Gut microbiota promoting propionic acid production accompanies caloric restriction-induced intentional weight loss in cats.

Rodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for 7 days, then calories were restricted to achieve 1-2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p < 0.0001). 16S rRNA gene amplicon sequencing and targeted SCFA metabolomics were performed on fecal samples. Fecal microbial community structure significantly differed between the four study phases (PERMANOVA p = 0.011). Fecal propionic acid was significantly higher during caloric restriction-induced weight loss (adjusted p < 0.05). Repeated measures correlation revealed the relative abundances of Prevotella 9 copri (correlation coefficient = 0.532, 95% CI (0.275, 0.717), p = 0.0002) significantly correlated with propionic acid composition. Like humans, obese cats experienced an altered microbial community structure and function, favoring propionic acid production, during caloric restriction-induced weight loss.

Gut microbiota promoting propionic acid production accompanies diet-induced intentional weight loss in cats.

Rodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for seven days, then calories were restricted to achieve 1-2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p < 0.0001). 16S rRNA gene amplicon sequencing and targeted SCFA metabolomics were performed on fecal samples. Fecal microbial community structure significantly differed between the four study phases (PERMANOVA p = 0.011). Fecal propionic acid was significantly higher during diet-induced weight loss (adjusted p < 0.05). Spearman correlation revealed the relative abundances of Prevotella 9 copri (ρ = 0.6385, p = 0.0006) and Blautia caecimuris (ρ = 0.5269, p = 0.0068) were significantly correlated with propionic acid composition. Like humans, obese cats experienced an altered microbial community structure and function, favoring propionic acid production, during diet-induced weight loss.

Re-evaluation of the low-dose dexamethasone suppression test in dogs.

OBJECTIVES: This study aims to re-evaluate the low-dose dexamethasone suppression test 8-hour cortisol cut-point for the diagnosis of hypercortisolism in dogs using a solid-phase, competitive chemiluminescent enzyme immunoassay. MATERIALS AND METHODS: Twenty-seven client-owned dogs with naturally occurring hypercortisolism and 30 healthy control dogs were prospectively recruited. Performance of the low-dose dexamethasone suppression test was assessed using sensitivity, specificity and a receiver operating characteristic curve compared to a clinical diagnosis of hypercortisolism including response to treatment. RESULTS: Twenty-four dogs were diagnosed with pituitary-dependent hypercortisolism and three with adrenal-dependent hypercortisolism. In 30 healthy control dogs, 8-hour post-dexamethasone cortisol concentrations ranged from 5.5 to 39 nmol/L. A receiver operating characteristic curve curve constructed from the 8-hour post-dexamethasone cortisol concentrations of hypercortisolism and control dogs demonstrated that the most discriminatory cut-point was more than 39 nmol/L with sensitivity of 85.2% (95% confidence interval, 67.5% to 94.1%) and specificity of 100% (95% confidence interval, 88.7% to 100.0%) and an area under the curve of 0.963. CLINICAL SIGNIFICANCE: The optimal cut-point of more than 36 nmol/L proposed by this study is similar to the currently accepted 8-hour cortisol concentration cut-point for diagnosing hypercortisolism when using a solid-phase, competitive chemiluminescent enzyme immunoassay.

The effect of capromorelin on glycemic control in healthy dogs.

Capromorelin is a ghrelin-receptor agonist widely used as an appetite stimulant in dogs. Capromorelin disrupts glucose homeostasis in cats but information regarding its effects on canine glucose homeostasis is lacking. The study objective was to evaluate the effect of capromorelin on glucose homeostatic mechanisms in healthy dogs. Eight clinically healthy client-owned adult dogs were enrolled in this prospective, cross-over, placebo-controlled study. Dogs were randomized to receive capromorelin (Entyce, 3 mg/kg) or placebo, q24h for 3 d. A wk later, treatments were crossed over. Interstitial glucose (IG) concentrations were measured using a flash glucose monitoring system throughout. On d 1 of each treatment, blood glucose (BG), insulin, glucagon, glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide-1 (GLP-1) concentrations were measured before drug administration, then before and 30-120 min after feeding a glucose-rich diet (Ensure Plus, 21 kcal/kg). Data were analyzed as a 2-period crossover design using generalized least squares estimation. Capromorelin administration increased mean 48 h IG by10% and mean BG by 20% at 90 and 120 min post-prandially (P < 0.0001). Post-prandially, there was a time-by-treatment effect for insulin (P = 0.03) and GIP (P = 0.0002) because capromorelin doubled geometric mean insulin concentrations at 120 min and increased geometric mean GIP concentrations more rapidly than after placebo. There were no differences in glucagon or GLP-1 concentrations between treatment groups. The increase in post-prandial blood glucose was not the result of overt suppression of incretin hormone secretion. There was also no suppressive effect of capromorelin on insulin.

One hundred years of insulin: Is it time for smart?

Smarter understanding of diabetes pathophysiology and pharmacology of insulin therapy can lead to better clinical outcomes. Rather than looking for an insulin formulation that is considered "best" for a general population, it could be appropriate to seek the "smart" insulin choice, tailored to the specific clinical situation. Different treatment goals should be considered, with pros and cons to each. Ideally, insulin therapy in most diabetic dogs should mimic a "basal-bolus" pattern. The "intermediate"-acting insulin formulations might provide better "bolus" treatment in dogs than the rapid-acting formulations used in people. In patients with some residual beta cell function such as many diabetic cats, administering only a "basal" insulin might lead to complete normalisation of blood glucose concentrations. Insulin suspensions (neutral protamine Hagedorn, neutral protamine Hagedorn/regular mixes, lente and protamine zinc insulin) as well as insulin glargine U100 and detemir are "intermediate"-acting formulations that are administered twice daily. For a formulation to be an effective and safe "basal" insulin, its action should be roughly the same every hour of the day. Currently, only insulin glargine U300 and insulin degludec meet this standard in dogs, whereas in cats, insulin glargine U300 is the closest option.

Consistency of faecal scoring using two canine faecal scoring systems.

OBJECTIVE: To determine the agreement of canine faecal scoring between individuals with different levels of experience using two available faecal scoring systems. MATERIALS AND METHODS: Naturally-voided, undisturbed bowel movements from 126 dogs were evaluated by veterinarians (n = 3) and members of the lay public (n = 126) within 15 minutes of defecation. Each participant was provided a copy of the Purina and Waltham faecal scoring charts in order to characterise the faeces. Agreement between veterinarians and lay people was assessed with kappa statistics, Bland-Altman analysis and visualised with Bland-Altman plots. RESULTS: Variable levels of consistency were observed in assessing faecal form among individuals with varying degrees of experience. Fair to substantial agreement existed between individual veterinarians scoring the same bowel movement (kappa statistic ranging from 0.40 to 0.77 on the Purina Scale and 0.54 to 0.61 on the Waltham Scale), while the agreement scores between the veterinarian and the lay public was fair (kappa statistic of 0.38 on the Purina Scale and 0.34 on the Waltham Scale). Disagreement in faecal scores occurred more frequently with lay people versus veterinarians. CLINICAL SIGNIFICANCE: The consistency of faecal scoring improved based on the level of experience with the highest agreement consistently noted between veterinarians. In all comparisons, there was inconsistency in faecal scoring which might have implications for veterinarians managing diarrhoeic canine patients. Further studies are needed to better investigate how faecal scoring can be optimised for use in clinical and research settings.

The effect of the ghrelin-receptor agonist capromorelin on glucose metabolism in healthy cats.

Somatostatin secretion from islet delta cells is important in maintaining low glycemic variability (GV) by providing negative feedback to beta cells and inhibiting insulin secretion. Capromorelin is a ghrelin-receptor agonist that activates the growth hormone secretagogue receptor on delta cells. We hypothesized that in cats, capromorelin administration will result in decreased GV at the expense of reduced insulin secretion and glucose tolerance. Seven healthy cats were treated with capromorelin from days 1-30. After the first day, fasting blood glucose increased (+13 ± 3 mg/dL, P < 0.0001), insulin decreased (+128 ± 122 ng/dL, P = 0.03), and glucagon was unchanged. Blood glucose was increased throughout an intravenous glucose tolerance test on day 1 with blunting of first-phase insulin response ([FPIR] 4,931 ± 2,597 ng/L/15 min) compared with day -3 (17,437 ± 8,302 ng/L/15 min, P = 0.004). On day 30, FPIR was still blunted (9,993 ± 4,285 ng/L/15 min, P = 0.045), but glucose tolerance returned to baseline. Mean interstitial glucose was increased (+19 ± 6 mg/dL, P = 0.03) on days 2-4 but returned to baseline by days 27-29 (P = 0.3). On days 2-4, GV was increased (SD = 9.7 ± 3.2) compared with baseline (SD = 5.0 ± 1.1, P = 0.02) and returned to baseline on days 27-29 (SD = 6.1 ± 1.1, P = 0.16). In summary, capromorelin caused a decline in insulin secretion and glycemic control and an increase in glucose variability early in the course of treatment, but these effects diminished toward the end of 30 d of treatment.

Comparison of pharmacodynamics between insulin glargine 100 U/mL and insulin glargine 300 U/mL in healthy cats.

Insulin glargine (IGla) is a synthetic human-recombinant insulin analog that is used routinely in people as a q24h basal insulin. The 300 U/mL (U300) formulation of IGla is associated with longer duration of action and less within-day variability, making it a better basal insulin compared with the 100 U/mL (U100) formulation. We hypothesized that in healthy cats, IGlaU300 has a flatter time-action profile and longer duration of action compared with IGlaU100. Seven healthy neutered male, purpose-bred cats were studied in a randomized, crossover design. Pharmacodynamics of IGlaU100 and IGlaU300 (0.8 U/kg, subcutaneous) were determined by the isoglycemic clamp method. The time-action profile of IGlaU300 was flatter compared with IGlaU100 as demonstrated by lower peak (5.6 ± 1.1 mg/kg/min vs 8.3 ± 1.9 mg/kg/min, respectively; P = 0.04) with no difference in total metabolic effect (ME; P = 0.7) or duration of action (16.8 h ± 4.7 h vs 13.4 h ± 2.6 h; P = 0.2). The greater fraction of ME in the 12- to 24-h period postinjection (35 ± 23% vs 7 ± 8% respectively; P = 0.048) and lower intraday GIR% variability (7.8 ± 3.7% vs 17.4 ± 8.2% respectively; P = 0.03) supports a flatter time-action profile of IGlaU300. There were no differences in onset and end of the action. In summary, although both formulations have a similar duration of action that is well below 24 h, the ME of IGlaU300 is more evenly distributed over a 24 h period in healthy cats, making it a better candidate for once-daily injection in diabetics compared with IGlaU100.

Machine learning algorithm as a diagnostic tool for hypoadrenocorticism in dogs.

Canine hypoadrenocorticism (CHA) is a life-threatening condition that affects approximately 3 of 1,000 dogs. It has a wide array of clinical signs and is known to mimic other disease processes, including kidney and gastrointestinal diseases, creating a diagnostic challenge. Because CHA can be fatal if not appropriately treated, there is risk to the patient if the condition is not diagnosed. However, the prognosis is excellent with appropriate therapy. A major hurdle to diagnosing CHA is the lack of awareness and low index of suspicion. Once suspected, the application and interpretation of conclusive diagnostic tests is relatively straight forward. In this study, machine learning methods were employed to aid in the diagnosis of CHA using routinely collected screening diagnostics (complete blood count and serum chemistry panel). These data were collected for 908 control dogs (suspected to have CHA, but disease ruled out) and 133 dogs with confirmed CHA. A boosted tree algorithm (AdaBoost) was trained with 80% of the collected data, and 20% was then utilized as test data to assess performance. Algorithm learning was demonstrated as the training set was increased from 0 to 600 dogs. The developed algorithm model has a sensitivity of 96.3% (95% CI, 81.7%-99.8%), specificity of 97.2% (95% CI, 93.7%-98.8%), and an area under the receiver operator characteristic curve of 0.994 (95% CI, 0.984-0.999), and it outperforms other screening methods including logistic regression analysis. An easy-to-use graphical interface allows the practitioner to easily implement this technology to screen for CHA leading to improved outcomes for patients and owners.

Comparison of pharmacodynamics and pharmacokinetics of insulin degludec and insulin glargine 300 U/mL in healthy cats.

Insulin glargine 300 U/mL (IGla-U300) and insulin degludec (IDeg) are synthetic insulin analogs designed as basal insulin formulations. In people, IGla-U300 is more predictable and longer acting compared with glargine 100 U/mL. The duration of action of IDeg in people is > 42 h, allowing flexibility in daily administration. We hypothesized that IDeg would have longer duration of action compared with IGla-U300 in healthy purpose-bred cats. Seven cats received 0.4 U/kg (subcutaneous) of IDeg and IGla-U300 on two different days, >1 wk apart. Exogenous insulin was measured and pharmacodynamic parameters were derived from glucose infusion rates during isoglycemic clamps and suppression of endogenous insulin. The Shapiro-Wilk test was used to assess normality, and normally distributed parameters were compared using paired t-tests. There was no difference between IDeg and IGla-U300 in onset, peak action, or total metabolic effect. On average, time to peak action (TPEAK) of IGla-U300 was 145 ± 114 min (95% confidence interval [CI] = 25-264) longer than TPEAK of IDeg (P = 0.03) and duration of action (TDUR) of IGla-U300 was 250 ± 173 min (95% CI = 68-432) longer than TDUR of IDeg (P = 0.02). The "flatness" of the time-action profile (as represented by the quotient of peak action/TDUR) was significantly greater for IGla-U300 compared with IDeg (P = 0.04). Overall, insulin concentration measurements concurred with findings from isoglycemic clamps. Based on these data, IDeg is not suitable for once-daily administration in cats. The efficacy of once-daily IGla-U300 in diabetic cats should be further investigated.

Pharmacodynamics and pharmacokinetics of insulin detemir and insulin glargine 300 U/mL in healthy dogs.

Insulin glargine 300 U/mL and insulin detemir are synthetic long-acting insulin analogs associated with minimal day-to-day variability or episodes of hypoglycemia in people. Here, 8 healthy purpose-bred dogs each received 2.4 nmol/kg subcutaneous injections of insulin detemir (0.1 U/kg) and insulin glargine 300 U/mL (0.4 U/kg) on 2 different days, >1 wk apart, in random order. Blood glucose (BG) was measured every 5 min, and glucose was administered intravenously at a variable rate with the goal of maintaining BG within 10% of baseline BG ("isoglycemic clamp"). Endogenous and exogenous insulin were measured for up to 24 h after insulin injection. The effect of exogenous insulin was defined by glucose infusion rate or a decline in endogenous insulin. Isoglycemic clamps were generated in all 8 dogs after detemir but only in 4 dogs after glargine. Median time to onset of action was delayed with glargine compared to detemir (4.0 h [3.3-5.8 h] vs 0.6 h [0.6-1.2 h], P = 0.002). There was no difference in time to peak (median [range] = 6.3 h [5.0-21.3 h] vs 4.3 h [2.9-7.4 h], P = 0.15) or duration of action (16.3 h [6.1-20.1 h] vs 10.8 h [8.8-14.8 h], P = 0.21) between glargine and detemir, respectively. Glargine demonstrated a peakless time-action profile in 4/8 dogs. The total metabolic effect and peak action of detemir was significantly greater than glargine. Significant concentrations of glargine were detected in all but 1 dog following administration. Glargine might be better suited than detemir as a once-daily insulin formulation in some dogs based on its long duration of action and peakless time-action profile. Day-to-day variability in insulin action should be further assessed for both formulations.

Pharmacodynamics and pharmacokinetics of insulin aspart assessed by use of the isoglycemic clamp method in healthy cats.

The objective of this study was to determine the pharmacodynamics (PD) and pharmacokinetics (PK) of insulin aspart in healthy cats following intramuscular (IM) and subcutaneous (SC) injection. Eight healthy, purpose-bred cats were used in a randomized, crossover study design. Each cat had 2 isoglycemic clamps performed, one after receiving 0.25 IU/kg of insulin aspart by IM injection and one after receiving the same dose by SC injection. The two isoglycemic clamps were performed on different days, at least 48 h apart. The blood glucose, plasma endogenous insulin, and plasma insulin aspart concentrations were measured and the glucose infusion rate (GIR) was recorded during the clamp. The GIR over time was used to create a time-action curve for each clamp which was used to describe the PD of insulin aspart. Data that are normally distributed are reported as mean ± SD, while data that are not normally distributed are reported as median (25-75 percentile). When compared to the PD data that have been reported for regular insulin in healthy cats, insulin aspart had a more rapid onset (IM: 10 min [10-21.25 min], SC: 12.5 min [10-18.75 min]) and shorter duration of action (IM: 182.5 ± 34.33 min, SC: 159.38 ± 41.87 min). The onset of action (P = 0.795), time to peak action (P = 0.499), duration of action (P = 0.301), and total metabolic effect (P = 0.603) did not differ with route of administration; however, SC administration did result in a higher maximum plasma insulin aspart concentration (IM: 1,265.17 pmol/L [999.69-1,433.89 pmol/L], SC: 3,278.19 pmol/L [2,485.29-4,132.01 pmol/L], P = 0.000) and larger area under the insulin aspart vs time curve (IM: 82,662 ± 30,565 pmol/L, SC: 135,060 ± 39,026 pmol/L, P = 0.010). Insulin aspart has a rapid onset of action and short duration of effect in healthy cats when administered by IM and SC injection. Although it cannot be assumed that the PD and PK of insulin aspart will be the same in cats with diabetic ketoacidosis (DKA), our data support further investigation into the use of SC insulin aspart as an alternative to regular insulin for the treatment of DKA in cats.

The effect of diet, adiposity, and weight loss on the secretion of incretin hormones in cats.

Degree of adiposity and dietary macronutrient composition affect incretin hormone secretion in humans and mice, but little is known about their effect in cats. In this study, 7 overweight cats were fed a maintenance diet (MD) for at least 2 wk followed by a reduced calorie diet (RCD), which was lower in fat and higher in carbohydrates and fiber. Cats were fed ad libitum initially, and then, food was restricted to achieve 1%-2% loss of body weight weekly (11 wk). When lean, cats were fed MD for 2 wk. A standardized meal test (SMT) using a third diet was performed after at least 7 d on each diet, before and after weight loss (four SMT's total). Glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) concentrations were measured immediately before and over 6 h after feeding the SMT. Area under the curve (AUC) was compared for GLP-1, GIP, and insulin concentrations using 2-way analysis of variance. Leaner cats had increased GIPAUC compared to obese cats (P = 0.025). There was a trend toward increased GIPAUC on RCD compared to the MD (P = 0.085). There was a moderate negative correlation between body fat percentage and GLP-1AUC (r = -0.45; P = 0.05). There was no effect of diet on GLP-1AUC. In conclusion, degree of adiposity and dietary macronutrient content could be important in determining GIP responses not only acutely but also on a long-term basis. Further investigation of GIP responses in cats should take both diet and degree of adiposity into account.

Therapy of Canine Hyperlipidemia with Bezafibrate.

BACKGROUND: Bezafibrate (BZF) is effective in the treatment of hypertriglyceridemia in human patients, but there are no data on its use in dogs. OBJECTIVE: To assess the safety of BZF in hyperlipidemic dogs and its efficacy in decreasing serum triglyceride (TG) and cholesterol (CHO) concentrations. ANIMALS: Forty-six dogs, 26 females and 20 males, mean (±SD) age of 9 (±3) years, with TG ≥150 mg/dL (33 dogs also were hypercholesterolemic [>300 mg/dL]). METHODS: Prospective, uncontrolled clinical trial. Dogs were treated with bezafibrate once daily, using 200 mg tablets at a dosage of 4-10 mg/kg (depending on body weight). Serum TG and CHO concentrations and alanine aminotransferase (ALT) and creatine kinase (CK) activity before and after 30 days of treatment were compared. RESULTS: Sixteen dogs (34.8%) had primary hyperlipidemia, and 30 dogs (65.2%) had secondary hyperlipidemia (including spontaneous hyperadrenocorticism [41.3%, n = 19/46], chronic treatment with glucocorticoids [10.8%, n = 5/46], and hypothyroidism [15.2%, n = 7/46]). After 30 days, serum TG concentration normalized (<150 mg/dL) in 42 dogs (91.3%) and CHO concentration normalized (<270 mg/dL) in 22 of 33 dogs (66.7%). There was no difference in baseline TG concentration between the primary and secondary hyperlipidemia subgroups, but the decrease in TG concentration after treatment was greater in the primary hyperlipidemia subgroup. No adverse effects were observed, but ALT activity decreased significantly after 30 days of treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Over 30 days, BZF was safe and effective in treatment of primary and secondary hyperlipidemia in dogs.

Dietary management of presumptive protein-losing enteropathy in Yorkshire terriers.

OBJECTIVES: To describe the clinical outcome of dietary management of Yorkshire terriers with protein-losing enteropathy without immunosuppressive/anti-inflammatory medications. METHODS: Records were searched for Yorkshire terriers with hypoalbuminaemia and a clinical diagnosis of protein-losing enteropathy that were managed with diet and without immunosuppressive/anti-inflammatory medications. Serum albumin changes were compared using a one-way repeated measures ANOVA. Canine chronic enteropathy clinical activity index scores were compared using a Wilcoxon signed-rank test. RESULTS: Eleven cases were identified. Clinical signs were variable including: diarrhoea, respiratory signs, vomiting, lethargy and weight loss. Diets fed included home cooked (n=5); Royal Canin Gastrointestinal Low Fat (n=4); Hill's Prescription Diet i/d Low Fat (n=1); or Purina HA Hypoallergenic (n=1). Clinical signs resolved completely in eight dogs, partially resolved in two dogs and failed to respond in one dog. In dogs that responded, albumin significantly improved from baseline (mean 14·9 g/L, sd ±3·7), at 2 to 4 weeks (mean 24·2 g/L, sd ±5·5, P=0·01), and at 3 to 4 months (mean 27·0 g/dL, sd ±5·9, P=0·01). CLINICAL SIGNIFICANCE: These results indicate that dietary management of protein-losing enteropathy is a potential management strategy in Yorkshire terriers. Randomised clinical trials in Yorkshire terriers with protein-losing enteropathy are necessary to compare success rate, survival and quality of life with dietary management versus combined dietary and immunosuppressive/anti-inflammatory therapy.

B-mode and Doppler ultrasonography of adrenal glands of healthy dogs / Ultrassonografia modo B e Doppler das glândulas adrenais de cães saudáveis

The aim of this study was to determine the vascular indices of adrenal blood flow in healthy dogs (systolic velocity - SV; diastolic velocity - DV; resistance index - RI). Eighteen dogs (thirty six adrenal) were studied. Physical examination, biochemical profile and dexamethasone suppression test were performed to determine general health status. Echotexture, size, contours and margins, and overall shape of the adrenal gland (right and left) were assessed via ultrasound. By spectral Doppler of the phrenic-abdominal artery, the SV, DV, and RI were acquired. Animals did not show alterations in clinical and laboratory examination and suppression of cortisol. Normal homogeneous and echotexture, regular contours and margins and normal shape and size were verified via B mode. Spectral Doppler of the phrenic-abdominal artery showed monophasic-patterned waves and low vascular resistance and systolic peak evident with means values: left adrenal - SV = 31.34cm/s, DV = 9.54cm/s and RI = 0.69; and right adrenal - SV = 27.83cm/s, DV = 7.71cm/s and RI = 0.68. Doppler evaluation of adrenal was easily implemented and may provide base line data in the study, allowing for the use of this technique as a diagnostic tool for diseases of the dog's adrenal.(AU)

Objetivou-se determinar os índices vasculares do fluxo sanguíneo das glândulas adrenais de cães saudáveis (velocidade sistólica - VS; velocidade diastólica - VD; o índice de resistência - IR). Foram utilizados neste estudo 18 cães (36 adrenais). Foram realizados exame físico, perfil bioquímico e teste de supressão com dexametasona para determinar o estado geral de saúde (higidez). Ecotextura, ecogenicidade, tamanho, contornos e margens e o formato das glândulas adrenais (direito e esquerdo) foram avaliados por meio da ultrassonografia convencional. Ao Doppler espectral da artéria frênico-abdominal, foram adquiridos a VS, a VD e o IR. Os animais não apresentaram alterações aos exames clínico, laboratorial e de supressão do cortisol. Ao exame ultrassonográfico, foram verificados ecotextura homogênea, ecogenicidade, formato e tamanhos normais, além de os contornos e as margens serem regulares. Ao Doppler espectral da artéria frênico-abdominal, verificaram-se ondas com padrão monofásico, com resistência vascular baixa e pico sistólico evidente, sendo os valores médios: adrenal esquerda - VS = 31,34cm/s, VD = 9,54cm/s e IR = 0,69; e adrenal direita - VS = 27,83cm/s, VD = 7,71cm/s e IR = 0,68. A avaliação Doppler das adrenais foi facilmente implementada e pode fornecer dados de referência, permitindo a utilização dessa técnica como uma ferramenta de diagnóstico para doenças das adrenais em cães.(AU)

What's in a Name? Classification of Diabetes Mellitus in Veterinary Medicine and Why It Matters.

Diabetes Mellitus (DM) is a syndrome caused by various etiologies. The clinical manifestations of DM are not indicative of the cause of the disease, but might be indicative of the stage and severity of the disease process. Accurately diagnosing and classifying diabetic dogs and cats by the underlying disease process is essential for current and future studies on early detection, prevention, and treatment of underlying disease. Here, we review the current etiology-based classification of DM and definitions of DM types in human medicine and discuss key points on the pathogenesis of each DM type and prediabetes. We then review current evidence for application of this etiology-based classification scheme in dogs and cats. In dogs, we emphasize the lack of consistent evidence for autoimmune DM (Type 1) and the possible importance of other DM types such as DM associated with exocrine pancreatic disease. While most dogs are first examined because of DM in an insulin-dependent state, early and accurate diagnosis of the underlying disease process could change the long-term outcome and allow some degree of insulin independence. In cats, we review the appropriateness of using the umbrella term of Type 2 DM and differentiating it from DM secondary to other endocrine disease like hypersomatotropism. This differentiation could have crucial implications on treatment and prognosis. We also discuss the challenges in defining and diagnosing prediabetes in cats.

Adrenal insufficiency secondary to lymphocytic panhypophysitis in a cat.

CASE REPORT: A 13-year-old male castrated Domestic Shorthair cat was presented for investigation of lethargy, vomiting, polydipsia and polyuria. Glucocorticoid-deficient hypoadrenocorticism was suspected based on hypocholesterolaemia, hypoglycaemia and lack of a stress leucogram, and confirmed with an ACTH stimulation test. Pituitary disease was suspected based on the clinical signs and the combination of hyposthenuria and hypernatraemia. Necropsy revealed bilaterally symmetric adrenocortical atrophy and the changes in the pituitary gland were suggestive of a T-cell-rich immune-mediated panhypophysitis. CLINICAL SIGNIFICANCE: Secondary adrenal insufficiency and panhypophysitis have not been previously reported in the cat. This report should raise awareness of this rare but potentially treatable disease process.

Duration of fasting but not diurnal variation affects the response to glucagon in healthy cats.

The role of glucagon disturbances in diabetes is increasingly recognized. Glucagon stimulation tests (GSTs) have been described in cats previously, but information is lacking on the response of cats to glucagon under specific conditions. The aim of this study was to assess a novel protocol for GST using human-recombinant glucagon and the effect of diurnal variation and duration of fasting using this protocol in healthy cats. All intravenous doses resulted in occasional vomiting and nausea, and eventually, a 20-µg/kg intramuscular dose was chosen. Five healthy cats were then used in a repeated-measures study. Cats were free-fed regularly at 7:30 AM and 5:30 PM for 30 min. In each cat, GST was performed at 7 PM after a 25-h fast (PM25), at 9 AM after a 25-h fast (AM25), and at 9 AM after a 15-h fast (AM15). Glucose and insulin concentrations were measured at -15, 0, 15, 25, 35, 45, and 60 min after stimulation. Baseline and peak concentrations were compared using the Friedman test. Baseline glucose and insulin did not differ significantly between treatment groups. Peak glucose concentrations occurred at 15 min and were significantly higher (P = 0.0085) at AM15 (mean ± standard deviation = 185.2 ± 43.0 mg/dL) vs AM25 (144.4 ± 10.5 mg/dL) and PM25 (128.0 ± 18.4 mg/dL). Similarly, peak insulin concentrations occurred at 15 min and were significantly higher (P = 0.04) at AM15 (1,911 ± 1,153 pg/mL) vs AM25 (739 ± 52 pg/mL) or PM25 (549 ± 366 pg/mL). In conclusion, prolonged fasting significantly blunted the glycemic response to glucagon compared with shorter fasting, but diurnal variation had no significant effect on glucose or insulin responses.

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats.

Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide. It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days -7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean ± standard deviation = -11 ± 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% [4%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring, glucose concentrations decreased and the frequency of readings <50 mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide ER was safe and effective in improving glucose tolerance 3 wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats.