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

BACKGROUND: Dogs 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. HYPOTHESIS: An MLM can accurately screen dogs for HA. ANIMALS: Dogs (n = 1025) examined at a veterinary hospital. METHODS: Dogs 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. RESULTS: Twelve 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 IMPORTANCE: This 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.

Day-to-day variability of porcine lente, insulin glargine 300 U/mL and insulin degludec in diabetic dogs.

BACKGROUND: Day-to-day variability impacts safety of insulin therapy and the choice of monitoring strategies. Side-by-side comparisons of insulin formulations in diabetic dogs are scarce. HYPOTHESIS/OBJECTIVES: Insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) are associated with less day-to-day glucose variability compared to porcine lente (PL) in diabetic dogs. ANIMALS: Seven intact male purpose-bred beagles with toxin-induced diabetes. METHODS: In this repeated measured study, PL, IGla300 and IDeg were compared in 2 phases: once-daily (q24h) and twice-daily (q12h) administration. Interstitial glucose concentrations (IG) were measured continuously throughout the study. For each formulation, maximal q24h dose was determined using the same algorithm (while avoiding hypoglycemia) and then maintained for 72 hours. In phase 2, 70% of the maximal q24h dose was administered q12h and maintained for 5 days regardless of hypoglycemia. Coefficient of variation (CV) and glycemic variability percentage (GVP) were calculated to determine day-to-day and intraday variability, respectively. RESULTS: There was no difference in day-to-day variability between PL, IGla300, and IDeg in the q24h phase. In the q12h phase, day-to-day variability was higher (P = .01) for PL (CV = 42.6 ± 6.8%) compared to IGla300 and IDeg (CV = 30.1 ± 7.7%, 25.2 ± 7.0%, respectively). The GVP of PL was lower (P = .02) compared to IGla300. There was no difference between PL, IGla300 and IDeg in %time IG < 70 mg/dL. CONCLUSIONS AND CLINICAL IMPORTANCE: Insulin degludec and IGla300 administered q12h were associated with lower day-to-day variability, which might be advantageous in minimizing monitoring requirements without increasing the risk of hypoglycemia.

Fenofibrate promotes PPARα-targeted recovery of the intestinal epithelial barrier at the host-microbe interface in dogs with diabetes mellitus.

Diabetes mellitus (DM) is associated with a dysfunctional intestinal barrier and an increased risk for systemic infection and inflammation in people, though the pathogenic mechanisms leading to this are poorly understood. Using a canine model of DM, we showed that the peroxisomal proliferator-activated receptor-α agonist fenofibrate modulates plasma lipid profiles and markers of intestinal barrier function. A 3-week course of fenofibrate reduced fasting interstitial glucose and inflammatory cytokine IL-8 and TNF-α concentrations, which correlated with reduced triglyceride levels. The lipidomic profile exhibited significantly lower levels of triacylglycerols, phosphatidylethanolamines, diacylglycerols, and ceramides following fenofibrate administration. On histopathological analysis, we observed an aberrant amount of intraepithelial CD3+ T lymphocytes (IEL) in the small intestine of dogs with spontaneous and induced-DM. Fenofibrate reduced IEL density in the duodenum of dogs with DM and enhanced markers of intestinal barrier function in vivo and in vitro. There were minimal changes in the intestinal microbial composition following fenofibrate administration, suggesting that repair of intestinal barriers can be achieved independently of the resident microbiota. Our findings indicate that lipid metabolism is critical to functionality of the intestinal epithelium, which can be rescued by PPARα activation in dogs with DM.