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.

A CTSA One Health Alliance guidance on institutional review of veterinary clinical studies.

Harmonized institutional processes and reviewer training are vital to maintain integrity and ethical rigor of the veterinary clinical research pipeline and are a prerequisite to future work that might establish centralized or single-site ethical and regulatory review to ease initiation of multi-center studies. Funded by a CTSA One Health Alliance (COHA) pilot award, a diverse working group of veterinary clinicians and institutional representatives was convened in February 2020 to develop a guidance document detailing broadly agreed upon practices for ethical review and approval of veterinary clinical studies conducted in the United States.The working group defined key areas of need for consensus, developed a set of associated guidelines, and circulated these for review by COHA's fifteen member institutions. Six focus areas were identified by the working group and included vital items of protocol review, composition of the review committee, post-approval monitoring and adverse event reporting, consideration of special circumstances such as satellite sites and the use of healthy veterinary subjects in research, and the informed consent process.This document outlines a broadly agreed-upon framework through which to approach vital items associated with veterinary clinical study protocol review and approval. These approaches represent current best practice in the review and approval of veterinary clinical studies, and can serve as a guidance for veterinary clinician-scientists and regulatory experts, to ensure robust and ethically conducted studies that can contribute to the advancement of both animal and human health.

Exploratory analysis of anti-insulin antibodies in diabetic dogs receiving recombinant human insulin.

OBJECTIVES: To quantify anti-insulin antibodies in diabetic dogs treated with recombinant human insulin and to determine if insulin dosage or duration of treatment differed between anti-insulin antibody-positive and -negative diabetic dogs. MATERIALS AND METHODS: Descriptive preliminary study using serum from 24 client-owned diabetic dogs treated for a minimum of 2 weeks with recombinant human insulin, and 24 client-owned healthy control dogs without diabetes. Sera were analysed by radioimmunoassay for anti-insulin antibodies. The proportion of antibody positive dogs was compared between groups by Fisher's exact test. RESULTS: Four diabetic (16.6%) and no control dogs were anti-insulin antibody positive. CLINICAL SIGNIFICANCE: These results indicate that treatment with recombinant human insulin may induce anti-insulin antibodies in dogs, although this finding needs to be re-investigated in a larger study to investigate the impact of anti-insulin antibodies on glycaemic control.

Untargeted metabolomic analysis in non-fasted diabetic dogs by UHPLC-HRMS.

INTRODUCTION: We recently identified variances in serum metabolomic profiles between fasted diabetic and healthy dogs, some having similarities to those identified in human type 1 diabetes. OBJECTIVES: Compare untargeted metabolomic profiles in the non-fasted state. METHODS: Serum from non-fasted diabetic (n = 6) and healthy control (n = 6) dogs were analyzed by liquid chromatography-high resolution mass spectrometry. RESULTS: Clear clustering of metabolites between groups were observed, with multiple perturbations identified that were similar to those previously observed in fasted diabetic dogs. CONCLUSION: These findings further support the development of targeted assays capable of detecting metabolites that may be useful as biomarkers of canine diabetes.

Canine sterile nodular panniculitis: a retrospective study of 14 cases.

BACKGROUND: Sterile nodular panniculitis (SNP) is an uncommon inflammatory condition of subcutaneous fat that can be idiopathic, but has also been associated with underlying conditions such as pancreatic disease or systemic lupus erythematosus (SLE). The pathogenesis and clinical course of the condition are not well understood. OBJECTIVES: To retrospectively review cases of SNP associated with systemic signs, concurrent disease, or both and characterize the clinical, laboratory, imaging, and histopathologic findings, treatment, and response to treatment. ANIMALS: Fourteen dogs with histologically confirmed SNP diagnosed between 1996 and 2008. METHODS: Retrospective study. RESULTS: Skin lesions were ulcerated or draining nodules in 9 dogs and nonulcerative subcutaneous nodules in 5. Most dogs had systemic signs, such as fever, inappetence, lethargy, and multiple lesions. Common clinicopathologic findings included neutrophilia with or without left shift, increased alkaline phosphatase activity, mild hypoglycemia, hypoalbuminemia, and proteinuria. Concurrent diseases included pancreatic disease, SLE, rheumatoid arthritis, polyarthritis, lymphoplasmacytic colitis, and hepatic disease. Dogs responded to immunosuppressive doses of corticosteroids when administered. Prognosis for recovery was related to the underlying disease process. CONCLUSIONS AND CLINICAL IMPORTANCE: SNP is not a single disease. Rather, it is a cutaneous marker of systemic disease in many cases. After thorough evaluation for concurrent disease and infectious causes, immunosuppressive treatment is often effective.