Nondiabetic Dogs Research Articles

Clinical and histological study of cold physical plasma jet in treatment of full thickness skin wounds of normal and diabetic dogs.

To study the effect of physical plasma jet in treating open wounds in diabetic and non-diabetic dogs. The experimental study was conducted at the College of Veterinary Medicine, University of Baghdad, Iraq, from 20 January, 2020 to 1st May 2020, according to (no. 1364/ P.G), and comprised adult male diabetic and nondiabetic dogs. They were divided into non-diabetic group N and diabetic group D. Each group was further divided into treatment subgroup T and control subgroup C. Each dog was subjected to 4 wounds 3×3cm in size. Homemade helium non-equilibrium atmospheric pressure plasma jet therapy was used for healing purposes. Clinical parameters were evaluated by observation, while histological images were scored based on the semi-quantitative evaluation of histological sections on days 3-, 7- and 21-days post-wound. Data was analysed using SPSS Version 26 with One-way ANOVA for statistical analysis between groups and sub-groups. Of the 24 dogs, 12(50%) were in each of the two groups, which were further divided into subgroups having 6(50%) dogs each. The therapy accelerated the process of wound healing in the NT and DT subgroups compared to NC and DC. Clinical observations revealed early and complete closure of plasma-treated wounds in NT and DT subgroups started at day 30 post-wounding, while in the NC subgroup it started at day 35, and in the DC subgroup, wounds failed to close even after 35 days post-wounding. Histological analysis suggested that a plasma jet supported epithelisation, angiogenesis, formation of new hair follicles and collagen fibres, while it also controlled inflammation. In addition, in NT and DT subgroups, it increased the proliferation of fibroblasts and deposition of collagen, and there is a very, highly significant difference between groups (P<0.001), and a significant difference between days (P<0.05). Home-made helium non-equilibrium atmospheric pressure plasma jet therapy improved the quality and pace of wound healing.

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.

Hip sensor location for flash interstitial glucose monitoring system provides adequate clinical accuracy in non-diabetic hypoglycemic dogs.

Flash glucose monitoring systems (FGMS) are frequently used for interstitial glucose monitoring in dogs with diabetes mellitus and are typically placed between the scapulae. We aimed to evaluate the variability between glucose measurements from FGMS placed in 2 locations (between the scapulae and over the hip) in non-diabetic dogs during rapidly induced hypoglycemia. 24 apparently healthy colony dogs that were subjects in a teaching laboratory. Prospective interventional study. FGMS sensors (FreeStyle Libre 14-day system) were placed between the scapulae and over the hip of all dogs. Regular insulin was administered (0.3 u/kg IV) and subsequent hypoglycemia was corrected. Before insulin administration and every 10 minutes over 90 minutes, interstitial glucose was recorded from both locations, and blood glucose was measured with a point-of-care blood glucose monitor (AlphaTRAK 2). There was a constant bias of 5.6 mg/dL (95% limits of agreement: -26.3 to 37.5 mg/dL) between locations, but the proportional bias was not apparent. There was a correlation between FGMS locations (r = 0.731, P = < .001). Sensor site B was clinically accurate with 100% of paired samples within Parkes error grid zones A (83%) and B (17%) but did not meet the criteria for analytical accuracy. In this model of induced hypoglycemia in healthy dogs, variation between measurements from FGMS locations was unlikely to have affected the clinical outcome. Placement of FGMS over the hip may be an acceptable alternative to placement between the scapulae, but the utility in hyperglycemic dogs is unknown.

Decreased corneal subbasal nerve fiber length and density in diabetic dogs with cataracts using in vivo confocal microscopy.

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. Twenty six domestic dogs with cataracts of various breeds presented for phacoemulsification, 13 with DM and 13 without DM. 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. The mean (±SD) CSNP fiber length was significantly decreased in diabetic (3.8 ± 3.0 mm/mm2 ) versus non-diabetic (6.7 ± 1.9 mm/mm2 ) dogs. Likewise, the mean (±SD) fiber density was significantly decreased in diabetic (8.3 ± 3.1 fibers/mm2 ) versus non-diabetic (15.5 ± 4.9 fibers/mm2 ) dogs. The corneal touch threshold was significantly reduced in diabetic (2.1 ± 0.8cm) versus non-diabetic (2.8 ± 0.4cm) dogs. There was a non-significant trend towards subclinical keratitis in diabetic (9/13) versus non-diabetic (4/13) dogs. 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.

Effect of site of sample collection on blood glucose concentrations measured with a portable blood glucose meter in healthy and diabetic dogs.

Blood glucose (BG) monitoring with portable blood glucose meters (PBGMs) is a critical aspect of managing canine diabetes mellitus. Some dogs best tolerate sampling from the ear, others from the lip, and others from other body sites. Therefore, it is relevant to know if the choice of the sampling site affects the glucose concentration. To compare different sampling sites for BG measurement in diabetic and non-diabetic dogs using veterinary PBGM. Moreover, determining the possible impact of body condition score (BCS) on BG concentration. Thirty-seven healthy and 12 diabetic dogs were included. A veterinary PBGM was used to measure BG concentrations in a total of 196 blood samples collected from the marginal ear vein (MEV), carpal pad, saphenous vein, and cephalic vein. The results obtained from the different sampling sites were compared. The carpal pad, MEV, cephalic vein, and saphenous vein BG values were not significantly different at the different blood collection sites. There was no significant difference between higher and lower BCS in BG measurements in the different sampling sites. Different sampling sites, likewise utilizing either a venous or capillary sample, had no significant effect on BG measurement using veterinary PBGMs. The BCS seems to have no relevant influence on dog BG measurement.

Changes in Lactate-related Fecal Microbiome in Hyperlactatemia Diabetic Dogs.

The correlation between the intestinal microbiome and endocrine disorders has recently been drawing attention as an important key for determining their pathology and clinical assessment. In this study, we evaluated the microbiome of dogs with insulin-dependent diabetes mellitus (IDDM) with respect to blood lactate. Fecal samples were obtained from 17 subjects and real-time quantitative polymerase chain reaction determinations were performed to quantify the gene expression levels of lactate-producing and dysbiosis index-related bacteria. Expression levels of the lactate-producing bacteria Lactobacillus spp., Enterococcus spp., and Bifidobacterium spp., were confirmed in patients with high concentrations of lactate in the blood. The abundance of Enterococcus and Bifidobacterium was higher in diabetic dogs compared to that of non-diabetic dogs. When blood lactate concentrations were high, the abundance of Bifidobacterium also increased. Blood lactate levels influence the gut microbiome in dogs with IDDM. This study will help understand the gut microbiota in the context of diabetes in human and veterinary medicine.

Retrospective investigation of perioperative risk factors for immediate postoperative corneal erosions in dogs undergoing phacoemulsification.

To characterize the incidence, contributing risk factors, and healing characteristics of immediate postoperative corneal erosions (IPCE) in dogs undergoing routine phacoemulsification. Medical records of 313 canine eyes (159 dogs) undergoing routine phacoemulsification surgery. 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. 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. 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.

LBSUN332 A Novel Drug To Modulate Auto-inflammation And Promote Glucose Control In Type 1 Diabetes Mellitus

Abstract Canine Diabetes (CD) is identical to human T1DM. Helper T cells expressing the CD40 receptor (TH40) are prominent in human T1DM. TH40 cell expansions occur regardless of HLA haplotype or auto-antibody status and remain elevated throughout disease. TH40 cells from T1DM respond to human islets, TH40 from healthy controls do not. At a Veterinary Hospital 6 female and 2 male dogs that met clinical criteria for T1DM were recruited. Physical exam, blood panels and CBC were done. Dogs were dosed with a OPT501 a drug targeting CD40 mediated inflammation by IV infusion. Doses were 2 and later 4 mg/kg, given on days 1, 4, 7, then weekly for 8 weeks. Diabetic dogs had significantly elevated TH40 numbers compared to non-diabetic dogs (p &amp;lt; 0. 0001). OPT501 reduced TH40 cell numbers to normal, following which insulin requirements reduced on average by 75% and up to 90%. The canine equivalent of HbA1c reduced 40.2% on average; 3 subjects were normal range. Daily blood glucose reduced significantly, 3 subjects maintained normal glucose levels. Time-in-range (TIR) increased to up to 90%, from a previous 10%. Increased c - peptide levels were universally detected after 8 weeks of treatment. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Evaluation of Candida spp. and Other Fungi in Feces from Dogs with Naturally Occurring Diabetes Mellitus.

Simple SummaryDiabetes mellitus is a common endocrine disorder in dogs that is similar to type 1 diabetes mellitus (T1DM) in humans. Candida spp. is a common non-pathogenic fungi that is identified more commonly and in higher amounts in humans with T1DM, including the gastrointestinal tract. This change to the distribution of microorganisms that inhabit the intestine has potential to affect glycemic control and even spread to other organs and cause severe illness. There are no studies that have investigated whether diabetic dogs, like humans, have alterations to the intestinal mycobiome. Therefore, our study sought to determine whether differences exist in the types of fungi cultured from feces in diabetic dogs and non-diabetic healthy control dogs. In addition, we wanted to find out if there were variables associated with fungi colonization. Diabetic dogs had more quantitative fungal growth than controls and females were more likely to yield growth than males. Diabetic dogs were also more likely to have Candida spp. colonized from feces. Glycemic control was also seemingly associated with growth of Candida spp. in diabetic dogs. Our results indicate that the intestinal mycobiome is altered in diabetic dogs with increased prevalence of Candida spp. and quantitative growth of fungi.Diabetes mellitus is a common endocrinopathy in dogs and in most cases is analogous to type 1 diabetes mellitus (T1DM) in humans. Candida spp. is a common commensal fungi with higher prevalence and magnitude of growth in humans with T1DM. There is currently no published information about the fungal microbiome in diabetic dogs. Therefore, the objectives of this study were to (i) determine whether diabetic dogs were more likely to have Candida spp. or other types of fungi from feces compared to non-diabetic controls, and (ii) identify variables associated with fungi colonization. Fourteen diabetic dogs and 14 age, sex, and breed matched non-diabetic healthy control dogs were included in this prospective case–control study. Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used for fungal identification. Diabetic dogs had greater quantitative fungal growth compared to controls (p = 0.004). Moreover, female dogs were more likely to have fungi colonization than males (p = 0.02). All instances of Candida spp. and Aspergillus spp. colonization were exclusively identified in diabetic dogs. Serum fructosamine concentration was higher in diabetic dogs with fecal colonization of Candida spp. compared to diabetic dogs without growth (p = 0.03). Our results indicate that the fungal microbiome in feces is altered in diabetic dogs, which seem to favor an increased prevalence of Candida spp. and higher quantitative fungal growth. Moreover, female sex and glycemic control could affect the intestinal mycobiome.

842-P: A Novel Drug to Modulate Autoinflammation and Promote Glucose Control in Type 1 Diabetes Mellitus

NOD mice are the accepted model for Type 1 Diabetes Mellitus (T1DM) Canine Diabetes (CD) demonstrates clinical outcomes identical to NOD and human T1DM. We described helper T cells that express the CD40 receptor, termed Th40 cells. In human T1DM Th40 cells expand significantly in number in peripheral blood prior to hyperglycemia; and respond to human islets. In NOD mice, Th40 cells increase first in the pancreatic lymph nodes, expand in number in the periphery prior to hyperglycemia, are the prominent T cell type detected in the pancreas during insulitis, and transfer diabetes to SCID recipients. Naturally occurring CD is insulin requiring and demonstrates the same clinical parameters as human disease. In a clinical pilot study using diabetic dogs we discovered significantly elevated Th40 cell numbers in PBMC compared to non-diabetic dogs (p &amp;lt; 0.0001) . Th40 cell numbers may help predict risk of development of T1DM as a subset of “at-risk” pre-T1DM human subjects who developed T1DM showed elevated Th40 numbers. Using a novel approach to target CD40-mediated inflammation we created a series of small peptides. The lead candidate, OPT101, has an approved IND and completed Phase 1a human clinical trials establishing human safety profiles. OPT501, a canine version caused a rapid reduction in Th40 cell numbers in diabetic dogs. Daily insulin requirements were reduced on average by 75% and in 2 cases by 90%. Fructosamine, the canine equivalent of HbA1c, was reduced 40.2% on average with 3 subjects achieving normal range. All participants had significantly reduced daily blood glucose averages, and 3 subjects maintained normal glucose levels and time-in-range (TIR) increased to greater than 50%, and in some cases greater than 90%, from a previous TIR of 10%. All participants demonstrated increased c-peptide levels, a measure of restored beta cell function, after 6 weeks of treatment. Equivalent clinical outcomes have not been reported for any other drug candidate in veterinary or human T1DM trials. Disclosure D.H.Wagner: Other Relationship; Op-T, LLC. G.M.Vaitaitis: None. Funding National Institutes of Health (AI131784; AI128592)

Evaluation of a flash glucose monitoring system in nondiabetic dogs with rapidly changing blood glucose concentrations.

BackgroundA flash glucose monitoring system (FGMS; FreeStyle Libre) is useful for monitoring hypoglycemic dogs with diabetes.ObjectiveTo assess the utility of this FGMS in dogs with induced hypoglycemia and rapid fluctuations in blood glucose (BG) concentrations.AnimalsTwenty‐four apparently healthy research (n = 10) and teaching (n = 14) dogs.MethodsProspective, observational study performed in tandem with a teaching laboratory. Regular insulin was administered to dogs and resulting hypoglycemia was corrected. Before insulin administration and every 10 minutes over a 90‐minute period, serial measurements of interstitial glucose (IG) with FGMS and BG with a portable blood glucose meter (PBGM) and clinical chemistry analyzer concentrations were made. Portable blood glucose meter and FGMS readings were compared to that of the clinical chemistry analyzer. Analytical and clinical accuracy were assessed using ISO 15197:2013 criteria, including Parkes error grid analysis.ResultsThe proportions of readings in the low BG range (BG <100 mg/dL) for which the test method measurement was within ±15 mg/dL of the reference BG for the PBGM and FGMS were 81.7% (161/197) and 39.1% (72/184), respectively. The proportions of readings for the PBGM and FGMS, which were not likely to affect clinical outcome according to Parkes error grid analysis, were 97.9% (233/238) and 80.1% (177/221), respectively.Conclusions and Clinical ImportanceIn this model, there was limited agreement between the FGMS and reference standard BG measurements. The FGMS (measuring IG concentrations) was compared to peripheral BG concentrations, not brain‐tissue glucose concentrations, and failed to reliably detect hypoglycemia.

ULTRASTRUCTURAL ANALYSIS OF DECELLULARIZED DIABETIC AND NON-DIABETIC CANINE PANCREAS FOR THE PRODUCTION OF BIOLOGICAL SCAFFOLDS

<h3>Background</h3> The canine species plays a significant role in the history of research related to Diabetes Mellitus, since it was in this species that the disease was first experimentally induced. The decellularization of organs and tissues is a recent technology for the creation of biomaterials. However, the production of scaffolds is already established and is a promising source to new tissues and organs in Regenerative Medicine. The aim of this study was to evaluate the ultrastructure of the decellularized canine pancreas extracellular matrix obtained from different protocols aiming to describe best protocol to preserve the extracellular matrix. <h3>Methods</h3> Pancreas was collected from diabetic and non-diabetic dogs, and samples were subsequently sectioned in ± 1 cm. Decellularization protocol was performed using 4% Sodium Deoxycholate (SDC) or 0.5% Sodium Dodecyl Sulfate (SDS) ionic detergents or 1% Triton X-100 non-ionic detergent under immersion and agitation during four days at room temperature. A final wash step was carried out in distilled water 3 times 30 minutes in orbital agitation. Histological techniques and Scanning Electron Microscopy analysis were carried out to evaluate physical structure, architectural and tissue ultrastructure, respectively. <h3>Results</h3> The surface of the native and decellularized diabetic and non-diabetic canine pancreas matrices were evaluated by Scanning Electron Microscopy to analyze the efficiency of the decellularization process in each protocols. Thethree decellularization protocols were efficient to remove the cells from the tissue. However, 4% SDC ionic detergent showed higher efficiency of cell removal and preservation of collagen fibers in the extracellular matrix. <h3>Conclusion</h3> The decellularized canine pancreas using 4% SDC ionic detergent presented better preservation of extracellular matrix fibers, when compared with the other protocols with 0.5% SDS or 1% Triton X-100, being this one recommended for production of pancreas scaffolds in Veterinary Medicine.

Topical Pirfenidone drops diminish opacity in dogs with corneal defects, in vitro safety, and in vivo efficacy – A pilot study

To evaluate pirfenidone topical drops as an adjunct therapy to reduce post-recovery opacity in dogs with corneal defects. Corneal epithelial cells were treated with moxifloxacin, flurbiprofen, with and without 0.5% pirfenidone to rule out any adverse effect of pirfenidone. Non-diabetic dogs with corneal defects were treated with 0.5% drops of pirfenidone along with topical drugs used to treat the control dogs. At the end of two weeks, all dogs were evaluated and graded for corneal healing and opacity under a slit-lamp biomicroscope. There was no adverse influence of co-treating corneal cells with pirfenidone, moxifloxacin, and flurbiprofen. Pirfenidone as an adjunct therapy was well tolerated by dogs with corneal defects. The corneal healing was complete and opacity was significantly reduced ( P = 0.0003) in dogs treated with pirfenidone drops in comparison to control dogs. Pirfenidone is effective in preventing corneal opacity; further investigation in a larger population is warranted.

Etiology and prognosis for dogs with abnormal blood glucose concentrations evaluated in an emergency room.

To determine the prevalence of glucose abnormalities in nondiabetic dogs presenting to a veterinary emergency room (ER) and their association with underlying disease processes, previous glucocorticoid administration, and overall mortality. Single-center, retrospective study from January 2013 to December 2014. University Teaching Hospital. A total of 660 dogs presenting to an ER with a blood glucose concentration measured within 6 hours of presentation. None. Medical records from dogs with a blood glucose concentration measured within 6 hours of hospital admission were reviewed. Medications administered prior to blood sampling, the presence of shock, final clinical diagnosis, and survival were recorded. Hypoglycemia and hyperglycemia were defined as a blood glucose<4.4mmol/L (80mg/dL) and>6.7mmol/L (120mg/dL), respectively. Diabetic patients were removed from analysis. Hyperglycemia was found in 40.1% of dogs, whereas hypoglycemia was present in 9.0%. Hyperglycemia was most often associated with gastrointestinal disease, trauma, neoplasia, and respiratory disease. The most common diseases associated with hypoglycemia were sepsis, gastrointestinal disease, and neoplasia. Dogs in shock or with hyperlactatemia had higher blood glucose values than dogs with normal perfusion and plasma lactate concentrations (P= 0.016 and P< 0.0001, respectively). Mortality was higher in dogs with hyperglycemia (33.2%, P= 0.03) or hypoglycemia (44.6%, P= 0.0024) compared to those with normoglycemia (24.9%). Dysglycemia in nondiabetic dogs evaluated in an ER was associated with a higher mortality rate than dogs in the same population with normoglycemia. Hyperglycemia in this population was common and may represent a stress response.

Imaging Diagnosis of Emphysematous Pyelonephritis in a Non-Diabetic Dog

Imaging Diagnosis of Emphysematous Pyelonephritis in a Non-Diabetic Dog

Analgesic effect of topical and subconjunctival morphine in dogs after phacoemulsification: A pilot study.

To determine the efficacy of a single treatment of topical and subconjunctival 0.1% preservative-free morphine sulfate (PFMS) in providing analgesia following phacoemulsification in dogs. Ten diabetic and ten non-diabetic client-owned dogs treated with bilateral phacoemulsification. A prospective, randomized, masked, negative-controlled clinical trial was performed. All dogs received topical (0.2mL) and subconjunctival (0.1mL) 0.1% PFMS in one eye following phacoemulsification. The other eye received an equal volume and mode of administration of balanced salt solution (BSS). Ophthalmic examination, blinking rates, tearing, conjunctival hyperemia, aqueous flare, and central corneal esthesiometry (CCE) were evaluated in all eyes 1day prior to surgery and at 4, 24, and 48hours after surgery. Complete physical examination, ocular ultrasound, electroretinogram, hemogram, and serum biochemistry panel were performed in all dogs prior to phacoemulsification. All dogs received the standard of care treatment before and after surgery, including uniform anesthetic protocol. Baseline ophthalmic exams were unremarkable, except for the presence of cataracts, in all dogs. The mean CCE (±SD) at 4hours post-operatively was 1.76±1.27g/mm2 and 1.85±1.5g/mm2 for the negative control and PFMS groups, respectively. There were no statistical differences in blepharospasm, conjunctival hyperemia, tearing, aqueous flare, blinking rates, CCE, or intraocular pressure (IOP) between the treatment groups for any of the time points for the non-diabetic and diabetic dogs, or for all dogs combined (P>.05). Topical and subconjunctival 0.1% PFMS did not affect the evaluated parameters after phacoemulsification in the study dogs at the timepoints assessed.

Comparison of serum fructosamine and glycated hemoglobin values for assessment of glycemic control in dogs with diabetes mellitus.

To evaluate the performance of 2 assays for measurement of serum fructosamine (SF) and glycated hemoglobin (HbA1c) values in dogs and to compare the usefulness of the 2 glycated proteins for assessment of glycemic control in dogs with diabetes mellitus (DM). Blood samples from 40 healthy dogs, 13 diabetic dogs, and 23 anemic normoglycemic nondiabetic dogs and results of 200 assessments of glycemic control in 46 diabetic dogs. Colorimetric and immunoturbidimetric methods were used for measurement of SF and HbA1c values, respectively. Linearity and precision were determined. The usefulness of SF and HbA1c values for assessment of glycemic control was evaluated with a clinical scoring method used as the reference standard. Cutoff values obtained from receiver operating characteristic curves were used to identify the percentage of dogs correctly categorized by means of SF and HbA1c values. Mean intra-assay and interassay coefficients of variation were 3.8% and 2.5%, respectively, for the SF assay, and 1.2% and 1.8%, respectively, for the HbA1c assay. Excellent linearity (R2 > 0.99) was obtained for both assays. Values for SF and HbA1c were inversely correlated (r = -0.40 and -0.33, respectively) with clinical score and correctly indicated glycemic control in 99 of 200 (50%) and 88 of 200 (44%) assessments, respectively. The SF and HbA1c assays were precise, had good linearity, and appeared to be suitable for routine use in veterinary medicine. However, they performed poorly for classifying glycemic control in diabetic dogs.

The mean cell volume difference (dMCV) reflects serum hypertonicity in diabetic dogs.

Serum hypertonicity may develop during diabetes mellitus due to hyperglycemia and other biochemical changes. Hypertonicity may produce detrimental cellular and systemic effects and has been identified as a serum marker for some clinical disorders. In non-diabetic dogs, the mean cell volume difference, a novel erythrocyte measure, is increased by serum hypertonicity. However, it is not known whether hyperglycemic hypertonicity produces a similar change. The hypothesis that the mean cell volume difference could detect serum hypertonicity in diabetes was investigated in a group of thirty-two dogs with naturally-occurring diabetes mellitus that were prospectively recruited over a 1-year period from the outpatient population of a veterinary teaching hospital. The effect of hyperglycemia on the mean cell volume difference and the ability of the mean cell volume difference to predict serum hypertonicity were examined. Serum hyperosmolality and hypertonicity due to hyperglycemia was present in 91% and 94% of dogs, respectively. Hyperglycemia was the principal cause identified for serum hypertonicity and hyperosmolality. Using a cut-off value of ≥ 3 μm3 for the mean cell volume difference, serum hypertonicity ≥ 320 mmol/kg was identified with 79% sensitivity and 61% specificity. The dMCV correlated with changes in serum glucose, tonicity, and measured osmolality. Dogs with a mean cell volume difference ≥ 3 μm3 were at risk for serum tonicity ≥ 320 mmol/kg (risk ratio = 2.2) and serum glucose ≥ 13.9 mmol/L (risk ratio = 2.3). In conclusion, the mean cell volume difference is a useful surrogate marker for detecting serum hypertonicity in diabetic dogs and elevated mean cell volume difference is associated with increased risks for clinically relevant serum hypertonicity and hyperglycemia.

Use of the turbidimetric method for determining hemoglobin (A1C) in diabetic and nondiabetic dogs

Canine diabetes mellitus is a multifactorial disease with a worldwide prevalence of 0.005 to 1.5%, affecting dogs between 4 and 14 years of age, males and females. Persistent fasting hyperglycemia and glycosuria confirm the diagnosis, and glycated hemoglobin (A1C) is an efficient biomarker for the risk of complications and monitoring. The scarcity of unvalidated reference values and commercial kits justifies its low application in veterinary medicine. The aim of this study was to identify A1C as a diagnostic biomarker of diabetes mellitus in dogs through immunoturbidimetry assay and to propose an A1C reference range for diabetic and nondiabetic dogs. We randomly selected 86 healthy dogs and 20 diabetic dogs of different ages and breeds, both male and female, neutered and not neutered. Hemogram, urea, creatinine, alanine aminotransferase, alkaline phosphatase, glycemia, and glycated hemoglobin were performed using the turbidimetry assay. The Spearman correlation test between A1C and the biochemical and hematological variables, ROC curve to analyze the diagnostic capacity of glucose, and A1C to predict diabetes in dogs was used. We obtained a median of 3.8% for A1C with a confidence interval of 3.8 to 4.0% for nondiabetic dogs and a cut off of 4.5% for diabetic dogs. Spearman’s correlation showed a direct relationship between A1C and glucose and a statistically significant association with glucose (p < 0.001) and creatinine (p < 0.002). The areas of the ROC curve of A1C and glucose had good indices in their individual use, and their association showed a positive and statistically significant correlation (p = 0.051). The diagnostic ability of A1C to predict diabetes mellitus in dogs was confirmed and A1C reference range established for nondiabetic and diabetic dogs, also showing association with creatinine, given this relevant and unprecedented data in the veterinary literature.

Evaluation of a human glycated hemoglobin test in canine diabetes mellitus.

Glycated hemoglobin A1c (HbA1c) is widely used for monitoring and diagnosing human diabetes mellitus, but is rarely used in veterinary clinics. The goal of our study was to validate the commercial HbA1c testing system SD A1cCare analyzer (Bionote, Gyeoggi-do, South Korea) for use in dogs. Dogs were recruited with owner's consent. Diabetic status was determined based on clinical signs, fasting hyperglycemia, and glycosuria. Intra-assay precision and linearity were evaluated with EDTA, heparin, or citrate as anticoagulants, and had excellent precision with mean coefficients of variation (CVs) of 2.47%, 2.26%, and 1.92%, respectively. Diluted anticoagulated blood samples showed excellent linear relationships with R2 of 0.991, 0.996, and 0.994, respectively. Inter-assay precision revealed that the mean CV of the normal control was 2.18% and that of the high control was 2.01% (30 repeats). Observed total error of a normal control was 7.81%, and 6.12% for the high control. HbA1c level measured before and after removal of plasma and replacement by saline showed minimal interference by lipid contents ( p = 0.929). The HbA1c concentrations of diabetic dogs were significantly higher than those of non-diabetic dogs ( p < 0.001). HbA1c value >6.2% indicated canine diabetes through a classification and regression tree model. In most cases, fructosamine and HbA1c were highly correlated ( r = 0.674, p < 0.001). The HbA1c testing system could be a valuable testing system to evaluate canine diabetes mellitus, providing an alternative in-house option for use by veterinary clinicians.