The Diabetic Dog as a Translational Model for Human Islet Transplantation.

The dog model has served as the primary method for early development of many diabetes therapies, including pancreatic islet transplantation techniques and immunosuppressive protocols. Recent trends towards the use of monoclonal antibody therapies for immunosuppression in human islet transplantation have led to the increasing use of primate models with induced diabetes. In addition to induced-disease models in large animals, scientists in many fields are considering the use of naturally-occurring disease models in client-owned pets. This article will review the applicability of naturally-occurring diabetes in dogs as a translational model for developing islet transplantation in the human diabetic patient

Agreeing language in veterinary endocrinology (ALIVE): diabetes mellitus - a modified Delphi-method-based system to create consensus disease definitions

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Agreeing Language in Veterinary Endocrinology (ALIVE): Diabetes mellitus - a modified Delphi-method-based system to create consensus disease definitions

[No abstract

Case report: Androgen-secreting adrenocortical tumors in eight cats

Urine marking, aggression, and other behavioral concerns are common reasons for cat owners to seek veterinary care. Empiric treatment for lower urinary tract disease or primary behavior disorders are commonly pursued, especially in those cases with normal routine laboratory evaluations. Herein, we report the clinicopathologic findings in eight sexually altered cats that were diagnosed with androgen-secreting adrenocortical tumors. Nearly all cats (n = 7) initially were evaluated for inappropriate urination and pungent urine, with additional behavioral concerns including aggression (n = 3) and excess vocalization (n = 4) commonly reported. Penile barbs (n = 5) were identified in all five male cats, and an enlarged clitoris was observed in one female cat. Testing of serum androgen concentrations revealed abnormally high androstenedione (n = 1) or testosterone (n = 7) concentrations. In the five cases with available adrenal tissue, histopathologic evaluation identified either an adrenocortical adenoma (n = 3) or adrenocortical carcinoma (n = 2). Hormonal abnormalities resolved and clinical signs improved in the four cats that underwent surgical adrenalectomy, with each of these cats surviving >1 year. However, clinical signs were minimally impacted with medical treatments, including one cat in which trilostane treatment failed to improve clinical signs or testosterone concentrations. This collection of cases underscores the importance of a detailed physical examination as well as the consideration of endocrine disturbances in cats undergoing evaluation for inappropriate urination or aggression. Furthermore, this report adds to the growing body of evidence that sex-hormone secreting adrenal tumors in cats may be an under-recognized syndrome

Physiology and pharmacology of diabetes therapies in the cat: insulin detemir, insulin glargine, exenatide and the incretin effect

Diabetes mellitus is a common disease in cats. Most diabetic cats depend on insulin therapy to survive but traditional insulin formulations are associated with adverse effects and poor compliance. Novel insulin analogs and incretin-based therapies are more effective and have fewer side effects than traditional therapies. We studied some of these novel therapies in healthy cats. We used the isoglycemic clamp method to compare the pharmacodynamics of the synthetic insulin analogs, insulin detemir and insulin glargine. An analog-sensitive insulin ELISA was used at the same time to measure exogenous insulin concentrations. We also used the isoglycemic clamp method to study the pharmacodynamics of the GLP-1 mimetic, exenatide. An exenatide-specific ELISA was used for evaluation of exenatide pharmacokinetics. Finally, we studied the incretin effect in cats and compared the effect of glucose, lipids or amino acids on secretion of the incretin hormones glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The isoglycemic clamp method was used to compare the effects of the 3 treatments on insulin secretion. We found that insulin detemir and insulin glargine have similar pharmacodynamics in healthy cats. With durations of actions of approximately 12 hours and significant variability in their time-action profiles, their efficacy and safety as once-a-day drugs is questionable. We found that exenatide stimulates insulin secretion in cats in a glucose-dependent manner, but it did not increase glucose tolerability. Its absorption after subcutaneous injection was rapid, but so was its clearance from the blood. Therefore, the use of exenatide, in its current formulation for treatment of diabetes in cats, is questionable. Finally, we found that a glucose-stimulated incretin effect does occur in cats, it is probably mediated by GLP-1, and its magnitude is lower than reported in other species. This small incretin effect is probably related to the fact that GIP secretion was not stimulated by oral glucose. GIP secretion was strongly stimulated by oral amino acids and even more so, by oral lipids. GLP-1 secretion was stimulated to a similar degree by all three nutrients

The Diabetic Dog as a Translational Model for Human Islet Transplantation.

The dog model has served as the primary method for early development of many diabetes therapies, including pancreatic islet transplantation techniques and immunosuppressive protocols. Recent trends towards the use of monoclonal antibody therapies for immunosuppression in human islet transplantation have led to the increasing use of primate models with induced diabetes. In addition to induced-disease models in large animals, scientists in many fields are considering the use of naturally-occurring disease models in client-owned pets. This article will review the applicability of naturally-occurring diabetes in dogs as a translational model for developing islet transplantation in the human diabetic patient

Evaluation of a machine learning tool to screen for hypoadrenocorticism in dogs presenting to a teaching hospital

BackgroundDogs with hypoadrenocorticism (HA) have clinical signs and clinicopathologic abnormalities that can be mistaken as other diseases. In dogs with a differential diagnosis of HA, a machine learning model (MLM) has been validated to discriminate between HA and other diseases. This MLM has not been evaluated as a screening tool for a broader group of dogs.HypothesisAn MLM can accurately screen dogs for HA.AnimalsDogs (n = 1025) examined at a veterinary hospital.MethodsDogs that presented to a tertiary referral hospital that had a CBC and serum chemistry panel were enrolled. A trained MLM was applied to clinicopathologic data and in dogs that were MLM positive for HA, diagnosis was confirmed by measurement of serum cortisol.ResultsTwelve dogs were MLM positive for HA and had further cortisol testing. Five had HA confirmed (true positive), 4 of which were treated for mineralocorticoid and glucocorticoid deficiency, and 1 was treated for glucocorticoid deficiency alone. Three MLM positive dogs had baseline cortisol ≤2 μg/dL but were euthanized or administered glucocorticoid treatment without confirming the diagnosis with an ACTH-stimulation test (classified as "undetermined"), and in 4, HA was ruled out (false positives). The positive likelihood ratio of the MLM was 145 to 254. All dogs diagnosed with HA by attending clinicians tested positive by the MLM.Conclusions and clinical importanceThis MLM can robustly predict HA status when indiscriminately screening all dogs with blood work. In this group of dogs with a low prevalence of HA, the false positive rates were clinically acceptable

Efficacy of a micronized, nanocrystal fenofibrate formulation in treatment of hyperlipidemia in dogs.

BackgroundSafe, effective, and readily available drug therapies are required for the management of hyperlipidemia and its associated complications in dogs.ObjectivesTo investigate the efficacy of a micronized, nanocrystal formulation of fenofibrate (Tricor) in the treatment of hyperlipidemia in dogs.AnimalsTen client-owned dogs with primary (n = 7) and secondary (n = 3) hyperlipidemia. All dogs had hypertriglyceridemia at baseline; 3 dogs also had hypercholesterolemia.MethodsProspective dose-escalation study. Dogs were treated with fenofibrate orally once daily in up to 3 cycles of 21 days each. Fenofibrate dose was increased at the end of each cycle if hypertriglyceridemia persisted and adverse effects were not documented. Complete blood count, biochemistry, and urine protein:creatinine ratio were collected serially. Baseline (T0) parameters were compared to time of maximal reduction in serum triglyceride concentrations (T1) and reported as median (range).ResultsTriglycerides normalized in all dogs (T0 = 662 mg/dL [189-2391]; T1 = 113 mg/dL [81-132]; P = .002). Fenofibrate dose at T1 = 6.4 mg/kg PO q24h (range, 2.2-13.5). T1 was achieved at 3 (n = 4), 6 (n = 4), and 9 (n = 2) weeks. Serum cholesterol concentrations decreased in 9 of 10 dogs. Quiet demeanor and firm stools in 1 dog were the only reported adverse reactions. Fenofibrate administration resulted in a significant reduction in median alkaline phosphatase activity (P = .049).Conclusions and clinical importanceOver 21 to 63 days, TriCor was effective in the management of primary and secondary hyperlipidemia in dogs