Effects of Pioglitazone on Insulin Sensitivity and Serum Lipids in Obese Cats

Background

Pioglitazone is a thiazolidinedione (TZD) insulin sensitizer approved for use in human type 2 diabetes mellitus. Therapeutic options for diabetes in cats are limited.

Objective

To evaluate the effects of pioglitazone in obese cats, which are predisposed to insulin resistance, to assess its potential for future use in feline diabetes mellitus.

Animals

A total of 12 obese purpose‐bred research cats (6 neutered males and 6 spayed females, 5–7 years of age, weighing 5.4–9.8 kg).

Methods

Randomized, placebo‐controlled 3‐way crossover study. Oral placebo or pioglitazone (Actos™; 1 or 3 mg/kg) was administered daily for 7‐week periods, with IV glucose tolerance testing before and after each period.

Results

Three mg/kg pioglitazone significantly improved insulin sensitivity (geometric mean [95% CI] 0.90 [0.64–1.28] to 2.03 [1.49–2.78] min ⁻¹pmol⁻¹L; P = .0014 versus change with placebo), reduced insulin area under the curve during IVGTT (geometric mean [range] 27 [9–64] to 18 [6–54] min∙nmol/L; P = .0031 versus change with placebo), and lowered serum triglyceride (geometric mean [range] 71 [29–271] to 48 [27–75] mg/dL; P = .047 versus change with placebo) and cholesterol (geometric mean [range] 187 [133–294] to 162 [107–249] mg/dL; P = .0042 versus change with placebo) concentrations in the obese cats. No adverse effects attributable to pioglitazone were evident in the otherwise healthy obese cats at this dosage and duration.

Conclusions and Clinical Importance

Results of this study support a positive effect of pioglitazone on insulin sensitivity and lipid metabolism in obese cats, and suggest that further evaluation of the drug in cats with diabetes mellitus or other metabolic disorders might be warranted.     

Linear-Accelerator-Based Modified Radiosurgical Treatment of Pituitary Tumors in Cats: 11 Cases (1997–2008)

Objective: Determine the efficacy and safety of a linear-accelerator-based single fraction radiosurgical approach to the treatment of pituitary tumors in cats.
Design: Retrospective study.
Animals: Eleven client-owned cats referred for treatment of pituitary tumors causing neurological signs, or poorly controlled diabetes mellitus (DM) secondary either to acromegaly or pituitary-dependent hyperadrenocortism.
Procedures: Cats underwent magnetic resonance imaging (MRI) of the brain to manually plan radiation therapy. After MRI, modified radiosurgery was performed by delivering a single large dose (15 or 20 Gy) of radiation while arcing a linear-accelerator-generated radiation beam around the cat's head with the pituitary mass at the center of the beam. Eight cats were treated once, 2 cats were treated twice, and 1 cat received 3 treatments. Treated cats were evaluated for improvement in endocrine function or resolution of neurological disease by review of medical records or contact with referring veterinarians and owners.
Results: Improvement in clinical signs occurred in 7/11 (63.6%) of treated cats. Five of 9 cats with poorly regulated DM had improved insulin responses, and 2/2 cats with neurological signs had clinical improvement. There were no confirmed acute or late adverse radiation effects. The overall median survival was 25 months (range, 1–60), and 3 cats were still alive.
Conclusions and Clinical Importance: Single fraction modified radiosurgery is a safe and effective approach to the treatment of pituitary tumors in cats.     

Adverse Neurologic Events Associated with Voriconazole Use in 3 Cats

Background: Voriconazole has a broader spectrum of activity in comparison to fluconazole, itraconazole, and amphotericin B. Little documentation regarding appropriate dosing, efficacy, or adverse effects exists for cats. Neurologic adverse effects have been reported as a result of administration in other species. Hypothesis: Voriconazole administration resulted in neurologic abnormalities in 3 cats. Animals: Three cats that received voriconazole. Methods: Observational study of adverse effects associated with voriconazole administration. Results: All 3 cats had ataxia, which in 2 cats progressed to paraplegia of the rear limbs. Two of the cats had visual abnormalities including mydriasis, decreased to absent pupillary light responses, and decreased menace response. Arrhythmia and hypokalemia were noted in 2 separate cats. Conclusions and Clinical Importance: Voriconazole has potential neurologic adverse effects in cats. Additional information regarding pharmacokinetics of the drug in this species must be gathered to help determine how it can be dosed most effectively with minimal adverse effects.     

Intensive Intravenous Infusion of Insulin in Diabetic Cats

Background

Remission occurs in 10–50% of cats with diabetes mellitus (DM). It is assumed that intensive treatment improves β‐cell function and increases remission rates.

Hypothesis

Initial intravenous infusion of insulin that achieves tight glycemic control decreases subsequent insulin requirements and increases remission rate in diabetic cats.

Animals

Thirty cats with newly diagnosed DM.

Methods

Prospective study. Cats were randomly assigned to one of 2 groups. Cats in group 1 (n = 15) received intravenous infusion of insulin with the goal of maintaining blood glucose concentrations at 90–180 mg/dL, for 6 days. Cats in group 2 (n = 15) received subcutaneous injections of insulin glargine (cats ≤4 kg: 0.5–1.0 IU, q12h; >4 kg 1.5–2.0 IU, q12h), for 6 days. Thereafter, all cats were treated with subcutaneous injections of insulin glargine and followed up for 6 months. Cats were considered in remission when euglycemia occurred for ≥4 weeks without the administration of insulin. Nonparametric tests were used for statistical analysis.

Results

In groups 1 and 2, remission was achieved in 10/15 and in 7/14 cats (P = .46), and good metabolic control was achieved in 3/5 and in 1/7 cats (P = .22), respectively. Overall, good metabolic control or remission occurred in 13/15 cats of group 1 and in 8/14 cats of group 2. In group 1, the median insulin dosage given during the 6‐month follow‐up was significantly lower than in group 2 (group 1: 0.32 IU/kg/day, group 2: 0.51 IU/kg/day; P = .013).

Conclusions and Clinical Importance

Initial intravenous infusion of insulin for tight glycemic control in cats with DM decreases insulin requirements during the subsequent 6 months.     

Changes in Systolic Blood Pressure over Time in Healthy Cats and Cats with Chronic Kidney Disease

Background

Hypertension is a common problem in older cats, most often associated with chronic kidney disease (CKD). Cross‐sectional studies have suggested that blood pressure in cats increases with age.

Hypothesis/Objectives

To determine whether blood pressure in cats increases with age and whether this occurs independently of the presence of CKD. To investigate risk factors for developing hypertension.

Animals/Subjects

Two hundred and sixty‐five cats with CKD and 133 healthy cats ≥9 years were retrospectively identified.

Methods

Four groups were created according to status at initial evaluation (CKD or healthy) and blood pressure at the last included visit (normotensive [NT] or developed hypertension [DH]): Healthy‐NT, Healthy‐DH, CKD‐NT and CKD‐DH. Systolic blood pressure (SBP) over time slopes were compared with 0 and between groups. Risk factors for the development of hypertension were investigated, and associations of biochemical and clinical variables with SBP were examined.

Results

Cats that were hypertensive at CKD diagnosis (n = 105) were not included in further analyses. Twenty‐seven cats with CKD and 9 healthy cats developed hypertension ≥3 months after diagnosis of CKD or their first visit. Systolic blood pressure significantly increased with age in all cats (P < .001). Healthy cats were at less risk than cats with CKD to become hypertensive (hazard ratio 0.2, P < .001), with creatinine being an independent risk factor for the development of hypertension.

Conclusions and Clinical Importance

The high prevalence of hypertension in azotemic cats in this study shows the importance of monitoring of SBP in elderly cats, and in particular in cats with CKD.     

Evaluation of a Novel Real-Time Continuous Glucose-Monitoring System for Use in Cats

Background: The Guardian REAL‐Time is a continuous glucose‐monitoring system (CGMS) recently developed to provide instantaneous interstitial glucose concentrations; the system does not require a monitor being fixed to the animal. Hypothesis: The CGMS provides accurate and reproducible real‐time readings of glucose concentration in cats. Animals: Thirty‐two diabetic cats, 2 cats with suspected insulinoma, and 5 healthy cats. Methods: Prospective, observational study. CGMS accuracy was compared with a reference glucose meter at normal, high, and low blood glucose concentrations using error grid analysis. Reading variability of 2 simultaneously used CGMS was determined in diabetic cats by calculating correlation and percentage of concordance of paired data at different glycemic ranges. The time interval between increasing glycemia and a rise in interstitial fluid glucose measured by the CGMS was assessed in healthy cats receiving glucose IV; the time point of maximal increase in interstitial glucose concentrations was calculated. Results: The CGMS was 100, 96.1, and 91.0% accurate at normal, high, and low blood glucose concentrations. Measurements deviated from reference by ?12.7 ± 70.5 mg/dL at normal, ?12.1 ± 141.5 mg/dL at high, and ?1.9 ± 40.9 mg/dL at low glucose concentrations. Overall, paired CGMS readings correlated significantly (r= 0.95, P < .0001) and concordance was 95.7%. The median delay after IV administration of glucose to an increase in interstitial glucose was 11.4 minutes (range: 8.8–19.7 minutes). Conclusions and Clinical Importance: Although some readings substantially deviated from reference values, the CGMS yields reproducible results, is clinically accurate in cats with hyperglycemia and euglycemia, and is slightly less accurate if blood glucose concentrations are low. Rapidly increasing interstitial glucose after a glycemic rise suggests that the CGMS is suitable for real‐time measurement under clinical conditions.     

Antithrombotic Effect of Enoxaparin in Clinically Healthy Cats: A Venous Stasis Model

Background: Systemic arterial thromboembolic events are a serious complication of cardiac disease in cats.
Objectives: To determine if enoxaparin induces an antithrombotic effect in cats at a dosage of 1 mg/kg SC q12h and if this antithrombotic effect is predicted by anti-Xa activity.
Animals: Fourteen clinically healthy cats were divided into 3 groups: control (4 cats), treated and assessed at 4 hours (5 cats), and treated and assessed at 12 hours (5 cats).
Methods: A venous stasis model was used and the extent of thrombus formation estimated by measuring thrombus weight and accretion of ¹²⁵I-fibrinogen. Plasma anti-Xa activity was measured in treated cats.
Results: There was a significant reduction in thrombus formation in the 4 h group compared with control (median weight, 0.000 versus 0.565 mg/mm, P < .01; median %¹²⁵I-fibrinogen accretion, 0.0 versus 42.0%, P < .01). There was a reduction in thrombus formation in the 12 h group (median weight, 0.006 mg/mm, P = .09; median %¹²⁵I-fibrinogen accretion, 3.83%, P = .09) but this reduction was not significant. The median percent thrombus inhibition for treated cats was 100.0% at 4 hours and 91.4% at 12 hours. Plasma anti-Xa activity was not significantly correlated with thrombus formation.
Conclusions and Clinical Importance: This pilot study demonstrates that enoxaparin, when administered at a dosage of 1 mg/kg SC q12h, produces an antithrombotic effect in a venous statsis model in clinically healthy cats. Furthermore, this study demonstrates that anti-Xa activity is a poor predictor of enoxaparin's antithrombotic effect.