Heart failure is common in diabetic cats: findings from a retrospective case-controlled study in first-opinion practice

OBJECTIVES: To study the prognosis and cause of death in cats with Experimental induction of diabetes mel diabetes mellitus. litus in various laboratory mammals also causes cardiovascular disease and heart METHODS: Twenty consecutive cases of feline diabetes mellitus failure so that the prevalence of cardiac diagnosed in first-opinion practice were followed. Three control cats, disease and failure in diabetic cats seemed worthy of examination. The purpose of without diabetes, were matched to each case of diabetes; these this study was to examine the progno were also followed. sis and cause of death for a cohort of con secutive cases of feline diabetes mellitus RESULTS: One Somali cat with diabetes could not be matched, so diagnosed in a first opinion veterinary practice, and to compare these with con complete data analysis considered only 19 diabetics and 57 trol cats matched for age, breed and sex. matched controls. Death occurred in 14 of 20 diabetics and 23 of 57 controls although one control cat was eventually lost to follow-up. MATERIALS AND METHODS Heart disease and heart failure led to death in six diabetic cats. One of these was the non-matched Somali; nevertheless, the death rate Selection of cases The computer records of Barton Veteri from heart disease in the diabetics was five of 19 compared with two nary Hospital (BVH) were searched for of 57 in controls. The relative risk of heart failure in diabetic cats was all cases of feline diabetes first diagnosed during a six year period between June 10 4 times that of the controls; this difference in rates was 1999 and June 2005. Searching was statistically significant. Survival amongst diabetics was achieved by identifying all cats for which a fructosamine assay had been performed, significantly worse than for controls. For the control cats median and/or where insulin therapy, or oral survival was 718 days after the index visit, whereas for the diabetic hypoglycaemic medication, and/or a diet designed for use with feline diabetes had cases median survival was 385 days after diagnosis. been dispensed. These raw records were CLINICAL SIGNIFICANCE: Heart disease and failure are common in then reviewed in detail to identify cases, which were confirmed as diabetic based diabetic cats. This observation deserves further attention. on compatible clinical signs, concurrent hyperglycaemia and glycosuria, or concur rent elevated fructosamine levels, or both. INTRODUCTION These records were further sorted to iden tify those cases, which had been diagnosed Diabetes mellitus is common in the cat in the first opinion stream of the practice and the prevalence of this condition and treated under our care thereafter. appears to be increasing (Peterson 1998, Rand and Marshall 2004, Rand and others Selection of controls 2004). The prognosis for cats with diabe For each case of diabetes diagnosed tes mellitus in first opinion practice has according to these criteria, three matched received little attention in the literature; non diabetic control cats were sought by few data indicate why diabetic cats die. the following routine. The date of diagno Death in people with diabetes is over sis of each diabetic was identified together Barton Veterinary Hospital, 34 New Dover Road Canterbury, CT1 3BH Kent whelmingly because of cardiovascular dis with their breed, sex and age on that date. ease (Grundy and others 1999, Almdal The hospital database was searched for *Department of Statistics and Modelling Science, University of Strathclyde, Glasgow and others 2004, Bell 2004, Bertoni and matching control cats of the same age G1 1XD others 2004, Nichols and others 2004). (to the nearest year), breed and sex which had been seen at the hospital, either for as well as compatible clinical signs. The from the case control study for which only a routine vaccination or a new episode principal clinical signs recorded from 19 diabetic cats were thus eligible. of illness, within a maximum of 90 days these animals were: polydipsia/polyuria Control cats (n=57) consisted of 45 before or after the date of diagnosis of (80 per cent), weight loss (75 per cent), DSH and 12 DLH. The sex ratio of these the index diabetic case. If more than three polyphagia (65 per cent), depression/leth cats was identical to the diabetic cases (36 control cases were found, three control argy (25 per cent), capricious/variable males, 21 females) and again all were neu cases were chosen at random. appetite (15 per cent), dysuria/haematuria tered. Age structure of the control group (15 per cent) and peripheral neuropathy strongly resembled the age of the cases (10 per cent). Following routine haema (range five to 16 years, median 11Á5 years). RESULTS tology, biochemistry and urinalyses, other laboratory tests were frequently used in the Treatment and clinical outcomes Diabetic cats evaluation of these diabetic cats; those tests of the diabetic cases A total of 28 cats with a new diagnosis of used most frequently were: fructosamine At the time of writing, of these 20 diabetic diabetes were examined and treated at assays for diagnosis and/or monitoring cats, 14 were dead and six were still alive. BVH during the six year period in ques (in 75 per cent of cases), serial glucose The cause(s) to which death or euthanasia tion. Of these 28 cats, six were excluded curves (70 per cent of cases) and measure was ascribed are given in Table 1. Of the from further detailed analysis because ments of thyroid hormone (50 per cent of 14 cats that died, six were caused by heart their condition was originally diagnosed cases). Systemic arterial blood pressure was failure. Details of the clinical and labora elsewhere and the cats were referred to not measured in these cats. tory findings which confirmed the pres our second opinion service and/or their The 20 cats consisted of 15 domestic ence of heart failure in these cats are condition was managed at another prac shorthairs (DSH), four domestic longhairs given in Tables 2 and 3. tice subsequent to the cat being seen at (DLH) and one Somali cat. Males out One cat was euthanased, without treat our practice. Another two cats had both numbered females (13:7); all were neu ment, three days after diagnosis (case 15). diabetes and hyperthyroidism. These cases tered. Most cats were middle aged or Most of the cats that were treated eventu were also excluded from further analysis. older at the time of diagnosis (range six ally received insulin therapy (n=17) and The remaining 20 cats were the subject to 16 years). Median age at diagnosis was a diet particularly designed for diabe of this study. 12 years. tic cats (n=11) (Hills Feline W/D n=6, All cats diagnosed as diabetic exhibited We were unable to find any matching Hills Feline M/D n=5). However, some marked and persistent hyperglycaemia control cats for the male Somali cat (case of the cats were initially treated with an and glycosuria at the time of diagnosis 16), consequently this cat was excluded oral hypoglycaemic agent (glipizide, see

Table 1. Causes of death in the 14 diabetic cats which have died

Cause of death/euthanasia Numbers Cases Details of diagnostic findings Other information

Heart failure 6/14 2, 4, 7, 10, 13, 16* See Tables 2 and 3 One died, five euthanased Chronic renal failure 2/14 17, 18 Azotaemia, cachexia and Two euthanased persistent polyuria In spite of reasonable control of the diabetes, based on fructosamine and plasma glucose monitoring Poor diabetic 2/14 9, 12 Persistent/frequent hyperglycaemia 2 euthanased control: ‘‘unstable’’ and glycosuria Elevated fructosamine One (12) treated with glipizide only Owners persisted with treatment for Other (9) treated 17 (case 9) and 16 months with PZI insulin (case 12) respectively. once a day Hypoglycaemia with convulsions 1/14 19 Hypoglycaemia. Neurological signs Euthanased persisted after euglycaemia Owner, a doctor, was achieved was managing this cat’s diabetes herself Owner requested 1/14 15 Euthanased euthanasia without treatment (three days after diagnosis) Profound anaemia 1/14 14 Investigation not permitted by owner Euthanased Sudden death 1/14 8 Glycaemic control being attempted Died with glipizide

*This cat was a male Somali and no matched controls were available. It was omitted from the case-control analyses Table 2. History and diagnostic findings used to diagnose heart failure in six diabetic cats

Case Interval between History at Physical examination. Plasma Radiography ECG Echo Pleural effusion Ascites Outcome diagnosis of diabetes time of Findings at time of [T4] and development of diagnosis diagnosis of heart failure of heart failure heart failure

2 10 weeks nappetence T38°C 21Á6 nmo / Patchy ncrease n S nus rhythm 1 (see Tab e 3) Scant effus on after – Euthanased we ght oss HR 164 bpm pu monary dens ty atter y frequent d abetes had been 10 months dyspnoea RR 80 brpm a r bronchograms ventr cu ar present for 12 months after d agnos s dyspnoea card omega y premature severe effus on three of heart fa ure hyperpnoea VHS 11Á5 comp exes weeks ater nsp ratory crack es on auscu tat on 10 30 months Du abdom na T37Á4°C Not done Not done S nus 1 (see Tab e 3) 250 m mod fied Large vo ume Euthanased swe ng HR 120 bpm bradycard a transudate mod fied one week after anorex a RR 40 brpm TP 38 g/ transudate d agnos s of m d dehydrat on Tr g 0Á47 mmo / TP 34 g/ heart fa ure co d p nnae Cho 2Á2 mmo / and feet Not cons stent w th chy e 7 16 months Du ness T38Á5°C Not done P eura effus on Not perm tted 1 (see Tab e 3) 50 m pure transudate – Euthanased anorex a HR 140 bpm TP 21 g/ Tr g 0Á51 three weeks after RR 60 brpm mmo / Cho heart fa ure nterm ttent 0Á76 mmo / d agnosed tachydysrhythm a 13 Seven months nappetence HR 168 bpm 22Á0 nmo / Card omega y Not done 1 (see Tab e 3) 220 m b oodsta ned – D ed 10 days open-mouth RR 60 brpm VHS 9Á1 (after after heart fa ure breath ng oud breath thoracocentes s) d agnosed sounds on auscu tat on ntractab e 4 12 months Lethargy T38Á9°C Not done Card omega y Atr a fibr at on Not done Absent Mod fied Euthanased we ght oss rregu ar heart VHS 9Á3 w th RBBB pattern transudate one day after abdom na HR ;200 bpm TP 42 g/ heart fa ure swe ng abdom na effort to d agnosed breathe flu d thr n abdomen 16* F ve weeks Du PUPD T38Á4°C HR 120 12Á9 nmo / P eura flu d Th rd degree heart 1 (see Tab e 3) 130 m c oudy – Euthanased ncreased RR 40 brpm b ock ventr cu ar flu d prote n Tr g and three days resp ratory bradycard a rate 70 bpm Cho content after heart fa ure effort worsened over not measured d agnosed 48 hours

*This cat was not used in the case control study ECG Electrocardiography Echo Echocardiography T body temperature HR Heart rate in beats per minute (bpm) RR Respiratory rate in breaths per minute (brpm) VHS Vertebral Heart Sum (Lister and Buchanan 2000) TP Total protein Trig Triglyceride Chol Cholesterol RBBB Right bundle branch block PUPD Polyuria and polydipsia Table 3. Echocardiographic findings, diabetic cats

Case LVED LVES FWED FWES IVSED IVSES Fractional MVI TVI AI PVI Ao LA LA : Ao Other Alive or (mm) (mm) (mm) (mm) (mm) (mm) shortening (mm) (mm) findings dead (per cent)

22011Á6 8Á1 12Á3 7Á8 8Á835111 2 2 2 8Á622Á5 2Á6:1 P eura effus on Dead ‘‘En arged’’ ‘‘Th ck’’ ‘‘Th ck’’ ‘‘Th ck’’ En arged En arged 10 13 6Á37Á7 8Á77Á3 8Á1522122 9Á59Á81Á03:1 P eura effus on, Dead ‘‘Th ck’’ ‘‘Th ck’’ per card a th cken ng, asc tes 717Á68Á77Á4 10Á1 5Á58Á0511222 11 25Á2 2Á3:1 P eura Dead ‘‘Th ck’’ ‘‘Th ck’’ En arged En arged effus on 13 15 10 5 6 4 7 33 NR NR NR NR Not ‘‘Very d ated’’ NR ‘‘Smoke’’ Dead measured but not n eft atr um, measured p eura effus on 4 Not done, not Card omega y, Dead perm tted atr a fibr at on w th RBBB

Á Á Á pattern, asc tes 16* 17Á19Á94Á87Á94Á86Á3421 111 2 2 2 2 2 Th rd degree Dead heart b ock, p eura effus on Reference va ues Jacobs and 12-19Á85Á2-10Á82Á2-4Á45Á4-8Á12Á2-4Á04Á7-7Á0 39-61 7Á2-11Á99Á3-15Á10Á95-1Á65 Kn ght (1985) P pers and 11Á2-21Á85Á2-10Á83Á2-5Á62Á8-6Á0 23-56 4Á0-11Á84Á5-11Á2 others (1979) S sson and 10Á8-21Á44Á0-11Á22Á5-6Á04Á3-9Á83Á0-6Á04Á0-9Á0 40-66Á7 22226Á0-12Á17Á0-17Á00Á88-1Á79 others (1991)

*This cat was not included in the case control study LVED Left ventricular diameter end diastole LVES Left ventricular diameter end systole FWED Left ventricular free wall thickness end diastole FWES Left ventricular free wall end systole VSED nterventricular septum end diastole VSES nterventricular septum end systole MV Mitral valve incompetence TV Tricuspid valve incompetence A Aortic valve incompetence PV Pulmonic valve incompetence Ao Aortic diameter LA Left atrial diameter La Ao Ratio of left atrial to aortic diameters Thick or Enlarged exceeds all reference values listed NR Not recorded below). Insulin therapy most frequently known to be still alive. One of these con was classified according to heart disease consisted of Lente insulin given twice trol cats has been lost to follow up. Of (presence or absence), survival outcome daily. Insulin dose was adjusted based the 23 deaths in this group, seven were (alive or dead at the end of the study), sur on plasma glucose curves and fructosamine attributed to chronic renal disease, four vival time since diagnosis (days), sex (male assays in most cases. Maximum dose of to neoplasia (mammary adenocarcinoma, or female neuter), age (years) and breed insulin recorded was six units twice daily. squamous cell carcinoma of the mouth, (DSH or DLH). Of the cats treated with insulin, four of salivary gland carcinoma and undiagnosed Cases and controls were compared 17 had insulin therapy withdrawn at some neoplasm of the lower bowel), four were using binary logistic regression to identify time because the requirement for exogenous attributed to hyperthyroidism (in two which factors were associated with (i) the insulin therapy eventually disappeared; in cases complicated by other conditions; risk of heart disease and (ii) the risk of three of these cases insulin therapy had to cholangiohepatitis and recurrent idio mortality during the course of the study. be reinstituted some months later. pathic cystitis) and two to heart failure. Factors found not to be significant were Glipizide (2Á5to5Á0 mg twice a day) For the cats where heart failure was diag retained as forced covariates within the was used initially to treat several cats nosed, details of the clinical and labora model after investigating the stability of (n=6) but this resulted in poor glycaemic tory findings, which confirmed the fitting other models with and without each control in five cases, one of which died presence of heart failure in these cats are factor. Two factor interactions between suddenly (case 8; Table 1). One cat given in Table 4. Various other abnormal fitted factors were examined. Results con treated in this way developed diabetic ities were listed as the immediate cause sisting of the odds ratios, 95 per cent hyperosmolar syndrome (case 3) and of death or euthanasia in one control confidence intervals (CI) and statistical another developed severe dehydration, case each (road traffic accident, feline significance of the final models were azotaemia and ketoacidosis with hypoka immunodeficiency virus, chronic abscess, obtained. laemia (case 11). Four of these cats initially undifferentiated anaemia with hypoalbu In addition, survival analysis and the treated with glipizide were eventually trea minaemia). In two control cases that were Weibull distribution model were used to ted with insulin. One cat receiving glipi euthanased, no diagnosis was recorded. identify those factors and their 95 per cent zide exhibited fair control of glycaemia Neither of these cats was showing signs CI which significantly influenced how for many months, but eventually, because attributable to cardiovascular or respira long case and control cats lived following of unstable blood glucose levels and ongo tory disease. recruitment. As some cats were still alive ing clinical signs, this cat was euthanased following the end of the study, the data at the owner’s request (case 12; Table 1). were adjusted for censored observations. Data management and Data were summarised using classifica Control cats’ clinical outcomes statistical analyses tion tables and a box plot used to compare At the time of writing, 23 of the control Information on each of the 19 eligible the distribution of life times of cases and cats are known to have died and 33 are cases and their three matched controls controls.

Table 4. History and diagnostic findings used to diagnose heart failure in two non-diabetic control cats

Controls History Physical examination Radiography ECG Echo Pleural Ascites Outcome findings effusion

Control Inappetence, T37Á4°C, HR 185 bpm, Diffuse increased Not done Not done Absent Absent Died four days 2b sudden RR 74 brpm, grade lung density with after heart failure onset III/VI systolic heart air bronchograms diagnosed dyspnoea murmur, crackles heard on pulmonary auscultation, normal percussion Pulmonary oedema Cardiac silhouette fluid expelled through partially obscured mouth, cardiopulmonary but cardiomegaly massage required, VHS 8Á7 given intravenous frusemide and placed in an oxygen cage Improved Control Weight T38Á4°C, HR 120 bpm Not permitted Not Not Not Modified Euthanased 14b loss, Grade II/VI systolic permitted permitted permitted transudate two months abdominal heart murmur, Retinal TP 40 g/l after heart failure swelling, haemorrhages, Fluid diagnosed blindness thrill in abdomen

ECG Electrocardiography, Echo Echocardiography, T Body temperature, HR Heart rate in beats per minute (bpm), RR Respiratory rate in breaths per minute (brpm), VHS Vertebral Heart Sum (Lister and Buchanan 2000) Statistical analyses were undertaken Table 5. Number of diabetic cats (cases) and non-diabetic cats (controls) using Minitab version 14 statistical soft in the case-control analyses classified according to the categorical variables ware and P values less than 0Á05 were con investigated in the study sidered to be significant. Variable Level Diabetic

Results of statistical evaluation Cases Controls Table 5 shows the incidence of heart dis Heart disease No 14 55 ease and the frequency of survival found Yes 5 2 Survival No 13 23 for diabetic cases and non diabetic control Yes 6 34 cats. The proportion of diabetic cats with Sex Female neuter 7 21 heart disease in the case control study was Male neuter 12 36 Breed Domestic longhair 4 13 five of 19 (26Á3 per cent) compared with Domestic shorthair 15 44 the lower rate of two of 57 (3Á5 per cent) for controls. Similarly, the mortality rate amongst diabetic cats was 13 of 19 Table 6. Results from the multivariate binary logistic regression analysis showing (68Á4 per cent), which was much higher the odds ratios, 95 per cent CI and significance (LRT P values) associated with the than that for controls at 23 of 57 (40Á4 risk of heart disease for each of the categorical variables sex, breed and diabetes after adjustment for age of cat per cent). As to be expected, there was lit tle difference in the proportions of cats of Predictor Odds ratio Lower 95 per cent CI Upper 95 per cent CI LRT P value different sex and breeds between diabetic Age (years) 0Á92 0Á69 1Á24 0Á50 and non diabetic cats in view of the con Sex (referent group FN) trols being selected to match cases. The MN 1Á93 0Á28 13Á22 0Á60 Breed (referent group DLH) mean ages of cases and controls were DSH 1Á93 0Á28 13Á22 0Á57 11Á6and11Á4 years respectively. Diabetes (referent group NO) Results of the binary logistic regression YES 10Á38 1Á76 61Á18 0Á01 analysis for an association between heart dis CI Confidence interval, LRT Likelihood ration test, FN Female neutered, MN Male neutered, DLH Domestic longhair, ease and the risk factors, age, sex, breed and DSH Domestic shorthair diabetes are shown in Table 6. Diabetes was identifiedasasignificantriskfactor(P=0Á01) Table 7. Results from the multivariate binary logistic regression analysis showing with cats suffering from diabetes being 10Á4 the odds ratios, 95 per cent CI and significance (LRT P values) associated with the times more likely to have heart disease (95 risk of death for each of the categorical variables sex, breed and diabetes after per cent CI from 1Á8to61Á2). There was adjustment for age of cat no association of heart disease with sex or Predictor Odds ratio Lower 95 per cent CI Upper 95 per cent CI LRT P value breed and age did not have any significant effect on the risk of heart disease. Age (years) 1Á15 0Á95 1Á38 0Á15 Sex (referent group FN) Table 7 similarly shows that the only MN 0Á66 0Á22 1Á95 0Á45 significant risk factor (P=0Á002) associated Breed (referent group DLH) with mortality was diabetes. Cats with DSH 0Á53 0Á14 1Á98 0Á35 Diabetes (referent group NO) diabetes were 3Á4 times more likely to die YES 3Á39 1Á08 10Á60 0Á036 (95 per cent CI 1Á1to10Á6). CI Confidence interval, LRT Likelihood ration test, FN Female neutered, MN Male neutered, DLH Domestic longhair, Examination of the distribution of the DSH Domestic shorthair survival times of cats following recruit ment to the study indicated that for con trols, 50 per cent did not survive more DISCUSSION tive study and retrospective studies should than 718 days, whereas for diabetics, 50 always be interpreted with caution. per cent did not survive more than 385 The epidemiological features of diabetes A matched case control design was days. The box plot of the survival times mellitus in this group of cats from first chosen for this study in order to derive the by diabetic category are shown in Fig 1. opinion practice are in keeping with those maximum amount of meaningful infor Multivariate regression analysis of the sur reported elsewhere with a notable pre mation from a small number of diabetic vival times indicated that sex and breed dominance of males (Panciera and others cats. Three controls were chosen from did not influence the survival times, 1990, Peterson 1998, Rand and Marshall the same practice as the cases; they were whereas age and diabetes did, as shown 2004, Rand and others 2004). None of the matched for age, breed and sex to each in Table 8. Diabetic cats had significantly cats were Burmese. index case of diabetes. Each control case lower survival times (P=0Á002) than con The present study is flawed because it was enrolled into the study having been trols and as age increased, the survival time addresses a small sample of diabetic cats seen for a routine vaccination or a new epi of cats decreased significantly (P=0Á004). seen at a single centre. It is also a retrospec sode of disease within a short time period echocardiography; in the other two cases Box plot of Survival time by Diabetic Category where echocardiography was permitted, 2500 the findings were also compatible with heart failure. In addition, three of these 2000 cats had serious dysrhythmias docu mented by electrocardiography (ECG; 1500 atrial fibrillation, ventricular premature complexes and third degree heart block). 1000 A fourth cat (case 7) also had a dysrhyth mia audible on auscultation in the latter

500 stages of the illness, ECG evaluation of Survival time (days) the rhythm was not sanctioned by the owner so the exact nature of this rhythm 0 disturbance remains obscure. One other Control Diabetic cat (case 10) exhibited sinus bradycardia. Diabetic Category In the past, particularly before the FIG 1. Box plot illustrating the difference in distribution of the survival times in days since advent of echocardiography, many cats recruitment to the study of control and diabetic cats. * represents outliers with heart failure were probably misdiag nosed, because the most frequent signs of heart failure recognised in other veterinary before or after the index case. This design and 3Á4 times (95 per cent CI 1Á1t species, such as coughing and tachycar was chosen to attempt to select controls 10Á6) more likely to die than their age dias, are infrequently found in cats with that did not differ systematically from matched and breed matched controls. heart failure. If a cat has a pleural effusion, the cases except for the absence of diabetes These results are consistent with diabetic cardiac auscultation is often very challeng and to avoid over representation of ani cats being more predisposed to heart dis ing so that heart murmurs or gallop mals with other chronic disease processes ease, which in turn increases the risk of sounds may not be identified with ease. in the control population. mortality. The survival time of diabetic Moreover, until fairly recently, cats with The most important finding from this cats from point of diagnosis did differ pleural effusions were often designated study is that heart failure was frequent in significantly from their controls and as having idiopathic effusions or other this sample of cats with diabetes mellitus. depended on the age of the cat. The thoracic disease without performing echo Moreover, all cats with heart failure died median survival time of diabetic cats cardiographic studies. These observations or were euthanased soon after the develop was just over one year (385 days) com may explain why heart failure has not been ment of this condition. The findings from pared with almost two years (718 days) identified as a frequent complication of the case control analyses have clearly iden for their controls. diabetes mellitus in cats. tified diabetes as the one significant risk Of the six diabetic cats in this study The forms of heart disease and failure, factor associated with both heart disease identified as having heart failure, five of which the cats in this study exhibited, were and mortality in this primary first opinion the six had a pleural effusion and two of by no means identical; some showed signs practice. Age, breed and sex of the cat were the six had ascites, a finding, which is compatible with hypertrophic cardio not identified as risk factors. Diabetic cats relatively uncommon in cats with heart myopathy, whereas others showed signs were 10Á4 times (95 per cent CI 1Á8to failure. Three of these diabetic cats were principally indicating right sided heart 61Á2) more likely to have heart disease found to have very enlarged left atria on failure. This heterogeneity in clinical ap pearance suggests that diabetes mellitus probably does not cause cardiac disease in Table 8. Results from the multivariate survival time (days) analysis showing the cats directly or simply. However, in this regression coefficients, 95 per cent CIs and significance (P values) associated with each of the categorical variables sex, breed and diabetes after adjustment for age species, as in the human sufferer, diabetes of cat and fitting a Weibull distribution taking account of right censoring mellitus may promote or exacerbate exist ing heart disease. It is unfortunate that sys Predictor Coefficient Lower 95 per cent CI Upper 95 per cent CI P value temic blood pressures were not measured Shape 1Á0219 0Á7787 1Á3411 in these diabetic cats because if hyperten Age (years) 20Á1877 20Á3168 20Á0586 0Á004 sion were present it might offer one expla Sex (referent group FN) MN 20Á1139 20Á8749 0Á6472 0Á769 nation for the development of heart Breed (referent group DLH) failure. Many human diabetics are hyper DSH 0Á4162 20Á4429 1Á2754 0Á342 tensive. On the contrary, limited data sug Diabetes (referent group NO) YES 21Á1052 21Á7899 20Á4206 0Á002 gest that hypertension is not common in feline diabetics (Sennello and others CI Confidence interval, FN Female neutered, MN Male neutered, DLH Domestic longhair, DSH Domestic shorthair 2003). It is possible that one or more of these 14 of 52 cases (27 per cent) where a chest 2005). Eighty years ago, Joslin drew atten diabetic cats with heart failure might have radiograph was taken. In another much tion to a link between diabetes, obesity had acromegaly, a disease which is known smaller study, which investigated the and cardiovascular disease in people to cause diabetes and heart failure in cats effects of diet on glycaemia in 16 diabetic (Joslin 1927). A similar link may exist (Peterson and others 1990). However, the cats (Nelson and others 2000), at the time in the cat. The implications of these find usual principal sign of acromegaly is of entry into the study two cats had heart ings for both veterinary and compara uncontrolled hyperglycaemia in spite of murmurs and another two cats exhibited tive medicine certainly warrant further insulin dosage exceeding 20 iu per day audible cardiac gallop sounds. A recent investigation. (Norman and Mooney 2000, Peterson publication, which focused on cats in an 2004). The maximum dose of insulin emergency hospital, also reported heart Acknowledgements given to a cat in this study was 12 iu murmurs and gallop sounds in a signifi We would like to thank the nursing and per day. Acromegaly is also much less cant proportion of cats with diabetes seen veterinary staff at Barton Veterinary Hos common than uncomplicated diabetes in crisis situations (Koenig and others pital for their dedication in the care of mellitus. However, in none of the cats 2004). Congestive heart failure was re these patients. We also thank the secretar in the present study was insulin like corded in five of 17 cats with hypergly ial and reception staff at Barton Veterinary growth factor measured and no other tests caemic hyperosmolar syndrome, one of Hospital, particularly Angela Francis, who were used to deliberately seek out cases of 33 cats with diabetic ketoacidosis and tirelessly interrogated our computer acromegaly. six of 78 cats with uncomplicated diabetes records for this study. One or more of the cats with diabetes mellitus. Again the authors did not recog The active support and encouragement and heart failure could have had hyperthy nise or report an overt relationship of CVS (UK) Ltd, owners of The Barton roidism, a disease which is very common between diabetes mellitus and heart fail Veterinary Hospital, is gratefully acknowl in older cats and which sometimes can ure. However, in two other retrospective edged. cause heart failure (Mooney and Petersen studies of diabetes mellitus, heart disease CL did much of this work whilst in 2004). Diabetic cats with known hyper or heart failure were not reported at all in receipt of a Blue Skies Research Grant thyroidism were deliberately excluded diabetic cats (Kraus and others 1997, from the RCVS Trust. from this study in the recruitment criteria. Goossens and others 1998). Signs of thyroid enlargement were regu In human beings, diabetes mellitus is References larly sought by clinical examination of an independent risk factor for the develop ALMDAL,T.,SCHARLING,H.,JENSEN,J.S.&VESTERGAARD,H. (2004) The independent effect of type 2 diabetes the diabetic cats and thyroid assays were ment of heart disease and heart failure. mellitus on ischaemic heart disease, stroke, and performed in 10 cats during the course The exact relationship between diabetes death: a population based study of 13,000 men and women with 20 years of follow up. Archives of their illness, including three of those and cardiovascular disease in people is of Internal Medicine 164, 1422 1426 cats found to develop heart failure. None complex. Diabetes causes an atherogenic BELL, D. S. H. (2004) Heart failure: a serious and com mon comorbidity of diabetes. Clinical Diabetes of these cats was diagnosed as suffer dyslipidaemia, which leads to accelerated 22, 61 65 ing from hyperthyroidism but, because coronary artery disease and myocardial BERTONI, A. G., HUNDLEY, W. G., MASSING, M. W., BONDS, D. E. & BURKE, G. L. (2004) Heart failure preva routine thyroid monitoring was not ischaemia. A specific myocardial disease, lence, incidence, and mortality in the elderly with performed in all cases, this possibility diabetic cardiomyopathy, is also reported. diabetes. Diabetes Care 27, 699 703 CRENSHAW,K.L.&PETERSON, M. E. (1996) Pretreat cannot be excluded. Hypertension, an autonomic neuropathy ment clinical and laboratory evaluation of cats Studies of the prognosis and outcome leading to decreased cardiac vagal tone, with diabetes mellitus: 104 cases (1992 1994). Journal of the American Veterinary Medical Asso for cats with diabetes have been relatively glycation of myocardial proteins and ciation 209, 943 948 few. However, if we examine some of endothelial dysfunction may all contribute GOOSSENS, M. M. C., NELSON, R. W., FELDMAN,E.C.& GRIFFEY, S. M. (1998) Response to insulin treat these publications, most of which describe to the development of diabetic cardiomy ment and survival in 104 cats with diabetes mel cases from secondary or tertiary referral opathy, but human diabetics are also fre litus (1985 1995). Journal of Veterinary Internal Medicine 12,16 hospitals, we discover that in common quently obese and chronically physically GRUNDY, S. M., BENJAMIN, I. J., BURKE, G. L., CHAIT,A., with the observations in the present study, inactive and this lifestyle appears to con ECKEL,R.H.,HOWARD,B.V.,MITCH,W.,SMITH,S.C.J. &SOWERS, J. R. (1999) Diabetes and cardiovas heart disease may have been present in tribute to both diabetes and heart disease cular disease: a statement for healthcare profes a considerable number of these diabetic (Julu 1993, Grundy and others 1999, sionals from the American Heart Association. Circulation 100, 1134 1146 cats. For instance, in a large study of McNally and Lawrence 2003, Almdal JACOBS,G.&KNIGHT, D. H. (1985) M mode echocardio 104 cats with diabetes (Crenshaw and and others 2004, Bell 2004, Bertoni and graphic measurements in non anaesthetised healthy cats: effects of body weight, heart rate, Peterson 1996), concurrency between dia others 2004, Nichols and others 2004). and other variables. American Journal of Veteri betes mellitus and heart disease was not Cardiovascular diseases are listed as the nary Research 46, 1705 1711 JOSLIN, E. P. (1927) Arteriosclerosis in diabetes. remarked upon as an important finding cause of death in about 65 per cent of per Annals of Clinical Medicine 5, 1061 1079 and yet heart murmurs (19 of 104) and sons with diabetes (Grundy and others JULU, P. O. O. (1993) Vagolytic effect of diabetes mel litus. Brain 116, 485 492 gallop rhythms (seven of 104) were fre 1999). KOENIG, A., DROBATZ, K. J., BEALE,A.B.&KING,L.G. quently identified during physical exami Diet and exercise probably are impor (2004) Hyperglycaemic, hyperosmolar syndrome in feline diabetics: 17 cases (1995 2001). Journal nation of these cats. Additionally, these tant in the aetiology of diabetes in cats, of Veterinary Emergency and Critical Care 14, authors reported cardiac enlargement in as they are in people (Rand and Marshall 30 40 KRAUS, M. S., CALVERT, C. A., JACOBS,G.J.&BROWN,J. tive heart failure in type 2 diabetes. Diabetes Care PIPERS, F. S., REEF,V.&HAMLIN, R. L. (1979) Echocar (1997) Feline diabetes mellitus: a retrospective 27, 1879 1884 diography in the domestic cat. American Journal mortality study of 55 cats (1982 1994). Journal ORMAN,E.J.&MOONEY, C. T. (2000) Diagnosis and of Veterinary Research 40, 882 886 of the American Animal Hospital Association management of diabetes mellitus in five cats with RAND,J.S.&MARSHALL, R. (2004) Feline diabetes mel 33, 107 111 somatotrophic abnormalities. 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