Therapy of Canine Hyperlipidemia with Bezafibrate.

BackgroundBezafibrate (BZF) is effective in the treatment of hypertriglyceridemia in human patients, but there are no data on its use in dogs.ObjectiveTo assess the safety of BZF in hyperlipidemic dogs and its efficacy in decreasing serum triglyceride (TG) and cholesterol (CHO) concentrations.AnimalsForty-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]).MethodsProspective, 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.ResultsSixteen 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 importanceOver 30 days, BZF was safe and effective in treatment of primary and secondary hyperlipidemia in dogs

Accuracy of a flash glucose monitoring system in cats and determination of the time lag between blood glucose and interstitial glucose concentrations

Background: The FreeStyle Libre (Abbott Laboratories) is a flash glucose monitoring system (FGMS) that measures interstitial glucose concentration (IG). The system is factory-calibrated, easy to use, inexpensive, and could be useful for monitoring diabetic cats. Objectives: To evaluate the analytical and clinical accuracy of the FGMS in cats and establish the lag-time between IG and blood glucose concentration (BG). Animals: Twenty client-owned diabetic cats and 7 purpose-bred healthy cats. Methods: Prospective study. Blood glucose concentration was measured using a portable glucose meter validated for use in cats that served as a reference method for IG, as measured by FGMS. In diabetic cats, data were collected for sensor wearing time with different methods of application and accuracy across glycemic ranges. Accuracy was determined by fulfillment of ISO15197:2013 criteria. In healthy cats, lag-time between IG and BG was established after IV administration of exogenous glucose. Results: Good agreement between IG and BG was obtained (r =.93). Analytical accuracy was not achieved, whereas clinical accuracy was demonstrated with 100% of the results in zones A + B of the Parkes consensus error grid analysis. In the immediate 30 minutes after an IV bolus of glucose, when BG was increasing rapidly (approximately 2%/min), IG increased slowly, resulting in a difference of as much as 579 mg/dL, and no positive correlation between BG and IG was found. Conclusions and Clinical Importance: The FGMS did not fulfill ISO requirements but is sufficiently accurate for glucose monitoring in cats, while considering the lag between IG and BG during periods of rapid changes in BG

Diabetes mellitus in dogs attending UK primary-care practices: frequency, risk factors and survival

Background: Diabetes mellitus (DM) is an important endocrine disorder of dogs. The objectives of this study were to estimate prevalence and incidence of DM in dogs, and to explore risk factors for DM and the survival of DM cases in primary-care clinics in the UK. Results: A case-control study nested in the cohort of dogs (n = 480,469) aged ≥3 years presenting at 430 VetCompass clinics was used to identify risk factors for DM, using multivariable logistic regression. Overall 409 new and 863 pre-existing DM cases (total 1272) were identified in 2016, giving an apparent annual prevalence of 0.26% (95% confidence interval (CI): 0.25–0.28%), and an annual incidence risk of 0.09% (95%CI: 0.08–0.09%) in dogs aged ≥3 years. Factors associated with increased odds for DM diagnosis were all age categories > 8 years, female entire dogs (odds ratio (OR): 3.03, 95% CI 1.69–5.44, p < 0.001) and male neutered dogs (OR: 1.99, 95% CI 1.18–3.34, p = 0.010) compared to male entire dogs, Border Terriers (OR: 3.37, 95% CI 1.04–10.98, p = 0.043) and West Highland White Terriers (WHWT) (OR: 2.88, 95% CI 1.49–5.56, p = 0.002) compared to crossbreeds. Dogs that had received previous glucocorticoid treatment (OR: 2.19, 95% CI 1.02–4.70, p = 0.044) and those with concurrent conditions (documented obese, pancreatitis, hyperadrenocorticism) also had increased odds for DM diagnosis. Cox regression modelling was used to evaluate factors associated with survival in the 409 incident DM cases in 2016. Increased hazard of death following diagnosis of DM was shown in dogs that were ≥ 10 years age, Cocker Spaniels (HR: 2.06, 95% CI 1.06–4.01, p = 0.034) compared to crossbreeds, had a blood glucose (BG) level at diagnosis > 40 mmol/L (HR: 2.73, 95% CI 1.35–5.55, p = 0.005) compared to < 20 mmol/L at diagnosis, or had received previous glucocorticoid treatment (HR: 1.86, 95% CI 1.21–2.86, p = 0.005). Dogs at reduced hazard of death included neutered dogs (HR: 0.58, 95% CI 0.42–0.79, p = 0.001), Border Collies (HR: 0.39, 95% CI 0.17–0.87, p = 0.022) and those starting insulin treatment (HR: 0.08 95% CI 0.05–0.12, p < 0.001). Conclusions: Certain breeds and concurrent health conditions are associated with an increased risk of DM. In addition to certain signalment factors, a high BG level at diagnosis and prior glucocorticoid treatment were adversely associated with survival of dogs with DM. Keywords: Diabetes mellitus, Risk factors, Survival, Case-control study, Benchmarking, VetCompas

Therapy of Canine Hyperlipidemia with Bezafibrate.

BackgroundBezafibrate (BZF) is effective in the treatment of hypertriglyceridemia in human patients, but there are no data on its use in dogs.ObjectiveTo assess the safety of BZF in hyperlipidemic dogs and its efficacy in decreasing serum triglyceride (TG) and cholesterol (CHO) concentrations.AnimalsForty-six dogs, 26 females and 20 males, mean (±SD) age of 9 (±3) years, with TG ≥150 mg/dL (33 dogs also were hypercholesterolemic [&gt;300 mg/dL]).MethodsProspective, 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.ResultsSixteen 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 (&lt;150 mg/dL) in 42 dogs (91.3%) and CHO concentration normalized (&lt;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 importanceOver 30 days, BZF was safe and effective in treatment of primary and secondary hyperlipidemia in dogs

Pharmacokinetics and pharmacodynamics of the glucagon-like peptide-1 analog liraglutide in healthy cats

Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that induces glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion. Glucagon-like peptide-1 also increases beta cell mass and satiation while decelerating gastric emptying. Liraglutide is a fatty-acid derivative of GLP-1 with a protracted pharmacokinetic profile that is used in people for treatment of type II diabetes mellitus and obesity. The aim of this study was to determine the pharmacokinetics and pharmacodynamics of liraglutide in healthy cats. Hyperglycemic clamps were performed on days 0 (HGC) and 14 (LgHGC) in 7 healthy cats. Liraglutide was administered subcutaneously (0.6 mg/cat) once daily on days 8 through 14. Compared with the HGC (mean +/- standard deviation; 455.5 +/- 115.8 ng/L), insulin concentrations during LgHGC were increased (760.8 +/- 350.7 ng/L; P = 0.0022), glucagon concentrations decreased (0.66 +/- 0.4 pmol/L during HGC vs 0.5 +/- 0.4 pmol/L during LgHGC; P = 0.0089), and there was a trend toward an increased total glucose infused (median [range] = 1.61 (1.11-2.54) g/kg and 2.25 (1.64-3.10) g/kg, respectively; P = 0.087). Appetite reduction and decreased body weight (9% +/- 3%; P = 0.006) were observed in all cats. Liraglutide has similar effects and pharmacokinetics profile in cats to those reported in people. With a half-life of approximately 12 h, once daily dosing might be feasible; however, significant effects on appetite and weight loss may necessitate dosage or dosing frequency reductions. Further investigation of liraglutide in diabetic cats and overweight cats is warranted. (C) 2015 Elsevier Inc. All rights reserved

B-mode and Doppler ultrasonography of adrenal glands of healthy dogs

ABSTRACT 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

Successful treatment of a dog with phenobarbital‐responsive sialadenosis and an oesophageal stricture

Background: Phenobarbital-responsive sialadenosis (PRS) can cause nausea and vomiting, and is rarely reported in dogs. Objectives: An 8-year-old neutered, male Pomeranian dog was presented to our teaching hospital with vomiting that began 2 years ago. The clinical signs repeatedly improved and deteriorated despite treatment. Methods: The only abnormality found on physical examination was salivary gland enlargement, and no specific findings were observed on blood analysis and imaging tests. The results of the fine needle aspirate cytology from the salivary glands revealed possible sialadenosis. Phenobarbital was prescribed, and the patient&apos;s symptoms resolved. However, upon discontinuing drug, the patient&apos;s clinical signs recurred and did not improve even after re-introduction of phenobarbital and the addition of other anticonvulsant drugs. An oesophageal stricture was observed on an oesophagram, and fibrosis was confirmed endoscopically. A balloon dilation was performed to expand the stenosis. Results: After the first procedure, the patient&apos;s clinical signs initially improved, but relapsed 2 weeks later. A total of three oesophageal dilation procedures were performed using a sequentially larger diameter balloon. After the third procedure, the patient&apos;s clinical signs were managed without recurrence. The cause of recurrent gastrointestinal signs following the initial successful treatment of phenobarbital-responsive sialadenosis was due to oesophageal stricture formation. Conclusions: This case report demonstrates the successful management of PRS with subsequent oesophageal stricture formation in a dog.Y

Co-impairment of autonomic and glucagon responses to insulin-induced hypoglycemia in dogs with naturally occurring insulin-dependent diabetes mellitus.

This study aimed to investigate the contributions of two factors potentially impairing glucagon response to insulin-induced hypoglycemia (IIH) in insulin-deficient diabetes: 1) loss of paracrine disinhibition by intra-islet insulin and 2) defects in the activation of the autonomic inputs to the islet. Plasma glucagon responses during hyperinsulinemic-hypoglycemic clamps ([Formula: see text]40 mg/dL) were assessed in dogs with spontaneous diabetes (n = 13) and in healthy nondiabetic dogs (n = 6). Plasma C-peptide responses to intravenous glucagon were measured to assess endogenous insulin secretion. Plasma pancreatic polypeptide, epinephrine, and norepinephrine were measured as indices of parasympathetic and sympathoadrenal autonomic responses to IIH. In 8 of the 13 diabetic dogs, glucagon did not increase during IIH (diabetic nonresponder [DMN]; ∆ = -6 ± 12 pg/mL). In five other diabetic dogs (diabetic responder [DMR]), glucagon responses (∆ = +26 ± 12) were within the range of nondiabetic control dogs (∆ = +27 ± 16 pg/mL). C-peptide responses to intravenous glucagon were absent in diabetic dogs. Activation of all three autonomic responses were impaired in DMN dogs but remained intact in DMR dogs. Each of the three autonomic responses to IIH was positively correlated with glucagon responses across the three groups. The study conclusions are as follows: 1) Impairment of glucagon responses in DMN dogs is not due to generalized impairment of α-cell function. 2) Loss of tonic inhibition of glucagon secretion by insulin is not sufficient to produce loss of the glucagon response; impairment of autonomic activation is also required. 3) In dogs with major β-cell function loss, activation of the autonomic inputs is sufficient to mediate an intact glucagon response to IIH.NEW &amp; NOTEWORTHY In dogs with naturally occurring, insulin-dependent (C-peptide negative) diabetes mellitus, impairment of glucagon responses is not due to generalized impairment of α-cell function. Loss of tonic inhibition of glucagon secretion by insulin is not sufficient, by itself, to produce loss of the glucagon response. Rather, impaired activation of the parasympathetic and sympathoadrenal autonomic inputs to the pancreas is also required. Activation of the autonomic inputs to the pancreas is sufficient to mediate an intact glucagon response to insulin-induced hypoglycemia in dogs with naturally occurring diabetes mellitus. These results have important implications that include leading to a greater understanding and insight into the pathophysiology, prevention, and treatment of hypoglycemia during insulin treatment of diabetes in companion dogs and in human patients