Isolation of feline islets of Langerhans by selective osmotic shock produces glucose responsive islets.

Introduction: Pancreatic islet isolation is essential for studying islet physiology, pathology, and transplantation, and feline islets could be an important model for human type II diabetes mellitus (T2D). Traditional isolation methods utilizing collagenases inflict damage and, in cats, may contribute to the difficulty in generating functional islets, as demonstrated by glucose-stimulated insulin secretion (GSIS). GLUT2 expression in ß cells may allow for adaptation to hyperosmolar glucose solutions while exocrine tissue is selectively disrupted. Methods: Here we developed a protocol for selective osmotic shock (SOS) for feline islet isolation and evaluated the effect of different hyperosmolar glucose concentrations (300 mmol/L and 600 mmol/L) and incubation times (20 min and 40 min) on purity, morphology, yield, and GSIS. Results: Across protocol treatments, islet yield was moderate and morphology excellent. The treatment of 600 mmol/L glucose solution with 20 min incubation resulted in the highest stimulation index by GSIS. Discussion: Glucose responsiveness was demonstrated, permitting future in vitro studies. This research opens avenues for understanding feline islet function and transplantation possibilities and enables an additional islet model for T2D.

Assessment of the FreeStyle Libre 2 interstitial glucose monitor in hypo- and euglycemic cats.

BACKGROUND: Continuous glucose monitoring systems have been validated for eu- and hyperglycemic cats. The FreeStyle Libre 2 (FSL2) is sufficiently accurate in people during hypoglycemia to guide critical treatment decisions without confirmation of blood glucose concentration (BG). OBJECTIVES: Assess FSL2 accuracy in cats with hypoglycemia. ANIMALS: Nine healthy, purpose-bred cats. METHODS: Hyperinsulinemic-hypoglycemic clamps were performed by IV infusion of regular insulin (constant rate) and glucose (variable rate). Interstitial glucose concentration (IG), measured by FSL2, was compared to BG measured by AlphaTrak2. Data were analyzed for all paired measurements (n = 364) and separately during stable BG (≤1 mg/dL/min change over 10 minutes). Pearson's r test, Bland-Altman test, and Parkes Error Grid analysis respectively were used to determine correlation, bias, and clinical accuracy (P < .05 considered significant). RESULTS: Overall, BG and IG correlated strongly (r = 0.83, P < .0001) in stable glycemia and moderately at all rates of change (r = 0.69, P < .0001). Interstitial glucose concentration underestimated BG in euglycemia, but the BG-IG difference was progressively smaller as BG decreased (12.9 ± 12.2, 8.8 ± 11.2, -3.2 ± 7.4, and -7.8 ± 5.2 mg/dL in the ranges of 80-120 [n = 64], 60-79 [n = 29], 50-59 [n = 71], and 29-49 mg/dL [n = 53], respectively). CONCLUSIONS: Although IG underestimates BG throughout most of the hypo-euglycemic range, IG generally overestimates BG in marked hypoglycemia (<60 mg/dL). It is therefore imperative to evaluate FSL2 results in this critical range with caution.

Establishment of a feline glycated hemoglobin reference interval for a novel dried-blood-spot assay and the effects of anemia on assay results.

BACKGROUND: Glycated hemoglobin A1c (HbA1c) reflects long-term (months) glycemic control and has been previously investigated as a monitoring and diagnostic tool in diabetic cats. However, a standardized, reliable, and globally available test and reference intervals (RIs) have not been established. A novel dried-blood-spot card system (A1Care, Baycom Diagnostics) allows for easy collection and evaluation of HbA1c levels in feline patients. OBJECTIVE: We aimed to establish an RI for HbA1c values in healthy adult cats using the A1Care (Baycom Diagnostics) dried-blood-spot card system. METHODS: Forty-one healthy client-owned adult cats were enrolled in this study. The RI for HbA1c was calculated according to the recommendation of the American Society for Veterinary Clinical Pathology. RESULTS: The A1Care HbA1c RI for cats was determined to be 1.9%-3.1%. In healthy cats, A1Care HbA1c values were positively correlated with age (Spearman rho = 0.4 [95% CI 0.1 to 0.6], P = 0.01). In 50% of anemic cats, the A1Care HbA1c value was above 3.1%. There was a weak negative correlation between the A1Care HbA1c value and PCV (Spearman rho = -0.4 [95% CI -0.6 to -0.1]). CONCLUSIONS: This study established an RI for HbA1c in healthy adult cats similar to previously reported RIs. Future clinical studies are necessary to substantiate that this RI can differentiate diabetic from nondiabetic cats. Further long-term clinical studies will be valuable to determine if HbA1c values can be used as a screening test for prediabetes in cats.

Glucose Counterregulation: Clinical Consequences of Impaired Sympathetic Responses in Diabetic Dogs and Cats.

Insulin induced hypoglycemia (IIH) is common in veterinary patients and limits the clinician's ability to obtain adequate glycemic control with insulin therapy. Not all diabetic dogs and cats with IIH exhibit clinical signs and hypoglycemia might be missed by routine blood glucose curve monitoring. In diabetic patients, counterregulatory responses to hypoglycemia are impaired (lack of decrease in insulin levels, lack of increase in glucagon, and attenuation of the parasympathetic and sympathoadrenal autonomic nervous systems) and have been documented in people and in dogs but not yet in cats. Antecedent hypoglycemic episodes increase the patient's risk for future severe hypoglycemia.

Radiographic, computed tomographic and histopathologic appearance of a presumed spinal chordoma in a dog.

A 4-year-old Labrador Retriever presented for urinary incontinence and constipation of 2 weeks duration. There was a tender abdomen, lumbar pain and conscious proprioceptive deficits in both pelvic limbs. Depressed pelvic limb reflexes were present consistent with a lower motor neuron lesion. In radiographs of the lumbar spine there was narrowing of the intervertebral disc space at L5-L6 with irregular, multifocal areas of mineralized opacities dorsal to the intervertebral disc space, presumably within the vertebral canal. On computed tomography, an intramedullary, partially mineralized mass was identified in the spinal cord at the level of caudal L5 through cranial L6. At necropsy there was a four-centimeter enlarged, irregular segment of spinal cord at the level of L5-L6. When sectioned, the spinal cord bad a mineralized texture. Histologically there were variable sized cells that were stellate in appearance with vacuolated cytoplasm (physaliferous cells) and mucinous background consistent with a chordoma. Chordoma is a rare, skeletal neoplasm that originates from mesoderm-derived notochord and has been reported in humans and animals. Extraskeletal development of a chordoma within the spinal cord is a rare manifestation of this neoplasm. However, based on other reports in dogs, solitary extraskeletal locations of chordomas may be the typical expression of this neoplasm in the dog. Differentiation of similar histologically appearing tumors, such as a parachordoma or myxoid chondrosarcoma, will require immunohistochemical characterization of these tumors in veterinary patients.