Pregnancy-related diabetes mellitus in two dogs

CASE SUMMARIES: Two cases of diabetes mellitus occurring in bitches in association with pregnancy are reported. In the first case, a bitch with suspected acromegaly developed diabetes mellitus within 2 weeks of the due date. Despite insulin therapy, euglycaemia was not achieved. Tw o live, small pups were delivered by elective Caesarean section but died within 2 days. Signs consistent with acromegaly resolved but diabetes mellitus was permanent in the bitch. In the second case, diabetic ketosis with severe gastrointestinal disease was diagnosed 2 days after Caesarean section was performed due to dystocia. The pups delivered all died within 5 days. The bitch recovered fully from diabetes mellitus within 2 weeks and has remained euglycaemic without insulin for a period of at least 18 months.

CLINICAL RELEVANCE: These two cases demonstrate that diabetes mellitus can occur in association with pregnancy in dogs, that diabetic ketosis can occur during transient diabetes mellitus in dogs, and suggest that acromegaly may occur during pregnancy-related dioestrus in dogs. The scarcity of previous reports of this nature, however, suggests that such cases are unusual.

Lack of prompt resolution of hyperglycaemia may result in secondary diabetes mellitus becoming permanent. Management should focus on immediate insulin therapy or ovariohysterectomy to minimise this risk. Even mild hyperglycaemia should not be ignored during pregnancy. The insulin antagonistic effects of pregnancy, stressful illness, surgery and dystocia can be enough to result in diabetic ketosis in the absence of permanent insulin deficiency. Maternal hyperglycaemia may contribute to adverse fetal outcomes in dogs but further study is required regarding the nature of the risk.     

Type 2 diabetes mellitus with pancreatic β cell dysfunction in 3 horses confirmed with minimal model analysis

Reasons for performing study: Type 2 diabetes mellitus (T2DM) is diagnosed rarely in equine practice although it may be under‐recognised. A greater awareness of the condition and therapeutic considerations would be to the benefit of such cases presenting in practice. More investigation into the pharmacological management of these cases is needed. Objectives: Three cases of diabetes mellitus were investigated using a specific test for insulin sensitivity and pancreatic β cell function in order to define accurately and characterise the existence of T2DM in all 3 subjects. Methods: The insulin‐modified frequently sampled i.v. glucose tolerance test was performed in each case and the data so obtained were subject to minimal model analysis of insulin‐glucose dynamics. Cases were then monitored following treatment using a combination of dietary modification, metformin, glibenclamide and pergolide. Results: Marked insulin resistance was identified in each case and, furthermore, severe pancreatic β cell dysfunction was present therefore classifying each case as end stage T2DM. Treatment was nevertheless associated with restoration of normoglycaemia in all cases. Conclusions: T2DM in horses may be more common than generally considered. In some cases individuals may respond to therapy aimed at restoring insulin sensitivity and pancreatic function. Drugs used in other species for the treatment of T2DM have not yet been adequately tested in horses. Potential relevance: T2DM should be considered as an important differential diagnosis in mature to elderly horses and ponies suffering from weight loss, polydipsia and polyuria. Clinicians should be encouraged to offer treatment and management advice when such cases are encountered.     

Transient hyperglycaemia in a prediabetic dog treated with prednisone and cyclosporin A

A dog with immune-mediated haemolytic anaemia developed transient hyperglycaemia and glucosuria requiring insulin therapy in association with prednisone and cyclosporin A therapy. Following short-term therapy with insulin and cyclosporin A, the dog remained on prednisone therapy but required no further insulin therapy for 12 weeks, at which time the dog became permanently diabetic. We hypothesise that prednisone and cyclosporin A contributed to insulin resistance in a prediabetic dog with suboptimal endogenous insulin concentration and that the degree of insulin resistance decreased when cyclosporin A therapy was discontinued.     

Evaluation of an insulin zinc suspension for control of naturally occurring diabetes mellitus in dogs

OBJECTIVE: To evaluate duration of action of an insulin zinc suspension (Caninsulin, Intervet) in spontaneously occurring cases of canine diabetes mellitus and suitability of its use as a once daily administered insulin for treatment of this disease. DESIGN: Eight client-owned canine diabetics were included in a prospective pilot study. All dogs had been treated with Caninsulin for a minimum of 2 months and were considered on clinical grounds to be adequately stabilised. PROCEDURE: Dogs were hospitalised for 24 h and blood collected every 2 h via indwelling venous catheters for blood glucose determination. RESULTS: Once daily Caninsulin administration failed to maintain glycaemic control for greater than 13 h in five of eight dogs, but acceptable blood glucose concentrations were maintained for 22 h and greater than 24 h in two others. One dog became distressed during hospitalisation and the blood glucose curve did not show an identifiable response to the insulin. CONCLUSION: Most diabetic dogs may require twice daily administration of Caninsulin for satisfactory glycaemic control, but once daily administration may be adequate in some animals. More comprehensive investigation into duration of activity of Caninsulin is warranted.     

Hypothyroidism in a dog associated with trimethoprimsulphadiazine therapy

Abstract Hypothyroidism and a neuromuscular disorder developed in a 4-year-old Golden Retriever after it received potentiated sulphonamide and metronidazole for 18 and 14 weeks, respectively. Serum total T4 concentrations were non-detectable before and 6 h after exogenous administration of 4IU bovine thyroidstimulating hormone. Thyroid gland biopsy revealed changes consistent with diffuse hyperplastic goitre. Serum T4 concentrations were normal 7 days after discontinuation of therapy. The long-term trimethoprim-sulphadiazine therapy was considered the most likely cause of this dog's hyperplastic goitre. The cause of the neuromuscular disorder was not determined. It is recommended that discontinuation of potentiated sulphonamide takes place at least 7 days prior to any assessment of thyroid function. Résumé— Une hypothyroïdie et des troubles neuromusculaires sont observés sur un Golden Retriever de 4 ans, après une thérapeutique à base de sulfonamides potentialisés et de métronidazole, respectivement de 18 et 14 semaines. Des concentrations sériques de T4 totale ne sont pas détectables avant et après 6 heures d'une stimulation à la TSH bovine (4 UI). Des biopsies de la thyroïde montrent un goitre hyperplasique diffus. Les concentrations sériques de T4 sont de nouveau normales 7 jours après l'arrêt du traitement. L'administration à long terme de triméthoprim-sulphadiazine semble être la cause la plus vraisemblable du goitre hyperplasique. La cause des troubles neuromusculaires n'a pas été déterminée. Il est recommandé d'arrêter l'administration de sulfonamides potentialisés au moins 7 jours avant une exploration de la function thyroïdienne. [Torres, S.M.F. Hypothyroidism in a dog associated with triméthoprim-sulphadiazine therapy (Hypothyroi'die en relation avec un traitement triméthoprim-sulphadiazine chez un chien). Veterinary Dermatology 1996; 7 : 105–108.] Resumen Un perro Golden Retriever de 4 años desarrolló hipotiroidismo y una afección neuromuscular después de recibir un tratamiento con sulfonamidas potenciadas y metronidazol 18 y 14 semanas, respectivamente. Las concentraciones séricas totales de T4 eran indetectables antes y a las 6 horas después de la administración exógena de 4 UI de TSH bovina. La biopsia de tiroides mostró alteraciones indicativas de gota hiperplásica difusa. Las concentraciones séricas de T4 fueron normales a los 7 dias de retirar la terapia. La terapia prolongada con trimetoprim-sulfadiazina fue considerada la causa más probable de gota hiperplásica en este perro. No se determinó la causa del cuadro neuromuscular. Se recomienda retirar la terapia con sulfonamida potenciada al menos 7 días antes de la evaluación de la función tiroidea. [Torres, S.M.F. Hypothyroidism in a dog associated with trimethoprim-sulphadiazine therapy (Hipotiroidismo en un perro asociado a la terapia con trimetoprim-sulfadiazina). Veterinary Dermatology 1996; 7 : 105–108.] Zusammenfassung— Hypothyreose und eine neuromuskuläre Störung entwickelten sich bei einem 4 Jahre alten Golden Retriever, nachdem er potenzierte Sulfonamide und Metronidazol über 18 beziehungsweise 14 Wochen erhalten hatte. Die Gesamt T4-Konzentrationen waren vor und 6 Stunden nach exogener Verabreichung von 4 IE bovinen TSH nicht meßbar. Eine Biopsie der Schilddrüse zeigte Veränderungen, die parallel mit diffusem hyperplasischem Kropf auftreten. Die Serum T4-Konzentrationen waren 7 Tage nach Abbruch der Therapie wieder normal. Die Langzeit-Trimethoprim-Sulfadiazin-Therapie wurde als wahr-scheinlichste Ursache dieses hyperplastischen Kropfes beim Hund angesehen. Die Ursache der neuro-muskulären Störung konnte nicht festgestellt werden. Es wird empfohlen, potenzierte Sulfonamide mindestens 7 Tage vor einer überprüfung der Schilddrüsenfunktion abzusetzen. [Torres, S. M. F. Hypothyroidism in a dog associated with trimethoprim-sulphadiazine therapy (Hyperthyreose bei einem Hund in Verbindung mit einer Trimethoprim-Sulfadiazin-Therapie). Veterinary Dermatology 1996; 7 : 105–108.]     

Pulmonary lesions in cats with diabetes mellitus

Diabetes mellitus (DM) is a common endocrinopathy of cats and humans. Although few studies have examined the effects of DM on the pulmonary system, changes in pulmonary function and immunology in humans with type I and II diabetes, and pulmonary lesions in a murine diabetic model have been documented. Our objective was to determine whether pulmonary lesions occurred in cats with DM. Medical records and necropsy evaluations of 42 cats with DM were compared with those of 45 age-matched, nondiabetic cats for the presence of clinical evidence of respiratory disease and pulmonary histopathological findings at the time of necropsy. No statistical difference was noted in the presence of clinical evidence of respiratory disease between cats with diabetes and control cats. Nevertheless, there was a significant association between the presence of abnormal pulmonary histopathology and DM (P = .018, odds ratio = 3 inclusive of all cats; P = .005, odds ratio = 5 when non-DM cats with overt clinical evidence of respiratory disease were excluded). Pulmonary abnormalities detected by histopathological examination in cats with diabetes included congestion and edema, histiocytosis, pneumonia, smooth muscle hypertrophy, fibrosis, mineralization, neoplasia, and type II pneumocyte hyperplasia. The observed association between DM and pulmonary lesions in cats, independent of clinical evidence of respiratory disease, emphasizes the need for careful assessment of the respiratory tract in sick cats with diabetes.     

Serum insulin-like growth factor-I concentration in cats with diabetes mellitus and acromegaly

BACKGROUND: Serum insulin-like growth factor-I (IGF-I) has been used in place of serum growth hormone quantification for identifying acromegaly in diabetic cats. The utility of IGF-I as a screening test for acromegaly has not been critically evaluated. This retrospective study was performed to evaluate the usefulness of serum IGF-I concentration for identifying acromegaly. HYPOTHESIS: Serum IGF-I is a useful screening test for acromegaly in diabetic cats. ANIMALS: A review was made of the medical records of 74 diabetic cats that had serum IGF-I quantified. The diabetes was classified as well controlled (15 cats), poorly controlled because of problems with the insulin treatment regimen, concurrent disease, or both (40), or poorly controlled with clinical findings consistent with acromegaly (19). METHODS: A review of medical records was made. RESULTS: Serum IGF-I concentration was significantly (P < .0001) increased in acromegalic diabetic cats, compared with well-controlled and poorly controlled diabetic cats. Sensitivity and specificity for serum IGF-I concentration were 84% (95%/ confidence interval [CI] = 60.4-96.6%) and 92% (95% CI = 81.3-97.2%), respectively. There was no significant correlation between serum IGF-I concentration and duration of insulin treatment (r = 0.23, P = .089), insulin dosage (r = 0.14, P = .30), age (r = 0.16, P = .12), and pituitary volume (r = 0.40, P = .11), but a modest correlation was found between serum IGF-I concentration and body weight (r = 0.48, P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Results support the use of serum IGF-I concentration as a screening test for acromegaly in diabetic cats that have clinical findings supportive of the disease.     

The prevalence of microalbuminuria and proteinuria in cats with diabetes mellitus

The prevalence of microalbuminuria (MA) and proteinuria was evaluated in 66 cats with diabetes mellitus (DM), 35 nondiabetic cats with other illness, and 11 healthy nondiabetic cats with use of the E.R.D.-HealthScreen Feline Urine Test. The MA prevalence was higher in the diabetic than in the nondiabetic sick and healthy control cats (70%, 39%, and 18% respectively, P < .0001). In addition, prevalence of proteinuria defined by a protein/creatinine ratio (UPC) > 0.4 was significantly higher in the diabetic cat than in the control cats (70%, 35%, and 9% respectively, P < .0001). There was a significant but weak correlation between the results of MA and UPC (P < .0001, r = 0.43). Our results showed that MA is common in cats with DM. Further studies are required to evaluate the prognostic value of the presence and the severity of MA in cats with DM.     

Transient diabetes mellitus in a neonatal Thoroughbred foal

Objective – To describe the clinical presentation, treatment, and outcome of a neonatal foal diagnosed with transient Type 1 diabetes mellitus. Case Summary – A 3‐day‐old Thoroughbred foal presented with a 24‐hour history of diarrhea and depression. Coronavirus particles were observed in the feces via electron microscopy. During hospitalization the foal developed hyperglycemia concomitantly with low insulin concentration and an adequate response to exogenous insulin therapy supported a diagnosis of Type 1 diabetes mellitus. The foal required SC insulin for 26 days, but developed complications associated with insulin therapy that resolved with appropriate care. On follow up assessment the foal was found to be a healthy euglycemic animal with normal insulin concentration at 11 months of age. New or Unique Information Provided – To our knowledge this is the first report of Type 1 diabetes in this age group and the first report of transient neonatal diabetes mellitus in horses. Type 1 diabetes mellitus should be considered a differential diagnosis for hyperglycemia in equine neonates and that it can be transient and managed successfully.     

Comparison of glucose concentrations in canine whole blood,plasma, and serum measured with a veterinary point-of-care glucometer

Previous studies have determined that, compared to whole blood, serum or plasma used in a portable blood glucometer (PBG) may provide more accurate results. We investigated the accuracy of a veterinary PBG (AlphaTRAK 2; Zoetis) for the measurement of glucose concentrations in serum, plasma, and whole blood compared to plasma glucose concentration measured by a biochemical analyzer. Blood samples from 53 client-owned dogs were collected. Lin concordance correlation coefficient (ρ_c) and Bland–Altman plots were used to determine correlation and agreement between the results obtained for the different sample types. Glucose concentration in whole blood measured by the veterinary PBG was more strongly correlated with the glucose concentration measured by the biochemical analyzer (ρ_c = 0.92) compared to plasma and serum glucose concentrations (ρ_c = 0.59 and 0.57, respectively). The mean differences between the glucose concentrations in whole blood, plasma, and serum measured by the veterinary PBG and the glucose concentration determined by the biochemical analyzer were 1.0, 6.3, and 6.7 mmol/L (18, 113, and 121 mg/dL), respectively. Our findings suggest that, when using this veterinary PBG, the accuracy of a glucose measurement obtained is higher when using whole blood compared to plasma or serum. Use of whole blood allows for more correct assessment and diagnosis, which are necessary for appropriate therapeutic intervention.     

Serum fructosamine in canine diabetes mellitus. An initial study

This study reports on a spectrophotometric assay for the determination of serum fructosamine concentration. The assay was evaluated for use in canine serum samples by assessment of the precision, accuracy, detectability and stability of serum fructosamine during storage. To evaluate the diagnostic usefulness of the assay, both the effect of acute changes in blood glucose on serum fructosamine concentration and the serum fructosamine concentration in canine diabetes mellitus and other canine diseases were studied.The main conclusions can be summarized as follows: Determination of canine serum fructosamines may be achieved by a precise and accurate assay with a detection limit well below the serum fructosamine concentration normally found in canine sera. Storage for 5 days at +4°C or +25°C, or for 28 days at –20°C caused no significant change in serum fructosamine concentration. The concentration is not affected by acute changes in blood glucose. In diabetic dogs, serum fructosamine concentration is significantly greater than in dogs with other diseases.     

Growth of rumen papillae in weaned calves is associated with lower expression of insulin‐like growth factor‐binding proteins 2, 3, and 6

This study aimed to characterize the relationship between the growth of rumen papillae in calves and the mRNA expression of insulin‐like growth factor‐binding proteins (IGFBPs) in the rumen papillae. The length of rumen papillae, the mRNA expression of IGFBPs in rumen papillae by quantitative real‐time PCR, and the presence of insulin‐like growth factors I and II (IGF‐I and II) by immunohistochemistry (IHC) were analyzed in nine Holstein calves divided into three groups: suckling (2 weeks, n = 3), milk‐continued (8 weeks, n = 3), and weaned (8 weeks, n = 3). The length of rumen papillae was greater (p < 0.01) in weaned calves than in suckling and milk‐continued calves, whereas the expressions of IGFBP2, IGFBP3, and IGFBP6 genes were lower (p < 0.05) in the rumen papillae of weaned calves than in milk‐continued calves. Thus, rumen papillae length and IGFBP2, 3, and 6 expressions were negatively correlated. The IHC analysis showed that IGF‐I and IGF‐II were present in the rumen epithelium of calves. These results suggested that the growth of rumen papillae after weaning is associated with the induction of IGFs by the low levels of IGFBP2, IGFBP3, and IGFBP6.     

Anti‐diabetic effect of camel milk in alloxan‐induced diabetic dogs: a dose–response experiment

This study was conducted to evaluate the effect of camel milk in alloxan‐induced diabetic dogs and to follow this effect at three doses of milk. Firstly, three groups of dogs were used: two groups composed each of four diabetic dogs and receiving raw camel milk (treatment 1) or cow milk (treatment 2), and four healthy dogs getting raw camel milk (treatment 3) were used as control. Each animal was treated with 500 ml of milk daily. Secondly, we compared the effects of three amounts of camel milk: 100 ml, 250 ml and 500 ml to treat the diabetic dogs. After week 3, the dogs treated with camel milk showed a statistically significant decrease in blood glucose (from 10.88 ± 0.55 to 6.22 ± 0.5 mmol/l) and total protein concentrations (from 78.16 ± 2.61 g/l to 63.63 ± 4.43 g/l). For cholesterol levels, there was a decrease from week 2 (from 6.17 ± 0.5 mmol/l to 4.79 ± 0.5 mmol/l). There were no significant difference in blood glucose, cholesterol or total protein concentrations in dogs drinking 250 and 500 ml of camel milk. The dogs treated with 100 ml of camel milk did not show any significant decrease in blood glucose levels, and cholesterol and total protein concentrations. The investigation was not limited to the improvement in glycemic balance, lipids and proteins control in diabetic dogs getting camel milk, but we also noted a stability of this state after the dogs stopped to drink milk. This effect depended on the quantity of camel milk used to treat diabetic dogs.     

Ruminal epithelial insulin‐like growth factor‐binding proteins 2, 3, and 6 are associated with epithelial cell proliferation

The aim of this study was to identify factors that regulate ruminal epithelial insulin‐like growth factor‐binding protein (IGFBP) expression and determine its role in rumen epithelial cell proliferation. Primary bovine rumen epithelial cells (BREC) were incubated with short‐chain fatty acids (SCFAs) at pH 7.4 or 5.6, lactate, lipopolysaccharide (LPS), insulin‐like growth factor‐I (IGF‐I), ‐II (IGF‐II), or recombinant bovine IGFBP2 (rbIGFBP2). The mRNA expression levels of IGFBP in BREC were analyzed using quantitative real‐time polymerase chain reaction (qRT‐PCR). The proliferation rate of BREC was analyzed using a WST‐1 assay. IGFBP2 gene expression tended to be lower with SCFA treatment (p < .1), and IGFBP6 gene expression was significantly lower with SCFA treatment (p < .05). IGFBP3 and IGFBP6 gene expression tended to be higher with d ‐Lactate treatment (p < .1). IGFBP3 gene expression was significantly higher (p < .05) with LPS treatment. BREC treated with IGF‐I grew more rapidly than vehicle control‐treated cells (p < .01); however, recombinant bovine rbIGFBP2 inhibited IGF‐I‐induced proliferation. IGF‐II and/or rbIGFBP2 did not affect BREC proliferation. Taken together, SCFA treatment decreased IGFBP2 and IGFBP6 expression in rumen epithelial cells, and lower expression of these IGFBP might promote rumen epithelial cell proliferation by facilitating IGF‐I.     

Coarse fractionated radiation therapy for pituitary tumours in cats: a retrospective study of 12 cases

This retrospective study describes the clinical progression of 12 cats with pituitary tumours treated with a coarse fractionated radiation protocol delivering a total dose of 37 Gy in five once weekly fractions. A pituitary macrotumour was identified in all 12 cats: 4 with neurological signs only and 8 with insulin‐resistant diabetes mellitus secondary to acromegaly. One of the cats with central neurological signs died before completing the radiotherapy course; the remaining three had partial or complete remissions of their central neurological signs. Of the cats with unstable diabetes mellitus, five no longer required insulin therapy, one required less insulin and two became stable. The overall median survival time was 72.6 weeks; four cats died from related causes, two from unrelated problems and six remain alive. Radiation therapy is confirmed as an effective treatment for feline pituitary tumours, giving prolonged survival and control of both paraneoplastic and mass effect signs.     

Relationship between anti-insulin antibody production and severe insulin resistance in a diabetic cat

A 5-year-old castrated male domestic shorthair cat was diagnosed with diabetic ketoacidosis and severe insulin resistance. Although the conventional treatment for diabetic ketoacidosis was provided, the cat required frequent hospitalization because of severe dehydration and repeated diabetic ketoacidosis. We detected anti-insulin antibodies for human in this cat. Serum insulin-binding IgG levels were markedly elevated compared with those in healthy cats and other diabetic cats. We initiated prednisolone to suppress the effects of anti-insulin antibodies. After initiation of prednisolone, the cat was gradually recovered with increasing activity and appetite. Furthermore, satisfactory glycemic control was achieved with combined subcutaneous injection of insulin detemir and insulin degludec.     

Outcome and toxicity associated with a dose‐intensified,maintenance‐free CHOP‐based chemotherapy protocol in canine lymphoma: 130 cases

A dose‐intensified/dose‐dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub‐stage b (58.5%). The median time to progression (TTP) and lymphoma‐specific survival were 219 and 323 days, respectively. These results are similar to previous less dose‐intense protocols. Sub‐stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma‐specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.