Diagnostic significance of serum glycated albumin in diabetic dogs

Measurements of serum fructosamine, glycated hemoglobin, and glycated albumin (GA) are increasingly used to complement serum glucose concentration for better management of diabetes mellitus. Fructosamine tests are currently not performed in veterinary medicine in Japan. As such, the measurement of GA may serve as a replacement test. Therefore, in the current study, serum GA and fructosamine were evaluated for a positive correlation in dogs, and, depending on the correlation, a reference range of GA percentage would also be determined from healthy control dogs. The degree of glycemic control in diabetic dogs was determined by fructosamine concentration. A positive correlation between GA and fructosamine was observed with both normal and diabetic animals. In addition, the reference interval of serum GA percentage in control dogs was determined to be 11.4-11.9% (95% confidence interval). Interestingly, no significant difference in serum GA percentages was observed between samples from diabetic dogs with excellent glycemic control and control dogs. However, good, fair, and poor glycemic control diabetic dogs resulted in a significant increase in serum GA percentages in comparison with control dogs. These results suggest that serum GA may be a useful diagnostic indicator, substituting for fructosamine, to monitor glycemic control in diabetic dogs.     

Relation of fructosamine to serum protein, albumin, and glucose concentrations in healthy and diabetic dogs.

The relation of the glycated serum protein, fructosamine, to serum protein, albumin, and glucose concentrations was examined in healthy dogs, dogs with hypo- or hyperproteinemia, and diabetic dogs. Fructosamine was determined by use of an adaptation of an automated kit method. The reference range for fructosamine in a composite group of control dogs was found to be 1.7 to 3.38 mmol/L (mean +/- SD, 2.54 +/- 0.42 mmol/L). Fructosamine was not correlated to serum total protein, but was highly correlated to albumin in dogs with hypoalbuminemia. To normalize the data with respect to albumin, it is suggested that the lower limit of the reference range for albumin concentration (2.5 g/dl) be used for adjustment of fructosamine concentration and only in hypoalbuminemic dogs. In 6 hyperglycemic diabetic dogs, fructosamine concentration was well above the reference range. It is concluded that although fructosamine may be a potentially useful guide to assess the average blood glucose concentration over the preceding few days in dogs, further study is required to establish its value as a guide to glucose control in diabetic dogs.     

Evaluation of IGF-I levels and serum protein profiles of diabetic cats and dogs

In this study, we measured the insulin-like growth factor (IGF)-I levels and evaluated the serum protein profiles of diabetic, insulin-treated, and healthy cats and dogs. The total IGF-I concentrations were 33.74 ± 3.4 ng/mL for normal, 25.8 ± 4.5 ng/mL for diabetic, and 180.4 ± 31.4 ng/mL for insulin-treated cats. IGF-I concentrations were 46.4 ± 6.6 ng/mL for normal, 25.1 ± 4.1 ng/mL for diabetic, and 303.0 ± 61.3 ng/mL for insulin-treated dogs. Total serum protein profiles were analyzed by SDS-PAGE. Fourteen bands ranging from 25 to 240 kDa in size were observed for cats, and 17 bands ranging from 25 to 289 kDa were observed for dogs. The densities of the bands differed among control, diabetic, and insulin-treated animals. In conclusion, we found that serum protein profiles and IGF-I concentrations were altered in both diabetic and insulin-treated animals. When judiciously interpreted in the light of other clinical and laboratory data, the techniques used in our study provide a valuable modality for measuring the severity of diabetes mellitus in dogs and cats.     

Glycosylated hemoglobin measurement in dogs and cats: implications for its utility in diabetic monitoring

The measurement of glycosylated hemoglobin (HbA₁) levels in humans is used to indicate the degree of long-term diabetic control. Using a commercially available kit for human HbA₁, values were obtained for normal and diabetic dogs and cats. The normal range established in dogs was broad and overlapped considerably with the range in diabetics. Under the assay conditions and with a limited number of diabetic animals, the test was not found to be of value for dogs or cats.     

Endogenous serum insulin concentration in dogs with diabetic ketoacidosis

Objective: To determine endogenous serum insulin concentration in dogs with diabetic ketoacidosis (DKA), and to compare it to endogenous serum insulin concentration in diabetic dogs with ketonuria but no acidosis (KDM), diabetic dogs with uncomplicated diabetes mellitus (DM) that did not have ketonuria or acidosis, and dogs with non‐pancreatic disease (NP). Design: Prospective study. Setting: Veterinary Hospital of the University of Pennsylvania. Animals: Forty‐four client‐owned dogs; 20 dogs with newly diagnosed diabetes mellitus (7 dogs with DKA, 6 dogs with KDM, and 7 dogs with DM) and 24 dogs with non‐pancreatic disease. Interventions: Blood and urine samples were obtained at the time of admission to the hospital. Measurements and main results: Signalment, clinical signs, physical examination findings, and concurrent disease were recorded for all dogs. Blood glucose concentration, venous blood pH, venous blood HCO3^? concentration, urinalysis, and endogenous serum insulin concentration were determined in all dogs. Dogs with DKA have significantly decreased endogenous serum insulin concentrations compared to dogs with DM (P = 0.03) and dogs with non‐pancreatic disease (P = 0.0002), but not compared to dogs with KDM (P = 0.2). Five of 7 dogs with DKA had detectable endogenous serum insulin concentrations, and 2 of these dogs had endogenous serum insulin concentration within the normal range. Conclusions: Diabetic dogs with ketoacidosis have significantly decreased endogenous serum insulin concentration compared to dogs with uncomplicated diabetes mellitus. However, most dogs with DKA have detectable endogenous serum insulin concentrations, and some dogs with DKA have endogenous serum insulin concentrations within the normal range.     

Experimental immune complex glomerulonephritis in dogs receiving cationized bovine serum albumin

Eight 16-week-old dogs were used to induce immune complex glomerulonephritis by daily intravenous injections of 120 mg highly cationized bovine serum albumin (pI9.5). Of four control dogs, two received unmodified native anionic bovine serum albumin (pI 4.5) while the other two received only phosphate buffered saline. The renal glomeruli were examined by light, electron (transmission and scanning) and immunofluorescence microscopy at intervals from five to 11 weeks after the start of the injections. Animals receiving cationic antigen all developed generalised diffuse granular deposits of IgG and C3 along the capillary walls; these were detected as early as five weeks and continued until the termination of the experiment at 11 weeks. Ultrastructural studies revealed many electron dense deposits along the subepithelial regions of the glomerular basement membrane. The experimental disease resembled in many respects naturally occurring membranous nephropathy, the most common form of immune complex glomerulonephritis in dogs.     

Relationship of serum total calcium to serum albumin in dogs, cats, horses and cattle

A retrospective study was performed in order to assess the relationship between serum calcium and serum albumin concentrations in domestic animals. Results of 9041 canine, 1564 feline, 2917 equine, and 613 bovine serum samples from hospitalized patients were examined by regression analysis. Subpopulations of cases with concurrent elevations in creatinine or that were less than six months of age were evaluated separately. Statistically significant linear relationships between calcium and albumin concentrations were established for each species (p <0.05). The coefficients of determination (r²) were 0.169 for dogs, 0.294 for cats, 0.222 for horses, and 0.032 for cattle. The correlation coefficients (r) computed were: dogs = 0.411, cats = 0.543, horses = 0.471, cattle = 0.182. Neither increases in creatinine concentration nor juvenile age appreciably influenced the relationship between calcium and albumin concentrations. Interspecies variation was marked, and a strong correlation between calcium and albumin concentrations was not established in any species.     

Response of healthy dogs to infusions of human serum albumin

OBJECTIVE: To evaluate the clinical and immunologic response in healthy dogs to infusions of human serum albumin (HSA). ANIMALS: 9 healthy purpose-bred mixed-breed dogs. PROCEDURES: Each dog was administered a 25% HSA solution once or twice. Various physical examination and laboratory variables were serially evaluated. Antibody against HSA was assayed before and after infusion by use of an ELISA. Intradermal testing was also conducted. A repeated-measures ANOVA or Friedman repeated-measures ANOVA on ranks was used to compare results for the variables. RESULTS: Adverse clinical reactions were observed after the first or second infusion in 3 dogs. Anaphylactoid reactions were observed in 1 of 9 dogs during the first infusion and in 2 of 2 dogs administered a second infusion. Two dogs developed severe edema and urticaria 6 or 7 days after an initial infusion. All dogs developed anti-HSA antibodies. Positive responses for ID tests were observed in 8 of 9 dogs. Short-term increases were detected in blood protein, total bilirubin, and calcium concentrations after HSA infusion. Serum cholesterol concentrations and platelet counts decreased after HSA infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of HSA resulted in profound reactions in 2 of 9 dogs administered a single infusion and in 2 of 2 dogs administered a second infusion. This indicates that there is risk of life-threatening adverse reactions to HSA infusion in healthy dogs.     

The use of 25% human serum albumin: outcome and efficacy in raising serum albumin and systemic blood pressure in critically ill dogs and cats

Objective: To report on the use of 25% human serum albumin (25% HSA) (Plasbumin®), associated outcome, and efficacy in raising serum albumin and systemic blood pressure (BP) in critically ill dogs and cats. Design: Retrospective clinical study. Animals: Client‐owned cats and dogs. Interventions: Administration of 25% HSA. Measurements and main results: The medical records of 66 animals (64 dogs, 2 cats) at the Ontario Veterinary College, which received 25% HSA (Plasbumin®) from June 1997 to December 2001 were reviewed for age, body weight, clinical problems, albumin and globulin (g/L) levels pre‐ and within 18‐hour post‐transfusion and upon discharge from hospital, total solids (TS), systolic and diastolic BP pre‐ and post‐transfusion total volume administered, adverse reactions, blood products and synthetic colloids used, and outcome. Twenty‐five percent HSA was prescribed for a range of clinical problems, which were grouped into 6 categories for analysis. The age range was 4 months–12 years and body weight range 1.4–65 kg. The maximum volume administered to any dog was 25 mL/kg, mean volume administered was 5 mL/kg, maximum volume given as a slow push or bolus was 4 mL/kg with a mean of 2 mL/kg volume. The range for a constant rate infusion (CRI) was 0.1–1.7 mL/kg/hr over 4–72 hours. Forty‐seven (71%) animals survived to discharge; 11(16%) were euthanized, and 8 (12%) died. Serum albumin and TS increased significantly (P<0.0001) above pre‐transfusion levels as did systolic BP (P<0.01). Conclusions: Twenty‐five percent HSA can be safely administered to critically ill animals, and an increase in albumin levels and systemic BP can be expected.     

Glycosylated haemoglobin in dogs: study of critical difference value

Measurement of glycated proteins can be of use in diagnosis and monitoring of diabetic dogs. Its use in monitoring can be facilitated by comparison of results with a reference interval derived from levels in normal dogs. In this study, a commercial immunoturbidometric assay was used to measure glycosylated haemoglobin in 15 normal dogs over a 5-week period. Following statistical analysis of the results a critical difference value of 0.38 per cent was obtained.     

Serum glycated albumin: Potential use as an index of glycemic control in diabetic dogs

Measurements of serum fructosamine, glycated hemoglobin, and glycated albumin (GA) complement serum glucose concentration for better management of diabetes mellitus (DM). Especially, the serum fructosamine test has long been used for diagnosing and monitoring the effect of treatment of DM in dogs. However, fructosamine tests are currently not performed in veterinary medicine in Japan. GA and fructoasmine levels have been shown to strongly correlate. However, the clinical implications of using GA remain to be elucidated. Therefore, the purpose of the current study was threefold: 1) Determine whether GA% is altered by acute hyperglycemia in normal dogs, simulating stress induced hyperglycemia; 2) Demonstrate that GA% does not dynamically change with diurnal variation of blood glucose concentration in diabetic dogs; and 3) Investigate whether GA% is capable of providing an index of glycemic control for 1–3 weeks in diabetic dogs as is the case with diabetic human patients. Our study demonstrated that serum GA% remains very stable and unaltered under acute hyperglycemic conditions (intravenous glucose injection) and in spite of diurnal variation of blood glucose concentration. Furthermore, serum GA% can reflect long-term changes (almost 1–3 weeks) in blood glucose concentration and the effect of injected insulin in diabetic dogs.     

Relationship between dietary protein concentration and serum trypsin-like immunoreactivity in dogs

Serum trypsinogen concentration was studied in 6 adult mixed-breed dogs randomly fed diets containing 6.8, 31.4, or 39.7% protein (dry weight) for 3 weeks each. Blood was collected on days 20, 21, and 22 of each feeding period, and serum trypsinogen concentrations were determined by radioimmunoassay of trypsin-like immunoreactivity (TLI). Mean serum TLI concentrations for each dog fed each diet were compared. A significant (P less than 0.05) positive linear relationship (P less than 0.02) was determined between serum TLI concentrations and the percentage of dietary protein. Mean serum TLI concentrations for each dog fed all diets ranged from 5.7 to 20.2 micrograms/L.     

The therapeutic use of 25% human serum albumin in critically ill dogs and cats.

Twenty-five percent human serum albumin (HSA) is a foreign protein and can potentially cause immune-mediated reactions. For this reason, the author only recommends 25% HSA use after risk analysis shows that the benefits outweigh the potential risks of adverse events. If it is apparent that a critically ill animal may succumb to its illness because of the problems associated with severe hypoalbuminemia, the benefit outweighs the risk. The veterinarian must inform the owner of potential delayed immune-mediated reactions, describe these lesions, and follow the case weekly to ensure that no reaction has occurred. Although there are many positive attributes to the administration of 25% HSA, there seems to be specific situations in which 25% HSA may be indicated and others in which it may not be indicated.     

Glycosylated hemoglobin in dogs: precision, stability, and diagnostic utility

The precision and stability of the ion exchange chromatography assay for canine glycosylated hemoglobin (HbA(1)) were examined. The coefficient of variation (CV) of within-run replicate assays was 1.3 to 2.6%; the CV of between-run duplicate assays was 3.1%. The mean HbA(1) content in 44 healthy dogs was 7.1% (SD = 1.1%, range = 5.1-9.7%). Paired aliquots of 12 blood samples were stored at 4 degrees C and 25 degrees C, and HbA(1) was measured on the day of collection and at 3, 5, and 7 days after collection. In the blood stored at 4 degrees C, no significant increase in the HbA(1) content was seen. No significant increase in HbA(1) content was found in the blood stored at 25 degrees C after 3 days, but dramatic increases were observed after 5 and 7 days of storage. No significant difference was observed in the HbA1 content in heart blood collected 18 hours after death from 9 dogs kept at 25 degrees C. The HbA(1) content was measured in 10 hospitalized diabetic dogs. Five of the dogs had received no insulin and all 5 had elevated HbA(1) values. The other 5 dogs had received insulin for 1 to 9 months; 2 of the 5 had increased HbA(1) content. The HbA(1) content was determined periodically for 9 months in one diabetic dog and it declined from 14% to 8.2%.     

A retrospective analysis of 25% human serum albumin supplementation in hypoalbuminemic dogs with septic peritonitis

This study describes the influence of 25% human serum albumin (HSA) supplementation on serum albumin level, total protein (TP), colloid osmotic pressure (COP), hospital stay, and survival in dogs with septic peritonitis. Records of 39 dogs with septic peritonitis were evaluated. In the HSA group, initial and post-transfusion TP, albumin, COP, and HSA dose were recorded. In the non-supplemented group, repeated values of TP, albumin, and COP were recorded over their hospitalization. Eighteen dogs survived (53.8% mortality). Repeat albumin values were higher in survivors (mean 23.9 g/L) and elevated repeat albumin values were associated with HSA supplementation. Repeat albumin and TP were higher in the HSA supplemented group (mean 24 g/L and 51.9 g/L, respectively) and their COP increased by 5.8 mmHg. Length of hospitalization was not affected. Twenty-five percent HSA increases albumin, TP, and COP in canine patients with septic peritonitis. Higher postoperative albumin levels are associated with survival.     

Accuracy of serum beta-hydroxybutyrate measurements for the diagnosis of diabetic ketoacidosis in 116 dogs

The aim of this study was to evaluate the accuracy of serum beta-hydroxybutyrate (beta-OHB) measurements for the diagnosis of diabetic ketoacidosis (DKA) in dogs. One hundred sixteen diabetic dogs were prospectively enrolled in the study: 18 insulin-treated (IT) diabetic dogs that had a positive urine ketone test and 88 untreated, newly diagnosed diabetic dogs. Venous blood gas tensions and pH, serum glucose and urea nitrogen (SUN), and electrolyte (Na+, Cl-, and K+) and urine acetoacetate (AA) concentrations were measured concurrently with serum beta-OHB concentrations. On the basis of laboratory findings, the patients were assigned to I of 3 groups: diabetic ketoacidosis (n = 43); diabetic ketosis (DK, n = 41); and nonketotic diabetes (NDK, n = 31). Serum beta-OHB concentrations differed significantly (P < .001) among the study groups. Although marked differences in beta-OHB concentrations were found, a considerable overlap exists between the distributions of dogs with DK and those with DKA. The overall accuracy of beta-OHB determination as a diagnostic test for DKA, determined by the area under the receiver operating characteristic (ROC) curve, was 0.92. In the 1.9- to 4.8-mmol/L range, serum beta-OHB determination sensitivity varied from 100 to 35.7%, whereas specificity varied from 39 to 100%. The cutoff value of 3.8 mmol/L showed the best equilibrium between specificity (95%), sensitivity (72%), and likelihood ratio (14.8). We concluded that the quantitative measurement of serum beta-OHB may be a potential tool for diagnosing and monitoring ketosis and ketoacidosis in diabetic dogs.     

Gentamicin pharmacokinetics in diabetic dogs

Reduction of the prolonged terminal elimination phase of gentamicin may be caused by diabetes mellitus, irrespective of the model of diabetes. To test this hypothesis, five normal dogs, three dogs with alloxan-induced diabetes mellitus, and four dogs with naturally occurring diabetes mellitus (all of which were given exogenous insulin to control hyperglycemia) were given 4.4 mg/kg gentamicin intravenously. Serum pharmacokinetics were analyzed using non-compartmental pharmacokinetics assuming a sum of exponential terms. Gentamicin pharmacokinetics during the first 8 h were the same in normal and diabetic dogs. Over 7 days, MRT in normal dogs (5830 +/- 2970 min, mean +/- SD) was longer (P less than 0.01) than in diabetic dogs (136 +/- 164 min). In diabetic dogs, Cls was greater (3.01 +/- 0.86 ml/min/kg) than in normal dogs (1.45 +/- 0.11 ml/min/kg; P less than 0.01), whereas Vd(ss) was smaller in diabetic dogs (0.405 +/- 0.508 l/kg) than in normal dogs (8.56 +/- 4.48 l/kg; P less than 0.01). Serum gentamicin concentrations were less than 0.020 microgram/ml by 2 days in all of the diabetic dogs, but were 0.048 +/- 0.018 microgram/ml at 7 days in normal dogs. Thus, diabetes mellitus, either induced by alloxan administration or naturally occurring, abolished the terminal elimination phase of gentamicin disposition in a non-rodent species.