1-Deoxynojirimycin containing Morus alba leaf-based food modulates the gut microbiome and expression of genes related to obesity.

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.

Evaluation of the presence of gingivitis as confounding factor in assessing inflammatory status in serum and saliva of dogs with diabetes mellitus.

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. .

Feline Comorbidities: Hypersomatotropism-induced diabetes in cats.

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.

Short-term glycemic variability in non-diabetic, non-obese dogs assessed by common glycemic variability indices.

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.

Spontaneous remission and relapse of diabetes mellitus in a male dog.

An 8-year-old male neutered Miniature Schnauzer was diagnosed with diabetes mellitus based on fasting hyperglycemia and glucosuria after a 2-week history of polydipsia and periuria, in line with the Agreeing Language in Veterinary Endocrinology consensus definition. Treatment of insulin and dietary management was initiated. The insulin dose was gradually reduced and eventually discontinued over the next year based on spot blood glucose concentrations that revealed euglycemia or hypoglycemia. After discontinuation, the dog remained free of clinical signs for 1 year until it was again presented for polyuria/polydipsia with fasting hyperglycemia and glucosuria. Insulin therapy was resumed and continued for the remainder of the dog's life. Although diabetic remission often occurs in cats and humans, the presumed etiopathogenesis of pancreatic beta cell loss makes remission rare in dogs, except for cases occurring with diestrus or pregnancy. This case demonstrates that diabetic remission is possible in dogs, even in cases without an identifiable reversible trigger.

Nesidioblastosis and Subsequent Diabetes Mellitus in a Dog with Hyperinsulinemic Hypoglycemia Treated with Partial Pancreatectomy.

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.

Diabetes Mellitus Following Resection of a Hepatocellular Carcinoma in a Dog Presented with Hypoglycemia.

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.

Transsphenoidal hypophysectomy for the treatment of hypersomatotropism secondary to a pituitary somatotroph adenoma in a dog.

Pituitary-dependent hypersomatotropism is rarely diagnosed in dogs and surgical treatment is not reported. A 6-year-10-month male neutered Patterdale Terrier presented with polyuria, polydipsia, progressive pharyngeal stertor, excessive hair growth and widened facial features and paws. Serum insulin-like growth factor-1 concentration via radioimmunoassay was consistent with hypersomatotropism (1783 ng/mL). A pituitary mass was identified on magnetic resonance and computed tomography imaging. Six weeks later, glucosuria, starved hyperglycemia and serum fructosamine above the reference range (467.6 µmol/L, RI 177-314) were documented, consistent with diabetes mellitus. Transsphenoidal hypophysectomy was performed under general anesthesia without complications. Pituitary histopathology identified an acidophil neoplasm, with positive immunostaining for growth hormone. Postoperatively, there was rapid resolution of clinical, biochemical and morphologic changes of hypersomatotropism with persistence of diabetes mellitus. This case demonstrates successful resolution of hypersomatotropism with ongoing diabetes mellitus in a dog after surgical treatment by transsphenoidal hypophysectomy.

Comparison of insulin infusion protocols for management of canine and feline diabetic ketoacidosis.

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 ß-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.

Preliminary evaluation of the impact of periodontal treatment on markers of glycaemic control in dogs with diabetes mellitus: A prospective, clinical case series.

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.

Invited review: Camel milk-derived bioactive peptides and diabetes-Molecular view and perspectives.

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 ß-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 ß-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.

Molecular docking studies on α-amylase inhibitory peptides from milk of different farm animals.

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-IC50 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-IC50 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.

Incidences of steroid-induced diabetes mellitus and congestive heart failure in cats given non-immunosuppressive doses of methylprednisolone acetate: 1042 cats.

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.

Incidences du diabète sucré et de l'insuffisance cardiaque congestive induits par les stéroïdes chez des chats ayant reçu des doses non immunosuppressives d'acétate de méthylprednisolone : 1042 chats. Objectif: Les corticoïdes sont indiqués pour traiter de nombreuses maladies félines. Cependant, les effets secondaires constituent un facteur limitant leur utilisation. Les effets secondaires les plus préoccupants sont le diabète sucré induit par les stéroïdes (SI-DM) et l'insuffisance cardiaque congestive induite par les stéroïdes (SI-CHF). Cette étude vise à déterminer l'incidence de ces maladies dans une large population de chats domestiques vus dans une pratique privée exclusivement féline. Animaux: Les chats de l'étude étaient des patients appartenant à des clients du Alamo Feline Health Center à San Antonio, au Texas. Les chats témoins (témoins) ont été examinés dans le cadre de leurs soins de santé de routine. Procédures: Les dossiers de 732 chats ayant reçu de l'acétate de méthylprednisolone (MPA) pour diverses indications cliniques ont été examinés afin de déterminer combien d'entre eux ont développé du SI-DM et du SI-CHF. Un examen similaire des dossiers de 310 témoins a été réalisé pour déterminer l'incidence du diabète sucré spontané (Sp-DM) et de l'insuffisance cardiaque congestive spontanée (Sp-CHF). Les chats témoins n'ont jamais reçu de corticostéroïdes oraux ou injectables. Résultats: Parmi les chats ayant reçu du MPA, 28 ont développé du SI-DM (3,83 %) et 6 ont développé du SI-CHF (0,82 %). Parmi les témoins, 22 ont développé du Sp-DM (7,10 %) et 6 ont développé du Sp-CHF (1,90 %). Conclusion: Les incidences de développement de SI-DM et de SI-CHF étaient respectivement de 3,83 % et 0,82 %; et le risque n'a pas augmenté même lorsque des doses répétées de MPA ont été administrées. Pertinence clinique: Les auteurs considèrent le rapport bénéfice/risque suffisant pour justifier l'utilisation du MPA lorsqu'il est indiqué, notamment si un autre médicament ne peut lui être substitué avec les mêmes résultats thérapeutiques.(Traduit par Dr Serge Messier).

Comparison of the outcomes of phacoemulsification versus topical medication alone in canine diabetic cataracts: a retrospective study.

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.

Complications associated with a flash glucose monitoring system in diabetic dogs.

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.

Les systèmes de surveillance du glucose interstitiel sont couramment utilisés chez les chiens diabétiques. Le but de cette étude était de documenter l'incidence des complications associées à l'utilisation d'un système de surveillance flash du glucose (FGMS) chez le chien. Les dossiers médicaux des chiens qui ont eu la mise en place pendant 14 jours d'un FGMS au cours d'une période d'un an ont été examinés. Les données récupérées comprenaient le nombre de jours pendant lesquels le capteur est resté attaché et fonctionnel, le détachement du capteur, la défaillance du capteur avant la fin de la période de surveillance de 14 jours et les changements dermatologiques au site du capteur. Des statistiques descriptives ont été utilisées pour caractériser les données. Trente-quatre chiens ont eu des FGMS placés. La plupart [32/34 (94 %)] des capteurs ont été placés sur la face dorsolatérale du thorax caudal à l'omoplate. Vingt-quatre capteurs (71 %) sont restés attachés pendant les 14 jours complets. L'incidence des complications associées à l'utilisation du FGMS était de 13/34 (38 %). La complication la plus fréquente était de légers changements dermatologiques au niveau du site du capteur [6/34 (18 %)]. L'érythème et la formation de croûtes au site de fixation étaient courants et pouvaient être liés à une dermatite de contact, à une hypersensibilité ou à la préparation cutanée avant la mise en place. Les systèmes de surveillance flash de la glycémie sont sans danger pour les chiens, bien qu'il existe certaines complications potentielles qui devraient être discutées avec les propriétaires de chiens.(Traduit par Docteur Serge Messier).

Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model.

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.

Association between Hyperglycemia and Canine Serum Pancreatic Lipase Immunoreactivity Concentration in Diabetic Dogs.

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.