[Polyendocrine syndromes in dogs]. / Polyendokrine Syndrome beim Hund.

The autoimmune polyendocrine syndrome (APS) refers to a combination of autoimmune endocrine disorders. It is rarely described in dogs. The most common combinations are hypoadrenocorticism and hypothyroidism, followed by diabetes mellitus, and less often hypoparathyroidism and orchitis. The diagnosis of the APS is based on the diagnosis of each endocrinopathy, as is the therapy, which involves the substitution of deficient hormones. If a patient was previously stable under treatment and is showing further signs (e.g. polyuria, polydipsia, or weight loss), the development of additional endocrinopathies like hypoadrenocorticism or diabetes mellitus should be considered. The diagnosis of the initially diagnosed endocrinopathy should also be critically questioned. This article summarizes some cases of our own animal hospital and selected cases published in the available literature.

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

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

Toceranib phosphate (Palladia) reverses type 1 diabetes by preserving islet function in mice.

In recent years, strategies targeting ß-cell protection via autoimmune regulation have been suggested as novel and potent immunotherapeutic interventions against type 1 diabetes mellitus (T1D). Here, we investigated the potential of toceranib (TOC), a receptor-type tyrosine kinase (RTK) inhibitor used in veterinary practice, to ameliorate T1D. TOC reversed streptozotocin-induced T1D and improved the abnormalities in muscle and bone metabolism characteristic of T1D. Histopathological examination revealed that TOC significantly suppressed ß-cell depletion and improved glycemic control with restoration of serum insulin levels. However, the effect of TOC on blood glucose levels and insulin secretion capacity is attenuated in chronic T1D, a more ß-cell depleted state. These findings suggest that TOC improves glycemic control by ameliorating the streptozotocin-induced decrease in insulin secretory capacity. Finally, we examined the role of platelet-derived growth factor receptor (PDGFR) inhibition, a target of TOC, and found that inhibition of PDGFR reverses established T1D in mice. Our results show that TOC reverses T1D by preserving islet function via inhibition of RTK. The previously unrecognized pharmacological properties of TOC have been revealed, and these properties could lead to its application in the treatment of T1D in the veterinary field.

Duration of the diabetic state altered platelet indices from baseline values in a streptozotocin-induced rat model for type 1 diabetes mellitus.

BACKGROUND: Changes in platelet indices in naturally occurring type I diabetes mellitus (T1DM) have been described in several studies. In this study, platelet indices such as platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), and MPV to PLT ratio were investigated according to diabetic duration after streptozotocin (STZ)-induced T1DM, as well as for their correlation with glucose. METHODS: Forty healthy adult Wistar rats were randomly assigned to four experimental groups of ten (5 rats of each sex), including the control group, the 7, 14, and 28 days diabetic groups (D7, D14, and D28, respectively). RESULTS: In diabetic groups, plasma glucose was significantly higher than in control (P < 0.01). D7, D14, and D28 groups presented significantly lower PLT than the control (P < 0. 01). A significant decrease in PCT was observed in D14 and D28 females (P < 0.05). Mean platelet volume was significantly higher in the D28 group than in to control. D28 females also showed a significant difference in PLT, MPV, and the MPV-to-PLT ratio compared with D7 females (P < 0.05). A comparison between D28 females and males showed a significant difference in PDW (P < 0.05). Both females and males showed a significant correlation between glucose and PLT, PCT, MPV, and the MPV-to-PLT ratio. CONCLUSIONS: Platelet indices change significantly with the duration of diabetes compared with the baseline values, and female and male rats did not have significant differences in platelet indices in any period except the 28 days.

Effects of gradient high-field static magnetic fields on diabetic mice.

Although 9.4 T magnetic resonance imaging (MRI) has been tested in healthy volunteers, its safety in diabetic patients is unclear. Furthermore, the effects of high static magnetic fields (SMFs), especially gradient vs. uniform fields, have not been investigated in diabetics. Here, we investigated the consequences of exposure to 1.0-9.4 T high SMFs of different gradients (>10 T/m vs. 0-10 T/m) on type 1 diabetic (T1D) and type 2 diabetic (T2D) mice. We found that 14 h of prolonged treatment of gradient (as high as 55.5 T/m) high SMFs (1.0-8.6 T) had negative effects on T1D and T2D mice, including spleen, hepatic, and renal tissue impairment and elevated glycosylated serum protein, blood glucose, inflammation, and anxiety, while 9.4 T quasi-uniform SMFs at 0-10 T/m did not induce the same effects. In regular T1D mice (blood glucose ≥16.7 mmol/L), the >10 T/m gradient high SMFs increased malondialdehyde ( P<0.01) and decreased superoxide dismutase ( P<0.05). However, in the severe T1D mice (blood glucose ≥30.0 mmol/L), the >10 T/m gradient high SMFs significantly increased tissue damage and reduced survival rate. In vitro cellular studies showed that gradient high SMFs increased cellular reactive oxygen species and apoptosis and reduced MS-1 cell number and proliferation. Therefore, this study showed that prolonged exposure to high-field (1.0-8.6 T) >10 T/m gradient SMFs (35-1 380 times higher than that of current clinical MRI) can have negative effects on diabetic mice, especially mice with severe T1D, whereas 9.4 T high SMFs at 0-10 T/m did not produce the same effects, providing important information for the future development and clinical application of SMFs, especially high-field MRI.

Exploration of autoantibody responses in canine diabetes using protein arrays.

Canine diabetes has been considered a potential model of human type 1 diabetes (T1D), however the detection of autoantibodies common in humans with T1D in affected dogs is inconsistent. The aim of this study was to compare autoantibody responses in diabetic and healthy control dogs using a novel nucleic acid programmable protein array (NAPPA) platform. We performed a cross-sectional study of autoantibody profiles of 30 diabetic and 30 healthy control dogs of various breeds. Seventeen hundred human proteins related to the pancreas or diabetes were displayed on NAPPA arrays and interrogated with canine sera. The median normalized intensity (MNI) for each protein was calculated, and results were compared between groups to identify candidate autoantibodies. At a specificity of 90%, six autoantibodies had sensitivity greater than 10% (range 13-20%) for distinguishing diabetic and control groups. A combination of three antibodies (anti-KANK2, anti-GLI1, anti-SUMO2) resulted in a sensitivity of 37% (95% confidence interval (CI) 0.17-0.67%) at 90% specificity and an area under the receiver operating characteristics curve of 0.66 (95% CI 0.52-0.80). While this study does not provide conclusive support for autoimmunity as an underlying cause of diabetes in dogs, future studies should consider the use of canine specific proteins in larger numbers of dogs of breeds at high risk for diabetes.

Effects of dapagliflozin in combination with insulin on cytochrome P450 activities in a diabetes type 1 rat model.

Previous studies reported that diabetes alters the activities of hepatic cytochrome P450 (CYP) enzymes, which, in turn, affects the disposition of some drugs. We herein examined and compared the effects of the combination of dapagliflozin with a low insulin dose, a full dose of insulin alone, and dapagliflozin alone for 3 and 8 weeks on CYP activities in a diabetes type 1 rat model. We induced type 1 diabetes in rats using a single intraperitoneal injection of 60 mg/kg streptozotocin (STZ). Daily treatment with the full dose of insulin alone, dapagliflozin alone, or dapagliflozin in combination with a low dose of insulin was then initiated. STZ-induced rats developed marked hyperglycemia and altered CYP2E activities. Dapagliflozin in combination with a low dose of insulin stabilized hyperglycemia and CYP1A, 2D, 2E and 3A activities. However, dapagliflozin alone did not improve blood glucose levels or CYP activities. These results suggest that the effects of dapagliflozin in combination with a low dose of insulin are similar to those of a full dose of insulin, and stabilize CYP activities in type 1 diabetes.

Autoimmune polyendocrine syndrome with hypoadrenocorticism and diabetes mellitus in a dog: A rare case.

BACKGROUND: Autoimmune polyendocrine syndrome, also called polyglandular autoimmune syndrome, is a rare immune-mediated disorder that involves various endocrine glands. PURPOSE: To report autoimmune polyendocrine syndrome in a dog. METHODS: A 9-year-old spayed female miniature poodle diagnosed with insulin-dependent diabetes mellitus emergently visited our clinic for anorexia, severe depression, and vomiting. Hyponatremia, hypochloridemia, and recurrent hypoglycaemia were found. Hypoadrenocorticism was diagnosed based on consistent clinical signs and repeated adrenocorticotropic hormone stimulation tests. RESULTS: After injecting deoxycorticosterone pivalate and increasing the oral prednisolone dose, the patient's systemic condition improved. CONCLUSIONS: To the best of our knowledge, this is the first case report of hypoadrenocorticism concurrent with diabetes mellitus in a dog. Furthermore, we would like to present the probability of an immune-mediated disorder with multiple organs involved, like type IV autoimmune polyendocrine syndrome in humans.

Sex difference feeding behaviour of NOD SCID mice in a pharmacological model of type 1 diabetes.

This study aimed to assess the sex differences in the feeding behaviour of non-obese diabetic severe combined immunodeficient (NOD SCID) mice in a pharmacological model of type 1 diabetes mellitus (T1Dm). In our study, we chose NOD SCID mice of both sexes and assessed their feeding behaviour, body weight, body fat and water content under identical experimental conditions and diets. After 1 month of diabetes mellitus in mice in the experimental group, males and females did not show any increase in body weight, and they weighed significantly less than the control group. However, compared with the control group, in females with a background of T1Dm, there was a significant decrease in body fat. The amount of water consumed in the experimental groups was higher than that in the control groups. The amount of food consumed by males increased when they increased their water consumption, whereas food consumption in females decreased significantly with an increase in water consumption. Thus, we discovered sex differences in the feeding behaviour, body weight and body fat and water content in the pharmacological model of T1Dm after 1 month in NOD SCID mice.