Quality of life and response to treatment in cats with hypersomatotropism: the owners' point of view.

OBJECTIVES: The aim of this study was to collect clinical information from owners of cats with hypersomatotropism (HS) distributed worldwide, assessing the impact of HS and its treatments on cats' quality of life (QoL) and survival time. METHODS: A survey focused on clinical presentation, diagnostic procedures, treatments, cats' QoL and disease progression was distributed worldwide to owners of cats with HS. The owner's perception of the cats' QoL before and after or during treatment was defined using a score ranging from 1 (poor) to 5 (excellent). Improvement following treatment (IFT) was quantified using a score ranging from 1 (absent) to 5 (obvious). Different treatment groups, including at least five cases, were compared. RESULTS: A total of 127 cats were included from at least 11 different countries. Among these, 120 (95%) were diabetic and 7 (5%) were not. Out of 120 diabetic cats, 55 (46%) were treated with insulin as a single treatment (INS). Other treatments were not mentioned to owners in 35/120 (29%) cases. The median QoL score at diagnosis was 2 (range 1-5) and improved after treatment in all groups. Cabergoline (4; range 1-5), radiotherapy (4; range 2-5) and hypophysectomy (5; range 4-5) showed better median IFT scores compared with INS (3; range 1-5) (P = 0.046, P <0.002 and P <0.0001, respectively). Hypophysectomy IFT proved superior to cabergoline (P = 0.047) and was equal to radiotherapy IFT (P = 0.32). No difference was found between cabergoline and radiotherapy IFT (P = 0.99). The median survival time (MST) was 24 months (range 0-75 months). Cats treated with INS showed shorter MST (22 months; range 0-69 months) compared with cats treated with causal treatments combined (36 months; range 3-75 months) (P = 0.04). CONCLUSIONS AND RELEVANCE: Not all cats with HS will have diabetes mellitus. Causal treatments seem associated with the greatest improvements in perceived cats' QoL and survival; such treatments should therefore be discussed with owners. Cabergoline could be an effective alternative management option.

Mapping the genetic basis of diabetes mellitus in the Australian Burmese cat (Felis catus).

Diabetes mellitus, a common endocrinopathy affecting domestic cats, shares many clinical and pathologic features with type 2 diabetes in humans. In Australia and Europe, diabetes mellitus is almost four times more common among Burmese cats than in other breeds. As a genetically isolated population, the diabetic Australian Burmese cat provides a spontaneous genetic model for studying diabetes mellitus in humans. Studying complex diseases in pedigreed breeds facilitates tighter control of confounding factors including population stratification, allelic frequencies and environmental heterogeneity. We used the feline SNV array and whole genome sequence data to undertake a genome wide-association study and runs of homozygosity analysis, of a case-control cohort of Australian and European Burmese cats. Our results identified diabetes-associated haplotypes across chromosomes A3, B1 and E1 and selective sweeps across the Burmese breed on chromosomes B1, B3, D1 and D4. The locus on chromosome B1, common to both analyses, revealed coding and splice region variants in candidate genes, ANK1, EPHX2 and LOX2, implicated in diabetes mellitus and lipid dysregulation. Mapping this condition in Burmese cats has revealed a polygenic spectrum, implicating loci linked to pancreatic beta cell dysfunction, lipid dysregulation and insulin resistance in the pathogenesis of diabetes mellitus in the Burmese cat.

Epidemiological study of dogs with diabetes mellitus attending primary care veterinary clinics in Australia.

BACKGROUND: The objectives of this study were to establish the prevalence, risk factors and comorbidities/sequelae for diabetes mellitus (DM) in Australian dogs presented to first-opinion veterinary practices. METHODS: Electronic patient records of dogs (n=134,329) attending 152 veterinary clinics during 2017 were sourced through VetCompass Australia. They included 418 dogs with DM; a prevalence of 0.36 per cent (95 per cent CI 0.33 per cent to 0.39 per cent) in Australian dogs attending these veterinary clinics. By comparing with the reference group of rarer breeds and unidentified crossbreeds, multivariable modelling was used to reveal breeds (and their crosses) with significantly higher odds of having DM. RESULTS: The results revealed that breeds (and their crosses) with significantly higher odds of having DM were Australian terriers (ORs=7.93 (95 per cent CI 2.83 to 22.27)), Siberian huskies (OR=6.24 (95 per cent CI 2.51 to 15.54)), English springer spaniels (OR=5.37 (95 per cent CI 1.48 to 19.53)), West Highland white terriers (OR=4.85 (95 per cent CI 2.55 to 9.25)), miniature schnauzers (OR=3.47 (95 per cent CI 1.16 to 10.35)), all types of poodles (OR=3.41 (95 per cent CI 2.07 to 5.61)), bichon frises (OR=3.41 (95 per cent CI 1.65 to 7.01)), schnauzers (OR=3.18 (95 per cent CI 1.42 to 7.11)) and cavalier King Charles spaniels (CKCS; OR=1.84 (95 per cent CI 1.08 to 3.13)). Breeds with lower risk were German shepherd dogs (OR=0.11 (95 per cent CI 0.01 to 0.84)), golden retrievers (OR=0.09 (95 per cent CI 0.01 to 0.68)) and boxers (no cases identified). Fisher's exact tests showed that labradoodles were diagnosed significantly more often than purebred Labradors (P=0.04) and did not differ significantly from poodles (P=0.81). Cavoodles did not differ significantly from either CKCS (p~1.00) or poodles (P=0.12). Spoodles were significantly less diagnosed than poodles (P=0.003) but did not differ from cocker spaniels (P=0.66). Desexed male dogs had a higher odds of DM than entire male (OR=0.62 (95 per cent CI 0.39 to 0.98)) and desexed female dogs (OR=0.76 (95 per cent CI 0.61 to 0.96)). Comorbidities/sequelae associated with canine DM included suspected pancreatitis (OR 10.58 (95 per cent CI 5.17 to 22.78)), cataracts (OR 9.80 (95 per cent CI 5.65 to 17.35)), hyperadrenocorticism (OR 6.21 (95 per cent CI 3.29 to 11.88)), urinary tract infection (OR 5.09 (95 per cent CI 1.97 to 13.41)) and hypothyroidism (OR 4.10 (95 per cent CI 1.08 to 15.58)). CONCLUSIONS: Breeds at most risk included Australian terriers and Siberian huskies as previously reported, as well as, for the first time, English springer spaniels. In contrast to other populations where there is female predisposition for DM, desexed male dogs in Australia were at increased risk for DM compared with both entire males and desexed females. This predisposition for desexed males to develop DM warrants further investigation.

Faecal microbiota of cats with insulin-treated diabetes mellitus.

Microorganisms within the gastrointestinal tract significantly influence metabolic processes within their mammalian host, and recently several groups have sought to characterise the gastrointestinal microbiota of individuals affected by metabolic disease. Differences in the composition of the gastrointestinal microbiota have been reported in mouse models of type 2 diabetes mellitus, as well as in human patients. Diabetes mellitus in cats has many similarities to type 2 diabetes in humans. No studies of the gastrointestinal microbiota of diabetic cats have been previously published. The objectives of this study were to compare the composition of the faecal microbiota of diabetic and non-diabetic cats, and secondarily to determine if host signalment and dietary factors influence the composition of the faecal microbiota in cats. Faecal samples were collected from insulin-treated diabetic and non-diabetic cats, and Illumina sequencing of the 16S rRNA gene and quantitative PCR were performed on each sample. ANOSIM based on the unweighted UniFrac distance metric identified no difference in the composition of the faecal microbiota between diabetic and non-diabetic cats, and no significant differences in the proportions of dominant bacteria by phylum, class, order, family or genus as determined by 16S rRNA gene sequencing were identified between diabetic and non-diabetic cats. qPCR identified a decrease in Faecalibacterium spp. in cats aged over ten years. Cat breed or gender, dietary carbohydrate, protein or fat content, and dietary formulation (wet versus dry food) did not affect the composition of the faecal microbiota. In conclusion, the composition of the faecal microbiota was not altered by the presence of diabetes mellitus in cats. Additional studies that compare the functional products of the microbiota in diabetic and non-diabetic cats are warranted to further investigate the potential impact of the gastrointestinal microbiota on metabolic diseases such as diabetes mellitus in cats.

Adiponectin profiles are affected by chronic and acute changes in carbohydrate intake in healthy cats.

Adiponectin is a key adipokine that regulates carbohydrate and lipid metabolism. It circulates in stable low (LMW) and high molecular weight (HMW) forms. The aims of this study were to characterize baseline adiponectin profiles (total, LMW and HMW multimers) in healthy cats and to assess the effects of varying dietary carbohydrate content on adiponectin profiles. Cats were maintained on a diet with moderate carbohydrate content (37% metabolisable energy [ME]) for 4 weeks and then randomly allocated to either a low carbohydrate (19% ME) or high carbohydrate (52% ME) diet for 4 weeks. Fasting and postprandial plasma adiponectin profiles were measured by ELISA and sucrose gradient/Western blot. After consuming the moderate carbohydrate diet for 4 weeks, fasting total, HMW and LMW plasma adiponectin concentrations were 5.0±0.6, 2.5±0.5 and 2.6±0.2 µg/mL, respectively. After changing to the low carbohydrate diet, fasting total adiponectin was unchanged but HMW adiponectin increased and LMW adiponectin decreased. No significant postprandial changes were observed. Cats consuming the high carbohydrate diet had increased fasting total and LMW adiponectin with no change in HMW adiponectin. In the postprandial state total adiponectin was reduced and there was a trend towards a decrease in HMW (p=0.086) but not LMW multimers. These data indicate that feline adiponectin multimer profiles are similar to those reported in other species and demonstrate that changes in plasma adiponectin occur in response to chronic and acute carbohydrate intake and these reflect differential changes in adiponectin multimers.

Evaluation of beta-cell sensitivity to glucose and first-phase insulin secretion in obese dogs.

OBJECTIVE: To compare beta-cell sensitivity to glucose, first-phase insulin secretion, and glucose tolerance between dogs with naturally occurring obesity of > 2 years' duration and lean dogs. ANIMALS: 17 client-owned obese or lean dogs. PROCEDURES: Frequently sampled IV glucose tolerance tests were performed with minimal model analysis on 6 obese dogs and matched controls. Glucagon stimulation tests were performed on 5 obese dogs and matched controls. RESULTS: Obese dogs were half as sensitive to the effects of insulin as lean dogs. Plasma glucose concentrations after food withholding did not differ significantly between groups; plasma insulin concentrations were 3 to 4 times as great in obese as in lean dogs. Obese dogs had plasma insulin concentrations twice those of lean dogs after administration of glucose and 4 times as great after administration of glucagon. First-phase insulin secretion was greater in obese dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Obese dogs compensated for obesity-induced insulin resistance by secreting more insulin. First-phase insulin secretion and beta-cell glucose sensitivity were not lost despite years of obesity-induced insulin resistance and compensatory hyperinsulinemia. These findings help explain why dogs, unlike cats and humans, have not been documented to develop type 2 diabetes mellitus.

Use of a meal challenge test to estimate peak postprandial triglyceride concentrations in dogs.

OBJECTIVE: To develop a standardized meal challenge test by assessing associations between food-withheld preprandial (ie, fasting) and postprandial triglyceride concentrations, determining the most appropriate sampling time to detect the peak concentration (highest postprandial concentration), and estimating reference intervals for fasting and postprandial concentrations in healthy dogs. ANIMALS: 12 lean healthy mixed-breed dogs. PROCEDURES: Dogs were fed a dry commercially available diet (fat, 31% metabolizable energy) for 3 weeks. After food was withheld for 23 to 24 hours, plasma triglyceride concentrations were measured 1 and 0.083 hours before and 1, 2, 3, 4, 5, 6, 9, and 12 hours after feeding of a standardized challenge meal (median amount eaten, 63 kcal/kg [127 kcal/kg°.75]). Correlation and agreement between concentrations at peak and other time points were assessed by use of correlation coefficients and Bland-Altman limits of agreement. Reference intervals were calculated by use of a robust method. RESULTS: Fasting and peak triglyceride concentrations were not closely associated. The highest concentration among samples obtained 2, 5, and 6 hours after meal consumption had closest agreement with peak concentration. In 5 of 12 dogs, concentrations 12 hours after eating were still significantly above baseline concentration (mean of each dog's fasting concentrations). CONCLUSIONS AND CLINICAL RELEVANCE: Fasting triglyceride concentration could not be used to accurately predict peak concentration. When estimating peak concentration, multiple samples should be collected 2, 5, and 6 hours after consumption of a standardized meal. Food may need to be withheld for > 12 hours when assessing fasting concentrations in healthy dogs.

Disease prevalence among dogs and cats in the United States and Australia and proportions of dogs and cats that receive therapeutic diets or dietary supplements.

OBJECTIVE: To estimate disease prevalence among dogs and cats in the United States and Australia and proportions of dogs and cats that receive therapeutic diets or dietary supplements. DESIGN: Telephone survey. Sample Population-Dog and cat owners located in 5 geographic areas. PROCEDURES: A telephone survey was administered to dog and cat owners. RESULTS: Of 18,194 telephone calls that were made, 1,104 (6%) were to individuals who owned at least 1 dog or cat and agreed to participate. Information was collected for 635 dogs and 469 cats. Only 14 (1%) respondents indicated that their pet was unhealthy, but 176 (16%) indicated that their pets had 1 or more diseases. The most common diseases were musculo-skeletal, dental, and gastrointestinal tract or hepatic disease. Many owners (n = 356) reported their pets were overweight or obese, but only 3 reported obesity as a health problem in their pets. Owners of 28 (2.5%) animals reported that they were feeding a therapeutic diet, with the most common being diets for animals with renal disease (n = 5), reduced-calorie diets (5), and reduced-fat diets (4). Owners of 107 of 1,076 (9.9%) animals reported administering dietary supplements to their pets. Multivitamins (n = 53 animals), chondroprotective agents (22), and fatty acids (13) were the most common dietary supplements used. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that most dogs and cats reported by their owners to have a health problem were not being fed a therapeutic diet. In addition, the rate of dietary supplement use was lower than that reported for people.

Canine and feline diabetes mellitus: nature or nurture?

There is evidence for the role of genetic and environmental factors in feline and canine diabetes. Type 2 diabetes is the most common form of diabetes in cats. Evidence for genetic factors in feline diabetes includes the overrepresentation of Burmese cats with diabetes. Environmental risk factors in domestic or Burmese cats include advancing age, obesity, male gender, neutering, drug treatment, physical inactivity, and indoor confinement. High-carbohydrate diets increase blood glucose and insulin levels and may predispose cats to obesity and diabetes. Low-carbohydrate, high-protein diets may help prevent diabetes in cats at risk such as obese cats or lean cats with underlying low insulin sensitivity. Evidence exists for a genetic basis and altered immune response in the pathogenesis of canine diabetes. Seasonal effects on the incidence of diagnosis indicate that there are environmental influences on disease progression. At least 50% of diabetic dogs have type 1 diabetes based on present evidence of immune destruction of beta-cells. Epidemiological factors closely match those of the latent autoimmune diabetes of adults form of human type 1 diabetes. Extensive pancreatic damage, likely from chronic pancreatitis, causes approximately 28% of canine diabetes cases. Environmental factors such as feeding of high-fat diets are potentially associated with pancreatitis and likely play a role in the development of pancreatitis in diabetic dogs. There are no published data showing that overt type 2 diabetes occurs in dogs or that obesity is a risk factor for canine diabetes. Diabetes diagnosed in a bitch during either pregnancy or diestrus is comparable to human gestational diabetes.

Evaluation of day-to-day variability of serial blood glucose concentration curves in diabetic dogs.

OBJECTIVE: To evaluate day-to-day variability of serial blood glucose concentration curves in dogs with diabetes mellitus. DESIGN: Prospective clinical study. ANIMALS: 10 dogs with diabetes mellitus. PROCEDURE: Paired 12-hour serial blood glucose concentration curves performed during 2 consecutive days were obtained on 3 occasions from each dog. Dogs received the same dose of insulin and meal every 12 hours on both days. For each pair of curves, comparison was made between the results of days 1 and 2. RESULTS: Mean absolute difference (without regard to sign) between days 1 and 2 for each parameter was significantly > 0, disproving the hypothesis that there is minimal day-to-day variability of serial blood glucose concentration curves when insulin dose and meals are kept constant. Coefficient of variation of the absolute difference between days 1 and 2 for each parameter ranged from 68 to 103%. Evaluation of the paired curves led to an opposite recommendation for adjustment of the insulin dose on day 2, compared with day 1, on 27% of occasions. Disparity between dosage recommendations was more pronounced when glucose concentration nadir was < 180 mg/dL (10 mmol/L) on 1 or both days. In this subset of 20 paired curves, an opposite recommendation for dosage adjustment was made on 40% of occasions. CONCLUSIONS AND CLINICAL RELEVANCE: There is large day-to-day variation in parameters of serial blood glucose concentration curves in diabetic dogs. Day-to-day variability of serial blood glucose concentration curves has important clinical implications, particularly in dogs with good glycemic control.