Pasireotide Long-Acting Release Treatment for Diabetic Cats with Underlying Hypersomatotropism.

BACKGROUND: Long-term medical management of hypersomatotropism (HS) in cats has proved unrewarding. Pasireotide, a novel somatostatin analogue, decreases serum insulin-like growth factor 1 (IGF-1) and improves insulin sensitivity in cats with HS when administered as a short-acting preparation. OBJECTIVES: Assess once-monthly administration of long-acting pasireotide (pasireotide LAR) for treatment of cats with HS. ANIMALS: Fourteen cats with HS, diagnosed based on diabetes mellitus, pituitary enlargement, and serum IGF-1 > 1000 ng/mL. METHODS: Uncontrolled, prospective cohort study. Cats received pasireotide LAR (6-8 mg/kg SC) once monthly for 6 months. Fructosamine and IGF-1 concentrations, and 12-hour blood glucose curves (BGCs) were assessed at baseline and then monthly. Product of fructosamine concentration and insulin dose was calculated as an indicator of insulin resistance (Insulin Resistance Index). Linear mixed-effects modeling assessed for significant change in fructosamine, IGF-1, mean blood glucose (MBG) of BGCs, insulin dose (U/kg) and Insulin Resistance Index. RESULTS: Eight cats completed the trial. Three cats entered diabetic remission. Median IGF-1 (baseline: 1962 ng/mL [range 1051-2000 ng/mL]; month 6: 1253 ng/mL [524-1987 ng/mL]; P < .001) and median Insulin Resistance Index (baseline: 812 µmolU/L kg [173-3565 µmolU/L kg]; month 6: 135 µmolU/L kg [0-443 µmolU/L kg]; P = .001) decreased significantly. No significant change was found in mean fructosamine (baseline: 494 ± 127 µmol/L; month 6: 319 ± 113.3 µmol/L; P = .07) or MBG (baseline: 347.7 ± 111.0 mg/dL; month 6: 319.5 ± 113.3 mg/dL; P = .11), despite a significant decrease in median insulin dose (baseline: 1.5 [0.4-5.2] U/kg; 6 months: 0.3 [0.0-1.4] U/kg; P < .001). Adverse events included diarrhea (n = 11), hypoglycemia (n = 5), and worsening polyphagia (n = 2). CONCLUSIONS AND CLINICAL IMPORTANCE: Pasireotide LAR is the first drug to show potential as a long-term management option for cats with HS.

Epidemiology of Diabetes Mellitus among 193,435 Cats Attending Primary-Care Veterinary Practices in England.

BACKGROUND: Diabetes mellitus (DM) is a common endocrine disease of cats. The prevalence of DM in cats in England is not well-defined. HYPOTHESIS/OBJECTIVES: To estimate the prevalence and identify risk factors for DM in a large population of cats attending primary-care practices. ANIMALS: A cohort of 193,563 cats in the VetCompass Programme attending 118 primary-care practices in England. METHODS: Cross-sectional analysis of cohort clinical data. Data were extracted covering September 1st 2009 and August 31st 2014. Period prevalence of DM was calculated. Associations between risk factors and DM were assessed using logistic regression modelling. RESULTS: Of 1,128 DM cases were identified among 194,563 cats (period prevalence 0.58%; 95% confidence interval [CI] 0.54-0.61). Multivariable modelling indicated that Tonkinese (OR 4.1; 95% CI 1.8-9.6; P = .001), Norwegian Forest (odds ratio [OR] 3.5; 95% CI 1.3-9.6; P = .001) and Burmese (OR 3.0; 95% CI 2.0-4.4; P < .001) cats had increased odds of DM compared with crossbred cats. DM odds increased as bodyweight categories increased above 4 kg (P < .001), as cats aged beyond 6 years old (P < .001) and in insured cats (OR 2.0; 95% CI 1.6-2.4; P < .001) but sex was not significantly associated with DM. CONCLUSIONS AND CLINICAL IMPORTANCE: Diabetes mellitus is an important component of the primary-care practice caseload with 1-in-200 cats affected. An increased risk of DM in certain cat breeds supports a genetic predisposition. These results can guide future research and preventative healthcare.

Pasireotide for the Medical Management of Feline Hypersomatotropism.

BACKGROUND: Feline hypersomatotropism (HST) is a cause of diabetes mellitus in cats. Pasireotide is a novel multireceptor ligand somatostatin analog that improves biochemical control of humans with HST. HYPOTHESIS/OBJECTIVES: Pasireotide improves biochemical control of HST and diabetes mellitus in cats. ANIMALS: Hypersomatotropism was diagnosed in diabetic cats with serum insulin-like growth factor-1 (IGF-1) concentration >1,000 ng/mL by radioimmunoassay and pituitary enlargement. METHODS: Insulin-like growth factor 1 was measured and glycemic control assessed using a 12-hour blood glucose curve on days 1 and 5. On days 2, 3, and 4, cats received 0.03 mg/kg pasireotide SC q12h. IGF-1, insulin dose, and estimated insulin sensitivity (product of the area under the blood glucose curve [BGC] and insulin dose) were compared pre- and post treatment. Paired t-tests or Wilcoxon signed rank tests were employed for comparison where appropriate; a linear mixed model was created to compare BGC results. RESULTS: Insulin-like growth factor 1 decreased in all 12 cats that completed the study (median [range] day 1: 2,000 ng/mL [1,051-2,000] and day 5: 1,105 ng/mL [380-1,727], P = .002, Wilcoxon signed rank test). Insulin dose was lower on day 5 than on day 1 (mean reduction 1.3 [0-2.7] units/kg/injection, P = .003, paired t-test). The product of insulin dose and area under the BGC was lower on day 5 than day 1 (difference of means: 1,912; SD, 1523; u × mg/dL × hours, P = .001; paired t-test). No clinically relevant adverse effects were encountered. CONCLUSIONS: Short-acting pasireotide rapidly decreased IGF-1 in cats with HST and insulin-dependent diabetes. The decrease in IGF-1 was associated with increased insulin sensitivity.

Plasma-free metanephrine and free normetanephrine measurement for the diagnosis of pheochromocytoma in dogs.

BACKGROUND: Measurement of plasma-free metanephrines is the test of choice to identify pheochromocytoma in human patients. OBJECTIVES: To establish the sensitivity and specificity of plasma-free metanephrine (fMN) and free normetanephrine (fNMN) concentrations to diagnose pheochromocytoma in dogs. ANIMALS: Forty-five client-owned dogs (8 dogs with pheochromocytoma, 11 dogs with adrenocortical tumors, 15 dogs with nonadrenal disease, and 11 healthy dogs.) METHODS: A prospective study. EDTA plasma was collected from diseased and healthy dogs and submitted for fMN and fNMN measurement by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Free MN concentration (median [range]) was significantly higher in dogs with pheochromocytoma (8.15 [1.73-175.23] nmol/L) than in healthy dogs (0.95 [0.68-3.08] nmol/L; P < .01) and dogs with adrenocortical tumors (0.92 [0.25-2.51] nmol/L; P < .001), but was not different from dogs with nonadrenal disease (1.91 [0.41-6.57] nmol/L; P ≥ .05). Free NMN concentration was significantly higher in dogs with pheochromocytoma (63.89 [10.19-190.31] nmol/L) than in healthy dogs (2.54 [1.59-4.17] nmol/L; P < .001), dogs with nonadrenal disease (3.30 [1.30-10.10] nmol/L; P < .001), and dogs with adrenocortical tumors (2.96 [1.92-5.01] nmol/L); P < 0.01). When used to diagnose pheochromocytoma, a fMN concentration of 4.18 nmol/L had a sensitivity of 62.5% and specificity of 97.3%, and a fNMN concentration of 5.52 nmol/L had a sensitivity of 100% and specificity of 97.6%. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma fNMN concentration has excellent sensitivity and specificity for the diagnosis of pheochromocytoma in dogs, whereas fMN concentration has moderate sensitivity and excellent specificity. Measurement of plasma-free metanephrines provides an effective, noninvasive, means of identifying dogs with pheochromocytoma.