A dose titration protocol for once-daily insulin glargine 300 U/mL for the treatment of diabetes mellitus in dogs.

BACKGROUND: In purpose-bred dogs, insulin glargine 300 U/mL (IGla300) has long duration of action, peakless time-action profile, and low potency, making it suitable for use as a basal insulin. HYPOTHESIS: To evaluate IGla300 in client-owned diabetic dogs monitored using a flash glucose monitoring system (FGMS). ANIMALS: Ninety-five client-owned diabetic dogs, newly diagnosed or previously treated with other insulin formulations, with or without concurrent diseases. METHODS: Prospective multi-institutional study. Clinical signs and standardized assessment of FGMS data, using treatment and monitoring guidelines established a priori, guided dose adjustments and categorization into levels of glycemic control. RESULTS: The initial IGla300 dose was 0.5 U/Kg q24h for newly diagnosed dogs and (median dose [range]) 0.8 U/Kg (0.2-2.5) q24h for all dogs. Glycemic control was classified as good or excellent in 87/95 (92%) dogs. The IGla300 was administered q24h (1.9 U/kg [0.2-5.2]) and q12h (1.9 U/kg/day [0.6-5.0]) in 56/95 (59%) and 39/95 (41%) dogs, respectively. Meal-time bolus injections were added in 5 dogs (0.5 U/kg/injection [0.3-1.0]). Clinical hypoglycemia occurred in 6/95 (6%) dogs. Dogs without concurrent diseases were more likely to receive IGla300 q24h than dogs with concurrent diseases (72% vs 50%, respectively; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Insulin glargine 300 U/mL can be considered a suitable therapeutic option for once-daily administration in diabetic dogs. Clinicians should be aware of the low potency and wide dose range of IGla300. In some dogs, twice-daily administration with or without meal-time bolus injections may be necessary to achieve glycemic control. Monitoring with FGMS is essential for dose titration of IGla300.

Hypothalamic-pituitary-adrenal axis recovery after intermediate-acting glucocorticoid treatment in client-owned dogs.

BACKGROUND: In dogs, duration of hypothalamic-pituitary-adrenal (HPA) axis suppression after systemic glucocorticoid treatment is reported to vary from a few days to up to 7 weeks after glucocorticoid discontinuation. These data are derived mainly from experimental studies in healthy dogs and not from animals with spontaneous disease. HYPOTHESIS AND OBJECTIVE: To determine the timeline for recovery of the HPA axis in a group of ill dogs treated with intermediate-acting glucocorticoids (IAGCs). ANIMALS: Twenty client-owned dogs that received IAGC for at least 1 week. METHODS: Single-center prospective observational study. An ACTH stimulation test, endogenous ACTH concentration, serum biochemistry profile, and urinalysis were performed at T0 (2-6 days after IAGC discontinuation) and then every 2 weeks (eg, T1, T2, T3) until HPA axis recovery was documented (post-ACTH cortisol concentration > 6 µg/dL). RESULTS: The median time of HPA axis recovery was 3 days (range, 2-133 days). Eleven of 20 dogs showed recovery of the HPA axis at T0, 6/20 at T1, and 1 dog each at T2, T5, and T9. Dose and duration of treatment were not correlated with timing of HPA axis recovery. Activities of ALT and ALP were significantly correlated with the post-ACTH cortisol concentration (rs = -0.34, P = .03; rs = -0.31, P = .05). Endogenous ACTH concentration was significantly correlated with pre (r = 0.72; P < .0001) and post-ACTH cortisol concentrations (r = 0.35; P = .02). The timing of HPA axis recovery of the dogs undergoing an alternate-day tapering dose was not different compared to dogs that did not (3.5 vs 3 days, P = .89). CONCLUSION AND CLINICAL IMPORTANCE: Most dogs experienced HPA axis recovery within a few days after IAGC discontinuation. However, 2/20 dogs required >8 weeks.

Prevalence of eunatremic, eukalemic hypoadrenocorticism in dogs with signs of chronic gastrointestinal disease and risk of misdiagnosis after previous glucocorticoid administration.

BACKGROUND: Dogs with eunatremic, eukalemic hypoadrenocorticism (EEH) typically show signs of chronic gastrointestinal disease (CGD). Previous glucocorticoid administration (PGA) can give false-positive results on the ACTH stimulation test (ACTHst). HYPOTHESIS/OBJECTIVES: To determine the prevalence of EEH in dogs with signs of CGD, and to identify clinical and clinicopathological features for EEH and PGA. ANIMALS: One hundred twelve dogs with CGD (101 non-PGA and 11 PGA), 20 dogs with EEH. METHODS: Multicenter prospective cohort study. Basal serum cortisol (BSC) concentration was measured in dogs with signs of CGD. When BSC was <2 µg/dL and in PGA dogs, ACTHst plus measurement of endogenous ACTH (eACTH) were performed. Records of dogs with EEH from 2009 to 2021 were reviewed. RESULTS: The BSC concentration was <2 µg/dL in 48/101 (47.5%) non-PGA and in 9/11 (82%) PGA dogs. EEH was diagnosed in 1/112 dog (prevalence 0.9%; 95% CI, 0.1%-4.8%); the ACTHst provided false-positive results in 2/11 PGA dogs. PGA dogs showed lower C-reactive protein-to-haptoglobin ratio (median 0.01, range 0.003-0.08; P = .01), and higher haptoglobin (140, 26-285 mg/dL; P = .002) than non-PGA dogs (0.04, 0.007-1.5; 38.5, 1-246 mg/dL, respectively). eACTH was higher (P = .03) in EEH (396, 5->1250 pg/mL) than in non-PGA dogs (13.5, 7.3-46.6 pg/mL). Cortisol-to-ACTH ratio was lower (P < .0001 and P = .01, respectively) in EEH (0.002, 0.0002-0.2) than in non-PGA (0.1, 0.02-0.2) and PGA dogs (0.1, 0.02-0.2). CONCLUSIONS AND CLINICAL IMPORTANCE: The prevalence of EEH in dogs with signs of CGD was lower than previously reported. The clinical and clinicopathological features herein identified could increase the index of suspicion for EEH or PGA in dogs with an unclear history of glucocorticoid administration.

Monitoring of Diabetes Mellitus Using the Flash Glucose Monitoring System: The Owners' Point of View.

The flash glucose monitoring system (FGMS) has recently become one of the most common monitoring methods in dogs and cats with diabetes mellitus. The aim of this study was to evaluate the impact of FGMS on the quality of life of diabetic pet owners (DPOs). Fifty DPOs were asked to answer a 30-question survey. More than 80% of DPOs considered FGMS easier to use and less stressful and painful for the animal compared to blood glucose curves (BGCs). Overall, 92% of DPOs reported that their pet had better diabetes control since using FGMS. The most challenging aspects of using the FGMS were ensuring proper sensor fixation during the wearing period (47%), preventing premature detachment (40%), and purchasing the sensor (34%). Moreover, 36% of DPOs reported that the device cost was difficult to afford in the long term. Comparing dogs and cats, a significantly higher number of dogs' owners found the FGMS to be well-tolerated (79% vs. 40%), less invasive than BGCs (79% vs. 43%), and easier to maintain in situ (76% vs. 43%). In conclusion, FGMS is considered by DPOs to be easy to use and less stressful compared to BGCs, while enabling better glycemic control. Nevertheless, the costs related to its long-term use might be difficult to sustain.

A Novel UHPLC-MS/MS Method for the Measurement of 25-Hydroxyvitamin D3 in Canine Serum and Its Application to Healthy Dogs.

Several studies have shown the importance of vitamin D3 supplementation in small animals. In dogs, a low vitamin D3 status is associated not only with bone metabolism but also with different kinds of disorders, such as congestive heart failure, gastrointestinal diseases, chronic kidney diseases, and some types of cancer. However, it is crucial to maintain balance and monitor the introduction of this essential nutrient through the diet because over-supplementation can result in toxicity. Due to the clinical importance of assessing the vitamin D3 status in small animal patients, a quick, simple, and highly performing analytical method for its measurement is needed. In this study, we describe the development of a novel liquid chromatography-tandem mass spectrometry method for 25-hydroxyvitamin D3 quantification in canine serum. The approach was successfully validated following current European guidelines, proving excellent linearity (R2 always ≥0.996), accuracy (always within ±13%) and precision (always <10%). The application of the validated approach to samples collected from 40 healthy dogs made possible the definition of a reliable reference interval for 25-hydroxyvitamin D3, the main biomarker of vitamin D3. In addition, variations below 5% in the results obtained quantifying the same samples using a water-based calibration curve demonstrated that a surrogate matrix may be used without affecting data accuracy. Thanks to its simplicity, the proposed technique represents a useful tool for supporting clinical routine and investigating correlations between serum concentrations of this metabolite and multiple diseases. Additionally, it could enable the monitoring of supplementation in small animal patients in veterinary clinical practice.

Prognostic Role of Red Cell Distribution Width and Other Routine Clinico-Pathological Parameters in Dogs with Acute Pancreatitis.

This study aimed to assess the prognostic value of red cell distribution width (RDW) RDW-to-calcium ratio (RDW/Ca), neutrophils-to-lymphocytes ratio (N/L), platelets-to-lymphocytes ratio (P/L) and other easy to obtain and inexpensive hematological and biochemical parameters in dogs with acute pancreatitis. This is a multicenter, retrospective cohort study including 70 client-owned dogs. The accuracy of clinical and laboratory variables to predict short-term death (i.e., dead by 14 days) was tested by calculating the area under the receiver-operating characteristic curve (AUC). Independent predictors of death were identified using the multivariable Cox proportional hazards regression model. The survival rate was 72.9% (51 dogs) and 19 dogs died within 14 days of admission from AP. RDW and blood urea nitrogen (BUN) had good accuracy to predict short-term dead with AUC of 0.74 and 0.70 at the cut-off of >12.7% and >42 mg/dL, respectively. According to the multivariable model, RDW (hazard ratio and 95% confidence interval [HR, 95% CI] = 5.08, 95% CI = 1.14−22.67; p = 0.03), BUN (HR = 1.00, 95% CI = 1.00−1.01; p < 0.01) and bilirubin (HR = 2.46, 95% CI = 1.38−4.39; p < 0.01) were independent predictors of death. The results indicate that RDW, BUN and bilirubin are useful predictors of short-term death in dogs with acute pancreatitis.

Clinical Use of a 180-Day Implantable Glucose Monitoring System in Dogs with Diabetes Mellitus: A Case Series.

The novel Eversense XL continuous glucose monitoring system (Senseonics, Inc., Germantown, Maryland) has recently been developed for monitoring diabetes in humans. The sensor is fully implanted and has a functional life of up to 180 days. The present study describes the use of Eversense XL in three diabetic dogs (DD) with good glycemic control managed by motivated owners. The insertion and use of the device were straightforward and well tolerated by the dogs. During the wearing period, some device-related drawbacks, such as sensor dislocation and daily calibrations, were reported. A good correlation between the glucose values measured by the Eversense XL and those obtained with two commercially available devices, previously validated for use in DD, was found (rs = 0.85 and rs = 0.81, respectively). The life of the sensor was 180 days in two of the DD and provided high satisfaction. This innovative device might be considered a future alternative for home glucose monitoring in DD.

Evaluation of Weight Gain, Clinicopathological and Radiographic Changes after Early Diagnosis and Treatment of Congenital Hypothyroidism in Cats.

Congenital hypothyroidism is uncommon in cats. This case report describes weight gain, clinicopathological and radiographic changes after early diagnosis and treatment of congenital hypothyroidism in three British shorthair cats' siblings. Data were assessed at 53 (diagnosis), 83, 185 and 365 days of age. Correlations between serum insulin-like growth factor-1 (IGF-1) and body weight, levothyroxine dose, total thyroxine, and thyroid-stimulating hormone concentrations were evaluated. The body weights of the congenital hypothyroid kittens were compared with those of their two healthy siblings and British shorthair kittens of the same age. At diagnosis, the congenital hypothyroid kittens showed a significantly lower body weight compared to the healthy siblings (p = 0.03). After diagnosis, oral levothyroxine supplementation was started. The difference in body weight was no longer observed after one month of treatment. The clinical signs, clinicopathological and radiographic abnormalities ameliorated after one month of treatment. IGF-1 concentration was significantly positively correlated with body weight (rs = 0.80, p < 0.002). In conclusion, resolution of the clinical signs, achieving a consistent within-breed weight, and improvement of the clinicopathological and radiographic parameters demonstrated the importance of the early diagnosis and treatment of feline congenital hypothyroidism.

Urinary cortisol-creatinine ratio in dogs with hypoadrenocorticism.

BACKGROUND: Basal serum cortisol (BSC) ≥2 µg/dL (>55 nmol/L) has high sensitivity but low specificity for hypoadrenocorticism (HA). OBJECTIVE: To determine whether the urinary corticoid:creatinine ratio (UCCR) can be used to differentiate dogs with HA from healthy dogs and those with diseases mimicking HA (DMHA). ANIMALS: Nineteen healthy dogs, 18 dogs with DMHA, and 10 dogs with HA. METHODS: Retrospective study. The UCCR was determined on urine samples from healthy dogs, dogs with DMHA, and dogs with HA. The diagnostic performance of the UCCR was assessed based on receiver operating characteristics (ROC) curves, calculating the area under the ROC curve. RESULTS: The UCCR was significantly lower in dogs with HA (0.65 × 10-6 ; range, 0.33-1.22 × 10-6 ) as compared to healthy dogs (3.38 × 10-6 ; range, 1.11-17.32 × 10-6 ) and those with DMHA (10.28 × 10-6 ; range, 2.46-78.65 × 10-6 ) (P < .0001). There was no overlap between dogs with HA and dogs with DMHA. In contrast, 1 healthy dog had a UCCR value in the range of dogs with HA. The area under the ROC curve was 0.99. A UCCR cut-off value of <1.4 yielded 100% sensitivity and 97.3% specificity in diagnosing HA. CONCLUSIONS AND CLINICAL IMPORTANCE: The UCCR seems to be a valuable and reliable screening test for HA in dogs. The greatest advantage of this test is the need for only a single urine sample.

Comparison of methods to monitor dogs with hypercortisolism treated with trilostane.

BACKGROUND: The use of adrenocorticotropic hormone stimulation test as method to monitor efficacy of trilostane treatment of hypercortisolism (HC) in dogs has been questioned. OBJECTIVES: To evaluate and compare 12 methods with which to monitor efficacy of trilostane treatment in dogs with HC. ANIMALS: Forty-five client-owned dogs with HC treated with trilostane q12h. METHODS: Prospective cross-sectional observational study. The dogs were categorized as well-controlled, undercontrolled, and unwell through a clinical score obtained from an owner questionnaire. The ability to correctly identify trilostane-treatment control of dogs with HC with the following variables was evaluated: before trilostane serum cortisol (prepill), before-ACTH serum cortisol, post-ACTH serum cortisol, plasma endogenous ACTH concentrations, prepill/eACTH ratio, serum haptoglobin (Hp) concentration, serum alanine aminotransferase (ALT), gamma-glutamyl transferase (γGT) and alkaline phosphatase activity, urine specific gravity, and urinary cortisol : creatinine ratio. RESULTS: Ninety-four re-evaluations of 44 dogs were included; 5 re-evaluations of 5 unwell dogs were excluded. Haptoglobin was significantly associated with the clinical score (P < .001) and in the receiver operating characteristic analysis, Hp cutoff of 151 mg/dL correctly identified 90.0% of well-controlled dogs (specificity) and 65.6% of undercontrolled dogs (sensitivity). Alanine aminotransferase (P = .01) and γGT (P = .009) were significantly higher in undercontrolled dogs. Cutoff of ALT and γGT greater than or equal to 86 U/L and 5.8 U/L, respectively, were significantly associated with poor control of HC by trilostane. CONCLUSIONS AND CLINICAL IMPORTANCE: Of all the 12 variables, Hp, and to a lesser degree ALT and γGT, could be considered additional tools to the clinical picture to identify well-controlled and undercontrolled trilostane-treated 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.

Survival estimates and outcome predictors in dogs with newly diagnosed diabetes mellitus treated in a veterinary teaching hospital.

BACKGROUND: Diabetes mellitus (DM) is one of the most common endocrine disorders in dogs, but prognostic factors are still largely unknown. The aim of this retrospective, single-centre, case series study was to determine overall survival time and identify the prognostic value of several clinical and clinicopathological variables in dogs with newly diagnosed DM. METHODS: Cases of DM were identified within the electronic medical records of one referral centre. Sixty-eight dogs with DM were included. Cox proportional hazards models were used to analyse variables associated with survival. RESULTS: The median survival time was 964 days (range 22-3140). In multivariable model analysis, length of survival was significantly shorter for dogs with higher haematocrit value (hazard ratio (HR) 1.06, 95 per cent confidence interval (CI) 1.00 to 1.13) and higher serum phosphate concentrations (HR 1.83, 95 per cent CI 1.13 to 2.97). Serum phosphate concentrations were above the reference interval in 24 of 65 (37 per cent) dogs. CONCLUSION: Diabetic dogs have a good life expectancy. Hyperphosphataemia is a relatively common finding in dogs with newly diagnosed DM and represents a negative prognostic factor. The presence of pancreatitis might not be associated with an unfavourable outcome.