Paper - Diabetes Canina

Vol 10 No 3Published Quarterly

WALTHAMVol 10 No 3Published Quarterly

Diagnosis of otitismedia in dogs

Diagnosis andtreatment of spinalneoplasia in dogsand cats

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FocusThe worldwide journal for the companion animal veterinarianFocus

Long termmanagement of thediabetic dog

Prolonging the lifeof the feline renalfailure patient

WALTHAM

INSIDEThe worldwide journal for the companion animal veterinarian

A low phosphate, low proteindiet can DOUBLE the lifespan of cats with chronicrenal failure see page 10

A low phosphate, low proteindiet can DOUBLE the lifespan of cats with chronicrenal failure see page 10

WALTHAM Focus is published quarterly.Editions are produced in English, Dutch,French, German, Italian, Polish, Spanish,

Japanese, Greek, and Russian.

How I treat . . . an anorexic rabbit 2Frances Harcourt-Brown BVSc, MRCVS

Harrogate, North Yorkshire, UK

Diagnosis and treatment of spinal neoplasia in dogs and cats 4Bernard Seguin DVM, MS, DipACVS

Colorado State University, USARodney S. Bagley DVM, DipACVIM (Neurology and Internal Medicine)

Gena M. Silver DVM, MS

Washington State University, USA

Prolonging the life of the feline renal failure patient 10Jonathan Elliott MA Vet MB, PhD, Cert SAC, DipECVPT, MRCVS

Royal Veterinary College, London, UK

WSAVA News 15

Long-term management of the diabetic dog 17Linda M. Fleeman BVSc, MACVSc

Jacquie Rand BVSc, DVSc, DipACVIM

University of Queensland, Australia

Diagnosis of otitis media in dogs 24Louis N. Gotthelf DVM

WALTHAM Research News 31

WALTHAM Viewpoint 32Dietary manipulation of canine odiferous flatulence

International Contacts 33

Cover picture:Cross-section of canine kidney

ISSN 1354-0157

Contents

Executive EditorKaryl Hurley BSc, DVM, DACVIM,DECVIM-CAVeterinary Communications,WALTHAM

Managing EditorSarah Rusholme BSc ARCS,PhD, MSc Comm. Sci.Communications Executive,WALTHAM

EditorRichard Harvey PhD, BVSc,DVD, DipECVD, MIBiol, MRCVSUK and European Diplomat inVeterinary Dermatology.Partner in a small animalpractice seeing first andsecond opinion cases

Editorial AdvisorsProf. J. E. Bauer DVM, PhD,DipACVNDept. of Small Animal ClinicalStudiesCollege of Veterinary MedicineTexas A&M UniversityCollege Station, Texas, USA

Prof. C .F. Burrows BVetMed,PhD, MRCVSDepartment of Small AnimalClinical Sciences, University ofFlorida, USA

Prof. Dr. J. Leibetseder DVMInstitut für ErnährungVeterinärmedizinischeUniversitätWien, Austria

Prof. Roger M. Batt BVSc, MSc,PhD, MRCVS, DipECVIM-CAHead of Veterinary Research,WALTHAM

Prof. Dr. R. Moraillon DVMEcole Nationale Vétérinaired’AlfortMaisons-Alfort, France

Dr. Ralf S. Mueller MAVSc,DipACVD, FACVScSchool of Veterinary Medicine,Colorado State University, USA

© Waltham Centre for Pet Nutrition 2000 Waltham-on-the-Wolds, Melton Mowbray, Leicestershire, England, LE14 4RT Tel: 44-1664-415400 Fax: 44-1664-415440

WALTHAMFocus

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WALTHAM FOCUSVOL 10 NO 3

2000

The licensing arrangements for therapeutic agents intended for use insmall animal species vary greatly worldwide. In the absence of a specificlicence, consideration should be given to issuing an appropriatecautionary warning prior to administration of any such drug.

THE WORLD’S LEADING AUTHORITY ON PET CARE AND NUTRITION

Introduction

Feline chronic renal failure (CRF) is a common clinical problem,particularly affecting the ageing cat population. The first goal in themanagement of clinical CRF is to identify and treat any underlying cause ofrenal disease. Where this is not possible, as is often the case, othertreatment goals are to manage the complications of renal failure to improvethe quality of life of the animal (1). In addition, by correcting some of thesecomplications, it has been suggested that the progression of CRF to its endstage may be slowed.

Progression of CRF to end stage is thought to be an inevitable process insome species (2). Experimental evidence seems to suggest that, followingsurgical reduction in renal mass in the cat, progressive deterioration of

renal function is difficult to demonstrate over a 12-month period (3, 4). Inclinical patients, however, progressive loss of remaining functioningnephrons does seem to occur (5, 6) albeit in stepwise decrements at highlyvariable intervals rather than as a gradual linear progression. Figures 1a toc show sequential data from three cats showing the patterns of progressivedeterioration of renal function observed in a recent study (6). Of the 39 cases that died or were euthanised during this study, 21 weredocumented to have suffered from deteriorating renal function as the causeof their death. Most cases that died of renal failure demonstrated stepwisedecrements in renal function as seen in Figures 1a and b. There were veryfew examples of cases that showed clear evidence of linear increases inplasma creatinine concentration accompanied by progressive loss of weightsuch as that shown in Figure 1c.

Why do cases of CRF tend to show progressive renaldysfunction?

There are two main reasons why renal function tends to deteriorate onceCRF has been diagnosed in a clinical patient (7). First, there may berepeated insults that damage the remaining functioning nephrons and leadto the stepwise falls in glomerular filtration rate. Secondly, the adaptiveresponses the body makes to loss of functional renal tissue, once this hasbeen reduced to a critical level, lead to the death of further nephrons and avicious cycle ensues culminating in end stage renal failure. These responsescan, therefore, be described as ‘maladaptation’.

Maladaptation may be contributed to by many of the body’s responses toazotaemia that lead to the uraemic syndrome (8). Examples include thefollowing.

Hypersecretion of parathyroid hormone Hyperparathyroidism results from accumulation of phosphate in the body(9). In a normal animal, parathyroid hormone (PTH) would causeincreased excretion of phosphate ions in the urine and a restoration ofphosphate balance. With severe loss of functioning nephrons, however, PTH

Prolonging the life of the feline renal failure patient

Jonathan Elliott MA, Vet MB, PhD, Cert SAC, DipECVPT, MRCVSRoyal Veterinary College, London, UK

KEY POINTS� Many cases of feline chronic renal failure (CRF) progress to end stage and die of their renal disease.� Progression can be due to repeated renal insults and/or to maladaptive responses to the uraemic syndrome leading to

loss of functioning nephrons.� Secondary renal hyperparathyroidism resulting from phosphate retention is one such maladaptive response.� Control of this syndrome by dietary phosphate restriction leads to increased survival in naturally occurring feline CRF.

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WALTHAM Focus � Vol 10 No 3 � 2000

Dr. Elliott is a 1985 graduate ofCambridge University VeterinarySchool. After graduating, hecompleted an Internship at VHUPin Philadelphia, a PhD in vascularbiology at the University ofCambridge and gained hisCertificate in Small AnimalCardiology. In 1990 he took up alectureship at the Royal VeterinaryCollege in London where he iscurrently Senior Lecturer inVeterinary Pharmacology. In 1998he was awarded the PfizerAcademic Award for his researchcontributions to companionanimal medicine in the areas offeline chronic renal failure andequine laminitis. In 1999 hebecame a Diplomate of theEuropean College of VeterinaryPharmacology and Toxicology.

Jonathan ElliottMA, Vet MB, PhD, Cert SAC, DipECVPT,

MRCVS


is unable to rid the body of excess phosphate and the response ismaladaptive because it adds to the problem of hyperphosphataemia byreleasing more phosphate from stores within bone. Calcium is releasedwith phosphate, soft tissue mineralisation occurs and, some hypothesise,mineralisation of renal tissues will lead to progressive loss of functioningnephrons (10).

Glomerular capillary hypertension and hyperfiltrationAnother maladaptation occurs at the level of the glomerulus itself and leadsto glomerular hypertension and hyperfiltration. This has been documentedto occur in cats with experimentally induced renal failure by surgicalreduction of renal mass (11). The change in glomerular haemodynamicsthat accompanies reduction in renal mass is postulated, in species such asthe rat, ultimately to damage the hyperfiltrating nephrons and lead to theirdemise.

Renal adaptation to metabolic acidosisA final example of a maladaptation in CRF is the response to metabolicacidosis, a common disturbance that accompanies CRF (12) but one thathas been poorly studied in the cat. Ammonia generation in the distal tubuleaids hydrogen ion secretion by the remaining functioning nephrons butexcess ammonia may itself be detrimental and lead to activation ofcomplement and damage to the failing kidney (13). In addition, metabolicacidosis can cause excessive potassium losses (14), which in turn can leadto hypokalaemic nephropathy (15).

Prognosis for cats presenting with CRF

It would be helpful for practising veterinary surgeons to be able to predict atinitial diagnosis, which cats with CRF will progress rapidly to end stage renalfailure regardless of the treatment they receive and which, given the righttreatment, will remain stable for a long period of time. One might expectthe plasma creatinine after rehydration at initial presentation to be areasonable guide. Many cases where the plasma creatinine concentrationremains above 500 µmol/l when the cat has been adequately rehydratedtend to represent very quickly for further fluid treatment and are often verydifficult to manage for the complications of their renal failure. For thosecats that present in stable CRF where the plasma creatinine concentrationis less than 500 µmol/l, this biochemical assessment at initial presentationdoes not predict which cats will progress and which will remain stable. In aretrospective study, the correlation between plasma creatinine and survivalin cats that presented with signs of stable CRF was very poor, with only 5%of the variation in survival time being predicted by the initial plasmacreatinine concentration (5). This finding perhaps merely confirms what acrude index of renal function plasma creatinine really is and highlights theneed for more sensitive indices to be developed that can be used in routine

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Figure 1 Graphs showing the changes in plasma creatinine and body weightwith time in three clinical cases of naturally occurring chronic renal failure.

(a) A 12-year-old female neutered domestic short-haired cat where therewere two progressive increases in creatinine, two and 15 months following

initial diagnosis. The cat was euthanised 17 months following diagnosis.(b) A 16-year-old male neutered domestic long-haired cat where stable renal

function was demonstrated for the first three months and a rapiddeterioration occurred five months following initial diagnosis. This cat was

euthanised after six months. (c) A four-year-old male neutered domesticlong-haired cat where a gradual increase in plasma creatinine

accompanied by loss of weight was noted at each visit. This cat waseuthanised nine months following initial diagnosis.

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clinical practice. Alternatively, it may support the contention thatprogressive deterioration of renal function is not a linear uniform processbut occurs in discrete steps separated by highly variable periods of timeduring which renal function remains very stable. This would mirror thesituation in experimental nephrectomy models of feline renal failure whereglomerular filtration rate (GFR) remains stable for at least 12 months afterinduction of renal failure (3, 4, 16).

One haematological finding that may be of prognostic value is that ofanaemia. In a retrospective study, one-third of the stable CRF cases wereanaemic at initial diagnosis and these fared much worse in terms of theirsurvival when compared with those whose packed cell volume was above0.27 l/l on first presentation (5). Further studies are required involvinglarge populations of cats with stable CRF to determine what other factorsmight be of useful prognostic value in determining their longevity followinginitial diagnosis.

Repeated renal insults from exogenous factors

One insult that may repeatedly damage the feline kidney was proposed overthirty years ago to be bacterial infection (17). A proportion of cases of felineCRF presenting for the first time, or those that represent after a period ofstability, will have subclinical bacteriuria. In a prospective survey of 36 catswith naturally occurring CRF, 268 urine samples were collected bycystocentesis and submitted for bacteriological culture (18). A positiveculture was found in 22 samples obtained from 11 cats giving theprevalence of subclinical bacteriuria as 8.2% and the incidence as 30.5%.A significantly higher incidence was noted in female cats (53%) whencompared with male cats (14.3%), suggesting these infections wereascending. Urine collected by cystocentesis and its submission for culturewould, therefore, seem to be a necessary part of any routine procedure inthe monitoring a cat with CRF. Examining the urine sediment for evidenceof bacteriuria (see Figure 2) is a fairly simple procedure that, whenperformed carefully, will detect the majority of cases where positive culturesare obtained. Thus, even if the owner is not prepared to pay for routinecultures, monitoring can be achieved in all clinical cases.

Early detection of a lower urinary tract infection and appropriatetreatment with antibiotic therapy may prevent an infection from ascendingto the kidney and causing further renal damage. It would be logical toassume that cats with CRF where bacterial urinary tract infections havebeen identified have some renal involvement and so should receiveantibacterial treatment that is appropriate for pyelonephritis (19). Thecourse of treatment should be of 4 to 6 weeks’ duration. In addition, thechoice of drug should be based on a sensitivity test that uses the plasmaconcentration of the drug achieved by the proposed dose rate. In theprospective study referred to above (18), all the isolates cultured wereE. coli and all proved sensitive to fluoroquinolone antibacterial drugs. The

only other groups of drugs to which more than 90% of the isolates weresensitive were potentiated sulphonamides and tetracyclines, neither ofwhich was particularly appropriate for these cases. Empirical treatmentshould be avoided and antibacterial drug selection should, where possible,be based on culture and sensitivity testing. What proportion of feline CRFcases seen in general practice deteriorate because of an ascending bacterialinfection remains to be determined but this is one cause of further renaldamage that, through careful monitoring and appropriate treatment, can beprevented.

Effects of phosphate and protein restriction onsurvival

Experimental studies in the rat and dog have demonstrated the positivevalue of phosphate restriction in slowing the progressive deterioration ofrenal function in animals with surgically reduced renal mass (20, 21). Asdiscussed above, hypersecretion of PTH can be considered maladaptive.How much PTH itself contributes directly to this process is controversialand difficult to determine because PTH, phosphate, and calcium are allintrinsically linked and difficult to study individually. At the very least,plasma PTH concentrations probably serve to indicate those animals thatare overloaded with phosphate and would therefore benefit from phosphaterestriction.

Secondary renal hyperparathyroidism is an extremely common finding infeline CRF, even in those animals that are normophosphataemic (9). Inmany cases where treatment is possible, dietary phosphate restrictionresults in a reduction in plasma PTH concentration, which lags behind thefall in plasma phosphate (22). A study of the effects of phosphate restrictionand control of PTH on the survival times of cats with naturally occurringCRF has been undertaken in a prospective clinical trial (6). Fifty cats wereentered into this trial, 29 were successfully fed phosphate-restricted (dietsused provided a phosphate intake of no more than 0.25 g/MJ) and 21received standard maintenance diets (estimated phosphate intake of about1.14 g/MJ) owing to limited intake of the renal diets by the cats or theowner being resistant to diet change. The clinical diets fed in this study(WALTHAM Veterinary Diet: Whiskas® Feline Low Phosphorus Low Protein)are also moderately restricted in protein, lower in sodium, higher in energyand supplemented with B vitamins when compared with standardmaintenance cat foods. Plasma phosphate and PTH concentrations wereassessed at the mid-survival time point in each group. A significant increasein PTH had occurred with time in the group that were not phosphaterestricted, whereas PTH concentrations were lower than at the time of entryto the study in 69% of the group receiving phosphate restriction (seeTable 1).

Kaplan Meier survival curves were constructed for the two groups of catsand are presented in Figure 3. The Kaplan Meier analysis gave median12


Plasma phosphate and parathyroid hormone values from cats with CRF at initial diagnosis and mid-survival timeValue (reference range)* Maintenance diet group Restricted phosphate group

Initial diagnosis (n) Mid-survival (n) Initial diagnosis (n) Mid-survival (n)

Plasma phosphate 1.85 ± 0.12 (21) 2.18 ± 0.22 (21) 2.04 ± 0.17 (29) 1.50 ± 0.08 (29)(0.68 to 1.86 mmol/l)Plasma PTH 119.7 ± 32.2 (21) 215.7 ± 50.4 (21) 162.7 ± 26.2 (29) 86.3 ± 18.2 (29)(2.5 to 25.5 pg/ml)* Where appropriate, the laboratory or aged-matched reference range is quoted(Data are taken from reference 6)

Table 1


survival times of 264 days (interquartile range of 190 to 535 days) and633 days (interquartile range of 338 to 950 days) for the maintenance dietand phosphate-restricted groups respectively. When the two curves werecompared by log rank analysis, a highly significant difference was found(P = 0.0036) suggesting that the effect of feeding the phosphate- andprotein-restricted diet was to increase survival time.

Although this study was non-randomised and open rather than doubleblind and placebo controlled, the cats that accepted the phosphate-restricted treatment regimen lived considerably longer than those that werefed standard maintenance diets. It cannot be concluded that phosphaterestriction was the only factor responsible for this finding but it seems likelyto have played a major part given the evidence from other species,

including the dog (21). Based on the results of this study and the evidencefrom experimental studies, phosphate restriction should be a standard partof any treatment regimen for CRF in cats.

Hypertension and progression

Systemic hypertension has been recognised to occur in a proportion of catswith naturally occurring CRF (23). In human medicine, prospective clinicalstudies have shown progressive renal damage can be slowed by loweringarterial blood pressure. Moreover, the target arterial blood pressurerequired should be based on the degree of proteinuria recorded in eachpatient (24). One maladaptation to renal failure described above was theincrease in glomerular capillary pressure and hyperfiltration that can bedetected in experimental models of CRF involving a reduction in renalmass. Hyperfiltration and glomerular hypertension will lead to increasedlosses of small amounts of albumin across the filtration membrane.Glomerular capillary pressure has been shown to be raised in cats whererenal mass has been surgically reduced and that hyperfiltration occursleading to increased protein loss (25).

From this information derived from experimental animal studies andhuman clinical studies there seem to be a number of questions that needto be addressed in cats with CRF. Currently, antihypertensive therapy isprescribed for those cats with systolic arterial blood pressures that arepersistently elevated above 175 mmHg. This is done primarily to protectthese cats from catastrophic events such as brain haemorrhage or retinaldetachments. Lowering blood pressure below 170 mmHg seems to achievethis goal and the drug that consistently produces this response is thecalcium channel blocker, amlodipine. In a recent study of the prevalence ofsystemic hypertension in cats with CRF, approximately 30% of the caseshad systemic blood pressure of between 130 and 175 mmHg (26). Howmany of these cats would benefit from antihypertensive therapy? Whatshould the target systemic arterial blood pressure be in order to produce aprotective effect on the nephrons of the failing kidney? What drugs shouldbe used to lower glomerular capillary pressure and will this therapy provebeneficial in naturally occurring feline CRF?

Glomerular pressure cannot be measured in clinical practice. The use ofdrugs to lower glomerular capillary pressure seems a logical therapeuticgoal. Angiotensin-converting enzyme inhibitors (ACE-I) would seem to bethe obvious choice of drugs for this purpose since angiotensin-IIpreferentially constricts the efferent arteriole in the glomerulus and henceraises intraglomerular pressure. Avoidance of systemic hypotension wouldbe an important precaution hence the introduction of an ACE-I such asbenazepril or enalapril should be accompanied by monitoring of systemicarterial blood pressure and should, ideally, be used only in cats where theywould be beneficial. The effect of amlodipine on glomerularhaemodynamics remains to be studied although several properties of thisdrug suggest that it too may be beneficial in counteracting the adaptationthat occurs within the glomeruli of failing kidneys.

At the present time there are no published data from cats with naturallyoccurring CRF to suggest that antihypertensive treatment slows progressionor that address the questions raised above. In one study, hypertensive catsthat responded to antihypertensive treatment fared no better than thosewhose blood pressure remained poorly controlled (27). The difficulty ofassessing the true arterial blood pressure of individual cats in the clinic isone problem that will hamper any clinical studies in this area. Nevertheless,this is certainly an area where further work may well lead to new drugtreatments that could prove to be renoprotective and prolong the survival ofcats with CRF.

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Figure 3 Kaplan Meier survival curves. Dotted line represents the data fromthe normal maintenance diet (NMD) group with the blue symbolsrepresenting those animals still alive at the time of analysis. Solid linerepresents the restricted phosphate diet (RPD) group with the red symbolsrepresenting those animals still alive at the time of analysis.Reprinted with permission from reference 6.

Figure 2 A photomicrograph of urine sediment viewed at 400xmagnification under a phase contrast microscope. The rod-shapedorganisms in focus were found to be E. coli on urine culture. White bloodcells were also present but are out of focus on this field of view.

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Conclusion

Improving the quality of life of our renal failure patients is far moreimportant than increasing their life span. Nevertheless, many do enjoy goodquality of life for extended periods such that some die of diseases otherthan their renal failure. It is important to remember that any treatmentneeds to be appropriate for the stage of renal failure in each individualpatient. Monitoring these patients for the presence of urinary tractinfections is an important part of any management regimen as prompt andeffective treatment may well prevent further renal damage occurring.Scientific evidence supports a beneficial effect of restricting phosphateintake in many cases and the positive benefit of this measure appears toinclude extending the survival of feline CRF patients. Many other areas ofmanagement remain to be explored in detail. Antihypertensive therapy may

well be a promising area for future development but several importantquestions remain to be answered.

Surgical renal transplantation may be an option for feline CRF cases inthe future on a more routine basis. We should remember, however, tocompare the quality of life of transplanted patients with that which cancurrently be achieved medically with current and future developmentsbefore adopting renal transplantation as the routine method.

.

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1. Brown, S. A. Chronic renal failure: recent developments in medicalmanagement. In: Bainbridge, J., Elliott, J. (eds.) Manual of Canine and FelineNephrology and Urology. Cheltenham: BSAVA, 1996: 195–208.

2. Hostetter, T. H., Olson, J. L., Rennke, H. G., Venkatachalam, M. A., Brenner,B. M. Hyperfiltration in remnant nephrons: a potentially adverse response torenal ablation. American Journal of Physiology 1981; 241: F85–F93.

3. Adams, L. G., Polzin, D. J., Osborne, C. A., O’Brien, T. D., Hostetter, T. H.Influence of dietary protein/calorie intake on renal morphology and function incats with 5/6 nephrectomy. Laboratory Investigation 1994; 70: 347–357.

4. Finco, D. R., Brown, S. A., Brown, C. A., Crowell, W. A., Sunvold, G. , Cooper,T. L. Protein and calorie effects on progression of induced chronic renal failurein cats. American Journal of Veterinary Research 1998; 59: 575–582.

5. Elliott, J., Barber, P. J. Feline chronic renal failure: clinical findings in80 cases diagnosed between 1992 and 1995. Journal of Small Animal Practice1998; 39: 78–85.

6. Elliott, J., Rawlings, J. M., Markwell, P. J., Barber, P. J. Survival of cats withnaturally occurring chronic renal failure: effect of conventional dietarymanagement. Journal of Small Animal Practice (in press).

7. Brown, S. A., Crowell, W. A, Brown, C. A., Barsanti, J. A., Finco, D. R.Pathophysiology and management of progressive renal disease. VeterinaryJournal 1997; 154: 93–109.

8. Squires, R. A. Uraemia. In: J. Bainbridge, J., Elliott, J. (eds.) Manual ofCanine and Feline Nephrology and Urology. Cheltenham: BSAVA, 1996:52–67.

9. Barber, P.J., Elliott, J. Feline chronic renal failure: calcium homeostasis in80 cases diagnosed between 1992 and 1995. Journal of Small Animal Practice1998; 39: 108–116.

10. Slatopolsky, E., Martin, K., Hruska, K. Parathyroid hormone metabolismand its potential as a uremic toxin. American Journal of Physiology 1980; 239:F1–F12.

11. Brown, S. A., Brown, C. A. Single-nephron adaptations to partial renalablation in cats. American Journal of Physiology 1995; 269: R1002–R1008.

12. Lulich, J. P., O’Brien, T. D., Osborne, C. A., Polzin, D. J. Feline renal failure:questions, answers, questions. Compendium of Continuing Education for thePractising Veterinarian 1992; 14: 127–152.

13. Nath, K. A., Hostetter, M. K., Hostetter, T. H. Pathophysiology of chronictubulo-interstitial disease in rats. Interactions of dietary acid load , amonia, andcomplement component C3. Journal of Clinical Investigation 1985; 76:667–675.

14. Scandling, J. D., Ornt, D. B. Mechanism of potassium depletion duringchronic metabolic acidsosi in the rat. American Journal of Physiology 1987;252: F122–F130.

15. Dow, W. S., Fettman, M. J., Smith, K. R., Hamar, D. W., Nagode, L. A., Refsal,K. R., Wilke, W. L. Effect of dietary acidification and potassium depletion onacid–base balance, mineral metabolism and renal function in adult cats.Journal of Nutrition 1990; 120: 569–578.

16. Ross, L. A., Finco, D. R., Crowell, W. A. Effect of dietary phosphorusrestriction on the kidneys of cats with reduced renal mass. American Journalof Veterinary Research 1982; 43: 1023–1026.

17. Lucke, V. M. Renal disease in the domestic cat. Journal of Pathology andBacteriology 1968; 95: 67–91.

18. Barber, P. J., Rycroft, A. N., Rawlings, J. M., Markwell, P. J., Elliott, J. Theincidence and prevalence of bacterial urinary tract infections in cats withchronic renal failure. Journal of Veterinary Internal Medicine 1999 13: 251(abstract 101).

19. Elliott, J. Management of bacterial urinary tract infections. In: Bainbridge,J., Elliott, J. (eds.) Manual of Canine and Feline Nephrology and Urology.Cheltenham: BSAVA, 1996: 221–227.

20. Ibels, L. S., Alfrey, A. C., Haut, L., Huffer W.E. Preservation of function inexperimental renal disease by dietary restriction of phosphate. New EnglandJournal of Medicine 1978; 298: 122–126.

21. Finco, D. R., Brown, S. A., Crowell, W. A., Groves, C. A., Duncan, J. R.,Barsanti, J. A. Effects of phosphorus/calcium-restricted andphosphorus/calcium-replete 32% protein diets in dogs with chronic renalfailure. American Journal of Veterinary Research 1992; 53: 157–163.

22. Barber, P. J., Rawlings, J. M., Markwell, P. J., Elliott, J. Effect of dietaryphosphate restriction on renal secondary hyperparathyroidism in the cat.Journal of Small Animal Practice 1999; 40: 62–70.

23. Kobayashi, D. L., Peterson, M. E., Graves, T. K., Lesser, M., Nichols, C. E.Hypertension in cats with chronic renal failure and hyperthyroidism. Journal ofVeterinary Internal Medicine 1990; 4: 58–62.

24. Peterson, J. C., Adler, S., Burkart, J. M., Greene, T., Hebert, L. A., Hunsicker,L. G., King , A. J., Klahr, S., Massry, S. G., Seifter, J. L. Blood pressure control,proteinuria, and the progression of renal disease. The modification of diet inrenal disease study. Annals of Internal Medicine 1995; 123: 754–762.

25. Brown, S. A., Brown, C. A. Single-nephron adaptations to partial renalablation in cats. American Journal of Physiology 1995; 269: R1002–R1008.

26. Elliott, J., Rawlings, J. M., Markwell, P. J, Barber, P. J. Prevalence ofhypertension in cats with naturally occurring chronic renal failure. Journal ofVeterinary Internal Medicine 1999; 13: 251 (abstract 100).

27. Littman, M. P. Spontaneous systemic hypertension in 24 cats. Journal ofVeterinary Internal Medicine 1994; 8: 79–86.

� REFERENCES �

Introduction

Diabetes mellitus is a common endocrine disease of middle-aged and olderdogs characterised by an absolute or relative deficiency of insulin (1).Insulin administration is the mainstay of therapy in all affected dogs, withlong-term treatment involving injections given once or twice each day by theowner. The cause of diabetes in dogs has been poorly characterised and isundoubtedly multifactorial. Genetic predisposition exists (1) and immune-mediated destruction of pancreatic beta-cells has been shown to occur inaffected dogs (2–5).

Clinical presentation

Dogs with uncomplicated diabetes mellitus classically present with polyuria,polydipsia, weight loss, an increased appetite, and lethargy. Most affecteddogs are over seven years of age and females are at greater risk than males(6, 7). The onset of these classic clinical signs is typically chronic, rangingfrom weeks to months (6), and may initially be unnoticed or consideredinsignificant by the dog’s owner. If ketosis and metabolic acidosis develop,more serious systemic signs, such as vomiting and anorexia, are seen andprompt owners to seek veterinary care more rapidly. Approximately 40% of

Long-term management of the diabetic dog

Linda M. Fleeman BVSc, MACVScJacquie S. Rand BVSc, DVSc, DipACVIM

University of Queensland, Australia

KEY POINTS� Insulin is the mainstay of therapy for diabetic dogs.� The majority of diabetic dogs require twice-daily administration of insulin to control their signs.� Insulin and dietary recommendations need to be tailored for each diabetic dog.� A consistent insulin-dosing and feeding routine is optimal, although not critical. For practical reasons, a certain amount

of compromise may be necessary, and is often not associated with significant clinical consequences.� The diet fed should primarily be palatable and nutritionally balanced.� Results of recent studies indicate that improved glycaemic control may be achieved in the majority of diabetic dogs if their

diet contains increased insoluble fibre.� Decreased dietary fat content is recommended if there is concurrent disease of the exocrine pancreas.� Blindness due to cataract formation occurs in the majority of diabetic dogs.

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Dr. Fleeman graduated withhonours from the University ofQueensland in 1984. She worked infirst opinion small animal practicefor eight years and subsequently inreferral practice for five years. Shecompleted a three year medicineinternship at Murdoch Universityand a Clinical Residency at theUniversity of Melbourne. Currentlyshe is completing a PhD researchproject investigating caninediabetes mellitus at the Universityof Queensland, working with Dr Rand.

Linda FleemanBVSc, MACVSc

Dr. Rand graduated with honoursfrom the University of Melbournein 1975. She worked in privatepractice for eight years beforecompleting a residency anddoctorate at the University ofGuelph in Canada. After a three-year position as a ClinicalRegistrar at the University ofZurich in Switzerland shereturned to Australia in 1990.Currently she is an AssociateProfessor in companion animalsciences at the University ofQueensland. Her primary area ofresearch is in canine and felinediabetes and obesity.Jacquie Rand

BVSc, DVSc, DipACVIM


diabetic dogs were found to have already developed ketosis by the time theywere first presented to a university teaching hospital (6). This progressionto a more complicated diabetic patient often coincides with thedevelopment of concurrent disease such as pancreatitis or bacterialinfection of the skin, mucosal surfaces, or urinary tract.

Cataract formation is the most common and one of the most importantlong-term complications associated with diabetes in the dog (1). It is anirreversible process once it begins, and can progress quite rapidly. Onesurvey found that approximately 30% of diabetic dogs already had reducedvision at presentation, and about half of the remaining dogs became blindwithin two years (8). A larger study concluded that cataracts will developwithin five to six months of diagnosis in the majority of diabetic dogs, andthat within 16 months approximately 80% will have significant cataractformation (9).

Insulin deficiency results in altered carbohydrate, fat, and proteinmetabolism. Abnormal carbohydrate metabolism manifests ashyperglycaemia and glycosuria and is responsible for the polyuria,polydipsia, and cataract formation seen in diabetic dogs. Thehyperlipidaemia, ketone production, and hepatic changes seen in thesedogs primarily result from altered fat metabolism. Decreased tissueutilisation of glucose, amino acids, and fatty acids is the cause of thelethargy, weight loss, reduced stimulation of the satiety centre, poor coat,and reduced immunity that is characteristic of untreated diabetic dogs.

Therapy

Aims of therapyThe three primary aims of long-term therapy for diabetic dogs are:� Resolution of all clinical signs� Avoidance of insulin-induced hypoglycaemia� Resumption of usual lifestyle and exercise level

Lethargy tends to resolve rapidly and dogs become more active andresponsive soon after initiation of insulin therapy. Weight loss is usuallyarrested before optimal glycaemic control is achieved, but completeresolution of the polyuria and polydipsia will not occur until the blood

glucose can be kept below the renal threshold. In the majority of diabeticdogs the process of cataract formation has unfortunately already beeninitiated before adequate control of hyperglycaemia can be achieved(Figure 1).

InsulinA variety of insulin preparations with both prompt and prolonged actionsare commonly available (Table 1). Regular and semilente insulins arecharacterised by rapid action and short duration of effect and are generallynot useful for the long-term management of diabetic dogs. Longer-actingpreparations such as ultralente, protamine zinc insulin (PZI), andisophane (NPH) are more suited as they provide continued insulinsupplementation for many hours after a single injection. Premixedcombinations of short- and longer-acting insulins are valuable for the 17


Figure 1 Diabetic cataracts: (a) Photograph of a diabetic dog shortly afterdiagnosis of diabetes mellitus. (b) The same dog three months later andafter successful stabilisation on insulin therapy. Diabetic cataracts haddeveloped rapidly and the dog’s owners had reported sudden loss of vision.(c) The same dog following phacoemulsification surgery to remove thecataract from the right eye.

a

b

c

Commonly available insulin preparations and their effectsfollowing subcutaneous injection in dogs.Type of Source Onset of Time of Duration insulin effect maximal effect of effect Regular* and Recombinant 10–30 min 1–5 h 4–10 hsemilente human

Bovine Isophane* (NPH) Recombinant 0.5–3 h 2–10 h 4–24 h

humanLente** Purified porcine < 1 h 4–8 h (10) 14–24 h (56)

Recombinant 2–10 h (1) 6–24 h (1) humanBovine

Protamine zinc insulin 90% bovine, 1–4 h 4–14 h (1) 6–28 h (10) (PZI) 10% porcine

100% bovine 8–20 h (10) Ultralente Recombinant 1–8 h 4–16 h 8–28 h

human *Premixed combinations of human NPH and regular insulin are available:20% Regular/80% NPH; 30% Regular/70% NPH; 50% Regular/50% NPH.**Lente insulin contains 30% semilente and 70% ultralente insulin.(Modified from reference 1)

Table 1

treatment of diabetic dogs. One common example is lente insulin, whichcontains a mixture of semilente and ultralente, and results in a relativelypredictable and rapidly obtained peak effect (10). A number ofcombinations of regular and NPH insulin are also widely available.

When choosing the type of insulin for long-term use in a diabetic dog,another consideration is the species of the exogenous insulin. Porcineinsulin has exactly the same amino acid sequence as canine insulin andinduces no anti-insulin antibodies with prolonged use in dogs (11–14).Human insulin differs by one amino acid from canine insulin and anti-insulin antibodies have been detected in only one dog treated withrecombinant human insulin (15). Bovine insulin differs by two aminoacids from canine insulin. Anti-insulin antibodies have been detected indogs treated with both purified bovine (11) and mixed bovine/porcineinsulin (13, 15). These anti-insulin antibodies may affect glycaemic controlin some diabetic dogs treated with bovine/porcine insulin (15) and so itmay be advisable to avoid preparations that contain bovine insulin.

Human recombinant insulins are usually sold at a concentration of100 IU/ml. In some countries, porcine lente insulin or bovine/porcine PZIinsulin are available at a concentration of 40 IU/ml. These more dilutepreparations are useful for smaller dogs, which may require a total insulindose of only one or two international units. Syringes that measureinternational unit increments are available for both insulin concentrations.Insulin-dosing pens are obtainable for NPH insulin and the premixedcombinations of regular and NPH insulin. Most of these dosing pens allowinjection of a minimum dose of 2 IU and increase in 1 IU increments,making them a practical tool for smaller patients.

In a small proportion of diabetic dogs, good glycaemic control can beattained with once-daily administration of one of the longer-acting insulins.The majority of diabetic dogs, however, require twice-daily administrationof insulin to control their clinical signs adequately (1, 12, 16). Althoughtreatment regimens comprising once-daily insulin injections are consideredby many to be simpler and more convenient, most of these regimensinvolve feeding meals twice daily. Owners of diabetic dogs often find thathaving to be at home with their dog at set times twice each day is the mainintrusion into their daily routine. Experienced owners rarely report anydifficulty with the administration of insulin injections and therefore if theyare required to be at home to feed the dog it is little more effort to give thedog an insulin injection at the same time. As a result, many cliniciansfavour treatment regimens that involve administration of the same dose ofinsulin along with feeding of the same-sized meal every 12 hours. If lenteinsulin (12) or a premixed combination of regular and NPH insulin ischosen, the onset of effect and the period of maximal insulin activity willthen roughly match the expected postprandial absorption of nutrients.

DietThe food fed to diabetic dogs should provide adequate calories to achieveand maintain optimal body condition. Dogs with poorly controlled diabeteshave a decreased ability to metabolise the nutrients absorbed from theirgastrointestinal tract and lose glucose in their urine, so require morecalories for maintenance than healthy dogs. The diet fed should benutritionally balanced and needs to be palatable so that food intake ispredictable. Meals should ideally be timed so that maximal exogenousinsulin activity occurs during the postprandial period (12). Because thedaily insulin-dosing regimen tends to be fixed for diabetic dogs, it is alsoimportant that a predictable glycaemic response is achieved following eachmeal. Consequently, every meal should contain roughly the sameingredients and calorie content, and should be fed at the same times eachday. The owners of diabetic dogs should be aware that a consistent insulin-dosing and feeding routine is optimal although, for practical reasons, acertain amount of compromise may be necessary in individual cases.

For several decades, there has been a great deal of interest in research

into the composition of an optimal diet for people diagnosed with thevarious forms of diabetes mellitus. As a result, it is now recognised thatdietary management plays a central role in the treatment of diabetic people.More recently, veterinary researchers have started to follow this trend andcomparison can now be made between the dietary recommendations fordiabetic people and those for dogs (Table 2).

Dietary fibre and complex carbohydrates – currentrecommendations for diabetic peopleBefore the advent of insulin therapy, fat and protein were the main sourcesof energy in the diets prescribed for people with diabetes. Dietarycarbohydrate was avoided in an effort to reduce hyperglycaemia. Dietscurrently recommended for diabetics are the result of substitution of thesaturated fat content with complex carbohydrates. The primary reason forthis change was the realisation that the risk of death due to cardiovasculardisease could be greatly reduced by lowering plasma cholesterol. Manyprotein sources contain significant amounts of fat and so are not practicalreplacements for dietary fat. Consequently, the only option that remainedwas to increase the carbohydrate component. It has been consistentlyshown that the cholesterol content of low-density lipoproteins issignificantly reduced in diabetic people when complex carbohydrates aresubstituted for the saturated fat content of their diet (20). It is now highlyrecommended that 55 to 60% of a diabetic person’s total energy should beprovided from carbohydrate and the majority of the carbohydrates shouldbe complex, containing high amounts of resistant starch and fibre (21).Classification of foods according to their acute glycaemic effects has beensuggested as a means of identifying which carbohydrate-containing foodsare optimal for people with diabetes (17). Foods such as pulses, oats, andbarley, which have been found to have a low glycaemic index, may be themost beneficial.

In human diabetics, high-carbohydrate intake can be associated withincreased blood glucose fluctuations and hypertriglyceridaemia. However,when the effects of high carbohydrate diets containing soluble fibre arecompared with those of high-carbohydrate/low-fibre diets, patientsconsuming soluble fibre tend to have lower glycosylated haemoglobin levels(22), lower postprandial blood glucose values, and thehypertriglyceridaemic effect is attenuated or abolished (23). Digestiblecarbohydrate needs to comprise more than 40% of caloric intake to ensuremaximal beneficial effects of the fibre. Only soluble fibre has ahypoglycaemic and hypolipidaemic effect, whereas insoluble fibre appearsto have no effect at all (24). The primary mechanism appears to be theability of certain soluble fibres, such as guar gum, to form a viscous gel andthus impair transfer of nutrients to the absorptive surface of the intestine(25).

It should be remembered that exogenous insulin has an overwhelmingeffect on carbohydrate metabolism. In diabetic people with absolute insulindeficiency, dietary manipulations are still an adjunct to insulin therapy. Theresults of a recent study help to put the role of diet into perspective (26).18


Current nutritional recommendations for human diabetics(17) and canine diabetics (1) compared with the nutritionalrequirements of non-diabetic populationsDietary factor Human diabetics Canine diabeticsCarbohydrate content Increased Increased

High proportion of soluble High proportion of insolublefibre and complex fibre and complex

carbohydrates carbohydrates (18, 19)Fat content Decreased DecreasedProtein content Same Same

Table 2


The effects of foods with different glycaemic indexes and fibre content wereexamined in a small number of well-controlled diabetic patients treatedwith intensive insulin therapy. It was found that, although diets with a lowglycaemic index resulted in lower fasting plasma glucose, and diets withincreased soluble fibre reduced the postprandial rise in plasma glucose, thedifference was not sufficient to require adjustment of the patients’ insulindoses.

What is dietary fibre?Fibre is a term used to describe the most complex and least definablecomponent of foods of plant origin, encompassing a diverse group of plantpolysaccharides, mucilages, and phenolic compounds (27). Dietary fibre isin fact a shorthand expression that covers a wide variety of entities andshould be considered a concept, rather than a definable substance. Diversemethods of fibre analysis exist, all measuring something different. Thesame analysis performed by different laboratories can produce dissimilarresults. Crude fibre is the figure most widely quoted on pet food labels andis the residue remaining after extraction of a food material with dilute acidor alkali. It substantially underestimates the total dietary fibre of commoningredients used in commercial pet food and dietary fibre supplements andis largely obsolete in the field of human nutrition (27).

Analysis techniques that quantify the individual sugars comprising thepolysaccharides also partition the dietary fibre into soluble and insolublefractions, a reflection of their properties in an aqueous media. Soluble fibrehas great water-holding capacity, forms a viscous solution in water, and isreadily degraded by colonic microflora in dogs to produce short-chain fattyacids that are absorbed across the intestinal mucosa. It has been proposedthat these fatty acids stimulate secretion of intestinal hormones thatmodulate the nutrient transport capacity of the gut and promote insulinsecretion, which together facilitate removal of glucose from the circulation(28). A recent study indicated that dogs fed diets with increased viscositymay actually have more rapid postprandial glucose absorption, resulting inhigher total postprandial glucose absorption, and are more likely to developsecretory diarrhoea than dogs fed diets with lower viscosity (29). Thissuggests that only diets with an intermediate viscosity level may beassociated with a delay in gastrointestinal transit time and optimal glucosehomeostasis in dogs. Dogs cannot digest the insoluble fibre component oftheir diet and it is excreted in the faeces. In contrast to soluble fibre,insoluble fibre seems to exert relatively little physiological effect in thecanine gut and can be tolerated in fairly high dietary levels (27). Most foodscontain more insoluble than soluble fibre, even those that are commonlyquoted as sources of soluble fibre, such as guar gum.

Perhaps the most useful method of defining dietary fibre is to considerthe source of the fibre. Fruits, legumes, oats, barley, and psyllium huskstend to contain more soluble fibre than cereals and vegetables, althoughthere are exceptions. Pea fibre (purified pea hulls), arbocell (purifiedcellulose), oat bran, wheat bran, and guar gum are all sources of fibre thatare used as ingredients in commercial pet food or as dietary fibresupplements (Figure 2). One of the main advantages of high-fibre diets isthat intestinal glucose absorption is slowed, so the fibre should always beincorporated in the food rather than given separately as a supplement.

Dietary fibre and complex carbohydrates – currentrecommendations for diabetic dogsStudies in diabetic dogs indicate that high-fibre diets may also be associatedwith improved glycaemic control in this species (18, 19, 30–32). Whendogs were fed a single meal containing either increased soluble fibre orincreased insoluble fibre, a greater reduction of postprandialhyperglycaemia was seen with the meal containing soluble fibre (30).However, when comparison was made following long-term feeding of high-soluble-fibre diets and high-insoluble-fibre diets for one or two months

(18, 19), a tendency for improved glycaemic control and fewer side effectswas seen with the diets containing increased insoluble fibre. In particular,significantly lower glycosylated haemoglobin (18) or fructosamine (19)levels were recorded. Regardless of the composition of the high-fibre diet,or the length of time over which the dogs are monitored, no significantdifference in daily insulin requirement (18, 19, 30–32) or fastingtriglyceride (18, 32) between groups of diabetic dogs fed low-fibre and high-fibre diets has been found.

Importantly, there seems to be marked variation between the responsesof individual diabetic dogs to dietary fibre. In one study (32), significantimprovement of all indices of glycaemic control, including lowered dailyinsulin requirement, was seen in nine of 11 dogs when they were fed ahigh-fibre diet. The remaining two dogs were found to have improvedglycaemic control on the low-fibre diet. A similar situation exists for peoplebecause high-carbohydrate high-fibre diets are not uniformly effective in alldiabetic subjects (21). This may be partly due to the side effects that aresometimes associated with high-fibre diets, which include poor palatability,poor weight gain, poor hair coat, voluminous faeces, flatulence, diarrhoea,and constipation.

In comparison with the bulk of literature addressing the influence ofdietary fibre on human diabetes, the number of studies that haveinvestigated this aspect of canine diabetes is very small. Although there isno doubt that a considerable amount of the information that is now knownabout dietary recommendations for human patients is also relevant to dogs,it is clear that the specific requirements of diabetic dogs need furtherclarification. The influence of high-fibre and low-fibre diets has beenstudied in diabetic dogs; however, little comparison has been made with 19


Figure 2 Analysis of five fibre supplements used in commercial dog food.NB. This illustration first appeared in Bauer, J.E., Maskell, I.E. Dietary fibre: Perspectives inclinical management. In: Wills, J. M., Simpson, K. W. (eds.) The WALTHAM Book of Clinical Nutritionof the Dog and Cat. Oxford: Pergamon, 1995: 87–104. Analysis of five fibre supplements,demonstrating the poor correlation between total dietary fibre and crude fibre. Data are from theanalytical laboratory at Pedigree Petfoods, Melton Mowbray.

0

20

40

60

80

100

DF

CF

CF

CF

CF

CF

DF

DF

DF

DF

Dotted line highlights difference between total dietaryfibre and crude fibre

PeaFibre

Arbocell OatBran

WheatBran

Guar

Insoluble DF Soluble DF Starch

Protein Fat Ash

Moisture Crude Fibre

typical maintenance diets to see if increased fibre results in measurablebenefits compared with a conventional diet. Future studies will help todetermine more accurately the optimal quantity, type, and source of dietaryfibre used. The influence of the manner of processing the dietary fibre andthe effect of the composition of the digestible carbohydrate component ofthe diet also require elucidation. Ultimately, clinicians will want to knowhow commercially available high-fibre diets, compared with the typicalmaintenance moderate-fibre diets, will influence the clinical managementof their patients. The owners of diabetic dogs, on the other hand, are likelyto be more interested in the palatability and side effects of any high-fibrediets that are recommended for their pets.

Dietary fatAltered lipid metabolism occurs in both people and dogs with insulindeficiency. In humans, the lipid disorders that occur in association withdiabetes are arthrogenic and predispose to coronary artery disease,cerebrovascular disease, and peripheral arterial disease (33). Low-fat dietshave been shown to reduce cardiovascular morbidity and mortality indiabetic people. Fortunately, atherosclerosis and arterial disease are notclinical concerns in diabetic dogs. However, it has been known for sometime that a large proportion of diabetic dogs have exocrine pancreaticdisease (6, 34–40). High-fat diets and hypertriglyceridaemia have beenproposed as possible inciting causes of canine pancreatitis (41) and low-fat

diets are recommended for dogs with chronic pancreatitis and exocrinepancreatic insufficiency. As it can be difficult to identify those diabetic dogswith subclinical exocrine pancreatic disease (42), it may be prudent toconsider feeding a reduced fat diet to all diabetic dogs.

Dietary proteinThe protein composition of the recommended diet for people with diabetesis the same as that recommended for the non-diabetic population.However, if microalbuminuria or persistent proteinuria develop, thenprotein restriction may help slow the progression of diabetic nephropathyin these people (24). The optimal dietary protein for diabetic dogs has notbeen determined. It is currently recommended that dietary protein shouldmeet daily requirements, but not be excessive (1). Microalbuminuria andproteinuria do occur in diabetic dogs (43) and lower dietary protein intakemay be indicated in these animals.

The dietary recommendations for diabetic dogs are summarised inTable 3.

Information from research using healthy dogs that may proverelevant for diabetic dogsLittle is known about the glycaemic responses of dogs to variouscarbohydrate-containing foods. It has been found that a semimoist foodcontaining corn syrup, compared with a canned and a dry food that did notcontain corn syrup, resulted in a significantly greater postprandialglycaemic response when fed to healthy dogs (44). A more recent studyexamining the postprandial effects of five diets with equivalent starchcontent from different cereal sources found marked differences in theglucose and insulin responses of healthy dogs (45). The rice-based dietresulted in significantly higher postprandial glucose and insulin responses.Sorghum generally caused the lowest postprandial glucose response whilebarley produced the lowest insulin response. These findings form aninteresting basis for future study on the effects of diets containing barleyand sorghum in diabetic dogs, but more work is required before specificrecommendations can be made. It is worth noting that studies in humanbeings have found a marked variability in the glycaemic response todifferent types of barley (46) and rice (47).

Chromium tripicolinate is a dietary mineral supplement that has beenshown to increase the clearance rate of glucose from the blood byapproximately 10% in healthy dogs (48). Chromium is an essentialnutrient, not a drug, and therefore supplementation may result in benefitsonly if the individual is deficient or marginally deficient in chromium. It isnow clear that dietary chromium levels of most people in industrialisedcountries are suboptimal (49). Similar information is not available for dogsand further studies are warranted to try and establish the minimumrecommended dietary chromium intake for healthy dogs. Chromium isthought to potentiate insulin’s ability to store glucose and wouldtheoretically be a useful adjunct to exogenous insulin therapy. It is alsopossible that inadequate dietary intake of chromium by dogs may increasetheir risk of developing diabetes. It has been postulated that some insulin-dependent diabetics may lose their ability to convert inorganic chromium tothe biologically active form and may actually need to consume foods thatcontain active forms of chromium (50). At this stage, there is littleinformation available on the effects of chromium supplementation inhuman patients requiring insulin therapy (51, 52). Feeding trials usingdiabetic dogs are indicated to determine the effects of dietary chromiumsupplementation in these animals.

Establishing a practical routine for the owner

The first aim of long-term therapy of diabetic dogs is resolution of the20


Summary of current dietary recommendations for diabeticdogsCalorie intake Achieve and maintain optimal body conditionPrimary nutritional Palatable requirements Nutritionally balanced

Consistency is importantThe same food containing a standard number of caloriesshould be fed following each insulin injection

Other nutritional Increased complex carbohydrate content with a high recommendations proportion of insoluble fibre incorporated into the food

Decreased fat content, particularly if there is concurrentdisease of the exocrine pancreas

Timing of meals Postprandial period should ideally coincide with the period ofmaximal exogenous insulin activity Feed multiple small meals or two equal-sized meals per day

Diabetic dogs with The nutritional requirements of any concurrent disease shouldconcurrent disease take precedence over the dietary therapy for diabetes

Regardless of the diet fed, glycaemic control can still bemaintained with exogenous insulin therapy

Table 3

Lethargy

Altered mentition; hypoglycaemic dogs often appear dulland unaware of their surroundings. Owners may find it

difficult to attract their attention

Weakness, trembling, ataxia

Collapse and loss of consciousness

Epileptiform seizures

Figure 3 Progression of clinical signs as hypoglycaemia becomes moresevere in dogs.


clinical signs. In other words, well-controlled diabetic dogs are notlethargic, maintain optimal body condition, drink less than 60 ml of waterper kg body weight during a 24-hour period, and have no ketonuria.

Many different regimens have been used to achieve this successfully andit is usually possible to introduce a number of modifications to thetreatment strategy of individual dogs without compromising their clinicalresponse. Ideally, exogenous insulin should remain effective throughoutevery 24-hour period and meal feeding should be timed so that thepostprandial periods coincide with maximal insulin activity. Typically, thisentails feeding the dog some time after each insulin injection. However, it isoften more convenient for owners to feed their dog at the time of injectionand many prefer this as they feel their pet is rewarded for submitting to theinjection. It is the authors’ experience that good control of clinical signs canreadily be achieved in diabetic dogs that are fed meals at the time of insulininjections. Care should be taken to consider each case individually. It isusually possible to make practical modifications to any treatment regimenin order to reduce the disruption to the owner’s lifestyle.

The second goal of therapy is avoidance of insulin-inducedhypoglycaemia. Every person in the diabetic dog’s household needs to beaware of this life-threatening complication, which can rapidly develop into afrightening emergency. The importance of avoiding an insulin overdosecannot be overemphasised. If some insulin is spilt during injection itshould never be ‘topped up’, even if it appears that the dog has received noinsulin. If the owner is ever uncertain, the safest option is to withhold theinjection as the consequences of missing a single insulin dose arenegligible. The clinical signs seen in dogs with hypoglycaemia are listed inFigure 3. If mild signs of hypoglycaemia develop, the owner should feed ameal of the dog’s usual food. If the dog is unwilling or unable to eat, syrupcontaining a high glucose concentration can be administered orally.Suitable syrups are marketed for use by human diabetics. When the dogrecovers, food should be fed as soon as possible. No more insulin should begiven to the dog until the case is discussed with a veterinarian, at whichpoint a 50% reduction in insulin dose is usually recommended. Care mustbe taken when dispensing insulin syringes to owners to ensure that there isno confusion regarding dosing. For example, the gradations on many 1 mlinsulin syringes are equal to 2 IU, while gradations of 1 IU are present onmost 0.5 ml insulin syringes. Gradations on syringes designed for use with100 IU/ml insulin represent a different volume from gradations on syringesdesigned for use with 40 IU/ml insulin, and this may lead to dosing errors.

The final goal of long-term therapy of diabetic dogs is resumption of thepet’s usual lifestyle and exercise level. Most owners of diabetic dogs will takeone to two weeks to establish a daily treatment routine and to becomeaccustomed to administration of subcutaneous injections. A period ofadjustment and stabilisation of therapy follows. Good glycaemic control isusually attained after at least two months of reappraisal and insulin dosageadjustment. Once this stage is reached, further clinical improvement maystill be seen for several weeks before the dog achieves an optimal healthand fitness level. Many diabetic dogs are elderly and are accustomed tomoderate daily exercise. Younger dogs may resume a very high activity leveland require further adjustment to their daily calorie intake and insulindose as a result.

Concurrent disease

Most diabetic dogs are middle aged and older and so are prone to diseasesthat commonly affect this age group. Consequently, many suffer concurrentproblems that cause insulin resistance and need to be managed incombination with the diabetes. Treated diabetic dogs have a similar chanceof survival to that of non-diabetic dogs of the same age and gender,although the hazard of death occurring is greatest during the first six

months of therapy (53). Insulin resistance associated withhyperadrenocorticism is a relatively common problem in diabetic dogs (40)and can present a diagnostic and therapeutic challenge. Chronicpancreatitis also complicates the management of some dogs with diabetes.Reduced immunity often remains a feature of treated diabetic dogs andmany are at increased risk for developing bacterial infections, particularlyof the skin and the urinary tract. Regular urine culture may be advisable,even if urinary tract signs are not present (54). Ovariohysterectomy isrecommended for entire bitches, as insulin resistance occurs during thelong progesterone phase of their cycle (1).

Blindness and lens-induced uveitis develop sooner or later in themajority of diabetic dogs and are the single most important sequelae forthis condition (1). Mild or subclinical uveitis is present in most dogs withdiabetic cataracts and can often be satisfactorily managed with oral non-steroidal anti-inflammatory drugs such as aspirin (55). Permanent oculardamage can result if lens-induced uveitis is not treated (Figure 4). Surgicalremoval of diabetic cataracts usually results in restoration of good visionand marked improvement of the dog’s quality of life.

Conclusion

Successful long-term management of a diabetic dog sometimes requirespermanent changes to the lifestyles of both owner and dog and so 21


Figure 4 (a) A hypermature cataract in a diabetic dog. Some scleralhyperaemia is present, indicating that there is also mild, lens-induceduveitis. (b) Severe, lens-induced uveitis in a diabetic dog. The eye is red andpainful. There is significant ocular discharge and posterior synechiae arepresent.

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individualisation of the advice given is imperative. A relationship based ontrust and co-operation between veterinarian and client invariably leads tothe most satisfactory outcome. The ongoing treatment of a diabetic dog canbe one of the more rewarding experiences of small animal practice andmany diabetic dogs and their owners come to occupy a special place withinthe clinic environment.

22


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25. Nuttall, F. Q. Dietary fiber in the management of diabetes. Diabetes 1993;42: 503–508.

26. Lafrance, L., Rabases-Lhoret, R., Poisson, D., Ducros, F., Chaisson, J.-L.Effects of different glycaemic index foods and dietary fibre intake on glycaemiccontrol in type 1 diabetic patients on intensive insulin therapy. DiabeticMedicine 1998; 15: 972–978.

27. Bauer, J. E., Maskell, I. E. Dietary fibre: Perspectives in clinicalmanagement. In: Wills, JM, Simpson, K. W. (eds.) The Waltham Book ofClinical Nutrition of the Dog and Cat. Oxford, Pergamon, 1995: 87–104.

28. McBurney, M. I., Massimino, S. P., Field, C. J., Sunvold, G. D., Hayek, M. G.Modulation of intestinal function and glucose homeostasis in dogs by theingestion of fermentable dietary fibers. In: Reinhart, G. A., Carey, D. P. (eds.)Recent Advances in Canine and Feline Nutrition. Vol II. Wilmington: OrangeFrazer Press, 1998: 113–122.

29. Nelson, R. W., Sunvold, G. D. Effect of carboxymethylcellulose onpostprandial glycaemic response in healthy dogs. In: Reinhart, G. A., Carey, D.P. (eds.) Recent Advances in Canine and Feline Nutrition. Vol II. Wilmington:Orange Frazer Press, 1998: 97–102.

30. Blaxter, A. C., Cripps, P. J., Gruffydd-Jones, T. J. Dietary fibre and postprandial hyperglycaemia in normal and diabetic dogs. Journal of Small AnimalPractice 1990; 31: 229–233.

� REFERENCES �

23


31. Graham, P. A., Maskell, I. E., Nash, A. S. Canned high fiber diet andpostprandial glycemia in dogs with naturally occurring diabetes mellitus.Journal of Nutrition 1994; 124: 2712S–2715S.

32. Nelson, R. W., Scott-Montcrieff, C., DeVries, S., Davenport, D., Neal, L. Effectof dietary insoluble fiber on control of glycaemia in dogs with naturally acquireddiabetes mellitus. Journal of the American Veterinary Medical Association1998; 212: 380–386.

33. Stamler, J., Vaccaro, O., Neaton, J. D., Wentworth, D. Diabetes, other riskfactors, and 12-yr cardiovascular mortality for men screened in the MultipleRisk Factor Intervention trial. Diabetes Care 1993; 16: 434–444.

34. Schlotthauer, C. F., Millar, J. A. S. Diabetes mellitus in dogs and cats.Journal of the American Veterinary Medical Association 1951; 118: 31–35.

35. Dixon, J. B., Sanford, J. Pathological features of spontaneous caninediabetes mellitus. Journal of Comparative Pathology 1962; 72: 153–167.

36. Cotton, R. B., Cornelius, L. M., Theran, P. Diabetes mellitus in the dog: Aclinicopathologic study. Journal of the American Veterinary MedicalAssociation 1971; 159: 863–870.

37. Anderson, N. V., Strafuss, A. C. Pancreatic disease in dogs and cats. Journalof the American Veterinary Medical Association 1971; 159: 885–891.

38. Haines, D. M., Penhale, W. J. Autoantibodies to pancreatic islet cells incanine diabetes mellitus. Veterinary Immunology and Immunopathology1985; 8: 149–156.

39. Haines, D. M. A re-examination of islet cell cytoplasmic antibodies indiabetic dogs. Veterinary Immunology and Immunopathology 1986; 11:225–233.

40. Hess, R. S., Saunders, H. M., Van Winkle, T. J., Ward, C. R. Evaluation ofconcurrent disorders in dogs with diabetes mellitus (abstract). In: Proceedingsof the 17th Forum of the American College of Veterinary Internal Medicine.Chicago, USA, 1999: 710.

41. Williams, D. A. Diagnosis and management of pancreatitis. Journal ofSmall Animal Practice 1994; 35: 445–454.

42. Wiberg, M. E., Nurmi, A.-K., Westermarck, E. Serum trypsin likeimmunoreactivity measurement for the diagnosis of subclinical exocrinepancreatic insufficiency. Journal of Veterinary Internal Medicine 1999; 13:426–432.

43. Struble, A. L., Feldman, E. C., Nelson, R. W., Kass, P. H. Systemichypertension and proteinuria in dogs with diabetes mellitus. Journal of theAmerican Veterinary Medical Association 1998; 213: 822–825.

44. Holste, L. C., Nelson, R. W., Feldman, E. C., Bottoms, G. D. Effect of dry, softmoist, and canned dog foods on postprandial blood glucose and insulinconcentrations in healthy dogs. American Journal of Veterinary Research1989; 50: 984–989.

45. Sunvold, G. D., Bouchard, G. F. The glycaemic response to dietary starch.In: Reinhart, G. A., Carey, D. P. (eds.) Recent Advances in Canine and FelineNutrition. Vol II. Wilmington: Orange Frazer Press, 1998: 123–131.

46. Liljeberg, H. G., Granfeldt, Y. E., Bjorck, I. M. Products based on a high fiberbarley genotype, but not on common barley and oats, lower postprandialglucose and insulin responses in healthy humans. Journal of Nutrition 1996;126: 458–466.

47. Jarvi, A.E., Karlstrom, B. E., Granfeldt, Y.E., Bjorck, I. M., Vessby, B. O., Asp,N. G. The influence of food structure on postprandial metabolism in patientswith non-insulin-dependent diabetes mellitus. American Journal of ClinicalNutrition 1995; 61: 837–842.

48. Spears, J. W., Brown, T. T., Sunvold, G. D., Hayek, M. G. Influence ofchromium on glucose metabolism and insulin sensitivity. In: Reinhart, G. A.,Carey, D.P. (eds.) Recent Advances in Canine and Feline Nutrition, Vol II.1998 Iams nutrition symposium proceedings. Wilmington: Orange FrazerPress, 1998: 103–113.

49. Anderson, R. A. Chromium, glucose intolerance and diabetes. Journal ofthe American College of Nutrition 1998; 17: 548–555.

50. Anderson, R. A. Chromium, glucose tolerance, and diabetes. BiologicalTrace Element Research 1992; 32: 19–24.

51. Ravina, A., Slezak, L., Rubal, A., Mirsky, N. Clinical use of the trace elementchromium (III) in the treatment of diabetes mellitus. Journal of TraceElements in Experimental Medicine 1995; 8: 183–190.

52. Fox, G. N., Sabovic, Z. Chromium picolinate supplementation for diabetesmellitus. Journal of Family Practice 1998; 46: 83–86.

53. Graham, P. A., Nash A. S. Survival data analysis applied to canine diabetesmellitus (abstract). In: 15th Annual Forum of the American College ofVeterinary Internal Medicine. Lake Buena Vista, USA. 1997: 689.

54. Forrester, S. D., Troy, G. C., Dalton, N., Huffman, J. W., Holtzman, G.Retrospective evaluation of urinary tract infection in 42 dogs withhyperadrenocorticism or diabetes mellitus or both. Journal of VeterinaryInternal Medicine 1999; 13: 557–560.

55. Bagley, L. H. II, Lavach, J. D. Comparison of postoperativephacoemulsification results in dogs with and without diabetes mellitus: 153cases (1991–1992). Journal of the American Veterinary Medical Association1994; 205: 1165–1169.

56. Graham, P. A., Nash, A. S., McKellar, Q. A. Pharmacokinetics of a porcineinsulin zinc suspension in diabetic dogs. Journal of Small Animal Practice1997; 38: 434–438.



31

From 14–17 February 2000, the 9th International Symposium onUrolithiasis took place in the city of Cape Town, South Africa, organisedby Professor Allen Rodgers and his team from The University of Cape

Town. Within this forum, the world’s leading experts in human urology andnephrology meet every four years to discuss recent innovations and researchin this field. This year, for the first time, a new addition was featured on theprogramme of scientific events: the WALTHAM Session on Stone Disease inAnimals. Urological diseases are a significant problem in companion animalsaccounting for approximately 3% of dogs and over 7% of cats seen atveterinary hospitals (1, 2). There are many aspects of stone pathogenesis andmanagement that are shared between humans and animals. For this reasonWALTHAM collaborated with the congress organisers to include a sessionexclusively for presentation of recent research abstracts and discussion oncompanion animal urolithiasis, with particular reference to the cat and dog.

Approximately 400 people attended the conference, which contained a mixof around 300 oral and poster presentations. In addition to the sessions onurolithiasis in animals, topics included supersaturation and physicalchemistry, crystallisation modulators and macromolecules, nutrition, dietaryrisk factors and water intake, epidemiology, genetics, metabolic evaluation,and medical therapy and endourology.

The WALTHAM session on Stone Disease in Animals was very wellsupported with an attendance of around 80 delegates. Some of these werelocal veterinarians invited by Masterfoods South Africa, but the majority werefrom the main conference, with particular interest shown by thephysiologists. A very stimulating scientific programme was presented with 17abstracts received from a number of authors and institutions. Peter Markwell,from the WALTHAM Centre for Pet Nutrition, opened the session bypresenting the overview lecture, entitled ‘Urolithiasis: a comparison ofhumans, cats, and dogs’. This paper discussed a number of topics includinganatomical distribution, mineral composition, mineral intake, and urinecomposition provided an insight into some of the similarities and differencesthat exist amongst these three species. Several abstracts addressed the shift instone formation away from struvite towards calcium oxalate formation inboth cats and dogs. Data were presented from both Europe (Stevenson et al.,Waltham Centre for Pet Nutrition; Hesse et al., University of Bonn) and NorthAmerica (Bartges et al., University of Tennessee). Professor A. Hesse alsopresented a paper on the occurrence of ammonium urate urolithiasis inEurasian otters.

A number of papers were presented by Bartges et al. around themanagement of urate urolithiasis both in Dalmatian and non-Dalmatiandogs. Of particular interest was a paper presented on the pharmacokinetics ofallopurinol (a xanthine oxidase inhibitor used in the dissolution andprevention of urate urolithiasis). WALTHAM presented two other paperscontaining recent research. The effect of urine pH on relativesupersaturations of feline urine outlined a study in which the urine pH of catswas manipulated by addition of either an acidifier or an alkaliniser to the diet.This study concluded that, when compared with a moderately acidic urine pHof between 6 and 6.5, further acidification (urine pH < 6.0) increasedurinary calcium concentration and calcium oxalate saturation, indicatingoveracidification may be a risk factor for calcium oxalate formation.Furthermore addition of an alkaliniser increased urine pH to around 6.8, butdid not reduce calcium oxalate saturation and resulted in urine oversaturated

with struvite. A second paper was presented showing that sodium levels of upto 1.6 g/400 kcal did not cause an increase in urinary calcium concentration,as claimed by some researchers. This may be because most human studieslooked at sodium levels far higher than those commonly contained within petfoods. Dr V. Biorge also presented a paper examining struvite and calciumoxalate activity product ratios in cats fed a number of acidifying diets. Thisgenerated a particularly interesting discussion comparing the use of activityproduct ratios (APR) and relative supersaturation (RSS) in assessing the riskof stone formation in cats and dogs. Dr W. G. Robertson challenged the use ofAPR rather than RSS, pointing out the pitfalls of the former technique and thefact that very few people in the human field used it.

At the Gala Banquet on the final evening of the conference several awardswere presented. Dr. W. G. Robertson received a Lifetime Achievement Awardfor 30 years of high-quality research within the field of stone disease inhumans. For the last four years Dr Robertson has been working as aconsultant for WALTHAM and in his speech he acknowledged the WALTHAMCentre for Pet Nutrition and the enjoyment he now gets from expanding hisportfolio into cats and dogs. Other awards included the Junior ResearcherAward and awards for the best poster and oral presentation within theWALTHAM Session on Stone Disease in Animals. The oral presentation waswon by the paper entitled ‘Urine pH and urinary relative supersaturationin healthy adult cats’ presented by Abigail Stevenson, WALTHAM ProjectScientist, while the award for the best poster was given to Joseph Barges forhis poster entitled ‘Pharmacokinetics of allopurinol in healthy adult dogs’.

See you at the 10th International Symposium on Urolithiasis to be held inHong Kong in 2004!!

Abstracts from WALTHAM scientists

Stevenson AE, Wrigglesworth, DJ, Markwell PJ: Urine pH and urinary relativesupersaturation in healthy adult cats. Proceedings of 9th Internationalsymposium on Urolithiasis 2000, 818-820

Stevenson AE, Wrigglesworth, DJ, Markwell PJ: Dietary sodium chloride, urinarycalcium and urinary oxalate in healthy adult dogs. Proceedings of 9thInternational symposium on Urolithiasis 2000, 794-796

Stevenson AE, Markwell PJ, Kasidas GP: Preliminary data from quantitativeanalysis of canine urolithiasis in Great Britain. Proceedings of 9th Internationalsymposium on Urolithiasis 2000, 792-793

Markwell, PJ, Robertson WG, Stevenson AE: Urolithaisis: A comparison ofhumans, cats and dogs. Proceedings of 9th International symposium onUrolithiasis 2000, 785-788

WALTHAM Research News

1. Lulich, J. P., Osborne, C. A., Bartges, J.W., Polzin, D. J. Canine lower urinarytract disorders. In: Ettinger, S. J., Feldman, E. C. (eds.) Textbook of VeterinaryInternal Medicine, 4th edn. Philadelphia: W. B. Saunders, 1995: 1833-1881.

2. Osborne, C. A., Kruger, J. M., Lulich, J. P., Polzin, D. J. Disorders of the felinelower urinary tract. In: Osborne, C. A., Finco, D. R. (eds.) Canine and FelineNephrology and Urology. Baltimore: Williams & Wilkins, 1995: 625-680.

� REFERENCES �

Urolithiasis 2000 – 9th InternationalSymposium on Urolithiasis


32

Flatulence is widely recognised in dogs as asocial nuisance, a source of humour, and anoccasional cause of abdominal discomfort.

There has been little research into the origins andnature of canine rectal gases, their physiologicaland clinical significance, or the efficacy of variousremedies purported to reduce flatulence in dogs.Flatulence is a frequent everyday occurrence and isusually associated with no or very mild discomfort.However, odoriferous gas production is a commoncause for complaint from the dog-owning public.

From human studies it is known that the majorhuman rectal gases are nitrogen and oxygen, whichare derived from air swallowing and diffusion fromthe blood, plus carbon dioxide, hydrogen, andmethane, which are the products of bacterialmetabolism and non-bacterial reactions within thebowel. Odoriferous gases constitute less than 1%by volume of flatus and much of the unpleasantodour is due to sulphur-containing gases,primarily hydrogen sulphide and methanethiol (1,2). Aside from their odoriferous qualities, sulphur-containing rectal gases are potentially toxic andhave been implicated in the pathogenesis ofulcerative colitis in humans (3). There are,therefore, potential health as well as social benefitsto be obtained from reducing the production oravailability (or both) of sulphur gases in the large bowel.

Studies at the WALTHAM Centre for Pet Nutrition have developed an invivo method for the assessment of odiferous canine flatulence (4). Thistechnique involves a monitoring pump with a hydrogen sulphide detectorthat generates a real-time measure of individual flatulence episodesallowing normal variation in canine rectal gas production to be determined.In addition, a predictive model has been developed that enables the relativenoxiousness of each emission to be determined from the levels of hydrogensulphide measured on-line. This WALTHAM flatulence detection system hasbeen used to determine the potential of dietary ingredients to amelioratethe frequency and odour characteristics of flatulence in dogs.

WALTHAM flatulence detection system

Rectal gases are collected via a perforated Teflon tube, which is held close tothe anus of the dog and is attached to a sulphur gas-monitoring pump

carried in a jacket over the dog’s shoulders (Figure 1). Dogs wear the coatsfor five hours during each measurement period. The sampling pump isfitted with a hydrogen sulphide sensor that measures hydrogen sulphidelevels, in parts per million (p.p.m.), at 20-second intervals (Figure 2).

WALTHAM Viewpoint

Dietary manipulation of canineodiferous flatulence


Catriona Giffard BSc, DPhilStella Collins BSc

WALTHAM Centre for Pet Nutrition, UK

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Figure 1 Schematic representation of rectal gas sampling device and a representative flatulenceprofile demonstrating flatulence episodes and flatulence freeintervals. The baseline is set at 1 ppmhydrogen sulphide and all readings below this are ignored.

Figure 2Correlation betweenhuman perception ratingof flatulence and levels ofhydrogen sulphide inrectal gas as measured bythe sampling pump. Thedata represents the meanstandard deviation andscores represent 1– noodour, 2 – slightlynoticeable, 3 – mildlyunpleasant, 4 – badodour, 5 – unbearable. Odour Score

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Three measures of flatulence can be calculated from the hydrogensulphide data: namely number of episodes (NOE), mean interval free time(MIFT), and human perception of malodour (Figure 1). The NOE is thenumber of times during the sampling period that pump readings weregreater than 1 p.p.m., which is the lower limit of sensory detection forhumans in the same room as dogs. The MIFT is a measure of the frequencyof flatulence and is calculated as the cumulative sum of flatulence-freeintervals (in minutes) divided by the number of flatulence-free intervals. Aflatulence-free interval was any 20-second period during which the level ofhydrogen sulphide was less than 1 p.p.m. Human perception of odourrating for each episode of flatulence is calculated according to a powerfunction, where rating (on a scale of 1 to 5) is equal to 1.51[H2S]0.28.These odour ratings are categorised as no odour (= 1), slightly noticeable(= 2), mildly unpleasant (= 3), bad (= 4), and unbearable (=5), asshown in Figure 3.

Effect of diet on in vivo odoriferous canine flatulenceproduction (5)

The potential for manipulation of the diet by the addition of activatedcharcoal, Yucca shidigera extract, and zinc acetate in an attempt to reducethe number, frequency, and odour characteristics of flatulence in dogs wasevaluated. A prospective double-blinded placebo controlled cross-over studywith eight dogs was used to assess the effects on the production of hydrogensulphide when fed a supplemented treat 30 minutes after the dogs ate theirdaily rations. The number, frequency and odour characteristics offlatulence were then measured for five hours using the WALTHAMflatulence detection system.

Feeding this supplemented treat was associated with a small reduction in

the number of flatulence episodes (2.05 ± 0.74 vs. 2.47 ± 0.82 ln/5 hours) and there was no difference between treatment groups andplacebo treats in the mean interval free time (7.55 ± 0.75 and 7.20 ±0.79 ln minutes, respectively). The distribution of odour ratings forflatulence episodes following feeding of test and placebo treats is shown inFigure 3. The percentage of episodes rated as 3 (mildly unpleasant), 4(bad), or 5 (unbearable) was reduced when the dogs were fed thesupplemented treat. Consumption of the activated treat reduced thepercentage of bad and unbearable episodes by 86% compared with theplacebo treats, such that episodes rated as 4 or 5 represented only 2.2% ofall episodes versus 16.1% for the placebo treats.

Conclusion

Oral ingestion of a supplemented treat containing the above-listedingredients is associated with a decrease in the frequency of malodorousflatulence episodes that will directly affect one of the social nuisances of dogownership and, by reducing the production or availability of hydrogensulphide, may be beneficial in diseases linked to the toxicity of this gas.

Results from this study form the basis of a patent application. This treatwill be available as Easydose™ Flatulence Control, as one of a range oftreats of this type within the United Kingdom.


Country Name Fax numberAustralia Duncan Hall +612 605 553 47Bahrain Mustafa El Rafey +971 481 5324Denmark Charlotte Nilsson +454 245 200Finland Tuomas Mantere +358 9773 94444Hong Kong Andrew Baker +852 2369 7920Ireland Niamh Grogan +353 1478 3687Korea Eusoo Kim +822 545 3291Malaysia Carmina R. Herrara +603 758 2861New Zealand Jeff Herkt +649 261 0901

Norway Christian Soerensen +4640 230 957

Phillippines Mark Antony Baguio +632 818 5307

Singapore Irinda Toh +603 758 2861

Sweden Henrik Birkfeldt +464 023 0957

Taiwan Sunghee Han +886 227 476 767

Thailand Rieantfa Puttekulangkura +662 742 6341

Turkey Elcin Eraksoy +9012 12651 2306

United Arab Emirates Susie Amann +971 481 5324

United Kingdom Sarah Harrod +44 1664 415661

For further information or any queries please contact your local office

1. Suarez, F., Furne, J., Springfield, X. et al. Insights into human colonicphysiology from the study of flatus composition. American Journal ofPhysiology 1997; 272: G1028–G1033.

2. Suarez, F. L., Springfield, J., Levitt, M. D. Identification of gases responsiblefor the odor of human flatus and evaluation of a device purported to reduce thisodor. Gut 1998; 43: 100–104.

3. Roediger, W. E., Moore, J., Babidge, W. Colonic sulfide in pathogenesis andtreatment of ulcerative colitis. Digestive Diseases and Sciences 1997; 42:1571–1579.

4. Collins, S. B., Perez, G., Gettingby, G., Batt, R., Butterwick, R., Giffard, C. J.Flatulence measurement in dogs: development of a technique, description ofnormal variability, and relationship to human organoleptic assessments(submitted for publication).

5. Collins, S. B., Stoodley, N., Batt, R., Butterwick, R., Giffard, C. Ability of ananti-flatulence treat to reduce the hydrogen sulfide content of canine flatulence.ACVIM Forum Proceedings 2000.

� REFERENCES �

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Figure 3 Distribution of flatulence episodes according to odour rating indogs fed active and control treats. Data are shown as mean frequency, withsignificant differences between treatments denoted by * (p<0.05).

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