Glycosylated albumin and serum protein in diabetic dogs

Glycosylated albumin and glycosylated protein in serum were measured in 4 well-controlled diabetic dogs, 4 poorly controlled diabetic dogs, and 21 nondiabetic dogs. Concentrations of both glycosylated components in the well-controlled dogs were similar to those in nondiabetic dogs. Serum concentrations of glycosylated albumin and protein in the poorly controlled diabetic dogs were higher (P less than 0.001) than those of the nondiabetic and well-controlled diabetic dogs. Because of the essentially irreversible nature of the glycosylation reaction and the relatively short turnover time of albumin and other serum proteins, measurements of glycosylated serum components may provide an index of glycemia during the preceding days or weeks.     

Study of the effect of total serum protein and albumin concentrations on canine fructosamine concentration.

The relationship among serum fructosamine concentration and total serum protein and albumin concentrations were evaluated in healthy and sick dogs (diabetics and dogs with insulinoma were not included). Fructosamine was determined using a commercial colorimetric nitroblue tetrazolium method applied to the Technicon RA-500 (Bayer). Serum fructosamine concentration was not correlated to total protein in normoproteinemic (r = 0.03) and hyperproteinemic dogs (r = 0.29), but there was a high correlation (r = 0.73) in hypoproteinemic dogs. Similar comparison between serum fructosamine and albumin concentrations showed middle correlation (r = 0.49) in normoalbuminemic dogs and high degree of correlation (r = 0.67) in hypoalbuminemic dogs. These results showed the importance of recognizing serum glucose concentration as well as total serum protein and albumin concentrations in the assay of canine serum fructosamine concentration.     

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.     

Effects of the alpha-glucosidase inhibitor acarbose on postprandial serum glucose and insulin concentrations in healthy dogs.

OBJECTIVE: To determine effects of acarbose on baseline and postprandial serum glucose and insulin concentrations in healthy dogs, if effects of acarbose were dosage related, and if acarbose caused any short-term adverse effects. ANIMALS: 5 healthy dogs fed a high-fiber diet. PROCEDURE: A Latin-square design was used. During each 1-week treatment period, dogs were given a placebo or 25, 50, 100, or 200 mg of acarbose, PO, twice daily immediately prior to feeding. There was a 1-week interval between periods. At the end of each treatment period, serum glucose and insulin concentrations were measured prior to feeding and at 30- to 60-minute intervals for 6 hours after feeding. RESULTS: Baseline serum glucose and insulin concentrations, insulin peak response, and total glucose absorption were not significantly different following treatment with placebo and treatment with acarbose; however, total insulin secretion was significantly decreased when dogs were treated with 100 or 200 mg of acarbose. Four dogs developed soft to watery stools when treated with 200 mg of acarbose, and 2 dogs lost weight during the study. Results of CBC and serum biochemical analyses were within reference ranges throughout the study. CONCLUSIONS: Acarbose did not induce any serious adverse effects and was effective in healthy dogs in reducing total postprandial insulin secretion when administered immediately prior to meals. CLINICAL RELEVANCE: Results suggest that acarbose may help control hyperglycemia in dogs with insulin-dependent diabetes mellitus. Additional studies designed to evaluate the effect of acarbose on postprandial blood glucose concentrations in dogs with diabetes mellitus are indicated.     

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.     

Clinical significance of plasma mannose concentrations in healthy and diabetic dogs

Circulating levels of monosaccharides can act as a reflection of systemic glucose/ energy metabolism. Characteristic changes observed in these levels can be seen in patients with diabetes and other metabolic disorders. There have been a few reports describing the significance of mannose metabolism as an energy source under physiological and pathological conditions. However, the relationship between circulating levels of mannose and the pathophysiology of diabetes mellitus are unknown in dogs. This study examined circulating levels of mannose between healthy control and diabetic dogs and evaluated the clinical significance of mannose levels in dogs. Diabetic dogs demonstrated a higher circulating level of mannose in comparison to normal healthy control dogs. Plasma mannose was positively correlated with plasma glucose and fructosamine, respectively. Interestingly, plasma mannose levels were affected by plasma insulin levels. In the context of feeding and glucose tolerance tests, plasma mannose levels responded to changes in circulating insulin levels. Circulating plasma mannose levels decreased after feeding in both control and diabetic animals in spite of observed insulin level differences. However, when glucose tolerance tests were given, a positive correlation between mannose levels and insulin levels was observed. Therefore, plasma mannose levels obtained via glucose tolerance testing may be used as a new diagnostic method for evaluating insulin resistance or deficiency in diabetic dogs.     

Effect of glipizide on serum insulin and glucose concentrations in healthy cats.

With the recent identification of non-insulin-dependent diabetes mellitus (NIDDM) in cats, new possibilities arise for the use of oral hypoglycaemic agents in the treatment of feline NIDDM, similar to their use in humans. To identify the future applicability of the oral hypoglycaemic agent, glipizide, in the treatment of feline NIDDM, its effects on serum insulin and glucose concentrations in healthy cats was examined. In addition, adverse effects seen clinically or on bloodwork following short-term use of the drug were looked for. Serum insulin and glucose concentrations were evaluated after the oral administration of 2.5, 5.0 and 10.0 mg glipizide and placebo in 10 healthy cats. For each drug trial, blood was obtained five minutes before, immediately before, and 7.5, 15, 30, 45, 60, 90 and 120 minutes after glipizide or placebo administration. Mean serum insulin concentration increased after glipizide administration, with peak mean serum insulin concentration occurring 15 minutes after administration and declining to baseline by 60 minutes. There was no significant difference in peak mean serum insulin concentration, mean serum insulin concentration at 60 minutes after glipizide administration, or mean total insulin secretion between the three glipizide dosages. Mean serum glucose concentration decreased within 15 minutes of glipizide administration, with the glucose nadir occurring 60 minutes after glipizide administration. Placebo trials showed no significant change in mean serum insulin or glucose concentrations from baseline concentrations.     

Serum C-reactive protein concentrations in healthy Miniature Schnauzer dogs

Background: C‐reactive protein (CRP) is a sensitive marker for inflammation in people and dogs. In people, an association between CRP concentration and atherosclerosis has been reported. Atherosclerosis is rare in dogs, but the Miniature Schnauzer breed may be at increased risk for developing this vascular disease. It is not known if CRP concentrations in Miniature Schnauzer dogs differ from those in other dog breeds. Objectives: Our objectives were to validate an automated human CRP assay for measuring CRP in dogs and compare CRP concentrations in healthy Miniature Schnauzer dogs with those in non‐Miniature Schnauzer breeds. Methods: Sera from 37 non‐Miniature Schnauzer dogs with inflammatory disease were pooled and used to validate a human CRP immunoturbidimetric assay for measuring canine CRP. Blood was collected from 20 healthy Miniature Schnauzer dogs and 41 healthy dogs of other breeds. Median serum CRP concentration of healthy Miniature Schnauzer dogs was compared with that of healthy non‐Miniature Schnauzer dogs. Results: The human CRP assay measured CRP reliably with linearity between 0 and 20 mg/L. CRP concentration for healthy Miniature Schnauzer dogs (median 4.0 mg/L, minimum–maximum 0–18.2 mg/L) was significantly higher than for the healthy non‐Miniature Schnauzer dogs (median 0.1 mg/L, minimum–maximum 0–10.7 mg/L); 17 of the 20 Miniature Schnauzer dogs had values that overlapped with those of the non‐Miniature Schnauzer dogs. Conclusions: Median CRP concentration of Miniature Schnauzer dogs was slightly higher than that of other breeds of dogs. A relationship between higher CRP concentration in Miniature Schnauzer dogs and idiopathic hyperlipidemia, pancreatitis, and possible increased risk for atherosclerosis remains to be determined.     

Prednisolone is associated with an increase in serum insulin but not serum fructosamine concentrations in dogs with atopic dermatitis

The aim of this study was to assess the effects of a standard therapeutic protocol of prednisolone (Pred) on glucose homeostasis in atopic dogs and compare it with previously published data for ciclosporin A (CsA). The central aim of the study was to assess and compare the effects of standard therapeutic protocols of prednisolone (Pred) and ciclosporin A (CsA) on glucose homeostasis in dogs with atopic dermatitis (CAD). Both treatments significantly reduced the physical signs of CAD, as determined by the canine atopic dermatitis extent and severity index version 3 (CADESI-03) and the Edinburgh Pruritus Scale (EPS). Post-treatment plasma glucose concentrations were not significantly different in the two groups, but serum insulin concentrations were significantly higher following Pred therapy (P<0.05). Serum fructosamine concentrations were not significantly different pre- and post-treatment with Pred, although previous studies had shown that CsA treatment increased fructosamine concentrations (P<0.005). The two treatment groups were recruited in a similar timeframe, were numerically matched and there were no differences in CADESI-03 and EPS scores between the CsA and Pred groups either before or after treatment. Thus, both CsA and Pred treatment were associated with mild disturbances in glucose metabolism, but only CsA therapy resulted in a significant increase in fructosamine concentrations. This information may be relevant to clinicians when considering therapeutic options for dogs with atopic dermatitis which already have impaired glucose homeostasis.     

The effects of body weight,body condition score,sex, and age on serum fructosamine concentrations in clinically healthy cats

Background: Serum fructosamine (SF) concentrations depend on plasma glucose concentrations and are used to evaluate glycemic control in animals with diabetes mellitus (DM). Despite the strong association between obesity and DM, the effects of body weight (BW) and body condition on SF concentrations in clinically healthy cats have not been reported. Objective: The aim of the study was to evaluate the effects of BW, body condition score (BCS), sex, and age on SF concentrations in healthy cats. Methods: BW, BCS, and SF concentrations were determined in 84 clinically healthy client‐owned cats (50 neutered males, 33 spayed females, and 1 intact female) of known age. The cats were enrolled prospectively in the study. Results: Mean BW, median BCS, and mean SF concentrations for the 84 cats were 5.4 kg, 5/9, and 268.7±45.5 μmol/L (range 197–399), respectively. BW was weakly but significantly correlated with SF (r=.26; P=.02), whereas BCS was not. Cats weighing >5.4 kg and cats with BCS>5/9 had higher mean SF concentrations compared with cats weighing <5.4 kg and cats with BCS <5/9, respectively. Cats categorized as normal weight to obese by BW (BW≥4.0 kg) had higher mean SF concentrations compared with cats categorized as lean (BW<4.0 kg). For domestic shorthair cats, the same was true for BCS: cats with BCS≥4/9 had higher mean fructosamine concentrations than those with BCS<4/9. Male cats had significantly higher mean SF concentrations compared with female cats (285.1±45.3 vs 244.5±33.9 μmol/L, P<.001). Age did not affect mean SF concentrations. Conclusions: BW is positively correlated with SF concentration, and lean cats have lower SF concentrations than normal and obese cats. In contrast to previous reports, mean SF concentrations were higher in male cats than in female cats, even when males and females were matched based on BW, BCS, and age.     

Elevated fructosamine concentrations caused by IgA paraproteinemia in two dogs

An 8-year-old male Austrian Pinscher and a 14-year-old male Golden Retriever were presented for evaluation due to unexplainable high fructosamine values despite euglycemia and epistaxis in combination with polydipsia/polyuria, respectively. Blood analysis revealed severe hyperglobulinemia, hypoalbuminemia and markedly elevated fructosamine concentrations in both dogs. Multiple myeloma with IgA-monoclonal gammopathy was diagnosed by serum and urine electrophoresis including immunodetection with an anti-dog IgA antibody and bone marrow aspirations. Diabetes mellitus was excluded by repeated plasma and urine glucose measurements. Fructosamine values were positively correlated with globulin, but negatively correlated with albumin concentrations. These cases suggest that, as in human patients, monoclonal IgA gammopathy should be considered as a possible differential diagnosis for dogs with high fructosamine concentrations.     

Various protein and albumin corrections of the serum fructosamine concentration in the diagnosis of canine diabetes mellitus

Fructosamines are formed when glucose reacts non-enzymatically with amino groups on proteins, and previous studies have indicated that the serum fructosamine concentration could be of importance in the diagnosis of canine diabetes mellitus. Owing to the connection between the protein/albumin concentration and serum fructosamine concentration, it has been suggested that the serum fructosamine concentration should be corrected for the protein/albumin concentration. Thus, the purpose of the present study was to evaluate the uncorrected serum fructosamine concentration and various protein and albumin corrections of the serum fructosamine concentration in the separation of dogs with diabetes mellitus from dogs with other diseases that presented with clinical signs suggestive of diabetes mellitus. The evaluation was assisted by relative operating characteristic curves (ROC curves), which may be used to compare various diagnostic tests under equivalent conditions (equal true positive ratios or false positive ratios) and over the entire range of cutoff values. A total of 58 dogs (15 dogs with diabetes mellitus and 43 dogs with other diseases) were included in the study. Serum fructosamine concentration, serum total protein concentration and serum albumin concentration were measured in each dog, and various corrections of the serum fructosamine concentration for protein or albumin concentration were made. Comparing the ROC curves of the uncorrected and each corrected serum fructosamine concentration indicated that there was no decisive difference between the uncorrected and the corrected serum fructosamine concentrations in discriminating between dogs with and without diabetes mellitus. Hence, correcting the serum fructosamine concentration as a routine procedure cannot be advocated from the results of the study. Moreover, the sensitivity and specificity of the uncorrected serum fructosamine concentration were very high, 0.93 and 0.95, respectively, further evidence of the value of the uncorrected serum fructosamine concentration in the diagnosis of canine diabetes mellitus.Abbreviations SFC serum fructosamine concentration - SFC-P serum fructosamine concentration corrected for the actual serum total protein concentration - SFC-A serum fructosamine concentration corrected for the actual serum albumin concentration - SFC-Po serum fructosamine concentration corrected for the actual serum total protein concentration, only when the serum total protein concentration is outside the reference interval - SFC-Ao serum fructosamine concentration corrected for the actual serum albumin concentration, only when the serum albumin concentration is outside the reference interval - SFC-K serum fructosamine concentration corrected according to Kawamotoet al. (1992)     

Circadian variations of serum thyroxine, free thyroxine and 3,5,3'triiodothyronine concentrations in healthy dogs

This study was to determine the daily fluctuation of serum thyroxine (tT₄), free thyroxine (fT₄), 3,5,3''-triiodothyronine (T₃) concentrations in healthy dogs. Thyroid function of these dogs was evaluated on the basis of results of TSH response test. Samples for the measurement of serum tT₄, fT₄, and T₃ concentrations were obtained at 3-hour intervals from 8 : 00 to 20 : 00. Serum tT₄, fT₄, and T₃ concentrations were measured by the enzyme chemiluminescent immunoassay (ECLIA). Mean T₃ concentrations had no significant differences according to the sample collection time during the day. Mean tT₄ and fT₄ concentrations at 11 : 00 were 3.28 ± 0.86 µg/dl and 1.30 ± 0.37 ng/dl, respectively and mean tT₄ and fT₄ at 14:00 were 3.54 ± 1.15 µg/dl and 1.35 ± 0.12 ng/dl, respectively. These concentrations were significantly high compared with tT₄ and fT₄ concentrations at 8:00, which were 1.75 ± 0.75 µg/dl and 0.97 ± 0.25 ng/dl, respectively (p < 0.05). According to the sample collection time, mean tT₄ and fT₄ concentrations changed with similar fluctuation during the day. Based on these results, it was considered that measurement of serum tT₄ and fT₄ concentrations from 11 : 00 to 14 : 00 might more easily diagnose the canine hypothyroidism in practice.     

Evaluation of serum and urine 1,5-anhydro-D-glucitol and myo-inositol concentrations in healthy dogs

1,5-anhydro-D-glucitol (1,5AG) is a pyranoid polyol compound found in human circulating blood. Myo-inositol (MI) is a stereoisomer of inositol and serves as a precursor of inositol phospholipids. 1,5AG and MI are filtered by the glomerulus and almost completely reabsorbed through the renal tubules. However, under hyperglycemic conditions, reabsorption through the renal tubules is competitively inhibited because the structures of 1,5AG and MI resemble that of glucose. In this study, we investigated the kinetics of serum and urine 1,5AG and MI levels in healthy dogs. We demonstrated that 1,5AG and MI exist in canine serum and urine by gas chromatography-mass spectrometry. Under continuous hyperglycemic conditions, the serum 1,5AG concentration in healthy dogs decreased while the serum MI concentration remained unchanged. Urinary excretion of 1,5AG and MI increased significantly after blood glucose concentrations reached 200 to 220 mg/dl. A significant negative correlation was observed between serum 1,5AG and glucose concentrations during hyperglycemia. However, no significant correlation was observed between serum MI and glucose concentrations. In this study, we demonstrated that serum and urine 1,5AG and MI levels were changed by blood glucose concentrations. The serum 1,5AG concentration was decreased by continuous hyperglycemia. However, the serum MI concentration does not reflect hyperglycemia.     

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.     

Serum fructosamine concentrations in 59 dogs naturally Infected with Angiostrongylus vasorum

Retrospectively, 89 cases of dogs infected with Angiostrongylus vasorum were examined. Fifty-nine of these 89 dogs fulfilled the criteria of not being dually infected with Crenosoma vulpis as well as having a full biochemistry profile including serum fructosamine available. The mean serum fructosamine value of the 59 dogs was 236 micromol/l (reference value 258-348 micromol/l) and significantly lower than the serum fructosamine level of 314 micromol/l in a control group of 42 clinically healthy dogs. Eleven dogs were available for follow up after successful treatment of angiostrongylosis. In this group, the serum fructosamine value rose from a mean of 244 micromol/l to a mean of 320 micromol/l following treatment. Serum glucose, albumin and protein were all within the respective reference ranges at all sampling points. The results indicate that serum fructosamine could be affected by infection with A. vasorum. Furthermore, this change cannot be explained by measurable changes in the level of glucose, albumin or protein. The clinical impact of this study is that a low fructosamine value may indicate infection with A. vasorum thereby suggesting a Baermann test to be performed.     

Home monitoring of blood glucose concentrations by owners of diabetic dogs and cats

Generation of blood glucose curves is essential to monitor glycemic control in dogs and cats with diabetes mellitus. Up till now blood collection and blood glucose measurements could only be performed in a hospital. However, glucose concentrations measured in a hospital environment can markedly differ from concentrations measured at home, due to reduced appetite, different activity level and stressful handling. At the Clinic of Small Animal Internal Medicine, University of Zurich, a new method to collect capillary blood from the ear and to measure blood glucose by means of a portable glucose meter has been developed. This method enables owners of diabetic dogs or cats to determine blood glucose concentrations and generate blood glucose curves at home. Three cases demonstrate, how much blood glucose concentrations at home may differ from those in the hospital and how home monitoring can help to establish diabetic control in dogs and cats.     

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma

The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 microg octreotide were studied in healthy dogs in the fasting state (n=7) and in dogs with insulinoma (n=12). Octreotide did not cause any adverse effects. In healthy dogs in the fasting state, both plasma insulin and glucagon concentrations declined significantly. Basal (non-pulse related) GH and ACTH concentrations were not affected. A slight but significant decrease in the plasma glucose concentrations occurred. Dogs with insulinoma had significantly higher baseline insulin concentrations and lower baseline glucose concentrations than healthy dogs in the fasting state. Plasma glucagon, GH, ACTH, and cortisol concentrations did not differ from those in healthy dogs. Baseline plasma insulin concentrations decreased significantly in dogs with insulinoma after octreotide administration, whereas plasma concentrations of glucagon, GH, ACTH, and cortisol did not change. In contrast to the effects in the healthy dogs, in the dogs with insulinoma plasma glucose concentrations increased. Thus, the consistent suppression of plasma insulin concentrations in dogs with insulinoma, in the absence of an suppressive effect on counter-regulatory hormones, suggests that further studies on the effectiveness of slow-release preparations in the long-term medical treatment of dogs with insulinoma are warranted.     

Serum fructosamine concentrations in hyperthyroid cats.

Serum fructosamine concentrations were measured in 35 healthy cats and in 30 hyperthyroid cats before and 30 days after curative radioiodine ((131)I) treatment. Hyperthyroid cats were divided into those with 30 day post-treatment total thyroxine (T4) concentrations within (EuT4) or below (HypoT4) the reference range. The median (semi-interquartile range, SIR) fructosamine concentration was significantly lower in hyperthyroid compared with healthy cats (295. 0 (18.5) micromol l(-1)) both before (254.0 (27.6) micromol l(-1)) and after (268.5 (28.0) micromol l(-1)) treatment (P < 0.001 in each case). (131)I therapy was associated with increases in serum fructosamine (mean increase 20.4 micromol l(-1), P = 0.039) and total protein (6.3 g l(-1), P < 0.002) in the HypoT4 group and in globulin concentration in both EuT4 (5.9 g l(-), P < 0.002) and HypoT4 (5.2 g l(-1), P = 0.023) groups. There were no direct relationships between the observed elevations in fructosamine concentration and those in total protein or globulin concentrations suggesting that the effect may be due to reduced rates of protein turnover. Reduced values may need to be considered when interpreting serum fructosamine concentrations for monitoring the degree of glycaemic control in diabetic cats with concurrent hyperthyroidism.