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Objective: To determine the accuracy of a continuous glucose monitoring system (CGMS) device by comparing glucose concentrations measured over time as determined by the CGMS to those of the chemistry analyzer (reference method)., Animals: 7 healthy goats and 7 dairy calves., Methods: A randomized, crossover design with 3 treatments: control, hypoglycemia, and hyperglycemia. The CGMS device was applied to the neck. Hypoglycemia and hyperglycemia were induced by insulin and xylazine, respectively. Glucose concentrations were measured by the chemistry analyzer CGMS, point-of-care glucometer, and intensive care unit machine at 0 (before treatment), 2, 4, 6, 8, 10, and 12 hours. Agreement between the CGMS and the chemistry analyzer was determined by Bland-Altman plots. The analytical and clinical accuracy of the CGMS was determined using the International Organization for Standardization (ISO) 15197:2013 criteria and the Parkes error grid analysis., Results: In goats, the CGMS overestimated glucose concentrations during the hypoglycemic, normoglycemia, and hyperglycemia treatments. In calves, the CGMS underestimated glucose concentrations during the hypoglycemic treatment but overestimated glucose concentrations in normoglycemia and hyperglycemic treatments. The CGMS met the ISO clinical accuracy criteria for goats and calves, with > 99% of the glucose measurements in zones A and B of the Parkes grid. However, the CGMS did not meet the ISO 15197:2013 criteria for analytical accuracy., Clinical Relevance: The CGMS evaluated in our study only met the ISO 15197:2013 clinical accuracy criteria, not the analytical accuracy. Therefore, the device might be considered for clinical use.

Background: It has been suggested that overt diabetes mellitus in dogs be defined based on a persistent fasting blood glucose concentration (BGC) >144 mg/dL., Objective: Determine the number of dogs with randomly identified hyperglycemia without insulin-treated diabetes mellitus (ITDM) that later develop a need for exogenous insulin treatment., Animals: A total of 1318 dogs examined at a university teaching hospital without ITDM and with randomly identified hyperglycemia., Methods: Retrospective longitudinal study. Hyperglycemia was defined as randomly identified BGC above >112 mg/dL, moderate hyperglycemia as BGC >144 mg/dL but <200 mg/dL and pronounced hyperglycemia as BGC ≥200 mg/dL. Dogs were defined as having ITDM if they were treated with insulin. Follow-up was attempted 7 to 12 years after hyperglycemia was documented to determine if over time dogs developed a need for exogenous insulin treatment., Results: Twenty-nine of 824 dogs (3.5%) with hyperglycemia and follow-up information developed ITDM, including 3/824 dogs (0.4%) with moderate hyperglycemia, and 2/824 dogs (0.2%) with pronounced hyperglycemia. Most dogs with hyperglycemia that developed ITDM (24/29, 83%) had BGC ≤144 mg/dL. Among dogs that eventually developed a need for exogenous insulin treatment, no association was found between the degree of hyperglycemia and the time interval between documentation of hyperglycemia and diagnosis of ITDM. Logistic regression determined that BGC is not significantly associated with ITDM., Conclusions and Clinical Importance: Most dogs with randomly identified hyperglycemia did not develop a need for exogenous insulin treatment. Other criteria could be required to augment the definition of overt DM in non-insulin treated dogs., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To determine the sodium correction factor for clinical use in hyperglycemic diabetic dogs., Sample: Retrospective analysis of 76 hospitalization episodes from 67 different dogs presenting to the University of Georgia Veterinary Teaching Hospital between January 1, 2015, and January 1, 2023., Methods: For each hospitalization episode, paired blood sodium and glucose concentration measurements were recorded from the time of presentation until glucose concentration was ≤ 201 mg/dL. Therapies administered, primary diagnosis, and concurrent diseases were also recorded for each episode. A linear mixed model was used to determine the sodium correction factor per 100-mg/dL increase in glucose. Piecewise linear mixed models were also constructed for blood glucose measurements ≤ 400 mg/dL and > 400 mg/dL to explore potential correction factor differences between low and high glucose concentrations., Results: A sodium correction factor of a 1.6-mEq/L (95% CI, 1.3 to 1.9 mEq/L) decrease in sodium concentration per 100-mg/dL increase in blood glucose concentration was calculated. Differences in the correction factor between conditions of low and high glucose concentrations could not be determined due to a small sample size of blood glucose values > 400 mg/dL. Most dogs received similar treatments throughout the study period, including balanced isotonic crystalloids (97% [74/76]), electrolyte supplementation (84% [64/76]), and regular insulin (97% [74/76]). Almost all patients (93% [71/76]) had 1 or more concurrent diseases., Clinical Relevance: A sodium correction factor of 1.6 mEq/L (decrease in sodium per 100-mg/dL increase in glucose) is recommended for clinical use in hyperglycemic diabetic dogs.

Objective: To determine whether rectal temperature, Hct, or blood glucose at presentation were associated with all-cause mortality in ferrets (Mustela putorius furo)., Animals: 321 client-owned ferrets., Methods: A medical record database was searched for ferrets from January 2012 through September 2022. Records from 1,189 individual examinations were evaluated. Inclusion criteria were rectal temperature, Hct, and/or blood glucose measured at presentation and data on survival status 7 days postpresentation. Data were included from 321 ferrets from 571 examinations. Rectal temperature in 244 ferrets from 346 examinations, Hct in 181 ferrets from 277 examinations, and blood glucose in 260 ferrets from 420 examinations were available., Results: The odds of death for hypothermic ferrets (< 37.8 °C) were 3.72 times (OR, 3.72; 95% CI, 2.30 to 6.01) the odds of death for normothermic ferrets (37.8 to 40 °C). For every 0.56 °C below normal rectal temperature, the odds of death increased 1.49 times (OR, 1.49; 95% CI, 1.21 to 1.90). The odds of death for anemic ferrets (Hct < 33%) were 4.74 times (OR, 4.74; 95% CI, 1.70 to 13.21) the odds of death for ferrets with a normal Hct (33% to 57%). The odds of death for hyperglycemic ferrets (> 152 mg/dL) were 2.61 times (OR, 2.61; 95% CI, 1.29 to 5.30) the odds of death for normoglycemic ferrets (74 to 152 mg/dL). The odds of death for severely hypoglycemic ferrets (< 40 mg/dL) were 9.45 times (OR, 9.45; 95% CI, 3.18 to 28.12) the odds of death for normoglycemic ferrets., Clinical Relevance: Hypothermia, anemia, hyperglycemia, and severe hypoglycemia were significant prognostic indicators of death in ferrets. Further investigation into the causes and management of these derangements is warranted.

Background: Hyperglycemia increases reactive oxygen species (ROS), which contributes to diabetic complications such as kidney cell damage. Antioxidant administration could inhibit ROS and kidney cell damage commonly seen in hyperglycemia., Aim: We want to demonstrate that the antioxidant properties of Swietenia macrophylla ethanol extract nanoparticles can prevent kidney cell damage brought on by streptozotocin (STZ) in the current investigation., Methods: This study employs high-energy ball milling to produce nanoparticles from S. macrophylla extract. Additionally, dynamic light scattering (DLS) is utilized to characterize the nanoparticle sizes of the S. macrophylla ethanol extract. Five groups, each consisting of 8 rats, were formed from 40 rats. Control rats received distilled water, the diabetic rats were administered STZ injections, while S. macrophylla rats were given S. macrophylla extract nanoparticles orally and STZ injection. After the trial, blood from a rat was drawn intracardially to check the levels of blood urea nitrogen (BUN) and creatinine. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were then assessed in kidney tissue samples. Histological alterations were evaluated in kidney section samples., Results: A DLS analysis estimated the size of the S. macrophylla ethanol extract nanoparticles to be about 91.50 ± 23.06 nm. BUN and creatinine levels were significantly raised after STZ treatment. STZ significantly decreased SOD and GPx levels in kidney tissue while raising MDA levels ( p < 0.05). Swietenia macrophylla ethanol extract nanoparticle caused the decreased levels of BUN and creatinine in blood to normal levels ( p < 0.05), indicating that S. macrophylla ethanol extract prevented the STZ-induced kidney cell damage. Additionally, S. macrophylla nanoparticles significantly raise GPx and SOD levels in kidney tissue while lowering MDA levels ( p < 0.05). These actions are thought to have prevented kidney histological alterations (degeneration and necrosis) in diabetic rats., Conclusion: According to these results, the anti-oxidative stress properties of S. macrophylla nanoparticles make them potentially effective nephroprotective therapies for STZ-induced kidney cell damage., Competing Interests: All authors declare that there is no conflict of interest.

It has been reported that hypertriglyceridemia can partially mediate between diabetes mellitus (DM) and pancreatitis in dogs, implying that another mediator, such as chronic hyperglycemia, might exist. Therefore, this study aimed to evaluate the relationship between hyperglycemia and serum canine pancreatic lipase immunoreactivity (cPLI) concentration in diabetic dogs. This retrospective cohort study included 26 client-owned diabetic dogs, divided according to their serum fructosamine levels (<500 μmol/L = well-controlled DM group; ≥500 μmol/L = untreated or poorly controlled DM group). Five of the 26 DM dogs (19.2%) had serum cPLI concentrations consistent with pancreatitis, among which two showed ultrasonographic evidence of pancreatitis without clinical signs. The serum cPLI concentrations (median [interquartile range]) were significantly higher in the untreated or poorly controlled group (520 μg/L [179.76-1000 μg/L]) than in the well-controlled group (77 μg/L [32.22-244.6 μg/L], P = 0.0147). The serum fructosamine concentration was positively correlated with the serum cPLI concentration (r = 0.4816; P = 0.0127). Multivariate analysis revealed serum triglyceride and fructosamine concentrations were associated with the serum cPLI concentration. In conclusion, this study suggests that chronic hyperglycemia may induce pancreatic inflammation in diabetic dogs; however, the clinical significance of increased cPLI concentration is unknown., (© 2023 by American Animal Hospital Association.)

Objective: To assess the agreement between measurements of total protein (TP) concentrations in canine serum samples between a commercially available veterinary digital refractometer (DR), an analog handheld refractometer (AR), and a laboratory-based chemistry analyzer (LAB). An additional objective was to assess the effects of various potential interferents (ie, hyperbilirubinemia, increased BUN, hyperglycemia, hemolysis, and lipemia) on DR measurements., Sample: 108 canine serum samples., Procedures: Serum samples were measured in duplicate on the DR, which reported TP concentration, assessed via optical reflectance and critical angle measurement. These serum samples were also assessed on the AR and LAB for comparison. Serum samples with grossly visible lipemia, hemolysis, and icterus were noted. Medical records were retrospectively assessed to determine concentrations of BUN, glucose, and bilirubin., Results: Method comparisons among the various data generated by the analyzers were completed using linear regression, Bland Altman, and calculation of intraclass coefficients. Mean bias between DRTP and LABTP in samples without potential interferents was 0.54 g/dL with 95% limits of agreement of -0.17 to 1.27 g/dL. One-third of DRTP samples without potential interferents had > 10% difference from their LABTP comparison. Interferents, particularly marked hyperglycemia, can result in inaccurate measurements on the DR., Clinical Relevance: There was a statistically significant difference between DRTP and LABTP measurements. TP measurements in samples with any potential interferent, particularly hyperglycemia, should be assessed cautiously on DR and AR.

Background: Bexagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. A pilot study has shown that bexagliflozin can decrease dependence on exogenous insulin in cats with diabetes mellitus (DM)., Objective: To evaluate the safety and effectiveness of bexagliflozin as a monotherapy for DM in previously untreated cats., Animals: Eighty-four client-owned cats., Methods: Historically controlled prospective open-label clinical trial. Cats were dosed PO with 15 mg bexagliflozin once daily for 56 days, with a 124-day extension to evaluate safety and treatment effect durability. The primary endpoint was the proportion of cats experiencing a decrease in hyperglycemia and improvement in clinical signs of hyperglycemia from baseline on day 56., Results: Of 84 enrolled cats, 81 were evaluable on day 56, and 68 (84.0%) were treatment successes. Decreases in mean serum glucose, fructosamine, and β-hydroxybutyrate (β-OHB) concentrations were observed, and investigator assessments of cat neurological status, musculature, and hair coat quality improved. Owner evaluations of both cat and owner quality of life were favorable. The fructosamine half-life in diabetic cats was found to be 6.8 days. Commonly observed adverse events included emesis, diarrhea, anorexia, lethargy, and dehydration. Eight cats experienced serious adverse events, 3 of which led to death or euthanasia. The most important adverse event was euglycemic diabetic ketoacidosis, diagnosed in 3 cats and presumed present in a fourth., Conclusion and Clinical Importance: Bexagliflozin decreased hyperglycemia and observed clinical signs in cats newly diagnosed with DM. As a once-daily PO medication, bexagliflozin may simplify management of DM in cats., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Orogastric decompression is regularly recommended as a part of both medical and pre-surgical treatment for small intestinal obstruction in rabbits. However, guidelines as to when orogastric decompression is indicated are sparse., Methods: The medical records of 35 rabbits diagnosed with gastrointestinal obstruction over a 3-year period were examined. Differences in presentation, clinicopathological and radiographic examination findings, treatments and outcome were evaluated., Results: Approximately 49% of the cases evaluated were considered to have non-life-threatening disease, while 51% were considered to have life-threatening disease. The severity of gastric obstruction was correlated with the severity of hyperglycaemia (average 25.7 mmol/L; 463 mg/dl) and corresponding hyponatraemia (Na < 138 mmol/L; 138 mEq/L). These patients were treated with orogastric decompression and medical management only., Limitations: This is a retrospective study and there are inherent limitations involving the quality of the data and data collection. Additional studies should be completed that strive for larger sample sizes to compare the differences in outcome between surgical and medical management, as well as investigate the outcomes of rabbits with hyperglycaemia and hyponatraemia that did not have an orogastric decompression performed., Conclusions: Blood glucose and sodium concentrations, in combination with radiographic findings, may aid clinicians in determining if orogastric decompression is indicated to stabilise rabbits with small intestinal obstructive disorders., (© 2022 British Veterinary Association.)

Isolated reports of new-onset diabetes in patients with coronavirus disease 2019 (COVID-19) have led researchers to hypothesize that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human exocrine and endocrine pancreatic cells ex vivo and in vivo. However, existing research lacks experimental evidence indicating that SARS-CoV-2 can infect pancreatic tissue. Here, we found that cats infected with a high dose of SARS-CoV-2 exhibited hyperglycemia. We also detected SARS-CoV-2 RNA in pancreatic tissues of these cats, and immunohistochemical staining revealed the presence of SARS-CoV-2 nucleocapsid protein (NP) in islet cells. SARS-CoV-2 NP and spike proteins were primarily detected in glucagon-positive cells, and most glucagon-positive cells expressed ACE2. Additionally, immune protection experiments conducted on cats showed that blood glucose levels of immunized cats did not increase postchallenge. Our data indicate cat pancreas as a SARS-CoV-2 target and suggest that the infection of glucagon-positive cells could contribute to the metabolic dysregulation observed in SARS-CoV-2-infected cats., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the effects of IM and IV administration of alfaxalone alone and in combination with medetomidine, midazolam, or both on key stress-related neurohormonal and metabolic changes in isoflurane-anesthetized cats undergoing ovariohysterectomy or castration., Animals: 72 client-owned mixed-breed cats undergoing ovariohysterectomy or castration between October 4, 2018, and January 10, 2020., Procedures: For each type of surgery, cats were assigned to 1 of 6 premedication protocols groups, with 6 cats/group: physiologic saline (0.9% NaCl) solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IV); physiologic saline solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IM); medetomidine (50 μg/kg, IM) and alfaxalone (5 mg/kg, IV); medetomidine (50 μg/kg, IM) and alfaxalone (5 mg/kg, IM); midazolam (0.5 mg/kg, IM), medetomidine (50 μg/kg, IM), and alfaxalone (5 mg/kg, IV); or midazolam (0.5 mg/kg, IM), medetomidine (50 μg/kg, IM), and alfaxalone (5 mg/kg, IM). Venous blood was taken before pretreatment, pre- and postoperatively during anesthesia with isoflurane and oxygen, and during early and complete recovery., Results: Compared with baseline concentrations, plasma adrenaline and noradrenaline concentrations decreased during anesthesia in cats premedicated with alfaxalone alone and in combination with medetomidine. The combination of medetomidine, midazolam, and alfaxalone prevented an excessive increase in catecholamines during anesthesia and surgery in cats. Postoperative plasma cortisol concentration after ovariohysterectomy was lower for cats premedicated with the combination of medetomidine and alfaxalone or the combination of medetomidine, midazolam, and alfaxalone, compared with cats premedicated with alfaxalone alone. Cats treated with combinations that included medetomidine and midazolam had hyperglycemia during anesthesia. Cats treated with medetomidine or medetomidine and midazolam in combination with alfaxalone, compared with alfaxalone alone, had lower concentrations of nonesterified fatty acids during anesthesia. Behavioral recovery scores were lower (better) for cats that received medetomidine in addition to alfaxalone, compared with alfaxalone alone., Clinical Relevance: Results indicated that pretreatments with medetomidine and alfaxalone or with medetomidine, midazolam, and alfaxalone were useful for preventing stress-related hormonal and metabolic responses, other than hyperglycemia, during isoflurane anesthesia and surgery in cats.

Background: No previous studies have quantified tear glucose (TG) levels in dogs or compared changes in TG and blood glucose (BG) concentrations., Objective: To quantify TG concentration and evaluate its correlation with BG level in dogs., Methods: Twenty repetitive tests were performed in alternate eyes of four dogs, with a minimum washout period of 1 week. Tears and blood were collected at 30-min intervals with successive glucose injections (1 g/kg) every 30 min. Cross-correlations of BG and TG levels were assessed. The delay and association between TG and corresponding BG levels were analysed for each dog; samples were collected at 5-min intervals. The tears were collected using microcapillary tubes. Collected tears and blood were analysed for glucose concentration using a colorimetric assay and commercially available glucometer, respectively., Results: The average baseline BG and TG levels were 4.76 ± 0.58 and 0.39 ± 0.04 mmol/L, respectively. Even with highly fluctuating BG levels, a significant cross-correlation coefficient (r = 0.86, p < 0.05) was observed between changes of BG and TG levels. The delay time between BG and TG levels was 10 min. On average, BG levels were 16.34 times higher than TG levels. There was strong correlation between BG and TG levels (r s  = 0.80, p < 0.01). Significant differences in TG concentrations between normoglycaemia, mild hyperglycaemia, and severe hyperglycaemia were found (p < 0.05)., Conclusions: Canine TG concentrations have not been quantified previously. Our findings suggest preliminary data for future research on TG levels in dogs and show TG measurement could be used to screen for diabetes mellitus in dogs., (© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Hyperglycemia and eosinopenia are well-known characteristics of hypercortisolism (HC) in humans, however, their association in dogs with HC has rarely been reported. This study aimed to evaluate the association between eosinophils and serum fasting glucose concentration in dogs with HC. Forty-seven dogs with HC and 43 dogs with non-adrenal illness were included. In this retrospective cohort study, the complete blood count, blood chemistry profile, and pre- and post-adrenocorticotropic hormone (ACTH) cortisol concentrations were analyzed. Significant differences were found in neutrophil, monocyte, eosinophil, and platelet counts; eosinophil percentage; neutrophil-to-lymphocyte ratio; aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase activities (P < 0.05) between the groups. In dogs with HC, the eosinophil percentage was inversely correlated with fasting blood glucose (r = -0.3515, P = 0.0154) and post-ACTH cortisol concentrations (r = -0.6509, P < 0.0001). The neutrophil-to-lymphocyte ratio was inversely correlated with the eosinophil percentage (r = -0.4573, P = 0.0012) and count (r = -0.3688, P = 0.0108), but positively correlated with the fasting blood glucose level (r = 0.3888, P = 0.0069). Such correlations were not identified in dogs with non-adrenal illness. A multivariate analysis showed that only eosinophil percentage was associated with the presence of hyperglycemia in dogs with HC (odds ratio = 2.100, 95% confidence interval = 1.051-4.199, P = 0.0360). Therefore, eosinopenia induced by excess cortisol might be associated with altered glucose metabolism in dogs with HC. A better understanding of this correlation could be valuable to predict and prevent the complications of HC., (Copyright © 2022. Published by Elsevier Inc.)

Transcriptional co-activator with PDZ-binding motif (TAZ) is a key mediator of the Hippo signaling pathway and regulates structural and functional homeostasis in various tissues. TAZ activation is associated with the development of pancreatic cancer in humans, but it is unclear whether TAZ directly affects the structure and function of the pancreas. So we sought to identify the TAZ function in the normal pancreas. TAZ defect caused structural changes in the pancreas, particularly islet cell shrinkage and decreased insulin production and β-cell markers expression, leading to hyperglycemia. Interestingly, TAZ physically interacted with the pancreatic and duodenal homeobox 1 (PDX1), a key insulin transcription factor, through the N-terminal domain of TAZ and the homeodomain of PDX1. TAZ deficiency decreased the DNA-binding and transcriptional activity of PDX1, whereas TAZ overexpression promoted PDX1 activity and increased insulin production even in a low glucose environment. Indeed, high glucose increased insulin production by turning off the Hippo pathway and inducing TAZ activation in pancreatic β-cells. Ectopic TAZ overexpression along with PDX1 activation was sufficient to produce insulin in non-β-cells. TAZ deficiency impaired the mesenchymal stem cell differentiation into insulin-producing cells (IPCs), whereas TAZ recovery restored normal IPCs differentiation. Compared to WT control, body weight increased in TAZ-deficient mice with age and even more with a high-fat diet (HFD). TAZ deficiency significantly exacerbated HFD-induced glucose intolerance and insulin resistance. Therefore, TAZ deficiency impaired pancreatic insulin production, causing hyperglycemia and exacerbating HFD-induced insulin resistance, indicating that TAZ may have a beneficial effect in treating insulin deficiency in diabetes., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: To determine the prevalence of stress hyperglycaemia in sick cats, and to investigate the association of stress hyperglycaemia with systemic inflammatory response syndrome and outcome., Materials and Methods: Medical records (2004 to 2013) from sick cats admitted to the Medicine Unit of a Veterinary Teaching Hospital were retrospectively reviewed. Cases were enrolled if a serum glucose measurement and a complete medical record were available. Cats that were healthy, hypoglycaemic, diabetic, sedated or had a previous administration of drugs (apart from vaccination and deworming) were excluded., Results: The study included 647 cats; stress hyperglycaemia (serum glucose >8.3 mmol/L) was found in 194 (30%) cats, while 453 (70%) cats were normoglycaemic. The prevalence of systemic inflammatory response syndrome was significantly higher in cats with stress hyperglycaemia (25/174, 14.4%) compared to normoglycaemic cats (26/399, 6.5%). Significantly, more cats with stress hyperglycaemia were hospitalised [97/194 (50.0%)] compared to normoglycaemic cats [171/453 (37.7%)]. However, the median duration of hospitalisation was not significantly different [4 (1 to 26) days and 4 (1 to 24) days, respectively]. The prevalence of cats with negative outcome was not significantly different between the two groups (cats with stress hyperglycaemia: 37.1%, normoglycaemic cats: 33.9%). Nonetheless, when modelling of outcome prediction included breed, age, stress hyperglycaemia and disease category as factors, cats with stress hyperglycaemia had 2.8 times the odds to have a negative outcome (95% confidence interval: 1.3 to 6.4)., Clinical Significance: Based on the cut-off employed in this study, Stress hyperglycaemia, as defined by the cut-off is common in sick cats. Stress hyperglycaemia is associated with systemic inflammatory response syndrome development and seem to be a negative prognostic indicator., (© 2021 British Small Animal Veterinary Association.)

Theileriosis can be manifested in appreciably variable clinical forms among domestic ruminants and may often become life-threatening. The present report narrates, the quick remarkable clinical recovery of a lactating goat infected with Theileria spp., exhibiting acute insulin-responsive hyperglycemia and hypocalcemia, by providing intensive therapy. A four year old doe was presented with the complaint of acute manifestation of weakness, ventroflexion of neck with flaccid muscles, recumbency, hypersalivation, severe abdominal breathing, anorexia and polyuria since last eighteen hours. The animal kidded three kids one month before, out of which one was mummified. Clinical examination revealed severe depression, dehydration, dyspnoea, congested mucous membrane, sluggish rumen motility and reduced pupillary light reflex. Laboratory investigation revealed severe granulocytopenia, thrombocytopenia, hypocalcemia, hyperglycemia and Theileria spp. infection. The animal showed significant improvement within a few minutes of initiating the evidence-based stabilization therapy to correct hydration status, cellular glucose uptake, calcium levels and Theileria spp. infection. This case indicates the significance of investigating the metabolic status of animals suffering from theileriosis for achieving better clinical responses. Also, future studies may focus on the endocrinological perspectives of metabolic impact of Theileria spp. infection in goats., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Diabetes is characterized by high blood glucose level termed hyperglycemia affecting skeletal muscle structure and function by an unclear molecular mechanism. This study aimed to investigate the effect and underlying mechanism(s) of hyperglycemia on skeletal muscle both in vitro and in vivo. Treatment with hyperglycemic condition (25 mM) for 48 h significantly inhibited C2C12 myoblast proliferation detected by MTT assay whilst flow cytometry revealed an interruption of the cell cycle at subG1 and G2/M phases. An exposure to hyperglycemic condition significantly decreased the myosin heavy chain (MHC) protein expression in the differentiated myotube and tibialis anterior (TA) muscle of Wistar rats. In addition, the muscle cross-section area (MCA) of TA muscle in diabetic rats were significantly decreased compared to the non-diabetic control. Western blotting analysis of C2C12 myoblasts and differentiated myotubes revealed the increased expressions of cleaved-caspase-9 and cleaved-caspase-3, but not cleaved-caspase-8. Of note, these caspases in the TA muscles were not changed under hyperglycemic condition. Quantitative real-time polymerase chain reaction (qRT-PCR) of the hyperglycemic myoblasts and TA muscles revealed modulation of the gene expression of sirtuins (SIRTs). In C2C12 myoblasts, the expressions of SIRT1, SIRT2 and SIRT4 were upregulated whilst SIRT7 was downregulated. Meanwhile, the expressions of SIRT1, SIRT2 in TA muscles were upregulated whilst SIRT4 was downregulated. Taken together, this study showed that hyperglycemia induced cell cycle arrest and apoptosis in myoblasts, and protein degradation and atrophy in skeletal muscle most likely via modulation of SIRTs gene expression., (Copyright© by the Polish Academy of Sciences.)

Objective: To describe the clinical course and novel biochemical findings in 3 dogs with amitraz toxicosis., Case Series Summary: Three Labrador Retrievers developed acute onset obtundation to stupor after being in a rice field. On admittance to the hospital, they all displayed bradycardia, hyperglycemia, hyperlactatemia, respiratory acidosis, and metabolic alkalosis. All clinical signs resolved in 18-48 hours with supportive care. One dog represented with similar clinical signs and biochemical abnormalities 3 days after discharge following spending time in a different rice field owned by the same owner. Toxicological analysis of serum from all 3 dogs and vomitus from 1 dog returned positive for amitraz and one of its metabolites., New or Unique Information Provided: This is the first case series of dogs with confirmed amitraz toxicosis following an environmental exposure. Novel biochemical findings of hyperlactatemia, respiratory acidosis, and metabolic alkalosis were documented in all 3 dogs. Clinicians should be concerned for amitraz toxicosis when presented with an animal with the constellation of signs including decreased mental status, bradycardia, and hyperglycemia, particularly if relevant acid-base abnormalities are also detected., (© Veterinary Emergency and Critical Care Society 2021.)

Objectives: To determine whether basal-bolus administration of glargine insulin is a safe and effective alternative treatment compared to the standard continuous rate infusion (CRI) protocol., Design: Prospective randomized clinical trial., Setting: University teaching hospital., Animals: Twenty cats diagnosed with diabetic ketoacidosis (DKA)., Interventions: The cats were block-randomized to either a CRI protocol using regular insulin (CRI-group; n = 10) or a basal-bolus SC and IM glargine protocol (glargine-group, n = 10). Baseline blood gases, electrolytes, glucose, and β-hydroxybutyrate (β-OHB) concentrations were measured at the time of admission and later at predefined intervals until reaching the primary endpoint of the study, defined as a β-hydroxybutyrate concentration < 2.55 mmol/L., Measurements and Main Results: The main outcome measure was time (h) to resolution of ketonemia. Secondary outcome measures were time until first improvement of hyperglycemia and ketonemia, decrease of glucose to ≤13.9 mmol/L (250 mg/dL), resolution of acidosis, consumption of first meal, and discharge from hospital. Additionally, occurrence of treatment-associated adverse events and death were compared. Seventeen cats (85%) survived to discharge, with no difference in survival between groups (P = 1.0). Median times to β-OHB < 2.55 mmol/L were 42 (CRI-group) and 30 (glargine-group) hours, respectively (P = 0.114). Median times to first improvement of hyperglycemia (glargine-group: 2 h; CRI-group: 6 h; P = 0.018) and until discharge from hospital (glargine-group: 140 h; CRI-group: 174 h; P = 0.033) were significantly shorter in the glargine-group. No significant differences were observed in any other parameter under investigation (P > 0.05)., Conclusions: Basal-bolus administration of glargine insulin appears to be an effective and safe alternative to the current standard CRI-protocol for the management of DKA in cats. The positive outcomes and simplicity make it a viable option for the treatment of feline DKA., (© 2021 The Authors. Journal of Veterinary Emergency and Critical Care published by Wiley Periodicals LLC on behalf of Veterinary Emergency and Critical Care Society.)

Background: Postprandial hyperglycemia (PPH) and circadian glucose concentration fluctuations recorded in the home environment of dogs with naturally occurring diabetes mellitus (DM) have not been reported., Objectives: To determine if a flash glucose monitoring system (FGMS; FreeStyle Libre) can detect PPH and circadian fluctuations in glucose concentrations in dogs with variably controlled DM., Animals: Fourteen client-owned dogs with DM., Methods: Prospective observational study. Interstitial glucose (IG) concentrations measured by the FGMS during a 13-day study period were analyzed., Results: A total of 17, 446 FGMS IG concentrations were analyzed. For all dogs analyzed together, median IG concentration measured within 30 (288 mg/dL), 60 (286 mg/dL), 90 (285 mg/dL), and 120 (285 mg/dL) minutes of meals was each significantly higher than the median IG concentration at all other times (260 mg/dL, 259 mg/dL, 258 mg/dL, and 257 mg/dL, respectively; range, 40-500 mg/dL; P < .001 for each). Median night-time IG concentration measured from all dogs on 3,547 samples recorded between 1:00 am and 6:00 am (268 mg/dL; range, 40-500 mg/dL) was significantly higher than median IG measured on 13, 899 samples at all other time points (259 mg/dL; range, 40-500 mg/dL; P < .001)., Conclusions and Clinical Importance: The FGMS can be used for future studies of PPH and circadian fluctuations of glucose concentrations in dogs with DM in their home environment., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Objectives: Prednisolone is a commonly used drug in cats and potential adverse effects include hyperglycaemia and diabetes mellitus. The aims of this study were to evaluate the frequency and investigate potential predisposing risk factors for the development of prednisolone-induced diabetes mellitus (PIDM) in cats., Methods: The electronic records of a tertiary referral centre were searched for cats receiving prednisolone at a starting dose of ⩾1.9 mg/kg/day, for >3 weeks and with follow-up data available for >3 months between January 2007 and July 2019. One hundred and forty-three cats were included in the study., Results: Of the 143 cats, 14 cats (9.7%) were diagnosed with PIDM. Twelve out of 14 cats (85.7%) developed diabetes within 3 months of the initiation of therapy., Conclusions and Relevance: Cats requiring high-dose prednisolone therapy should be closely monitored over the first 3 months of therapy for the development of PIDM.

Objective: To describe the clinical features, clinicopathological features, treatment, and outcome of dogs presented for albuterol exposure., Design: Retrospective case series from January 2007 to December 2017., Setting: Tertiary veterinary facility., Animals: Thirty-six client-owned dogs presenting for known or suspected albuterol exposure secondary to chewing on albuterol metered-dose inhalers (MDIs)., Interventions: None., Measurements and Main Results: All dogs presented with clinical signs attributable to albuterol exposure. The most common physical examination abnormality was sinus tachycardia, noted in 34 of 36 (94%) dogs. Twenty-seven patients (75%) were admitted to the hospital for therapy, with a median length of hospitalization of 20.5 hours (16.75-24.5). Thirty-two of 36 dogs had serum electrolytes evaluated at admission, with 22 of 32 (69%) presenting with hypokalemia ([K+] < 3.62 mmol/L]). Hyperlactatemia ([lactate] > 2.80 mmol/L) was noted in 23 of 28 (82%) dogs. A negative correlation was found between serum lactate and potassium (r = -0.64, r 2  = 0.40, P = 0.0003). Hyperglycemia ([glucose] > 6.44 mmol/L) was noted in 20 of 30 (67%) dogs. Beta antagonist therapy was utilized in 20 of 36 (56%) of dogs., Conclusions: Although uncommon, albuterol intoxication can lead to significant clinical and electrolyte abnormalities. Albuterol-induced hypokalemia and associated tachyarrhythmias can be successfully managed, and albuterol intoxication has an excellent prognosis for survival to discharge. A minimum database should be evaluated in all dogs presenting for suspected albuterol exposure, with lactate and glucose monitored carefully in dogs with moderate or severe hypokalemia given the correlation found., (© Veterinary Emergency and Critical Care Society 2020.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Relative to other vertebrates, birds have unusually high blood glucose levels. In humans, the hyperglycemia observed in birds would be associated with diabetes mellitus and the non-enzymatic glycation of proteins, which leads to the accumulation of advanced glycation products and to a plethora of microvascular pathologies. How do birds avoid the negative effects of hyperglycemia? Anthony-Regnitz et al. (J Mol Evol 88: 653-661, 2020) discovered that birds might have evolved glycation-resistant proteins. Serum albumin is an important multifunctional protein susceptible to glycation. Anthony-Regnitz et al. (J Mol Evol 88: 653-661, 2020) found that chicken albumin is resistant to glycation relative to bovine serum albumin. Protein glycation takes place primarily in lysine residues, which are less abundant in chicken than in bovine serum albumin. A multispecies comparison of serum albumin sequences revealed lower numbers of lysine residues in birds than in mammals. Benign hyperglycemia is a shared derived trait of birds and glycation resistance mechanisms appear to have accompanied its evolution. The evolution of benign hyperglycemia in birds coincided with a genomic upheaval that included the loss of important genes, including the one that codes for GLUT4, the transporter responsible for insulin-dependent glucose transport in other vertebrates' insulin-sensitive cells. This loss seems to have resulted in the remodeling of the insulin-signaling pathway in bird tissues. Avian hyperglycemia has been considered a mystery for a long time. Although we remain ignorant of its origins and its repercussions for the physiology of birds, the discovery of resistance to glycation in bird serum albumin offers a path forward to solve this mystery.

Portunus pelagicus is exposed to different kinds of microorganisms leading to high metabolic stress that affects its life. The present study evaluates the activity of Phenoloxidase (PO), which is an enzyme that is actively involved in the activation of the immune defense system and hyperglycemia in P. pelagicus challenged with Escherichia coli and Vibrio harveyi injections. The results revealed a major impact of microbial injection on PO activity and significant variations in hemolymph glucose and CHH levels. Reduction of glucose level was observed after 24 h microbial incubation (275.26 ± 28.85 and 175.23 ± 21.70 μg/ml in V. harveyi and E. coli injected crabs, respectively). An elevated level of CHH (13.54 ± 0.55 fmol/ml) was observed in V. harveyi-injected crabs, and increased PO activity was recorded in E. coli-injected crabs. The results of the present study indicate that microbial stress leads to the activation of the defense system and hyperglycemia in P. pelagicus., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To determine the prevalence of glucose abnormalities in nondiabetic dogs presenting to a veterinary emergency room (ER) and their association with underlying disease processes, previous glucocorticoid administration, and overall mortality., Design: Single-center, retrospective study from January 2013 to December 2014., Setting: University Teaching Hospital., Animals: A total of 660 dogs presenting to an ER with a blood glucose concentration measured within 6 hours of presentation., Interventions: None., Measurements and Main Results: Medical records from dogs with a blood glucose concentration measured within 6 hours of hospital admission were reviewed. Medications administered prior to blood sampling, the presence of shock, final clinical diagnosis, and survival were recorded. Hypoglycemia and hyperglycemia were defined as a blood glucose <4.4 mmol/L (80 mg/dL) and >6.7 mmol/L (120 mg/dL), respectively. Diabetic patients were removed from analysis. Hyperglycemia was found in 40.1% of dogs, whereas hypoglycemia was present in 9.0%. Hyperglycemia was most often associated with gastrointestinal disease, trauma, neoplasia, and respiratory disease. The most common diseases associated with hypoglycemia were sepsis, gastrointestinal disease, and neoplasia. Dogs in shock or with hyperlactatemia had higher blood glucose values than dogs with normal perfusion and plasma lactate concentrations (P = 0.016 and P < 0.0001, respectively). Mortality was higher in dogs with hyperglycemia (33.2%, P = 0.03) or hypoglycemia (44.6%, P = 0.0024) compared to those with normoglycemia (24.9%)., Conclusion: Dysglycemia in nondiabetic dogs evaluated in an ER was associated with a higher mortality rate than dogs in the same population with normoglycemia. Hyperglycemia in this population was common and may represent a stress response., (© Veterinary Emergency and Critical Care Society 2020.)

Background: Erythrocytes of diabetic cats have decreased superoxide dismutase activity, possibly indicative of oxidative stress., Hypothesis: Erythrocytes of diabetic cats undergo oxidative stress, which is caused by hyperglycemia and hyperlipidemia, and improves with treatment., Animals: Twenty-seven client-owned cats with diabetes mellitus, 11 matched healthy cats, and 21 purpose-bred healthy cats., Methods: Prospective study. Advanced oxidized protein products, carbonyls (protein oxidation by-products), and thiols (antioxidants) were quantified in erythrocyte membrane, thiobarbituric acid reactive substances (TBAR, lipid peroxidation by-products), and thiols in erythrocyte cytoplasm of all cats. Comparison were performed between diabetic and matched healthy cats, between diabetic cats achieving remission or not, and among purpose-bred cats after 10 days of hyperglycemia (n = 5) or hyperlipidemia (n = 6) versus controls treated with saline (n = 5) or untreated (n = 5)., Results: Compared with controls, erythrocytes of diabetic cats initially had higher median membrane carbonyls (4.6 nmol/mg total protein [range: 0.1-37.7] versus 0.7 [0.1-4.7], P < .001) and lower cytoplasmic TBAR (1.9 nmol/mg [0.5-2.4] versus 2.4 [1.4-3.5] P < .001), and thiols (419 nmol/mg [165-621] versus 633 [353-824], P < 0.001). After 12-16 weeks of treatment in diabetic cats, carbonyls decreased by 13% (P < .001), but remained higher (P < .001) and TBAR and thiols lower (P = .02, P < .001) than those in controls. No differences were observed between diabetic cats achieving remission or not, and among purpose-bred cats., Conclusions and Clinical Importance: Diabetes mellitus is associated with increased protein oxidation and reduced antioxidant defenses, which persist during treatment and remission, although mild improvement in protein oxidation occurs. Short-term hyperglycemia or hyperlipidemia does not cause oxidative stress. The reason for decreased TBAR remains unknown., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objective: To assess effects of basal-bolus insulin treatment (BBIT) with lispro and neutral protamine Hagedorn (NPH) insulins, compared with NPH insulin alone, on serum fructosamine concentration (SFC) and postprandial blood glucose concentration (BGC) in dogs with clinically well-controlled diabetes mellitus and postprandial hyperglycemia fed a high insoluble fiber-content diet., Animals: 6 client-owned dogs with diabetes mellitus., Procedures: Blood samples were collected for BGC and SFC measurement in hospitalized dogs just before feeding and routine SC NPH insulin administration (time 0); samples were collected for BGC measurement every 30 minutes for 2 hours, then every 2 hours for up to 10 additional hours. Postprandial hyperglycemia was identified when BGC 30 minutes after insulin administration exceeded BGC at time 0 or the 1-hour time point. For BBIT, owners were instructed to continue NPH insulin administration at the usual dosage at home (q 12 h, with feeding) and to administer lispro insulin (0.1 U/Kg, SC) separately at the time of NPH injections. Two weeks later, SFC and BGC measurements were repeated; results at the start and end of the study were compared statistically., Results: Median SFC was significantly higher at the start (400 μmol/L) than at the end (390 μmol/L) of the study. Median 1-hour (313 mg/dL) and 1.5-hour (239 mg/dL) BGC measurements at the start of the study were significantly higher than those at the end of the study (117 and 94 mg/dL, respectively)., Conclusions and Clinical Relevance: In this sample of dogs with well-controlled diabetes mellitus, addition of lispro insulin to an existing treatment regimen of NPH insulin and dietary management significantly decreased postprandial BGCs. Further study of BBIT for dogs with diabetes mellitus is warranted.

Point-of-care glucometry is used commonly in clinical and research settings; however, accuracy and precision of this method are concerns. The objectives of this study were to determine the accuracy of glucometry in adult horses and the precision of duplicate measurements. Blood samples were collected from 62 horses into one plain syringe, one EDTA tube and three fluoride oxalate (FO) tubes. Immediately after collection, glucose concentrations in whole blood were determined, in duplicate, by glucometry from the syringe (plain whole blood [WB] group), EDTA tube (EDTA group) and one FO tube (FO group). One FO sample was used to measure plasma glucose concentration by a laboratory chemistry analyser (LAB group) ≤1 h after collection. The third FO tube was used to measure plasma glucose concentration by glucometry after 3 h storage (FO3hr group). Adequate precision was present for all groups (coefficient of variation: 0.7-3.5%) except WB (5.5-9.4%). Between groups, correlations were significant (P < 0.05; except for WB-EDTA), varied with group comparison, and tended to be lowest for comparisons involving WB. Mean bias was lowest for WB-LAB and greatest for FO-LAB and FO3hr-LAB; however, the limits of agreement were ≥4.65 mmol/L for WB-LAB and ≤2.75 mmol/L for most other comparisons. For the glucometer used, performance was influenced by sample type: WB was unsuitable, while FO or EDTA samples resulted in adequate precision and accuracy, provided under-estimation of glucose concentrations is accounted for by using method-specific reference ranges. Glucometer performance and optimal sample type(s) should be determined prior to use in horses., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

A novel strategy for the isolation of anthocyanins was developed by a combination of high-speed countercurrent chromatography (HSCCC) and HPLC techniques. Using this strategy, a novel α-glucosidase inhibitor (pelargonidin-3-O-rutinoside, a natural anthocyanin) was isolated from strawberries. Structural determinants for inhibition of α-glucosidase by Pg3R and the SAR of natural anthocyanins were revealed in detail by enzymatic kinetics and molecular docking analysis.

Background: A short period of overfeeding can lead to severe hepatic steatosis in the goose, which is physiological, suggesting that geese, as a descendent of a migrating ancestor, may have evolutionally developed a unique mechanism that operates in contrast to the mechanism underlying pathological fatty liver in humans or other mammals. In this study, we report that suppression of miR29c and upregulation of its target genes in goose fatty liver vs. normal liver could be part of a unique mechanism that contributes to the regulation of energy homeostasis and cell growth., Results: Our data showed that miR29c expression was comprehensively inhibited in energy homeostasis-related tissues (the liver, fat and muscle) of overfed vs. normally fed geese, which is different from miR29c induction that occurs in tissues of the diabetic rat. To address the function of miR29c, three predicted target genes (i.e., Insig1, Sgk1 and Col3a1) that participate in energy homeostasis or cell growth were validated by a dual-fluorescence reporter system and other in vitro assays. Importantly, expression of Insig1, Sgk1 and Col3a1 was upregulated in goose fatty liver. In line with these observations, treatment of goose hepatocytes with high glucose or palmitate suppressed the expression of miR29c but induced the expression of the target genes, suggesting that hyperglycemia and hyperlipidemia, at least partially, contribute to the suppression of miR29c and induction of the target genes in goose fatty liver. In addition, pharmacological assays indicated that RFX1 was a transcription factor involved in the expression of miR29c., Conclusions: This study suggests that miR29c may play a role in the regulation of energy homeostasis and tissue growth via its target genes, contributing to the tolerance of the goose to severe hepatic steatosis.

In the present study, the hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂), a typical carnivorous fish, was chosen as a model to investigate the regulation of glycogen metabolism owning to its characteristic of glucose intolerance. The variation of plasma glucose concentration, glycogen content, and expressions of glycogen metabolism-related genes under acute hyperglycemia stress were measured. Following glucose administration, plasma glucose concentration increased immediately, and the glucose level remained elevated for at least 12 h. The prolonged glucose clearance and hyperglycemia revealed glucose intolerance of this fish species. Meanwhile, the glycogen content in both liver and muscle changed significantly during the clearance of plasma glucose. However, the peak value of hepatic glycogen (1 and 12 h post injection) appeared much earlier than muscle (3 and 24 h post injection). To investigate the regulation of glycogen metabolism from molecular aspect, the complete coding sequence (CDS) of glycogen synthase (GS) and glycogen phosphorylase (GP) in both liver and muscle types were obtained, encoding a polypeptide of 704, 711, 853, and 842 amino acid residues, respectively. The results of gene expression analysis revealed that the expression of liver type and muscle type GS was significantly higher than other time points at 12 and 24 h post glucose injection, respectively. Meanwhile, the highest expressions of GP in both liver and muscle types occurred at 24 h post glucose injection. The response of GS and GP to glucose load may account for the variation of glycogen content at the transcriptional level to some extent.

Background: Systemic inflammation is a cause of insulin dysregulation in many species, but the insulin and glucose dynamics in adult horses diagnosed with systemic inflammatory response syndrome (SIRS) are poorly documented., Hypothesis/objectives: In SIRS in horses, insulin and glucose dynamics will be altered and associated with survival., Animals: Adult horses diagnosed with SIRS admitted to a referral hospital., Methods: Prospective study enrolling horses diagnosed with SIRS in which serum insulin and glucose concentrations were measured. Horses were grouped by outcome (survival, hyperinsulinemia, and hyperglycemia) and compared with P < .05 considered significant., Results: Fifty-eight horses were included in the study and 36 (62%) survived. At admission, 21 horses (36%) were hyperinsulinemic and 44 horses (88%) were hyperglycemic, with survivors having significantly higher serum insulin and a significantly lower serum glucose concentration. Horses diagnosed with hyperinsulinemia at any time during hospitalization were 4 times more likely to survive whereas horses that were hyperglycemic at any time during hospitalization were 5 times less likely to survive. Serum glucose concentration and presence of hyperglycemia both were associated with severity of disease. Insulin/glucose ratio, reflecting insulin secretion, was significantly higher in survivors whereas glucose/insulin ratio, reflecting peripheral tissue insulin resistance, was significantly lower in nonsurvivors. Only in survivors was there a significant correlation between serum insulin and glucose concentrations., Conclusions and Clinical Importance: Hyperinsulinemia and hyperglycemia are common features of SIRS in horses, but those presenting with relative hypoinsulinemia and corresponding hyperglycemia suggestive of endocrine pancreatic dysfunction have a worse prognosis., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Organisms experience stressors, and the physiological response to these stressors is highly conserved. Acute stress activates both the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, increasing epinephrine, norepinephrine, and glucocorticoids, collectively promoting glucose mobilization. While this is well characterized in mammals, the hyperglycemic response to stress in avian and nonavian reptiles has received less attention. A number of factors, ranging from time of day to blood loss, are reported to influence the extent to which acute stress leads to hyperglycemia in birds. Here we characterized the glycemic response to acute handling stress in two species of free-living sparrows: white-throated sparrows (WTSPs: Zonotrichia albicollis) in St. Mary's County, Maryland, and white-crowned sparrows (WCSPs: Zonotrichia leucophrys) in Tioga Pass Meadow, California. We validated a novel technique for rapid field measurement of glucose using a human blood glucose meter, FreeStyle Lite. As expected, acute handling stress elevated blood glucose at both 15 and 30 min postcapture as compared to baseline for both WTSPs and WCSPs. In addition, handling for 30 min without bleeding had the same hyperglycemic effect as handling with serial bleeds in WCSPs. Finally, body condition that was measured as abdominal fat score predicted stress-induced blood glucose in WTSPs but not in WCSPs. Our results are consistent with the mammalian literature on acute stress and energy mobilization, and we introduce a new field technique for avian field biologists.

Supplementing conjugated linoleic acid (CLA) is supposed to spare glucose due to the milk fat-depressing effect of the trans-10, cis-12 CLA isomer, and allows repartitioning nutrients despite an energy deficiency in early lactation. However, there is still a lack of knowledge in terms of the dynamic pattern of the glucose turnover in transition dairy cows. We hypothesized that dairy cows supplemented with CLA have an altered rate of glucose turnover and insulin sensitivity during early lactation. We conducted three consecutive hyperglycaemic clamps (HGC) in weeks -2, +2 and +4 relative to parturition in Holstein cows supplemented daily either with 70 g of lipid-encapsulated CLA (6.8 g trans-10, cis-12 and 6.6 g of the cis-9, trans-11 CLA isomer; CLA; n = 11) or with 56 g of control fat (CON; n = 11). From week -3 up to week +4 relative to parturition, milk yield and dry matter intake (DMI) were recorded daily, while body weight (BW) and milk composition were obtained once weekly. Blood samples were taken once weekly and every 30 min during the HGC. Plasma was analysed for concentrations of glucose, fatty acids (FFA), beta-hydroxybutyrate (BHB), insulin, triglycerides and cholesterol. The CLA supplementation did not affect performance and metabolic parameters except for BHB and cholesterol. Furthermore, insulin concentrations and insulin sensitivity were affected by treatment. During the HGC in early lactation, insulin response was lower and decrease in FFA and BHB greater compared with the HGC in week -2 although glucose target concentration achieved during the steady-state period was similar for all three HGC. Our findings in terms of insulin and cholesterol suggest that body reserves are preserved through CLA feeding without restraining animal's performance. Furthermore, CLA effects on cholesterol and triglyceride concentrations indicated beneficial effects on hepatic lipid export contributing to an improved efficiency of prevailing metabolites in circulation., (© 2017 Blackwell Verlag GmbH.)

The glucose transporter family proteins play pivotal roles in glucose metabolism. In this study, we successfully cloned the orange spotted grouper (Epinephelus coioides) glucose transporter 1 (EcGlut1) gene (GenBank accession: JQ623903). The full-length EcGlut1 cDNA was 2126 bp with a 1476 bp ORF, a 437bp5'-UTR and 223bp3'-UTR. EcGlut1 is predicted to encode a 491 amino acid protein with a MW of 53.9 kDa, a pI of 8.66 and a Pfam domain. Bioinformatics analysis revealed that EcGlut1 was evolutionally conserved between fishes with 80-89 % amino acid identities. EcGlut1 was expressed predominantly in heart and liver and at lower levels in muscle, intestine, stomach and brain. We also investigated the effect of acute hyperglycemia stress on EcGlut1 expression. In glucose tolerance test, changes in EcGlut1 mRNA expression in response to glucose injection and glucose metabolism-related indictors were assessed at the same time. Glucose injection significantly suppressed EcGlut1 mRNA expression in liver at 12 h and in brain at 24 h postinjection (P < 0.05). EcGlut1 mRNA levels in heart were increased at 6 h (P < 0.05). Plasma glucose level increased significantly and reached its maximum at 3 h postinjection (P < 0.05). The spatiotemporal expression of EcGlut1 and glucose metabolism suggested that orange spotted grouper might rely on fat anabolism to reduce acute hyperglycemia stress and the delayed transcription of EcGlut1 gene might be one reason for glucose intolerance in E. coioides.

Objectives: Rebound hyperglycaemia (also termed Somogyi effect) is defined as hyperglycaemia caused by the release of counter-regulatory hormones in response to insulin-induced hypoglycaemia, and is widely believed to be common in diabetic cats. However, studies in human diabetic patients over the past quarter century have rejected the common occurrence of this phenomenon. Therefore, we evaluated the occurrence and prevalence of rebound hyperglycaemia in diabetic cats., Methods: In a retrospective study, 10,767 blood glucose curves of 55 cats treated with glargine using an intensive blood glucose regulation protocol with a median of five blood glucose measurements per day were evaluated for evidence of rebound hyperglycaemic events, defined in two different ways (with and without an insulin resistance component)., Results: While biochemical hypoglycaemia occurred frequently, blood glucose curves consistent with rebound hyperglycaemia with insulin resistance was confined to four single events in four different cats. In 14/55 cats (25%), a median of 1.5% (range 0.32-7.7%) of blood glucose curves were consistent with rebound hyperglycaemia without an insulin resistance component; this represented 0.42% of blood glucose curves in both affected and unaffected cats., Conclusions and Relevance: We conclude that despite the frequent occurrence of biochemical hypoglycaemia, rebound hyperglycaemia is rare in cats treated with glargine on a protocol aimed at tight glycaemic control. For glargine-treated cats, insulin dose should not be reduced when there is hyperglycaemia in the absence of biochemical or clinical evidence of hypoglycaemia., (© ISFM and AAFP 2015.)

Acarbose (AC) and Sitagliptin (STGP) are oral hypoglycemic agents currently used either alone or in conjunction with human diabetic (Type 2) patients. AC has been used with diabetic cats, but not STGP thus far. Therefore, the objective of this study was to determine the potential use of AC or STGP alone and in combination for diabetic cats, by observing their effect on short-term post-prandial serum glucose, insulin, and incretin hormone (active glucagon-like peptide-1 (GLP-1) and total glucose dependent insulinotropic polypeptide (GIP)) concentrations in five healthy cats, following ingestion of a meal with maltose. All treatments tended (p<0.10; 5-7.5% reduction) to reduce postprandial glucose area under the curve (AUC), with an accompanying significant reduction (p<0.05, 35-45%) in postprandial insulin AUC as compared to no treatment. Meanwhile, a significant increase (p<0.05) in postprandial active GLP-1 AUC was observed with STGP (100% higher) and combined treatment (130% greater), as compared to either AC or no treatment. Lastly, a significant reduction (p<0.05) in postprandial total GIP AUC was observed with STGP (21% reduction) and combined treatment (7% reduction) as compared to control. Overall, AC, STGP, or combined treatment can significantly induce positive post-prandial changes to insulin and incretin hormone levels of healthy cats. Increasing active GLP-1 and reducing postprandial hyperglycemia appear to be the principal mechanisms of combined treatment. Considering the different, but complementary mechanisms of action by which AC and STGP induce lower glucose and insulin levels, combination therapy with both these agents offers great potential for treating diabetic cats in the future., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Monitoring of an animal's blood glucose concentration is critical for diagnostic and therapeutic decisions. Over the past few decades, portable blood glucose meters (PBGMs) have been used to monitor blood glucose concentrations in animals. Recently, new and improved PBGMs have been made available on the market., Objective: The purpose of this study was to evaluate four PBGMs for use in dogs and cats., Animals and Methods: A total of 155 venous blood samples of dogs and 85 venous blood samples of cats were tested using four PBGMs. Control solutions from manufacturers were used to determine the precision of each meter. The coefficient of variation was calculated to determine precision during a set of replicates. Pearson's correlation analysis, Passing-Bablok regression, and Bland-Altman analysis were used to determine the accuracy of four PBGMs against the hexokinase reference method. Error grid analysis was used to evaluate clinical relevance., Results: All PBGMs, except CERA-PET®, were clinically acceptable for monitoring blood glucose concentrations; AlphaTrak® and VetMate® appeared to be the most accurate ones, demonstrating that to use PBGMs for glucose monitoring, it is important to understand the strengths or limitations of each meter. The difference in results between the PBGMs and the reference method increased at high glucose concentration ranges, which were also affected by the hematocrit., Conclusions: Although readings of the PBGMs and the reference method varied across glycemic ranges (low, normal, and high glucose concentrations), most PBGMs were clinically acceptable for monitoring blood glucose concentrations in dogs and cats.

Nutrient levels dictate the activity of O-linked N-acetylglucosamine transferase (OGT) to regulate O-GlcNAcylation, a post-translational modification mechanism to "fine-tune" intracellular signaling and metabolic status. However, the requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function is unclear. Here, we reveal that mice lacking β cell OGT (βOGT-KO) develop diabetes and β cell failure. βOGT-KO mice demonstrated increased ER stress and distended ER architecture, and these changes ultimately caused the loss of β cell mass due to ER-stress-induced apoptosis and decreased proliferation. Akt1/2 signaling was also dampened in βOGT-KO islets. The mechanistic role of these processes was demonstrated by rescuing the phenotype of βOGT-KO mice with concomitant Chop gene deletion or genetic reconstitution of Akt2. These findings identify OGT as a regulator of β cell mass and function and provide a direct link between O-GlcNAcylation and β cell survival by regulation of ER stress responses and modulation of Akt1/2 signaling., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Adults born preterm are at increased risk of impaired glucose tolerance and diabetes. Late gestation fetuses exposed to high blood glucose concentration also are at increased risk of impaired glucose tolerance as adults. Preterm babies commonly become hyperglycemic and are thus exposed to high blood glucose concentration at an equivalent stage of pancreatic maturation. It is not known whether preterm birth itself, or complications of prematurity, such as hyperglycemia, alter later pancreatic function. To distinguish these, we made singleton preterm lambs hyperglycemic (HYPER) for 12 days after birth with a dextrose infusion and compared them with vehicle-treated preterm and term controls and with HYPER lambs made normoglycemic with an insulin infusion. Preterm birth reduced β-cell mass, apparent by 4 weeks after term and persisting to adulthood (12 mo), and was associated with reduced insulin secretion at 4 months (juvenile) and reduced insulin mRNA expression in adulthood. Hyperglycemia in preterm lambs further down-regulated key pancreatic gene expression in adulthood. These findings indicate that reduced β-cell mass after preterm birth may be an important factor in increased risk of diabetes after preterm birth and may be exacerbated by postnatal hyperglycemia.

The pathophysiology of canine diabetes remains poorly understood, in part due to enigmatic clinical features and the lack of detailed histopathology studies. Canine diabetes, similar to human type 1 diabetes, is frequently associated with diabetic ketoacidosis at onset or after insulin omission. However, notable differences exist. Whereas human type 1 diabetes often occurs in children, canine diabetes is typically described in middle age to elderly dogs. Many competing theories have been proposed regarding the underlying cause of canine diabetes, from pancreatic atrophy to chronic pancreatitis to autoimmune mediated β-cell destruction. It remains unclear to what extent β-cell loss contributes to canine diabetes, as precise quantifications of islet morphometry have not been performed. We used high-throughput microscopy and automated image processing to characterize islet histology in a large collection of pancreata of diabetic dogs. Diabetic pancreata displayed a profound reduction in β-cells and islet endocrine cells. Unlike humans, canine non-diabetic islets are largely comprised of β-cells. Very few β-cells remained in islets of diabetic dogs, even in pancreata from new onset cases. Similarly, total islet endocrine cell number was sharply reduced in diabetic dogs. No compensatory proliferation or lymphocyte infiltration was detected. The majority of pancreata had no evidence of pancreatitis. Thus, canine diabetes is associated with extreme β-cell deficiency in both new and longstanding disease. The β-cell predominant composition of canine islets and the near-total absence of β-cells in new onset elderly diabetic dogs strongly implies that similar to human type 1 diabetes, β-cell loss underlies the pathophysiology of canine diabetes.

The present study aimed to assess hyperglycaemia with special reference to diabetes mellitus in cattle by clinico-biochemical estimation and evaluation of oxidative stress indices. A total of 256 cattle exhibiting weakness, poor body condition and reduced milk yield in lactating cattle were included in the study. These animals were screened with blood glucose level, urine glucose and ketone bodies. Out of these, 32 (12.5%) cattle showed hyperglycaemia and glycosuria, of which 25% exhibited ketonuria. Diabetes was confirmed in five cattle by estimation of fasting blood glucose, glycated haemoglobin, serum fructosamine, intravenous glucose tolerance test and insulin level. This reports first confirmation of diabetes in cattle in India. All these five animals revealed low level of serum insulin suggestive of insulin-dependent diabetes mellitus in cattle. The level of aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT) was found to be increased in diabetic cattle. Oxidant/antioxidant balance was assessed in hyperglycaemic cattle and five age-matched Holstein Friesian (HF) cross-bred healthy control animals. Diabetic cattle revealed significantly higher (P ≤ 0.01) levels of erythrocytic lipid peroxides in comparison with other hyperglycaemic cattle and healthy controls whereas the level of superoxide dismutase (SOD) and catalase was found to be significantly lower in diabetes-affected animals in comparison to healthy controls. Reduced glutathione did not show a significant difference between hyperglycaemic and control groups. It is concluded from the present study that oxidative stress associated with diabetes in cattle is obvious compared with other hyperglycaemic cattle.

Prevalence of hyponatraemia has not been extensively studied in pet rabbits, and the reference data for calculated plasma tonicity and osmolarity are not available. This retrospective clinical study reports the prevalence of hyponatraemia, hyposmolarity and hypotonicity in ill pet rabbits (n=356). The relationship between sodium and glucose levels was studied (n=134). Mortality rates within seven days associated with different sodium levels were calculated in ill rabbits (n=322). Venous blood samples in lithium heparin were processed using iStat EC8+ cartridges. The 95% RI for plasma sodium, calculated osmolarity and tonicity from 51 healthy pet rabbits were 136-147 mEq/l, 284-312 mOsm/l and 278-302 mOsm/l, respectively. The prevalence of hyponatraemia, hypotonicity and hyposmolarity was 39.0 per cent, 28.7 per cent and 18.0 per cent, respectively. Pseudohyponatraemia was present in 28.1 per cent and true hyponatraemia was present in 71.9 per cent of the cases of hyponatraemia. Sodium levels less than 129 mEq/l were found to be associated with 2.3-fold increase in mortality risk. Plasmatic sodium levels in rabbits decrease in conditions of hyperglycaemia in a similar manner as it occurs in human beings. As hyperglycaemia is quite a common condition in rabbits, simultaneous measurement of plasmatic sodium along with glucose in ill rabbits is advised. Hyponatraemia is a common condition in ill rabbits and, depending on its type (true hyponatraemia or pseudohyponatraemia), of varying clinical relevance. Calculation of plasmatic tonicity is necessary for differentiation of types of hyponatraemia., (British Veterinary Association.)

Background: Portable blood glucose meters (PBGMs) are useful for serial measurements of blood glucose and creation of blood glucose curves in veterinary practice. However, it is necessary to validate PBGMs designed for people for veterinary use., Objectives: Our objective was to evaluate the accuracy of 2 PBGMs designed for people for use in dogs and cats., Methods: The blood glucose levels were determined in blood samples collected from 69 dogs and 26 cats admitted to the Kagoshima University Veterinary Teaching Hospital, using a MEDISAFE [PBGM-T] and an Antsense III [PBGM-H], and a FUJI DRI-CHEM 7000V as reference method. The correlations and agreements among the results were statistically analyzed., Results: Simple regression analyses revealed a high correlation between values from both PBGMs and the reference method in both dogs and cats. However, Passing-Bablok regression and Bland-Altman analyses revealed that the data from both PBGMs did not show statistical agreement with the reference values. Concordance correlated coefficients were moderate for the PBGM-T and almost perfect for the PBGM-H for canine samples, and were poor for the PBGM-T and substantial for the PBGM-H for feline samples. Hematocrit values significantly affected the results of the PBGM-T, but not the PBGM-H. Error grid analyses revealed that all measurements from both PBGMs would lead to acceptable treatment decisions., Conclusions: Our findings suggest that both PBGMs, especially the PBGM-H, would be clinically useful in small animal practice, although there was a bias between each PBGM and the reference method., (© 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.)

The pig, which shares several similarities with humans, is increasingly used for biomedical research, particularly in nutrition and neurosciences. Recent studies in minipigs have shown that a deleterious nutritional environment (e.g. a high-fat and high-sugar diet) induces obesity which, as in humans, is associated with increased adiposity, insulin resistance, modified eating behaviour, and altered gastric function and intestinal sensitivity. These changes are accompanied by differences in the activation matrices and metabolic activity of several brain areas. Using this animal model, we have revisited the concept of dual hedonic and homeostatic control of food intake. We have thus developed a minimally invasive and potentially reversible surgical approach to the control of food intake, as an alternative to bariatric surgery, based on chronic vagal stimulation at the abdominal level.