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Objectives: The aim of this study was to describe signalment, clinicopathological findings, management practices and the occurrence of comorbidities in feline diabetes mellitus (DM) in Germany., Methods: This was a cross-sectional study using questionnaires and laboratory submissions to a commercial laboratory, Antech Lab Germany, between May 2021 and July 2022. Inclusion criteria were diagnosis of DM by the attending veterinarian and submission of a completed questionnaire besides blood samples. Laboratory testing included haematology, serum biochemistry, concentration of total thyroxine (TT4), insulin-like growth factor 1 (IGF-1), cobalamin (COB), fructosamine, b-hydroxybutyrate and DGGR (1,2- O -dilauryl- rac -glycero-3-glutaric acid-[6'-methylresorufin] ester) lipase activity. Data are presented as the median (range) and analysed by non-parametric tests. P  <0.05 was considered statistically significant., Results: The median (range) age of the 144 diabetic cats at diagnosis was 11 years (0.9-18.7), 66.4% were male, 84.6% were domestic shorthair, 50.4% were currently overweight and 61.5% were previously overweight (body condition score >5/9). Most cats were treated with insulin (84%), most commonly protamine zinc insulin (57.5%). Blood glucose curves or continuous glucose monitoring alone or in combination with other methods were performed to adjust insulin therapy in 70.6% of cats. Based on questionnaires, 78.6% were poorly controlled and 21.4% were well controlled. Increased TT4 occurred in 3/139 and hyperthyroidism was known in 5/139 cats (frequency of known/suspected hyperthyroidism: 5.8% [n = 8/139]); 17.5% (n = 17/97) had increased IGF-1 (IGF-1 >746 ng/ml, cut-off for hypersomatotropism with the chemiluminescence assay used in this study); 24.5% (n = 34/139) had COB <295.2 pmol/l and 54.2% (n = 78/144) had increased DGGR. Cats with IGF-1 >746 ng/ml were receiving a higher insulin dose than cats with IGF-1 ≤746 ng/ml (median 1.63 vs 0.86 U/kg/day, P  = 0.018)., Conclusion and Relevance: Increased DGGR and increased IGF-1 indicating hypersomatotropism are common in diabetic cats and should be tested for. Almost one-quarter of diabetic cats might require COB supplementation., Competing Interests: Conflict of interestThe laboratory data used in this study were provided by Antech Lab Germany. Judith Langenstein is an employee of Antech Lab Germany GmbH.

The FreeStyle Libre (Abbott) is a human continuous glucose monitor sensor that has been used to monitor glucose concentrations in dogs and cats with diabetes. This sensor and other similar continuous glucose monitoring sensors are increasingly popular in veterinary medicine, specifically for management of diabetes mellitus. The sensor decreases veterinary visits and reduces the stress (and expense) of multiple blood sample collections needed to produce glucose curves. However, there are no established guidelines for sensor placement in small animals and, to date, no substantial complications have been reported. A 15-year-old neutered male cairn terrier dog with a history of diabetes and suspected inflammatory bowel disease with progressive weight loss was presented with acute dyspnea <24 h after placement of a FreeStyle Libre 2 sensor. He was diagnosed with a continuous pneumothorax suspected secondary to a FreeStyle Libre 2 sensor placement. Multiple thoracocenteses were completed but further treatment was declined, and the dog was euthanized. Key clinical message: This case highlights the importance of sensor placement selection, especially in small animals, and documents the first reported pneumothorax suspected to be secondary to a continuous glucose monitor placement. This specific complication has apparently not been documented previously., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Hypoattenuation of the liver, consistent with hepatic steatosis or lipidosis, has been reported in veterinary patients. In people, measuring CT hepatic attenuation is diagnostic for hepatic steatosis, and hypoattenuation of the liver is defined as absolute if less than 40 HU or relative if the liver is 10 HU less than the spleen. The purpose of this study is to describe hepatic parenchymal attenuation in dogs with diabetes mellitus with or without diabetic ketosis (DK) or diabetic ketoacidosis (DKA), using the above categorization for absolute and relative hypoattenuation, as with humans. We hypothesized dogs with DK or DKA were more likely to have hypoattenuating livers. Twenty-seven diabetic dogs were included; fifteen were categorized in Group 1 as without DK or DKA, six in Group 2 as DK, and six in Group 3 as DKA. In Group 3, four of six dogs had absolute and relative hypoattenuating livers. Three of these were visually hypoattenuating to the vasculature, with one having negative attenuation and a histopathologic diagnosis of severe hepatic lipidosis. In Group 2, four of six dogs had relative hypoattenuating livers. In Group 1, only one of 15 dogs had a relatively hypoattenuating liver. Groups 2 and 3 had significantly lower absolute liver attenuation than Group 1. Presumed hepatic steatosis was present on CT and was more common with DK or DKA. These findings may help provide hepatic sampling recommendations and alter patient prognosis. Further research is needed to establish absolute and relative liver attenuation in dogs with correlation to histopathology and patient outcome., (© 2024 The Author(s). Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Background: Obesity is a risk factor for diabetes mellitus, which commonly coexists with pancreatitis in cats. However, obesity has not previously been associated with pancreatitis in cats., Objectives: To evaluate factors affecting serum concentrations of pancreatic lipase immunoreactivity (fPLI), trypsin-like immunoreactivity (fTLI), cobalamin and folate in clinically healthy lean, overweight and obese, or diabetic cats., Animals: Seventy-nine client-owned cats (27 healthy lean [LN, BCS 4-5/9], 30 healthy overweight and obese [OW, BCS 7-9/9], and 22 diabetic [DM]) were included., Methods: Cross-sectional study. The cats underwent physical examination, and blood tests. Linear regression models compared differences in fPLI, fTLI, cobalamin, and folate concentrations. Fisher's exact test assessed the proportions of cats with fPLI and fTLI indicative of pancreatitis, and hypocobalaminemia. A random forest algorithm identified explanatory variables for cats having fPLI levels indicative of pancreatitis., Results: No LN cats, while 6/30 (20%) of OW and 10/22 (45%) of DM cats had fPLI concentrations indicative of pancreatitis. Body condition score (P = .02) and body weight (P = .002) were positively associated with fPLI levels in LN and OW cats. Higher fPLI, and lower cobalamin concentrations were associated with higher age across groups., Conclusions and Clinical Importance: Body condition score and body weight were associated with higher fPLI levels in nondiabetic cats. A larger proportion of OW and DM cats had fPLI concentrations indicative of pancreatitis compared to LN cats. Whether this indicates subclinical pancreatitis remains to be determined. Hypocobalaminemia was less frequent in OW compared to DM cats., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Birds (class Aves) have 1.5 to 2 times higher blood glucose concentrations than mammals of comparable sizes. The reasons for this have been studied and are believed to be multifactorial. There is low expression of insulin receptors, decreased sensitivity of the pancreatic β-cells to glucose, an absent or dysfunctional glucose transporter type 4 pathway, and increased blood glucagon concentrations. Glucagon and somatostatin appear to play a greater role than insulin in glucose homeostasis in birds. Severe hyperglycemia in birds can be attributed to diabetes mellitus, necessitating therapy to prevent short-term and long-term deleterious effects., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The purpose of this review is to examine the current scientific literature regarding the interplay between the exocrine and endocrine pancreas, specifically the role of the exocrine pancreas in the pathogenesis of canine diabetes mellitus. β-cell death caused by exocrine pancreatic inflammation is thought to be an under-recognised contributor to diabetes mellitus in dogs, with up to 30 % of canine diabetic patients with concurrent evidence of pancreatitis at post-mortem examination. Current diagnostics for pancreatitis are imprecise, and treatments for both diseases individually have their own limitations: diabetes through daily insulin injections, which has both welfare and financial implications for the stakeholders, and pancreatitis through treatment of clinical signs, such as analgesia and anti-emetics, rather than targeted treatment of the underlying cause. This review will consider the evidence for exocrine pancreatic inflammation making an active contribution to pancreatic β-cell loss and insulin-deficiency diabetes in the dog and explore current and potential future diagnostic and treatment avenues to improve outcomes for these patients., Competing Interests: Declaration of Competing Interest None of the authors of this paper has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Incretin hormones potentiate the glucose-induced insulin secretion following enteral nutrient intake. The best characterised incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) which are produced in and secreted from the gut in response to nutrient ingestion. The property of incretins to enhance endogenous insulin secretion only at elevated blood glucose levels makes them interesting therapeutics for type 2 diabetes mellitus with a better safety profile than exogenous insulin. While incretin therapeutics (especially GLP-1 agonists, and more recently also GLP-1 / GIP dual agonists and other drugs that influence the incretin metabolism (e.g., dipeptidyl peptidase-4 (DPP-4) inhibitors)) are already widely used treatment options for human type 2 diabetes, these drugs are not yet approved for the therapy of feline diabetes mellitus. This review provides an introduction to incretins and feline diabetes mellitus in general and summarises the current study situation on incretins as therapeutics for feline diabetes mellitus to assess their possible future potential in feline medicine. Studies to date on the use of GLP-1 receptor agonists (GLP-1RA) in healthy cats largely confirm their insulinotropic effect known from other species. In diabetic cats, GLP-1RAs appear to significantly reduce glycaemic variability (GV, an indicator for the quality of glycaemic control), which is important for the management of the disease and prevention of long-term complications. However, for widespread use in feline diabetes mellitus, further studies are required that include larger numbers of diabetic cats, and that consider and test a possible need for dose adjustments to overweight and diabetic cats. Also evaluation of the outcome of GLP-1RA monotherapy will be neceessary., Competing Interests: Declaration of competing interest Thomas A. Lutz is a consultant for Novo Nordisk, Boehringer Ingelheim, Zealand Pharma, Prolynx, Eracal and Structure Therapeutics. Thomas A. Lutz has ongoing collaborations with Novo Nordisk., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Adiponectin plays an important role in carbohydrate and lipid metabolism. However, the evidence regarding the association between adiponectin and diabetes mellitus in obese dogs is sparse. The aim of this study is to investigate the associations of adiponectin with the risk of diabetes mellitus in obese dogs on the basis of a prospective cohort study., Materials and Methods: Serum adiponectin levels in obese dogs recruited from three small animal hospitals between 2015 and 2018 were measured by ELISA. Electronic health records were used to record the incidence of diabetes mellitus during follow-up for 3 years., Results: A total of 862 dogs were included. Amongst the 862 dogs, 51 developed diabetes. Adiponectin levels were associated with diabetes mellitus after adjusting for sex, age, breed, exercise, body condition score, fasting plasma glucose, serum triglyceride and total cholesterol. When adjusting for sex, age, breed, exercise, body condition score, fasting plasma glucose, serum triglyceride and total cholesterol, the adjusted hazard ratios were 7.83 (95% confidence interval: 2.67 to 30.13) in the lowest adiponectin group and 1.96 (95% CI: 1.10 to 8.55) in the medium adiponectin group relative to that in the highest adiponectin group. The area under a curve of adiponectin's Receiver operating characteristic curve was 0.81 (95% CI: 0.76 to 0.86)., Clinical Significance: Low adiponectin is associated with diabetes mellitus and has a high risk of incident diabetes mellitus, implying the potential of adiponectin as a predictive biomarker of diabetes mellitus in obese dogs., (© 2024 British Small Animal Veterinary Association.)

Objectives: The aims of this study were to compare signalment and laboratory parameters between diabetic (D) and non-diabetic (ND) cats and poorly-controlled diabetic (PD) and well-controlled diabetic (WD) cats in Germany., Methods: Laboratory data from Antech Lab Germany between 2015 and 2018 were retrospectively analysed. Age, sex, red blood cell count (RBC), creatinine (CREA), alkaline phosphatase (AP), alanine aminotransferase (ALT), bilirubin (BILI), cholesterol (CHOL), triglycerides (TRI), glucose (GLU) and total thyroxine (TT4) were compared between D (fructosamine ⩾340 µmol/l) and ND cats, and PD (fructosamine >500 µmol/l) and WD (fructosamine 340-500 µmol/l) cats. The proportion of cats with anaemia (RBC ⩽4.21 ×10 12 /l), CREA >250 µmol/l, ALT >455 U/l, AP >315 U/l, BILI ⩾35 µmol/l and TT4 > reference interval (RI) was compared between PD and WD cats. Data are presented as median and interquartile range (IQR) and analysed using non-parametric tests. Significance was P <0.05, and effect size was assessed by Cramér V or r., Results: In total, 129,505 cats were included (D: n = 9334 [prevalence 7.2%], WD: n = 5670/9334 [60.7%]). The median age of D and ND cats was 12 years (IQR D 9-14; ND 9-15); there was no difference in sex. A significant difference was found between groups (D vs ND; PD vs WD) for all parameters studied. Considering the effect sizes and medians outside the RI, the only relevant difference was higher CHOL, TRI, AP and GLU in PD compared with WD (CHOL: PD 7.46 [5.85-9.32] vs WD 5.44 [4.32-6.97] mmol/l, P <0.001, r = 0.39; TRI: PD 1.44 [0.84-3.66] vs WD 0.78 [0.5-1.35] mmol/l, P <0.001, r = 0.35; AP: PD 66 [47-92] vs WD 35 [23-59] U/l, P <0.001, r = 0.39; GLU: PD 23.7 [20.15-27.3] vs WD 6.89 [5-11.31] mmol/l, P  <0.001, r = 0.69)., Conclusions and Relevance: Laboratory changes in diabetic cats were mild and mainly associated with lipid derangements., Competing Interests: Conflict of interestThe laboratory data used in this study was provided by Antech Lab Germany. Judith Langenstein is an employee of Antech Lab Germany.

A 6-year-old spayed female domestic short-hair cat was presented for primary complaints of anorexia and lethargy. The cat was being treated with cyclosporine (25 mg/cat, PO q24h) and prednisolone (1 mg/kg, PO q12h) for feline hypersensitivity dermatitis and inflammatory bowel disease for 1 year, wherein prednisolone was withdrawn 2 weeks prior to presentation. At presentation, dehydration, hyperglycaemia, ketonaemia, increased fructosamine, glucosuria, ketonuria and metabolic acidosis were observed. The cat was diagnosed with diabetic ketoacidosis (DKA). Immediate treatments with insulin continuous-rate infusion and intravenous fluid therapy were initiated. A serum cyclosporine concentration was >2100 ng/mL, indicating cyclosporine toxicity. Cyclosporine was discontinued immediately. The cat's acidosis and ketonaemia were resolved within a week, allowing a switch from insulin continuous-rate infusion to subcutaneous glargine (1 IU/cat), which was eventually discontinued due to persistent normoglycaemia 12 days after initial presentation. Hyperglycaemia was not observed for 28 days thereafter without insulin, indicating remission of diabetes mellitus. This report suggests that using prednisolone, particularly immune suppressive doses, could be problematic in cats receiving long-term cyclosporine therapy. Additionally, diabetic cats receiving immune-suppressive agents can possibly achieve diabetic remission after surviving DKA through regular monitoring of blood glucose concentration, elimination of prednisolone and intensive blood glucose management., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Objective: To investigate safety and effectiveness of velagliflozin oral solution as sole therapy in naïve and previously insulin-treated diabetic cats., Animals: 252 client-owned cats receiving ≥ 2 doses of velagliflozin; 214 (85%) naïve diabetics and 38 (15%) insulin-treated diabetics., Procedures: Prospective, baseline-controlled, open-label clinical field trial. Cats received velagliflozin orally, once daily. Physical examinations and blood collections were performed days 0, 3, 7, 30, 60, 120, and 180., Results: Data are median (range). Screening blood glucose (BG) was 436 mg/dL (272 to 676 mg/dL). On days 30, 60, 120, and 180, single BG after receiving velagliflozin was 153 mg/dL (62 to 480 mg/dL), 134 mg/dL (64 to 414 mg/dL), 128 mg/dL (55 to 461 mg/dL), and 125 mg/dL (77 to 384 mg/dL), respectively. Screening fructosamine was 538 µmol/L (375 to 794 µmol/L). On the same recheck days, fructosamine was 310 µmol/L (204 to 609 µmol/L), 286 µmol/L (175 to 531 µmol/L), 269 µmol/L (189 to 575 µmol/L), and 263 µmol/L (203 to 620 µmol/L). At day 180, 81% of 158 cats remaining had BG and/or fructosamine within reference ranges; 88.6% (124 of 140) and 87.7% (121 of 138) showed improvement in polyuria and polydipsia, respectively. Ketonuria developed in 35 cats (13.9%), including 18 (7.1%) that had ketoacidosis. Ketoacidosis was less common in naïve diabetic cats (11 of 214 [5.1%]) compared to insulin-treated diabetic cats (7 of 38 [18.4%]). At ketoacidosis diagnosis, 14 of 18 cats (77.8%) were euglycemic (ie, BG < 250 mg/dL). Most episodes of ketosis or ketoacidosis (30 of 35 [85.7%]) occurred within the first 14 days of treatment. Insulin-treated diabetic cats were less likely to complete the trial. No clinical hypoglycemia occurred., Clinical Relevance: Velagliflozin improved glycemic parameters and clinical signs in diabetic cats. Velagliflozin provides an alternative to insulin as a stand-alone treatment of diabetic cats.

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., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Options for treatment of diabetes mellitus in cats are limited to insulin injections and monitoring for hypoglycemia., Hypothesis: Once daily sodium-glucose cotransporter-2 inhibitor velagliflozin PO is noninferior to insulin injections., Animals: Client-owned diabetic cats (127 safety; 116 efficacy assessment)., Methods: Prospective, randomized (1 mg/kg velagliflozin), positive controlled (titrated Caninsulin), open label, noninferiority field trial, comparing number of cats with treatment success in ≥1 clinical variable and ≥1 glycemic variable (margin Δ: 15%) on Day 45; secondary endpoints included glycemic and clinical assessments during 91 days., Results: On Day 45, 29/54 (54%) velagliflozin-treated cats and 26/62 (42%) Caninsulin-treated cats showed treatment success, demonstrating noninferiority (difference -11.8%; upper 1-sided 97.5% confidence interval, -∞ to 6.3%). By Day 91, quality of life (QoL), polyuria, and polydipsia had improved in 81%, 54% and 61% (velagliflozin); on blood glucose (BG) curves, mean BG was <252 mg/dL in 42/54 (78%; velagliflozin) and 37/62 (60%; Caninsulin); minimum BG was <162 mg/dL in 41/54 (76%; velagliflozin) and 41/62 (66%; Caninsulin); serum fructosamine was <450 μmol/L in 41/54 (76%; velagliflozin) and 38/62 (61%; Caninsulin). Velagliflozin's most frequent adverse events were loose feces/diarrhea (n = 23/61, 38%), positive urine culture (n = 19/61, 31%), and nonclinical hypoglycemia (BG <63 mg/dL; n = 8/61, 13%); Caninsulin's: clinical and nonclinical hypoglycemia (n = 35/66, 53%), positive urine culture (n = 18/66, 27%), and loose feces/diarrhea (n = 10/66, 15%). Diabetic ketoacidosis occurred in 4/61 (7%; velagliflozin) and 0/66 (Caninsulin)., Conclusions and Clinical Importance: Once daily oral administration of velagliflozin was noninferior to insulin injections, showed good QoL and glycemia without clinical hypoglycemia., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: The utility of sodium-glucose cotransporter 2 inhibitors (SGLT2i) has not been reported in insulin-treated diabetic dogs., Hypothesis: Canagliflozin, a PO-administered SGLT2i, decreases interstitial glucose concentration (IG) in insulin-treated diabetic dogs., Animals: Five insulin-treated diabetic dogs., Methods: Uncontrolled open label longitudinal study. Canagliflozin (2-4 mg/kg/day PO) was added to an unchanged insulin dose for 7 days. Fractional excretion of glucose was calculated by dividing the product of urine glucose and serum creatinine concentrations by the product of serum glucose and urine creatinine concentrations. Hypoglycemia was defined as IG <60 mg/dL., Results: Median IG in 2869 measurements obtained while dogs were treated with insulin and canagliflozin was 87 mg/dL (range, 40-500 mg/dL) and was significantly lower than median IG in 1426 measurements obtained while dogs were treated with insulin alone (212 mg/dL; range, 41-500 mg/dL; P < .001). Median fractional excretion of glucose when dogs were treated with insulin and canagliflozin was 1.1% (range, 0.9%-2.0%), significantly higher than when dogs were treated with insulin alone (0.3%; range, 0.01%-1.0%; P = .04). The frequency of hypoglycemia was higher in dogs treated with insulin and canagliflozin (544 of 2869 IG measurements, 19%) compared with the frequency of hypoglycemia in dogs treated with insulin alone (52 of 1426 IG measurements, 4%; P < .001)., Conclusions and Clinical Importance: Canagliflozin may have a role in improving glycemic control in insulin-treated diabetic dogs, but the dose of insulin should be decreased when adding canagliflozin to insulin treatment., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of anti-hyperglycaemic agents., Objective: This study aimed to evaluate the safety and the adjuvant glycaemic control effect of an SGLT2 inhibitor, DWP16001, in diabetic dogs receiving insulin treatment., Methods: Nineteen diabetic dogs receiving insulin treatment (NPH, porcine lente and glargine insulin) were divided into two groups according to dosing frequency: DWP TOD group (n = 10) and DWP SID group (n = 9). In the DWP TOD group, 0.025 mg/kg of DWP16001 was administered once every 3 days, whereas, in the DWP SID group, 0.025 mg/kg of DWP16001 was administered once a day. Food intake was maintained during the trial period. Hypoglycaemia, ketoacidosis or unexpected life-threatening reactions were assessed as adverse effects before and after DWP16001 administration. We compared insulin requirement reduction and blood glucose level control between two groups., Results: No specific adverse effects were observed during the clinical trial, and haematological parameter remained unchanged. Moreover, the fasting glucose levels and daily insulin dose in the DWP TOD group were lower than the pre-administration values, but not significantly different for 8 weeks. Systolic blood pressure, fructosamine and insulin dose decreased significantly in the DWP SID group compared to the DWP TOD group at 8 weeks (p < 0.05) without affecting food consumption. Among these patients, 10 patients were monitored while receiving DWP16001 for 12 months (DWP TOD group n = 5, DWP SID group n = 5). The fasting glucose and fructosamine levels and daily insulin dose were reduced in both groups at 12 months compared with those before receiving DWP16001., Conclusion: When DWP16001, an SGLT2 inhibitor, was supplied to dogs with type 1 diabetes, no adverse effects were observed, and it was confirmed that the administered insulin dose can be reduced in controlling blood glucose., (© 2024 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

A 3.5-year-old male intact domestic short hair cat presented for a chronic wound and crusts over the claw and claw folds over several months. The cat was diagnosed with diabetes mellitus based on the presence of persistent hyperglycemia, glucosuria, and compatible clinical signs which consist of polyuria, polydipsia, polyphagia, and weight loss. Glipizide (Glucotrol XL, Pfizer, Indonesia) 2.5 mg orally twice daily was prescribed. By the seventeenth day, the patient's claws and skin around the paw had normalized and the abnormal claw sloughed off, revealing a normal claw underneath. Blood glucose, urinalysis and serum fructosamine were also normalized by the thirtieth day. The patient underwent diabetic remission, and the skin and claw lesions have remained in remission and not recurred since the treatment of the diabetes mellitus. This is the first report of a diabetic cat with dermatologic changes to the skin and claw regions. As the diabetes mellitus went into clinical remission, so too did the dermatologic manifestations, even without any specific dermatologic treatment., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Milk-derived peptides have emerged as a popular mean to manage various lifestyle disorders such as diabetes. Fermentation is being explored as one of the faster and efficient way of producing peptides with antidiabetic potential. Therefore, in this study, an attempt was made to comparatively investigate the pancreatic α-amylase (PAA) inhibitory properties of peptides derived from milk of different farm animals through probiotic fermentation. Peptide's identification was carried out using liquid chromatography-quadrupole time-of-flight mass spectrometry and inhibition mechanisms were characterized by molecular docking. Results obtained showed a PAA-IC 50 value (the amount of protein equivalent needed to inhibit 50% of enzymes) between 2.39 and 36.1 µg protein equivalent for different fermented samples. Overall, Pediococcus pentosaceus MF000957-derived fermented milk from all animals indicated higher PAA inhibition than other probiotic derived fermented milk (PAA-IC 50 values of 6.01, 3.53, 15.6, and 10.8 µg protein equivalent for bovine, camel, goat, and sheep fermented milk). Further, molecular docking analysis indicated that camel milk-derived peptide IMEQQQTEDEQQDK and goat milk-derived peptide DQHQKAMKPWTQPK were the most potent PAA inhibitory peptides. Overall, the study concluded that fermentation derived peptides may prove useful in for managing diabetes via inhibition of carbohydrate digesting enzyme PAA., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment., Results: After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups., Conclusions: 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity., (© 2024. The Author(s).)

Objectives: The aim of the present study was to retrospectively assess remission rates and survival in diabetic cats managed using a moderate-intensity, low-cost protocol of home blood glucose measurements and insulin adjustment by clients of a cat-only practice, and to determine if predictors of remission, relapse or survival could be identified., Methods: The records of a cat-only practice were used to identify 174 cats with newly diagnosed diabetes managed using only pre-insulin home blood glucose measurements for insulin dose adjustments based on a protocol provided to clients aimed at maintaining pre-insulin blood glucose in the range of 6.5-11.9 mmol/l (117-214 mg/dl). Cats were excluded for the following reasons: insufficient follow-up in the records; a lack of owner compliance was recorded; they were receiving ongoing corticosteroids for the management of other conditions; they were euthanased at the time of diagnosis; or they were diagnosed with acromegaly or hyperadrenocorticism., Results: Using only pre-insulin blood glucose measurements at home to adjust the insulin dose to maintain glucose in the range of 6.5-11.9 mmol/l, 47% of cats achieved remission, but 40% of those cats relapsed. A minority (16%) of cats were hospitalised for hypoglycaemia. The survival time was significantly longer in cats in remission and Burmese cats., Conclusions and Relevance: The cost and time burden of treating diabetic cats may cause some clients to choose euthanasia over treatment. While the highest rates of diabetic remission have been reported in studies of newly diagnosed cats treated with intensive long-acting insulin protocols and low carbohydrate diets, these protocols may not be suitable for all clients. Nearly 50% of cats with newly diagnosed diabetes achieved remission with this low-cost, moderate-intensity, insulin dosing protocol. As remission was significantly associated with survival time, discussing factors in treatment to optimise remission is important, but it is also important to offer clients a spectrum of options. No cats that started treatment in this study were euthanased because the owner did not wish to continue the diabetes treatment., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Diabetes mellitus (DM) is an uncommon, poorly documented metabolic disorder of birds. Extrapolating knowledge from DM in mammals is challenging because of marked differences in avian physiology and metabolism. A literature review from December 1991 to January 2022 identified 14 publications covering 16 diabetic birds, 63% (10/16) of which belonged to the order Psittaciformes with Ara as the predominant genus. No sex predilection was noted, but males generally presented at a younger age. Commonly reported clinical signs included polyuria 94% (15/16), polydipsia 88% (14/16), weight loss 75% (12/16), lethargy 63% (10/16), and polyphagia 38% (6/16). Diagnosis of DM was based on the presence of clinical signs and persistent hyperglycemia 100% (16/16), often with glucosuria 93% (13/14), response to insulin therapy 80% (8/10), and pancreatic pathology 90% (9/10). Specific treatment for DM was initiated in 14 patients, but blood glucose regulation for 6 months or longer was only achieved in 6 birds. Five of the regulated birds were managed with injectable long-acting insulin and 1 with oral glipizide combined with dietary modifications. However, glipizide yielded poor results in other cases, likely attributable to a lack of functional beta cells. Three diabetic birds progressed to remission. Treatment proved unsuccessful for 7 patients with a mean survival time of 36 days from diagnosis. One patient was lost to follow-up, and 2 were euthanized immediately following diagnosis. Histological examination of the pancreas frequently (90%, 9/10) revealed abnormalities including atrophy, fibrosis, and vacuolization of the endocrine islets with or without lymphoplasmacytic pancreatitis. Comorbidities, including hemosiderosis and infection, were common. This review suggests that birds diagnosed with DM are primarily affected by a type I diabetes as observed in dogs and humans. In contrast to mammalian species, avian DM is often associated with underlying disease and a complete clinical workup is essential to diagnose and address secondary disease conditions prior to initiating long-term insulin therapy.

The aim of this study was to evaluate the changes in the serum and salivary inflammatory markers induced by Diabetes mellitus (DM) in dogs and to assess the possible confounding effect of gingivitis. A panel of 13 cytokines was measured in the serum and saliva of dogs diagnosed with DM and compared with healthy dogs without gingivitis (control group 1; CG1) and dogs with gingivitis but otherwise healthy (control group 2; CG2). The results of the present study showed statistically significantly higher levels of IL-8, KC-like and MCP1 in the serum of dogs with DM compared to CG1 dogs. In the case of saliva, the DM group presented statistically higher GM-CSF, IL6, IL15, and MCP1 levels compared to CG1, and lower KC-like chemokine compared to CG2. Finally, gingivitis produced changes in saliva, with salivary levels of GM-CSF, IL-6, IL-7, IL-15, IP-10, KC-like, IL-10, IL-18, MCP1, TNFα being statistically significantly higher in the saliva of CG2 dogs compared to CG1. The results of the present study indicate that dogs with DM have altered cytokine levels in serum and saliva compared to healthy dogs. In addition, this study highlights the importance of taking oral health into account when determining cytokines in dogs, as gingivitis can significantly alter their concentrations. ., (© 2024. The Author(s).)

Glycemic variability (GV) refers to swings in blood glucose levels and is an emerging measure of glycemic control in clinical practice. It is associated with micro- and macrovascular complications and poor clinical outcomes in diabetic humans. Although an integral part of patient assessment in human patients, it is to a large extent neglected in insulin-treated diabetic dogs. This prospective pilot study was performed to describe canine within-day GV in non-diabetic dogs with the aim to provide a basis for the interpretation of daily glucose profiles, and to promote GV as an accessible tool for future studies in veterinary medicine. Interstitial glucose concentrations of ten non-diabetic, non-obese beagles were continuously measured over a 48-h period using a flash glucose monitoring system. GV was assessed using the common indices MAGE (mean amplitude of glycemic excursion), GVP (Glycemic variability percentage) and CV (coefficient of variation). A total of 2260 sensor measurements were obtained, ranging from 3.7 mmol/L (67 mg/dL) to 8.5 mmol/L (153 mg/dL). Glucose profiles suggested a meal-dependent circadian rhythmicity with small but significant surges during the feeding periods. No differences in GV indices were observed between day and night periods (p > 0.05). The MAGE (mmol/L), GVP (%) and CV (%) were 0.86 (± 0.19), 7.37 (± 1.65), 6.72 (± 0.89) on day one, and 0.83 (± 0.18), 6.95 (± 1.52), 6.72 (± 1.53) on day two, respectively. The results of this study suggest that GV is low in non-diabetic dogs and that glucose concentrations are kept within narrow ranges., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Practical Relevance: Diabetes mellitus is the second-most common feline endocrinopathy, affecting an estimated 1/200 cats. While the underlying causes vary, around 15-25% of cats with diabetes mellitus develop the condition secondarily to progressive growth hormone (GH)-induced insulin resistance. This typically results in a form of diabetes that is challenging to manage, whereby the response to insulin is very variable or high doses are required to achieve even minimal diabetic control., Clinical Challenges: Although uncontrolled chronic excessive GH may result in phenotypic changes that raise suspicion for acromegaly, many cats with hypersomatotropism (HST) do not have these changes. In these situations, a clinician's index of suspicion may be increased by the presence of less dramatic changes such as marked polyphagia, stertor or uncontrolled diabetes mellitus. The current diagnostic test of choice is demonstration of a markedly increased serum insulin-like growth factor 1 (IGF1) concentration, but some affected cats will have only a marginal increase; additionally, chronic insulin administration in cats results in an increase in serum IGF1, making the diagnosis less clear cut and requiring additional confirmatory tests., Evidence Base: Over the past two decades, HST has increasingly been recognised as an underlying cause of diabetes mellitus in cats. This review, which focuses on diagnosis and treatment, utilises data from observational studies, clinical trials and case series, as well as drawing on the experience of the authors in managing this condition., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In dairy science, camel milk (CM) constitutes a center of interest for scientists due to its known beneficial effect on diabetes as demonstrated in many in vitro, in vivo, and clinical studies and trials. Overall, CM had positive effects on various parameters related to glucose transport and metabolism as well as the structural and functional properties of the pancreatic β-cells and insulin secretion. Thus, CM consumption may help manage diabetes; however, such a recommendation will become rationale and clinically conceivable only if the exact molecular mechanisms and pathways involved at the cellular levels are well understood. Moreover, the application of CM as an alternative antidiabetic tool may first require the identification of the exact bioactive molecules behind such antidiabetic properties. In this review, we describe the advances in our knowledge of the molecular mechanisms reported to be involved in the beneficial effects of CM in managing diabetes using different in vitro and in vivo models. This mainly includes the effects of CM on the different molecular pathways controlling (1) insulin receptor signaling and glucose uptake, (2) the pancreatic β-cell structure and function, and (3) the activity of key metabolic enzymes in glucose metabolism. Moreover, we described the current status of the identification of CM-derived bioactive peptides and their structure-activity relationship study and characterization in the context of molecular markers related to diabetes. Such an overview will not only enrich our scientific knowledge of the plausible mode of action of CM in diabetes but should ultimately rationalize the claim of the potential application of CM against diabetes. This will pave the way toward new directions and ideas for developing a new generation of antidiabetic products taking benefits from the chemical composition of CM., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Periodontal disease (PD) can adversely affect glycaemic control in humans. However, it is unknown if a similar association exists in dogs., Methods: Ten client-owned dogs with poorly regulated diabetes mellitus (DM) and PD were prospectively enrolled. A complete blood count, serum biochemistry, urinalysis and measurement of C-reactive protein, interleukin-6 (IL-6), tumour necrosis factor-α, haemoglobin A1c (HbA1c) and fructosamine concentrations were performed before periodontal treatment (PT) and monthly thereafter for 3 months. A periodontal disease severity score (PDSS) was determined during PT. The effects of time post-PT and PDSS on markers of inflammation and glycaemic control were determined by generalised estimating equation analysis., Results: HbA1c (mean; 95% confidence interval [CI]) decreased 3 months post-PT (32.1 mmol/mol; 21.1-43.1 mmol/mol vs. 44.3 mmol/mol; 36.4-52.0; p = 0.003). PDSS at enrolment was significantly (p = 0.031) positively associated with HbA1c concentration. Due to a significant (p < 0.001) interaction between PDSS and time post-PT in the analysis of fructosamine, dogs with low (1-3) PDSS and high (7-9) PDSS were analysed separately. Fructosamine (mean; 95% CI) significantly decreased 1 month post-PT (570 μmol/L; 457-684 μmol/L vs. 624 μmol/L; 499-748; p = 0.001) in the high PDSS group but not in the low PDSS group. Fructosamine concentration upon enrolment and PDSS were correlated (r = 0.73, p = 0.017). IL-6 concentration significantly decreased 3 months post-PT (9.9 pg/mL; 8.5-11.3 pg/mL vs. 11.2 pg/mL; 9.7-12.7; p = 0.002)., Limitations: Limitations of the study included the small number of dogs, the lack of a control group and the inability to assess PDSS during follow-ups., Conclusions: These findings support a potential detrimental interaction between PD and DM. The apparent beneficial effect of PT on markers of glycaemic control was most conspicuous in dogs with more severe PD., (© 2023 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

A 5 yr old male neutered Labradoodle presented for an episode of acute collapse. Point-of-care blood work showed hypoglycemia and abdominal ultrasonography revealed a liver mass arising from the caudate liver lobe. The dog underwent a partial liver lobectomy, and histopathology confirmed a fully resected hepatocellular carcinoma. Blood glucose levels normalized initially after surgery, but 1 wk later, the patient was diagnosed with diabetes mellitus based on the development of polyuria, polydipsia, hyperglycemia, and glucosuria. Appropriate treatment with insulin was initiated, and 1 yr following the diagnosis, the dog was still requiring administration of insulin twice daily. This case describes the uncommon development of diabetes mellitus in a dog following surgical resection of a hepatocellular carcinoma initially associated with hypoglycemia. Although very unusual, this should be considered as a potential complication of surgical treatment of such tumors, and affected patients may require long-term medical management., (© 2024 by American Animal Hospital Association.)

A 6.5 yr old castrated male mixed-breed dog was presented for clinical signs associated with hypoglycemia. Hyperinsulinemic hypoglycemia was diagnosed as the cause of the persistent hypoglycemia. No obvious pancreatic mass was seen on abdominal computed tomography and exploratory laparotomy. A partial pancreatectomy was performed with the suspicion of an insulinoma-causing hyperinsulinemic hypoglycemia. Nesidioblastosis was diagnosed based clinical, biochemical, and histopathologic findings. There was beta cell hyperplasia and no evidence of neoplasia. The dog was euglycemic postoperatively after a partial pancreatectomy. Long-term follow-up after 2 yr revealed that the dog was diagnosed with diabetes mellitus., (© 2024 by American Animal Hospital Association.)

Objective: Describe the use of fixed-rate intravenous insulin infusions (FRIs) in cats and dogs with diabetic ketoacidosis (DKA) and determine if this is associated with faster resolution of ketosis compared to variable-rate intravenous insulin infusions (VRIs). Secondary objectives were to evaluate complication rates, length of hospitalization (LOH), and survival to discharge (STD)., Design: Randomized clinical trial (January 2019 to July 2020)., Setting: University veterinary teaching hospital and private referral hospital., Animals: Dogs and cats with DKA and venous pH <7.3, blood glucose concentration >11 mmol/L (198 mg/dL), and β-hydroxybutyrate (BHB) concentration >3 mmol/L were eligible for inclusion. Patients were randomly assigned to receive either FRI or VRI., Interventions: Neutral (regular) insulin was administered IV as an FRI or VRI. For FRI, the rate was maintained at 0.01 IU/kg/h. For VRI, the dose was adjusted according to blood glucose concentration., Measurements and Results: Sixteen cats and 20 dogs were enrolled. Population characteristics, mean insulin infusion rate, time to resolution of ketosis (BHB <0.6 mmol/L), complications, LOH, and STD were evaluated. In cats, overall resolution of ketosis was low (9/16 [56.3%]), limiting comparison of protocols. In dogs, resolution of ketosis was high (19/20 dogs [95.0%]) but the time to resolution in the FRI group was not different than that in the VRI group (P = 0.89), despite a 25% higher average insulin infusion rate in the FRI group (P = 0.04). The incidence of complications was low and did not differ between protocols. In cats, LOH and STD did not differ between protocols. All cats that died (5/16) did so within 78 hours and none had resolution of ketosis. Dogs receiving FRI had a shorter LOH (P = 0.01) but STD did not differ between protocols. Six dogs (30.0%) did not survive to hospital discharge but all had resolution of ketosis., Conclusions: FRIs can be used in veterinary species but may not hasten resolution of ketosis., (© 2023 The Authors. Journal of Veterinary Emergency and Critical Care published by Wiley Periodicals LLC on behalf of Veterinary Emergency and Critical Care Society.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity. However, the precise mechanisms responsible for the combined impact of corona virus disease 2019 (COVID-19) and diabetes have not yet been elucidated, and effective treatment options for SARS-CoV-2-infected diabetic patients remain limited. To investigate the disease pathogenesis, K18-hACE2 transgenic (hACE2 Tg ) mice with a leptin receptor deficiency (hACE2-Lepr -/- ) or high-fat diet (hACE2-HFD) background were generated. The two mouse models were intranasally infected with a 5×10 5 median tissue culture infectious dose (TCID 50 ) of SARS-CoV-2, with serum and lung tissue samples collected at 3 days post-infection. The hACE2-Lepr -/- mice were then administered a combination of low-molecular-weight heparin (LMWH) (1 mg/kg or 5 mg/kg) and insulin via subcutaneous injection prior to intranasal infection with 1×10 4 TCID 50 of SARS-CoV-2. Daily drug administration continued until the euthanasia of the mice. Analyses of viral RNA loads, histopathological changes in lung tissue, and inflammation factors were conducted. Results demonstrated similar SARS-CoV-2 susceptibility in hACE2 Tg mice under both lean (chow diet) and obese (HFD) conditions. However, compared to the hACE2-Lepr +/+ mice, hACE2-Lepr -/- mice exhibited more severe lung injury, enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α, and increased apoptosis. Moreover, combined LMWH and insulin treatment effectively reduced disease progression and severity, attenuated lung pathological changes, and mitigated inflammatory responses. In conclusion, pre-existing diabetes can lead to more severe lung damage upon SARS-CoV-2 infection, and LMWH may be a valuable therapeutic approach for managing COVID-19 patients with diabetes.

Objective: Corticosteroids are indicated to treat many feline diseases. However, side effects are a limiting factor in their use. The most concerning side effects are steroid-induced diabetes mellitus (SI-DM) and steroid-induced congestive heart failure (SI-CHF). This study aims to determine the incidences of these diseases in a large population of domestic cats seen at a privately-owned, feline-only practice., Animals: Cats in the study were client-owned patients of Alamo Feline Health Center in San Antonio, Texas. Control cats (controls) were examined as part of their routine health care., Procedures: The records of 732 cats that received methylprednisolone acetate (MPA) for various clinical indications were reviewed to determine how many developed SI-DM and SI-CHF. A similar record review of 310 controls was made to determine the incidence of spontaneous diabetes mellitus (Sp-DM) and spontaneous congestive heart failure (Sp-CHF). Control cats never received any oral or injectable corticosteroids., Results: Of the cats that received MPA, 28 developed SI-DM (3.83%) and 6 developed SI-CHF (0.82%). Of the controls, 22 developed Sp-DM (7.10%) and 6 developed Sp-CHF (1.90%)., Conclusion: The incidences of developing SI-DM and SI-CHF were 3.83% and 0.82%, respectively; and the risk was not increased even when repeated doses of MPA were given., Clinical Relevance: The authors consider the risk-benefit ratio sufficient to justify the use of MPA when it is indicated, especially if another drug cannot be substituted with the same therapeutic results., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: Long-term comparisons of phacoemulsification with topical medication are limited in canine diabetic cataracts., Objectives: To compare outcomes of eyes submitted to phacoemulsification with those of topical medication for canine diabetic cataracts and identify risk factors for complications., Methods: Through medical records review, 150 eyes (76 dogs) with diabetic cataracts were included; 58 eyes (31 dogs) underwent phacoemulsification (phaco-group) and 92 eyes (48 dogs) received ophthalmic solution alone (medication-group). The medication-group was divided into owner-led and vet-led groups depending on who elected not to perform surgery. Comparisons involved time-to-complications, vision, and the number and type of ophthalmic solutions administered. The association between complications and pretreatment clinical findings was investigated., Results: No difference was found in complication risk between the phaco and owner-led medication groups. Conversely, the vet-led medication-group had a higher complication risk than the other groups. At the last follow-up, 94.8% of the phaco-group had vision, whereas 7.6% of the medication-group restored some visual axis. Poor glycemic control in the medication-group and younger age in the phaco-group increased complication risk. At 1-year post-treatment, the average number of ophthalmic solutions administered was 1.7 and 2.6 in the phaco and medication groups, respectively. The medication-group used anti-inflammatories the most throughout the follow-up, whereas the phaco-group used anti-inflammatories the most until 1-year post-treatment and lacrimostimulants at 1.5-year post-treatment., Conclusions: For canine diabetic cataracts, phacoemulsification is recommended because it is superior to topical management alone in terms of maintaining vision and reducing the number of ophthalmic solutions required in the long term., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Korean Society of Veterinary Science.)

Objective: To determine whether there is a difference in corneal sensitivity and corneal subbasal nerve plexus (CSNP) morphology in cataractous dogs with diabetes mellitus (DM) versus without DM., Animals Studied: Twenty six domestic dogs with cataracts of various breeds presented for phacoemulsification, 13 with DM and 13 without DM., Procedure: The inclusion criteria for the study were dogs with bilateral cataracts and no clinical evidence of corneal disease. The diabetic group had documented hyperglycemia and was currently treated with insulin. The non-diabetic group had no evidence of DM on examination and bloodwork. Complete ophthalmic examination, corneal esthesiometry, and in vivo confocal microscopy of the CSNP was performed for both eyes of each dog. The CSNP was evaluated using a semi-automated program and statistically analyzed., Results: The mean (±SD) CSNP fiber length was significantly decreased in diabetic (3.8 ± 3.0 mm/mm 2 ) versus non-diabetic (6.7 ± 1.9 mm/mm 2 ) dogs. Likewise, the mean (±SD) fiber density was significantly decreased in diabetic (8.3 ± 3.1 fibers/mm 2 ) versus non-diabetic (15.5 ± 4.9 fibers/mm 2 ) dogs. The corneal touch threshold was significantly reduced in diabetic (2.1 ± 0.8 cm) versus non-diabetic (2.8 ± 0.4 cm) dogs. There was a non-significant trend towards subclinical keratitis in diabetic (9/13) versus non-diabetic (4/13) dogs., Conclusions: Morphological and functional abnormalities of the CSNP were present in dogs with DM, including decreased fiber length, fiber density, and corneal sensitivity. These findings are consistent with diabetic neuropathy and could contribute to clinically significant corneal complications after cataract surgery., (© 2023 American College of Veterinary Ophthalmologists.)

Interstitial glucose monitoring systems are commonly being used in diabetic dogs. The aim of this study was to document the incidence of complications associated with the use of a flash glucose monitoring system (FGMS) in dogs. Medical records of dogs that had placement of a 14-day FGMS during a 1-year period were reviewed. Data retrieved included the number of days the sensor remained attached and functional, sensor detachment, sensor failure prior to the end of the 14-day monitoring period, and dermatologic changes at the sensor site. Descriptive statistics were used to characterize the data. Thirty-four dogs had FGMSs placed. Most [32/34 (94%)] sensors were placed over the dorsolateral aspect of the thorax caudal to the scapula. Twenty-four sensors (71%) remained attached for the full 14 days. Incidence of complications associated with FGMS use was 13/34 (38%). The most frequent complication was mild dermatologic changes at the sensor site [6/34 (18%)]. Erythema and crusting at the attachment site were common and could be related to contact dermatitis, hypersensitivity, or skin preparation prior to placement. Flash glucose monitoring systems are safe in dogs, although there are some potential complications that should be discussed with dog owners., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

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., (© 2023 American Society for Veterinary Clinical Pathology.)

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.)

Endothelial dysfunction is an early complication of diabetes and it is related to both micro- and macroangiopathies. In addition, >70% of diabetic patients develop autonomic neuropathies. Increased oxidative stress has a major role in the development of both nitrergic and endothelial dysfunction. The aim of this work is to evaluate whether rutin, a potent antioxidant, could ameliorate nitrergic and/or endothelial dysfunction in diabetic animals. Primary and secondary treatment protocols with rutin were investigated on rat aortic rings and the mesenteric arteriolar bed, and on rabbit aortic rings and corpora cavernosa (RbCC) from both euglycemic and alloxan-diabetic animals. Acetylcholine endothelium-dependent and sodium nitroprusside endothelium-independent relaxations were compared in tissues from euglycemic or diabetic animals. Electrical field stimulation (EFS)-induced relaxation was performed only in the RbCC. Endothelial-dependent relaxations were blunted by 40% in vessels and neuronal relaxation was blunted by 50% in RbCC taken from diabetic animals when compared to euglycemic animals. Pre-treatment with rutin restored both neuronal and endothelial dependent relaxations in diabetic animals towards the values achieved in control euglycemic tissues. Rutin was able to ameliorate both endothelial dysfunction and nitrergic neuropathy in animal experimental models. Rutin could be a lead compound in the primary or secondary preventive ancillary treatment of endothelial and nitrergic dysfunction in the course of diabetes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Trilostane and insulin requirements and survival time of dogs with concurrent naturally-occurring Cushing's syndrome (CS) and diabetes mellitus (DM) has not been fully investigated. This retrospective study evaluated trilostane and insulin doses in dogs with concurrent CS and DM compared to dogs with only CS or DM. Additionally, a survival analysis was performed using a Kaplan-Meier survival curve. Survival time was compared through Log-rank test. Cox proportional regression method was used to screen predictor factors of death in dogs with CS, DM or concurrent CS and DM. A total of 95 dogs were included, 47 dogs had CS, 31 dogs had DM and 17 dogs had concurrent CS and DM. After long-term follow-up, dogs with concurrent CS and DM required higher final median doses of insulin than dogs with DM [0.90 (0.73-1.1) vs 0.67 (0.55-0.73) u/kg/12 h; P = 0,002]. Conversely, the median trilostane requirements in dogs with concurrent CS and DM did not differ from the median trilostane requirements of dogs with CS [1.52 (0.76-2.80) vs 1.64 (1.19-4.95) mg/kg/day; P = 0.283]. No statistical difference was found for the median survival time between dogs with CS and dogs with concurrent CS and DM (1245 vs 892 days; p = 0.152). Although, median survival time of dogs with DM was not reached, it was longer than median survival time of dogs with CS and DM (892 days; P = 0.002). In conclusion, diabetic dogs with concurrent CS need higher insulin doses and have a shorter survival time compared to diabetic dogs without CS., Competing Interests: Declaration of Competing Interest The authors declare not conflict of interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of the present study was to report the concurrent disorders and treatment success of cats with diabetes mellitus (DM) and arterial systolic hypertension (SH)., Methods: A retrospective longitudinal study was conducted of 17 cats with DM and SH that were examined at a university teaching hospital between 1 January 2011 and 31 December 2021. The medical records of diabetic cats were searched for the keywords 'hypertension', 'blood pressure', 'amlodipine', 'benazepril' and 'telmisartan' to identify cats with SH, which was defined as systemic arterial blood pressure (SABP) ⩾160 mmHg, documented at least twice, over several days. Comorbidities, including chronic kidney disease and hyperthyroidism, were recorded. Medications used for the treatment of SH and the SABP response to treatment were also noted., Results: Most cats (13/17, 76%) with DM and SH had at least one other documented concurrent illness that could contribute to SH, including chronic kidney disease (12/17 cats, 71%), hyperthyroidism (4/17, 23%) and functional adrenocortical mass secreting either aldosterone alone (1/17, 6%) or glucocorticoids, and possibly also aldosterone (1/17, 6%). Out of 17 cats, 15 (88%) were treated with amlodipine, and none were treated with an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker. Mean SABP at the time of diagnosis of SH was 210 ± 23 mmHg and was significantly higher than the mean SABP at the first and second follow-up examinations after the introduction of amlodipine treatment (175 ± 33 mmHg, P  = 0.008 and 172 ± 26 mmHg, P  = 0.01, respectively)., Conclusions and Relevance: Cats with DM and SH should be evaluated for the presence of chronic kidney disease, hyperthyroidism and functional adrenal masses. Treatment with amlodipine appears to be effective in lowering SABP in cats with DM and SH.

Background: Diabetes mellitus (DM) is an important endocrine disorder in dogs. This study explored prior exposure to glucocorticoids or antibiotic treatment as risk factors for developing DM in dogs attending primary-care VetCompass clinics in the UK., Methods: A breed frequency matched case-control study nested in a cohort of dogs (n = 480,469) aged 3 years or over was used to explore associations between glucocorticoid and antibiotic exposure and the odds of developing DM., Results: A total of 565 cases and 2179 controls were included. Dogs with DM had over four times the odds of exposure to glucocorticoids within 6 weeks prior to diagnosis (odds ratio [OR] 4.07, 95% confidence interval [CI] 2.41-6.89, p < 0.001) compared to controls within 6 weeks prior to a randomly selected quasi-date of diagnosis. Dogs that had only one unique documented antibiotic course had a decreased odds of developing DM (OR 0.65, 95% CI 0.46-0.91, p = 0.012) compared to dogs that had no documented courses of antibiotics., Limitations: This study only included selected breeds, so the results may not be generalisable to all dog breeds., Conclusions: Exposure to glucocorticoids is associated with a substantial increase in the risk of developing DM for the dog breeds included in this analysis., (© 2023 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

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.)

No insulin formulation should be considered best by default for management of feline diabetes. Rather, the choice of insulin formulation should be tailored to the specific clinical situation. In most cats that have some residual beta cell function, administering only a basal insulin might lead to complete normalization of blood glucose concentrations. Basal insulin requirements are constant throughout the day. Therefore, for an insulin formulation to be effective and safe as a basal insulin, its action should be roughly the same every hour of the day. At present, only insulin glargine U300 approaches this definition in cats., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To characterize the incidence, contributing risk factors, and healing characteristics of immediate postoperative corneal erosions (IPCE) in dogs undergoing routine phacoemulsification., Animals Studied: Medical records of 313 canine eyes (159 dogs) undergoing routine phacoemulsification surgery., Procedures: Medical records of dogs undergoing planned cataract surgery at UW Veterinary Care were retrospectively reviewed. Patient-related variables including age, skull conformation, diabetes status, and cataract stage at the time of surgery were recorded. Intraoperative variables per eye were also recorded including surgical technique, surgeon expertise level, average phacoemulsification power, and phacoemulsification time. Diagnosis of IPCE ≤ 24 h after completion of surgery and time to IPCE healing were recorded where follow-up data were available., Results: Immediate postoperative corneal erosions were observed in 48/313 (15.3%) operated eyes. The presence of diabetes mellitus or brachycephalic skull conformation, preoperative Schirmer tear test (STT) value, surgical technique and surgeon experience level, phacoemulsification time, and absolute phacoemulsification time were not statistically significant risk factors for IPCE. Average phacoemulsification power was associated with IPCE (RR 1.52, p = .001). Time to IPCE healing was similar in diabetic and non-diabetic dogs (median [IQR] 8 [6-11] days and 8 [6-15] days, respectively). Diabetes mellitus, brachycephaly, and phacoemulsification parameters were not associated with IPCE healing at 7 or 14 days postoperatively., Conclusions: Higher average phacoemulsification power may be associated with the development of IPCE in canine eyes. The presence of diabetes mellitus or brachycephaly are not risk factors for the development of IPCE, nor are they factors that influence IPCE healing., (© 2022 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Canine diabetes results from a wide spectrum of clinical pathophysiological processes that cause a similar set of clinical signs. Various causes of insulin deficiency and beta cell loss, insulin resistance, or both characterize the disease, with genetics and environment playing a role. Understanding the genetic and molecular causes of beta cell loss will provide future opportunities for precision medicine, both from a therapeutic and preventative perspective. This review presents current knowledge of the etiology and pathophysiology of canine diabetes, including the importance of disease classification. Examples of potential targets for future precision medicine-based approaches to therapy are discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)