Search

Naturally occurring diabetes mellitus (NODM) is one of the most common endocrine disorders in dogs and its etiology closely resembles type 1 diabetes mellitus (T1DM) in people. Human patients with T1DM commonly have cellular derangements consistent with inflammation, impaired immune function, and hypovitaminosis D. There is little information available regarding inflammatory biomarkers, immune function, and vitamin D status in diabetic dogs. Therefore, our objectives were to assess inflammatory biomarkers, vitamin D metabolites, and phagocytic capacity in diabetic dogs and determine whether associations exist with these variables and the level of clinical control or vitamin D metabolites. This was a prospective case--control study that included 20 otherwise healthy diabetic dogs (clinically controlled, n = 10; uncontrolled, n = 10) and 20 nondiabetic, healthy, age (± 2 years), breed, and sex matched controls. Complete blood count, biochemical panel, urinalysis, and fructosamine were performed at a single commercial reference laboratory. Basal plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10 were measured using a canine-specific multiplex bead-based assay. Serum C-reactive protein (CRP) was measured using a commercially available ELISA kit. Serum 25-hydroxyvitamin (OH)D3 and 24,25-dihydroxyvitamin (OH)2D3 were measured with HPLC. Phagocytosis of opsonized-Escherichia coli (E. coli) was evaluated with flow cytometry. Diabetic dogs had higher serum CRP concentrations than controls (p = 0.02). Plasma IL-8 concentrations were higher in diabetic dogs with uncontrolled clinical disease compared to controls (p = 0.02). Diabetic dogs had a lower percentage of leukocytes that phagocytized opsonized-E. coli (p = 0.02), but an increased number of bacteria phagocytized per cell (p < 0.001) compared to controls. No between-group differences were identified in vitamin D metabolites, nor were associations found between vitamin D and any variables. Fructosamine had a positive association with serum CRP concentration (rho = 0.35, p = 0.03) and number of bacteria phagocytized per cell (rho = 0.45, p = 0.004) in our cohort (n = 40). Like people with T1DM, diabetic dogs have a proinflammatory phenotype and phagocytic dysregulation that may be correlated with glycemic control. [ABSTRACT FROM AUTHOR]

Simple Summary: Naturally occurring diabetes mellitus (NODM) is one of the most common endocrine disorders in dogs and is most similar to type 1 diabetes mellitus (T1DM) in human patients. Immune responses in people with T1DM are abnormal and may contribute to a variety of long-term complications. There is very little information regarding immune function in dogs with NODM. Vitamin D deficiency is a relatively frequent finding in diabetic human patients. This is important because vitamin D has several positive effects on the immune system. Therefore, it is unsurprising that some studies demonstrate that vitamin D supplementation is beneficial in people with T1DM. While vitamin D interacts with the immune system in dogs, there have been no studies evaluating its effect in diabetic dogs. Therefore, our study sought to evaluate several components of immune function and the modulatory effects of calcitriol in diabetic dogs. We found that like human patients with T1DM, the diabetic state causes cytokine and phagocytic dysregulation in dogs. Vitamin D affected leukocyte cytokine secretion but not phagocytosis. The level of clinical control in diabetic dogs did not affect the immune function variables investigated in this study. Human patients with type 1 diabetes mellitus (T1DM) are susceptible to several long-term complications that are related to glycemic control and immune dysregulation. Immune function remains relatively unexplored in dogs with naturally occurring diabetes mellitus (NODM). Calcitriol improves various aspects of immune function in a variety of species, but its effect in diabetic dogs remains unexplored. Therefore, the objectives of this study were to (i) evaluate immune function in dogs with NODM and determine if differences exist based on the level of clinical control and (ii) assess the immunomodulatory effects of calcitriol. Twenty diabetic dogs (clinically controlled, n = ten, not controlled, n = ten) and 20 non-diabetic, healthy control dogs were included in this prospective, case–control study. Whole blood was incubated with calcitriol (10−7 M) or negative control, after which the samples were divided for phagocytosis and leukocyte cytokine response experiments. The phagocytosis of opsonized Escherichia coli (E. coli) was evaluated with flow cytometry. The samples for leukocyte cytokine response evaluations were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or phosphate buffer solution (PBS; negative control), and tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10 were measured in supernatant using a canine-specific multiplex bead-based assay. The leukocytes from diabetic dogs produced higher concentrations of IL-10 (p = 0.01), IL-6 (p < 0.0001), and IL-8 (p < 0.0001) than the control dogs while controlling for the intervention and stimulant. Calcitriol decreased the supernatant concentrations of TNF-α (p < 0.001) and IL-8 (p = 0.04) with concomitant increases in IL-6 (p = 0.005). Diabetic dogs had a lower percentage of leukocytes undergoing phagocytosis (p < 0.0001) but a higher number of bacteria phagocytized per cell (p = 0.001) when compared to the control dogs. Calcitriol had no effect on phagocytic capacity. Lastly, the status of clinical control in diabetic dogs did not yield differences in immune function. These results support that dogs with NODM exhibit immune dysregulation and warrant additional investigation. [ABSTRACT FROM AUTHOR]

The objective was to evaluate the effects of dietary macronutrients and feeding frequency on blood glucose, insulin, total ghrelin and leptin. A total of twelve adult lean neutered male cats were used in three tests, all cross-over studies composed of a 15 d adaptation and blood sampling on day 16. In trial 1, differences between two- and four-meal feeding were tested. On day 16, blood samples were collected every 2 h for 24 h. In trial 2, macronutrient boluses were tested. Instead of the control diet, the morning meal on day 16 was replaced with an isoenergetic bolus of carbohydrate (maltodextrin), protein (chicken meat), fat or water. Fasted and ten postprandial blood samples were collected. In trial 3, diets high in fat (HF), protein (HP), carbohydrate (HC) or a control diet were tested. On day 16, fasted and ten postprandial blood samples were collected. Data were analysed to identify baseline and AUC changes. Cats fed four meals daily had greater (P = 0·03) leptin incremental AUC0-24 h compared with cats fed twice daily. The carbohydrate bolus increased glucose (P < 0·001) and insulin (P < 0·001) incremental AUC0-6 h and tended to increase (P = 0·09) leptin net AUC0-6 h. Cats fed the control and HC diets had greater (P = 0·03) glucose incremental AUC compared with the HF and HP conditions. Circulating hormone data were highly variable and indicated changes due to dietary macronutrients and feeding frequency, but further study is needed to identify impacts on appetite and contributing mechanisms. [ABSTRACT FROM AUTHOR]