Clinicians should be vigilant for the development
of diabetic complications or the presence of
concomitant disease, particularly if treatment
response is poor or erratic.
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O w n e r e d u c a t i o n r e s o u r c e s
Examples of web-based owner resources that are available are those on the
International Cat Care website (www.icatcare.org) and YouTube channel
(www.youtube.com/user/iCatCare). These include several owner videos
illustrating BG sampling, insulin injection, and urine collection and testing,
among others (see below).
Acknowledgements
The iSFM wuld lke t thank Behrnger ingelhem, whchhelped t supprt the devel-pment f these Gudelnes.
Funding
These Gudelnes were supprted by an educatnal grantfrm Behrnger ingelhem t the iSFM.
Conflict of interest
The Panel members have n cnflcts f nterest t declare.
References
1 Baral RM, Rand JS, Catt MJ, et al.Prevalence of feline diabetes mel-litus in a feline private practice. J Vet Intern Med 2003; 17: 433–434.
2 McCann TM, Smpsn KE, Shaw DJ, et al. Feline diabetes melli-tus in the UK: the prevalence within an insured cat population
and a questionnaire-based putative risk factor analysis. J Feline
Med Surg 2007; 9: 289–299.3 Sallander M, Elassn J and Hedhammar Å. Prevalence and risk
factors for the development of diabetes mellitus in Swedish
cats. Acta Vet Scand 2012; 54: 61.4 Prahl A, Guptll L, Glckman NW, et al. Time trends and risk fac-
tors for diabetes mellitus in cats presented to veterinary teach-
ing hospitals. J Feline Med Surg 2007; 9: 351–358.5 Callegar C, Mercural E, Hafner M, et al. Survival time and
Printed and
web-based
resources
should be
made
available toowners of
diabetic cats.
The ISFM welcomes endorse-ment of these Guidelines by
the American Association of
Feline Practitioners (AAFP).
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248 JFMS CLINICAL PRACTICE
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are associated with relatively rapid changes in circulating fruc-
tosamine concentrations in cats. J Feline Med Surg 2008; 10:583–592.
27 Pler ML, Grndem CB, MacWllams PS, et al. Serum fruc-tosamine concentration in nondiabetic and diabetic cats.
Vet Clin Pathol 1998; 27: 34–39.28 Reusch CE and Haberer B. Evaluation of fructosamine in dogs
and cats with hypo- or hyperproteinaemia, azotaemia, hyperlip-
idaemia and hyperbilirubinaemia. Vet Rec 2001; 148: 370–376.29 Frcada Y, German AJ, Nble PJ, et al. Determination of serumfPLI concentrations in cats with diabetes mellitus. J Feline Med
Surg 2008; 10: 480–487.30 Nessen SJ, Pwney S, Gutan J, et al. Evaluation of a quality-of-
life tool for cats with diabetes mellitus. J Vet Intern Med 2010; 24:1098–1105.
31 Kruth SA and Cwgll LD. Renal glucose transport in the cat[abstract]. Prceedngs f the Amercan Cllege f Veternaryinternal Medcne Frum, 1982, p 78.
32 Lnk KR, All i, Rand JS, et al. The effect of experimentallyinduced chronic hyperglycaemia on serum and pancreatic
insulin, pancreatic islet IGF-I and plasma and urinary ketones
in the domestic cat ( Felis felis). Gen Comp Endocrinol 2013; 188:
269–281.33 Marshall RD, Rand JS and Mrtn JM. Treatment of newly diag-
nosed diabetic cats with glargine insulin improves glycaemic con-
trol and results in higher probability of remission than protamine
zinc and lente insulins. J Feline Med Surg 2009; 11: 683–691.34 Nack R and DeClue AE. In cats with newly diagnosed diabetes
mellitus, use of a near-euglycemic management paradigm
improves remission rate over a traditional paradigm. Vet Q 2014;25: 1–5.
35 Rmp K and Rand J. Intensive blood glucose control is safeand effective in diabetic cats using home monitoring and treat-
ment with glargine. J Feline Med Surg 2009; 11: 668–682.36 Rmp K and Rand J. Evaluation of detemir in diabetic cats
managed with a protocol for intensive blood glucose control. J Feline Med Surg 2012; 14: 566–572.
37 McMllan FD and Feldman EC.Rebound hyperglycemia follow-ing overdosing of insulin in cats with diabetes mellitus. J Am
Vet Med Assoc 1986; 188: 1426–1431.38 Burge V, Nelsn RW, Feldman EC, et al. Effect of weight gain
and subsequent weight loss on glucose tolerance and insulin
response in healthy cats. J Vet Intern Med 1997; 11: 86–91.39 Mazzaferr EM, Grec DS, Turner AS, et al. Treatment of feline
diabetes mellitus using an alpha-glucosidase inhibitor and a
low-carbohydrate diet. J Feline Med Surg 2003; 5: 183–189.40 Tvarjnavcute A, Cern JJ, Hlden SL, et al. Effects of weight
loss in obese cats on biochemical analytes related to inflamma-
tion and glucose homeostasis. Domest Anim Endocrinol 2012; 42:129–141.
41 We A, Fascett AJ, Vllaverde C, et al. Effect of water content in acanned food on voluntary food intake and body weight in cats.
Am J Vet Res 2011; 72: 918–923.42 Buckley CM, Hawthrne A, Clyer A, et al. Effect of dietary
water intake on urinary output, specific gravity and relative
supersaturation for calcium oxalate and struvite in the cat. Br J
Nutr 2011; 106 Suppl 1: S128–S130.43 Carcf AC, Bazzl RS and Zann A.Influence of water content
and the digestibility of pet foods on the water balance of cats.
Braz J Vet Res Anim Sci 2005; 42: 429–434.44 Seefeldt SL and Chapman TE. Body water content and turnover
in cats fed dry and canned rations. Am J Vet Res 1979; 40: 183–185.
prognostic factors in cats with newly diagnosed diabetes melli-
tus: 114 cases (2000–2009). J Am Vet Med Assoc 2013; 243: 91–95.6 Gssens MM, Nelsn RW, Feldman EC, et al. Response to
insulin treatment and survival in 104 cats with diabetes melli-
tus (1985–1995). J Vet Intern Med 1998; 12: 1–6.7 Kraus MS, Calvert CA, Jacbs GJ, et al. Feline diabetes mellitus:
a retrospective mortality study of 55 cats (1982–1994). J Am Anim
Hosp Assoc 1997; 33: 107–111.
8 Heng M. Carbohydrate metabolism and pathogenesis of dia-betes mellitus in dogs and cats. Prog Mol Biol Transl Sci 2014; 121:377–412.
9 Nelsn RW and Reusch CE. Animal models of disease: classifi-cation and etiology of diabetes in dogs and cats. J Endocrinol
2014; 222: T1–T9.10 ost M, Zn E, Reusch CE, et al. Diabetes from humans to cats.
Gen Comp Endocrinol 2013; 182: 48–53.11 Rand JS. Pathogenesis of feline diabetes. Vet Clin North Am Small
Anim Pract 2013; 43: 221–231.12 Heng M, Reusch C and Petersn ME. Beta cell and insulin anti-
bodies in treated and untreated diabetic cats. Vet Immunol
Immunopathol 2000; 77: 93–102.13 Webb CB and Falkwsk L. Oxidative stress and innate immuni-
ty in feline patients with diabetes mellitus: the role of nutrition.
J Feline Med Surg 2009; 11: 271–276.14 Zn E, ost M, Mrett S, et al. Hyperglycaemia but not hyper-
lipidaemia decreases serum amylase and increases neutrophils
in the exocrine pancreas of cats. Res Vet Sci 2010; 89: 20–26.15 Heng M, Thmaseth K, Waldrn M, et al. Insulin sensitivity,
fat distribution, and adipocytokine response to different diets
in lean and obese cats before and after weight loss. Am J Physiol
Regul Integr Comp Physiol 2007; 292: R227–R234.16 Appletn DJ, Rand JS and Sunvld GD. Insulin sensitivity
decreases with obesity, and lean cats with low insulin sensitiv-
ity are at greatest risk of glucose intolerance with weight gain.
J Feline Med Surg 2001; 3: 211–228.
17 Mr A, Sak T, Lee P, et al. Comparison of three commerciallyavailable prescription diet regimens on short-term post-prandi-
al serum glucose and insulin concentrations in healthy cats.
Vet Res Commun 2009; 33: 669–680.18 Pancera DL, Thmas CB, Ecker SW, et al. Epizootiologic pat-
terns of diabetes mellitus in cats: 333 cases (1980–1986). J Am Vet
Med Assoc 1990; 197: 1504–1508.19 Scarlett JM and Dnghue S. Associations between body condi-
tion and disease in cats. J Am Vet Med Assoc 1998; 212: 1725–1731.20 Lederer R, Rand JS, Jnssn NN, et al. Frequency of feline dia-
betes mellitus and breed predisposition in domestic cats in
Australia. Vet J 2009; 179: 254–258.21 Rand JS, Bbbermen LM, Hendrkz JK, et al.Over representation of
Burmese cats with diabetes mellitus. Aust Vet J 1997; 75: 402–405.22 Slngerland Li, Fazlva VV, Plantnga EA, et al.Indoor confine-
ment and physical inactivity rather than the proportion of
dry food are risk factors in the development of feline type 2
diabetes mellitus. Vet J 2009; 179: 247–253.23 Crenshaw KL, Petersn ME, Heeb LA, et al. Serum fructosamine
concentration as an index of glycemia in cats with diabetes mel-
litus and stress hyperglycemia. J Vet Intern Med 1996; 10: 360–364.24 Lwe AD, Campbell KL and Graves T.Glucocorticoids in the cat.
Vet Dermatol 2008; 19: 340–347.25 Petersn ME. Effects of megestrol acetate on glucose tolerance
and growth hormone secretion in the cat. Res Vet Sci 1987; 42:354–357.
26 Lnk KR and Rand JS. Changes in blood glucose concentration
by guest on February 19, 2016 jfm.sagepub.comDownloaded from
http://jfm.sagepub.com/http://jfm.sagepub.com/http://jfm.sagepub.com/http://jfm.sagepub.com/
8/19/2019 Journal of Feline Medicine and Surgery-2015-Sparkes
15/16
JFMS CLINICAL PRACTICE 249
SPEC IAL ART ICLE / ISFM guidelines on diabetes mellitus
45 Bennett N, Grec DS, Petersn ME, et al. Comparison of a lowcarbohydrate–low fiber diet and a moderate carbohydrate–high
fiber diet in the management of feline diabetes mellitus. J Feline
Med Surg 2006; 8: 73–84.46 Hall TD, Mahny o, Rzansk EA, et al.Effects of diet on glucose
control in cats with diabetes mellitus treated with twice daily
insulin glargine. J Feline Med Surg 2009; 11: 125–130.47 de-olvera LD, Carcf AC, olvera MC, et al. Effects of six
carbohydrate sources on diet digestibility and postprandialglucose and insulin responses in cats. J Anim Sci 2008; 86:2237–2246.
48 Farrw HA, Rand JS, Mrtn JM, et al.Effect of dietary carbohy-drate, fat, and protein on postprandial glycemia and energy
intake in cats. J Vet Intern Med 2013; 27: 1121–1135.49 Hewsn-Hughes AK, Glham MS, Uptn S, et al. The effect of
dietary starch level on postprandial glucose and insulin concen-
trations in cats and dogs. Br J Nutr 2011; 106 Suppl 1: S105–S109.50 Mmura K, Mr A, Lee P, et al.Impact of commercially available
diabetic prescription diets on short-term postprandial serum
glucose, insulin, triglyceride and free fatty acid concentrations
of obese cats. J Vet Med Sci 2013; 75: 929–937.51 Appletn DJ, Rand JS, Prest J, et al. Dietary carbohydrate source
affects glucose concentrations, insulin secretion, and food
intake in overweight cats. Nutr Res 2004; 24: 447–467.52 Farrw H, Rand JS, Mrtn JM, et al. Postprandial glycaemia in
cats fed a moderate carbohydrate meal persists for a median of
12 hours – female cats have higher peak glucose concentrations.
J Feline Med Surg 2012; 14: 706–715.53 Kenzle E. Blood sugar levels and renal sugar excretion after the
intake of high carbohydrate diets in cats. J Nutr 1994; 124:2563S–2567S.
54 Martn GJ and Rand JS. Food intake and blood glucose in normaland diabetic cats fed ad libitum. J Feline Med Surg 1999; 1:241–251.
55 Zran DL and Rand JS. The role of diet in the prevention and
management of feline diabetes. Vet Clin North Am Small AnimPract 2013; 43: 233–243.
56 Palm CA and Feldman EC. Oral hypoglycemics in cats withdiabetes mellitus. Vet Clin North Am Small Anim Pract 2013; 43:407–415.
57 Feldman EC, Nelsn RW and Feldman MS. Intensive 50-weekevaluation of glipizide administration in 50 cats with previously
untreated diabetes mellitus. J Am Vet Med Assoc 1997; 210: 772–777.58 Frd SL. NIDDM in the cat: treatment with the oral hypo-
glycemic medication, glipizide. Vet Clin North Am Small Anim
Pract 1995; 25: 599–615.59 Nelsn RW, Feldman EC, Frd SL, et al. Effect of an orally
administered sulfonylurea, glipizide, for treatment of diabetes
mellitus in cats. J Am Vet Med Assoc 1993; 203: 821–827.60 Bennett N, Papch MG, Heng M, et al. Evaluation of transder-
mal application of glipizide in a pluronic lecithin gel to healthy
cats. Am J Vet Res 2005; 66: 581–588.61 Mr A, Lee P, Yamashta T, et al. Effect of glimepiride and
nateglinide on serum insulin and glucose concentration in
healthy cats. Vet Res Commun 2009; 33: 957–970.62 Heng M, Hall G, Fergusn D, et al. A feline model of experimen-
tally induced islet amyloidosis. Am J Pathol 2000; 157: 2143–2150.63 Glr C, Graves TK, Glr S, et al. The GLP-1 mimetic exenatide
potentiates insulin secretion in healthy cats. Domest Anim
Endocrinol 2011; 41: 42–49.64 Padrutt i, Zn E, Kaufmann K, et al. Comparison of the GLP-1
analogues exenatide short-acting, exenatide long-acting and the
DPP-4 inhibitor sitagliptin to increase insulin secretion in
healthy cats [abstract]. J Vet Intern Med 2012; 26: 1520–1521.65 Reusch C and Padrutt i. New incretin hormonal therapies in
humans relevant to diabetic cats. Vet Clin North Am Small Anim
Pract 2013; 43: 417–433.66 Sngh R, Rand JS, Cradn M, et al. Effect of acarbose on post-
prandial blood glucose concentrations in healthy cats fed low
and high carbohydrate diets. J Feline Med Surg. Epub ahead f
prnt 24 octber 2014. Doi: 1098612X14556559.67 Nelsn R, Spann D, Elltt D, et al. Evaluation of the oral anti-hyperglycemic drug metformin in normal and diabetic cats.
J Vet Intern Med 2004; 18: 18–24.68 Mchels GM, Budnt FD, Fergusn DC, et al. Pharmacokinetics
of the antihyperglycemic agent metformin in cats. Am J Vet Res
1999; 60: 738–742.69 Mchels GM, Budnt FD, Fergusn DC, et al. Pharmacokinetics
of the insulin-sensitizing agent troglitazone in cats. Am J Vet Res
2000; 61: 775–778.70 Clark M, Thmaseth K, Drklu L, et al. Effects of pioglitazone
on insulin sensitivity and serum lipids in obese cats. J Vet Intern
Med 2014; 28: 166–174.71 Heng M and Fergusn DC. Effect of darglitazone on glucose
clearance and lipid metabolism in obese cats. Am J Vet Res 2003;64: 1409–1413.
72 Appletn DJ, Rand JS, Sunvld GD, et al. Dietary chromiumtripicolinate supplementation reduces glucose concentrations
and improves glucose tolerance in normal-weight cats. J Feline
Med Surg 2002; 4: 13–25.73 Chn LA, Ddam JR, McCaw DL, et al.Effects of chromium sup-
plementation on glucose tolerance in obese and nonobese cats.
Am J Vet Res 1999; 60: 1360–1363.74 Fndacar JV, Grec DS and Crans DC. Treatment of feline dia-
betes mellitus with protamine zinc analine insulin (PZI) alone
compared with PZI and oral vanadium dipicolinate [abstract]. J Vet Intern Med 1999; 13: 244.
75 Marshall RD, Rand JS and Mrtn JM. Insulin glargine has along duration of effect following administration either once
daily or twice daily in divided doses in healthy cats. J Feline Med
Surg 2008; 10: 488–494.76 Martn GJ and Rand JS. Pharmacology of a 40 IU/ml porcine
lente insulin preparation in diabetic cats: findings during the
first week and after 5 or 9 weeks of therapy. J Feline Med Surg
2001; 3: 23–30.77 Mchels L, Reusch CE, Bar A, et al. Treatment of 46 cats with
porcine lente insulin – a prospective, multicentre study. J Feline
Med Surg 2008; 10: 439–451.78 Brussard JD and Petersn ME. Comparison of two ultralente
insulin preparations with protamine zinc insulin in clinically
normal cats. Am J Vet Res 1994; 55: 127–131.79 Marshall RD, Rand JS and Mrtn JM. Glargine and protamine
zinc insulin have a longer duration of action and result in lower
mean daily glucose concentrations than lente insulin in healthy
cats. J Vet Pharmacol Ther 2008; 31: 205–212.80 Nelsn RW, Lynn RC, Wagner-Mann CC, et al. Efficacy of prota-
mine zinc insulin for treatment of diabetes mellitus in cats. J Am
Vet Med Assoc 2001; 218: 38–42.81 Nelsn RW, Henley K and Cle C. Field safety and efficacy of
protamine zinc recombinant human insulin for treatment of
diabetes mellitus in cats. J Vet Intern Med 2009; 23: 787–793.82 Wallace MS, Petersn ME and Nchls CE. Absorption kinetics
of regular, isophane, and protamine zinc insulin in normal cats.
Domest Anim Endocrinol 1990; 7: 509–515.
by guest on February 19, 2016 jfm.sagepub.comDownloaded from
http://jfm.sagepub.com/http://jfm.sagepub.com/http://jfm.sagepub.com/http://jfm.sagepub.com/
8/19/2019 Journal of Feline Medicine and Surgery-2015-Sparkes
16/16
102 Martn GJ and Rand JS. Comparisons of different measurementsfor monitoring diabetic cats treated with porcine insulin zinc
suspension. Vet Rec 2007; 161: 52–58.103 Fnc DR, Adams DD, Crwell WA, et al. Food and water intake
and urine composition in cats: influence of continuous versus
periodic feeding. Am J Vet Res 1986; 47: 1638–1642.104 Grant DC. Effect of water source on intake and urine concentra-
tion in healthy cats. J Feline Med Surg 2010; 12: 431–434.
105 Hashmt M, Funaba M, Abe M, et al. Dietary protein levelsaffect water intake and urinary excretion of magnesium andphosphorus in laboratory cats. Exp Anim 1995; 44: 29–35.
106 Kane E, Rgers QR and Mrrs JG. Feeding behavior of thecat fed laboratory and commercial diets. Nutr Res 1981; 1:499–507.
107 Kane E, Leung PM, Rgers QR, et al. Diurnal feeding and drink-ing patterns of adult cats as affected by changes in the level of
fat in the diet. Appetite 1987; 9: 89–98.108 Xu H, Laflamme DP and Lng GL. Effects of dietary sodium
chloride on health parameters in mature cats. J Feline Med Surg
2009; 11: 435–441.109 Elltt DA, Nelsn RW, Reusch CE, et al. Comparison of serum
fructosamine and blood glycosylated hemoglobin concentrations
for assessment of glycemic control in cats with diabetes
mellitus. J Am Vet Med Assoc 1999; 214: 1794–1798.110 Nrswrthy GD, Lynn R and Cle C. Preliminary study of prot-
amine zinc recombinant insulin for the treatment of diabetes
mellitus in cats. Vet Ther 2009; 10: 24–28.111 Thresen Si and Bredal WP. Clinical usefulness of fructosamine
measurements in diagnosing and monitoring feline diabetes
mellitus. J Small Anim Pract 1996; 37: 64–68.112 Glr C, Graves TK, Lascelles BD, et al. The effects of body
weight, body condition score, sex, and age on serum fruc-
tosamine concentrations in clinically healthy cats. Vet Clin Pathol
2010; 39: 322–328.113 Reusch CE and Tmsa K. Serum fructosamine concentration in
cats with overt hyperthyroidism. J Am Vet Med Assoc 1999; 215:1297–1300.
114 Marshall RD, Rand JS, Gunew MN, et al. Intramuscular glarginewith or without concurrent subcutaneous administration for
treatment of feline diabetic ketoacidosis. J Vet Emerg Crit Care
(San Antonio) 2013; 23: 286–290.115 Rand JS. Diabetic ketoacidosis and hyperosmolar hyper-
glycemic state in cats. Vet Clin North Am Small Anim Pract 2013;43: 367–379.
116 Whtley NT, Drbatz KJ and Pancera DL. Insulin overdose indogs and cats: 28 cases (1986–1993). J Am Vet Med Assoc 1997; 211:326–330.
117 opplger S, Hartnack S, Rnd B, et al. Agreement of the serumSpec fPL and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6’-
methylresorufin) ester lipase assay for the determination of
serum lipase in cats with suspicion of pancreatitis. J Vet Intern
Med 2013; 27: 1077–1082.118 opplger S, Hartnack S, Reusch CE, et al. Agreement of serum
feline pancreas-specific lipase and colorimetric lipase assays
with pancreatic ultrasonographic findings in cats with suspi-
cion of pancreatitis: 161 cases (2008–2012). J Am Vet Med Assoc
2014; 244: 1060–1065.119 Xenuls PG and Stener JM. Canine and feline pancreatic lipase
immunoreactivity. Vet Clin Pathol 2012; 41: 312–324.
250
SPEC IAL ART ICLE / ISFM guidelines on diabetes mellitus
Available online at jfms.com
/
83 Glr C, Rdge TK, Attermeer KJ, et al. Pharmacodynamics ofinsulin detemir and insulin glargine assessed by an isoglycemic
clamp method in healthy cats. J Vet Intern Med 2010; 24: 870–874.84 Glr C and Graves TK. Synthetic insulin analogs and their use
in dogs and cats. Vet Clin North Am Small Anim Pract 2010; 40:297–307.
85 Rmp K and Rand JS.Management of diabetic cats with long-act-ing insulin. Vet Clin North Am Small Anim Pract 2013; 43: 251–266.
86 Brn-Crvellent S, Bnagura JD and Glr C. Comparison of pre-cision and accuracy of U100 and U40 insulin syringes [abstract]. J Vet Intern Med 2014; 28: 1029.
87 Burgaud S, Rant S and Pau N. Comparative laboratory evalua-tion of dose delivery using a veterinary insulin injection pen.
Prceedngs f the Brtsh Small Anmal Veternary AsscatnCngress [pster]; 2012 Aprl 12–15; Brmngham, UK.
88 Detker-Mrett S, Muller C, Seber-Ruckstuhl N, et al.Comparison of a continuous glucose monitoring system with a
portable blood glucose meter to determine insulin dose in cats
with diabetes mellitus. J Vet Intern Med 2011; 25: 1084–1088.89 Hafner M, Lutz TA, Reusch CE, et al. Evaluation of sensor sites
for continuous glucose monitoring in cats with diabetes melli-
tus. J Feline Med Surg 2013; 15: 117–123.
90 Kley S, Casella M and Reusch CE. Evaluation of long-term homemonitoring of blood glucose concentrations in cats with dia-
betes mellitus: 26 cases (1999–2002). J Am Vet Med Assoc 2004; 225:261–266.
91 Reusch CE, Kley S and Casella M. Home monitoring of the dia-betic cat. J Feline Med Surg 2006; 8: 119–127.
92 Casella M, Hassg M and Reusch CE. Home-monitoring of blood glucose in cats with diabetes mellitus:
evaluation over a 4-month period. J Feline Med Surg 2005; 7:163–171.
93 Casella M, Wess G and Reusch CE. Measurement of capillaryblood glucose concentrations by pet owners: a new tool in the
management of diabetes mellitus. J Am Anim Hosp Assoc 2002; 38:
239–245.94 Wess G and Reusch C. Capillary blood sampling from the ear of
dogs and cats and use of portable meters to measure glucose
concentration. J Small Anim Pract 2000; 41: 60–66.95 Zeugswetter FK, Rebuzz L and Karlvts S. Alternative sam-
pling site for blood glucose testing in cats: giving the ears a rest.
J Feline Med Surg 2010; 12: 710–713.96 Alt N, Kley S, Haessg M, et al. Day-to-day variability of blood
glucose concentration curves generated at home in cats with
diabetes mellitus. J Am Vet Med Assoc 2007; 230: 1011–1017.97 Zn E, Mrett S, Tschur F, et al. Evaluation of a new portable
glucose meter designed for the use in cats. Schweiz Arch Tierheilkd
2009; 151: 448–451.98 Dbrmylskyj MJ and Sparkes AH. Assessing portable blood
glucose meters for clinical use in cats in the United Kingdom.
Vet Rec 2010; 167: 438–442.99 Dmr A, Sunahara A, Taten M, et al.The clinical utility of two
human portable blood glucose meters in canine and feline prac-
tice. Vet Clin Pathol 2014; 43: 55–62.100 Wess G and Reusch C. Assessment of five portable blood glu-
cose meters for use in cats. Am J Vet Res 2000; 61: 1587–1592.101 Helmkjaer KM, Spdsberg EM and Bjrnvad CR. Insulin
detemir treatment in diabetic cats in a practice setting. J Feline
Med Surg 2015; 17: 144–151.