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.     

An evaluation of serum fructosamine as a marker of the duration of hypoproteinaemic conditions in dogs

Serum samples were collected from 153 normoglycaemic, hypoproteinaemic dogs of known case histories, and assayed for fructosamine, glucose, total protein and albumin concentrations. This study was conducted to evaluate the relationship between serum fructosamine and total serum proteins, or more specifically serum albumin. Serum fructosamine was positively correlated with both total serum protein (r=0.47, p>0.00001) and serum albumin (r=0.77, p>0.00001). Mean serum albumin concentrations were significantly different when the data were grouped as dogs with normal versus subnormal serum fructosamine concentrations. The data indicate the value of the serum fructosamine assay in estimating the duration of hypoalbuminaemia. Concurrent hypoalbuminaemia and normal serum fructosamine indicate hypoalbuminaemia of less than one week. Concurrent hypoalbuminaemia and hypofructosaminaemia indicate persistent hypoalbuminaemia of more than one week, and concurrent normal albumin and hypofructosaminaemia indicate recovery from a condition including hypoalbuminaemia or hypoglycaemia.     

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)     

Serum fructosamine measurement: a new diagnostic approach to renal glucosuria in dogs

Measurement of serum fructosamine, 1-amino-1-deoxyfructose, is commonly used in diagnosing and monitoring hyperglycaemic disorders, such as diabetes mellitus in dogs. Serum fructosamine indicates long-term serum glucose concentrations and replaces serial serum glucose measurements. This study investigates the clinical usefulness of serum fructosamine in differentiating conditions other than diabetes mellitus characterised by glucosuria. Four dogs presented with glucosuria all had serum fructosamine concentrations within or close to the reference range (313 micromol 1(-1), 291 micromol 1(-1), 348 micromol 1(-1), 262 micromol 1(-1) reference range: 250 to 320 micromol 1(-1) indicating that a single serum fructosamine measurement is a simple and efficient way of verifying concurrent persistent normoglycaemia. Therefore, serum fructosamine is a useful parameter not only in diabetic patients, bu also in differentiating conditions in dogs characterised by glucosuria without hyperglycaemia, such as primary renal glucosuria and the Fanconi syndrome. To distinguish between primary renal glucosuria and the Fanconi syndrome, measurement of the amino acid concentration in urine was performed.     

Haematological and biochemical changes in dogs naturally infected with Angiostrongylus vasorum before and after treatment

Haematological and biochemical parameters were studied prospectively in 48 dogs naturally infected with Angiostrongylus vasorum in a primary care setting. Samples for analysis were obtained when treatment was started and 42days afterwards. Prior to treatment, 21% of affected dogs exhibited eosinophilia, whereas increased total white blood cell (WBC) counts and neutrophilia were observed in only 4.2%. WBC counts and concentrations of neutrophils, eosinophils and monocytes decreased significantly from days 0 to 42, indicating that, even in dogs without elevated absolute blood values, a low grade inflammatory response may be present in dogs with A. vasorum infection. Biochemical changes (especially an increase in serum globulins and a decrease in serum fructosamine) were in agreement with the findings of other studies. The results show that the diagnosis of canine angiostrongylosis should not be excluded based on unremarkable haematological and blood biochemical parameters. They also support our recent finding that a low serum fructosamine concentration may be associated with infection with A. vasorum.     

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.     

Serum Fructosamine Concentrations in Dogs with Hypothyroidism

Serum fructosamine concentrations were measured in 11 untreated hypothyroid dogs with normal serum glucose and serum protein concentrations. The fructosamine level ranged between 276 and 441 mol/L (median 376 mol/L; reference range 207–340 mol/L). Nine of the 11 dogs had fructosamine levels above the reference range. The fructosamine levels decreased significantly during treatment with levothyroxine. It is suggested that serum fructosamine concentrations may be high in hypothyroid dogs because of decelerated protein turnover, independent of the blood glucose concentration.     

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.     

Changes in blood glucose concentration are associated with relatively rapid changes in circulating fructosamine concentrations in cats

The aim of the study was to determine the time required for plasma fructosamine concentration to increase after the onset of hyperglycaemia and decrease after resolution of hyperglycaemia. Healthy cats (n=14) were infused to maintain either moderate hyperglycaemia (n=5) (actual mean glucose 17 mmol/l) or marked hyperglycaemia (n=9) (actual 29 mmol/l) for 42 days. Fructosamine exceeded the upper limit of the reference range (331 micromol/l) after 3-5 days of marked hyperglycaemia, took 20 days to plateau and, after cessation of infusion, took 5 days to return to baseline. Fructosamine concentration for moderate hyperglycaemia took longer to exceed the reference range (7 days, range 4-14 days), and fewer days to plateau (8 days) and return to baseline (1 day). In cats with moderate hyperglycaemia, fructosamine concentration mostly fluctuated under the upper limit of the reference range. The range of fructosamine concentrations associated with a given glucose concentration was wide. The critical difference for fructosamine was 33 micromol/l.     

A case of diabetes mellitus in Japanese Black cattle.

A 3 year-old female Japanese Black cattle was diagnosed as diabetes mellitus (DM). Hyperglycemia (295 mg/dl), increase of serum fructosamine (487 micromol/l), elevated glycosylated hemoglobin A1 (GHbA1; 10.9%), low concentration of serum insulin (< 1.0 microU/ ml), increased serum glucagon (399 pg/ml), and glucose intolerance (glucose disappearance rate; k=0.53) were noted. On the histopathologic findings in pancreas, insulitis with infiltration of mononuclear cells was found. This case suggests that serum fructosamine and GHbA1 are available parameters for understanding of pathophysiological conditions of bovine DM.     

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.     

The Long-term Biological Variability of Fasting Plasma Glucose and Serum Fructosamine in Healthy Beagle Dogs

The aim of this study was to estimate the long-term (month-to-month) between-dog, within-dog and analytical components of variance for fasting plasma glucose and serum fructosamine in healthy dogs to assess the usefulness of a single measurement of these analytes in a single dog.Fasting plasma glucose and serum fructosamine were measured in blood samples collected every month for 9 months from 23 clinically healthy dogs, and the results were subjected to nested analysis of variance. The between-dog variation, the within-dog variation, and the analytical variation were 3.8%, 9.5% and 3.7%, respectively, for plasma glucose and 4.2%, 11.1% and 2.8%, respectively, for serum fructosamine.The maximum allowable analytical imprecision, analytical inaccuracy and difference between analytical methods were 4.8%, 2.6% and 3.2%, respectively, for plasma glucose and 5.6%, 3.0% and 3.7%, respectively, for serum fructosamine.The index of individuality, 2.7 for both analytes, indicated that the test results from single dogs can be compared usefully to the corresponding population-based reference intervals.The number of samples required to estimate the true individual mean value ±5% for a single dog was 16 for fasting plasma glucose and 20 for serum fructosamine.The one- and two-sided critical differences expressing the difference needed for two serial results from the same dog to be significantly different at a 5% level was 24% and 28%, respectively, for plasma glucose and 27% and 32%, respectively, for serum fructosamine.     

Evaluation of diabetes determinants in woolly monkeys (Lagothrix lagotricha)

Woolly monkeys (Lagothrix lagotricha) are a threatened specie in the wild with limited successful management in captivity due to diagnosed hypertension and suspected diabetic conditions. Six woolly monkeys with known hypertension problems were tested to determine if diabetes mellitus and current daily diet are underlying links to health problems for the captive population of this species. Blood and urine were collected and serum was analysed for fructosamine, glucose, glycated haemoglobin, insulin, triacylglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-Chol) and low-density lipoprotein cholesterol (LDL-Chol) while urine was tested for glucose concentrations. Diet disappearance was determined for 3 days prior to blood collection and nutrient content was calculated using Zoo Diet Analysis computer program. Serum analyses were within normal ranges (fructosamine (139-242 micromol/l), glucose (2.22-4.78 mmol/l), glycated haemoglobin (3.52-4.73%), insulin (6.2-13.0 microU/ml), triacylglycerides (0.38-3.4 mmol/l), total cholesterol (2.5-5.1 mmol/l), HDL-Chol (0.4-1.6 mmol/l) and LDL-Chol (1.8-3.4 mmol/l)). Urine glucose concentrations were below the detection limit. Diets were not limiting in starch and total sugars and were similar in non-starch polysaccharides. Potential dietary deficiencies were noted for vitamin A, vitamin D, calcium, phosphorus and selenium. When compared with the available primate reference ranges, the results do not indicate problems with diabetes mellitus or with glucose metabolism and therefore they are not causes of the diagnosed hypertension. Further research to ascertain the true cause of health related problems and the role of dietary factors is needed.     

Autochtonous infection of dogs and slugs with Angiostrongylus vasorum in Hungary

On the course of a helminthological survey of the dogs of Baranya County, Hungary Angiostrongylus vasorum infection was detected in two asymptomatic dogs. Identification of the parasite was based on morphology of the first-stage larvae (L1) isolated from droppings, and successful experimental infection with first stage larvae to laboratory reared Discus rotundatus and Lissachatina fulica snails, in order to exclude species of the family Filaroididae that have similar larvae to A. vasorum. While angiostrongylosis is widespread among foxes, this is the first report of A. vasorum infection in housedog in Hungary. In gardens, where infected dogs were being kept 91 specimens of 6 species of limacid and arionid slugs were collected of which 5 specimens of Arion lusitanicus were found to carry larvae of A. vasorum. Dogs usually do not ingest such large slugs willingly. Frogs are known to act as paratenic hosts in the life cycle of A. vasorum. Since one of the infected dogs harboured also infection with the intestinal trematode Alaria alata, of which frogs certainly play the role of the second intermediate host, therefore it is assumed that in this case the dog became infected with A. vasorum by eating frogs.     

Serum protein response and renal failure in canine Babesia annae infection

Babesia annae piroplasms have recently been recognised as a cause of infection and disease among dogs in Europe. The pathogenesis and clinical implications of this emerging disease remain poorly understood. We conducted this study to describe the electrophoretic profiles associated with the infection and to determine if B. annae associated azotaemia is caused by renal failure. We examined by microscopy 2,979 canine blood samples submitted to a diagnostic laboratory in NW Spain between September 2001 and April 2002. Small ring-shaped piroplasms were detected in blood smears of 87 samples and the identity of 58 of these presumptive cases were confirmed by PCR. This group of 58 infected dogs and a reference group of 15 healthy non-infected dogs were our study population. For all the dogs, serum protein response to -albumin, alpha-1 globulin, alpha-2 globulin, beta globulin and gamma globulin- was measured by capillary electrophoresis. The response of infected and non-infected dogs was compared and within infected dogs, the response of those with azotaemia (19) was compared with that of non-azotaemic dogs (39). Infected dogs presented a significant elevation of total proteins and all the different globulin fractions, and significantly lower levels of albumin compared to non-infected dogs. Among infected dogs, those presenting azotaemia had significantly lower concentrations of total proteins, albumin, beta and gamma globulins, and significantly higher values of alpha-2 globulin. Specific gravity was below the threshold of 1,025 for all dogs with azotaemia for which a urine sample was available (7) suggesting that azotaemia, in these dogs was of renal origin. Azotaemic dogs had higher concentrations of cholesterol and triglycerides, probably as a result of a liver compensatory response to the loss of proteins. We conclude that serum protein response in B. annae infected dogs corresponds to the pattern of a haemolytic syndrome with intense inflammatory reaction and that the azotaemia associated to the infection is very likely of renal origin.     

Serum fructosamine concentration in cats with overt hyperthyroidism.

OBJECTIVE: To determine the effect of hyperthyroidism on serum fructosamine concentration in cats. DESIGN: Cohort study. ANIMALS: 22 cats with overt hyperthyroidism. PROCEDURE: Hyperthyroidism was diagnosed on the basis of clinical signs, detection of a palpable thyroid gland, and high total serum thyroxine (T4) concentrations. Hyperthyroid cats with abnormal serum albumin, total protein, and glucose concentrations were excluded from the study. Samples for determination of serum fructosamine concentration were obtained prior to initiating treatment. Results were compared with fructosamine concentrations in healthy cats, cats in which diabetes had recently been diagnosed, and cats with hypoproteinemia. In 6 cats, follow-up measurements were obtained 2 and 6 weeks after initiating treatment with carbimazole. RESULTS: Serum fructosamine concentrations ranged from 154 to 267 mumol/L (median, 198 mumol/L) and were significantly lower than values in healthy cats. Eleven (50%) of the hyperthyroid cats had serum fructosamine concentrations less than the reference range. Serum fructosamine concentrations in hyperthyroid, normoproteinemic cats did not differ from values in hypoproteinemic cats. During treatment, an increase in serum fructosamine concentration was detected. CONCLUSIONS AND CLINICAL RELEVANCE: In hyperthyroid cats, concentration of serum fructosamine may be low because of accelerated protein turnover, independent of blood glucose concentration. Serum fructosamine concentrations should not be evaluated in cats with overt hyperthyroidism and diabetes mellitus. Additionally, concentration of serum fructosamine in hyperthyroid cats should not be used to differentiate between diabetes mellitus and transitory stress-related hyperglycemia.     

Fructosamine

Fructosamines are glycated serum proteins that, depending on their life span, reflect glycemic control over the previous 2 to 3 weeks. The nitroblue tetrazolium reduction method adapted to autoanalysis appeared to be a practical means to assay fructosamine quickly, economically, and accurately. The upper limit of the reference range is 374 μmol/L in dogs (95% percentile) and 340 μmol/L in cats (95% percentile). Newly diagnosed diabetic dogs and cats that had not undergone previous insulin therapy had significantly higher fructosamine concentrations than nondiabetic animals. In diabetic dogs that were receiving insulin therapy, the fructosamine test reflected the glycemic state far more accurately than did individual blood glucose measurements. Animals with satisfactory metabolic control revealed fructosamine concentrations within the reference range, whereas fructosamine concentrations above 400 μmol/L indicated insufficient metabolic control. On the basis of fructosamine concentrations, cats with a transitory hyperglycemia and cats with diabetes mellitus were differentiated. The fructosamine test is a valuable parameter for the diagnosis and metabolic control of diabetes mellitus in dogs and cats.     

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.     

Investigation of renal protein loss in dogs with acute experimentally induced Ehrlichia canis infection.

Urinary protein-to-creatinine ratios and serum albumin concentrations were measured in 8 adult male dogs experimentally inoculated with Ehrlichia canis. Urinary protein concentration increased significantly, but transiently, during the acute phase of infection. Urinary protein-to-creatinine ratios were highest (mean, 8.6) during the third and fourth weeks after infection, and decreased to less than 0.5 by 6 weeks after infection. Correspondingly, albumin concentration decreased significantly during the acute phase. Serum albumin concentrations were lowest (mean, 2.1 g/dl) the fourth week after infection and increased to greater than 3.0 g/dl by 11 weeks after infection. There was an inverse linear correlation between urinary protein-to-creatinine ratio and serum albumin concentration. The magnitude of proteinuria and its inverse relationship with serum albumin concentration suggested that hypoalbuminemia associated with acute E canis infection may be attributable primarily to increased renal loss of protein, rather than decreased hepatic synthesis as previously suggested. Another dog was subsequently inoculated with E canis from 1 of the experimentally infected dogs and a renal biopsy was performed during peak proteinuria (urinary protein-to-creatinine ratio = 22 and serum albumin = 1.1 g/dl). Immunofluorescent staining revealed mild to moderate deposits of anti-canine IgM, and to a lesser extent, anti-canine IgG and complement factor C3 in the glomerular tufts and mesangium. Ultrastructural evaluation revealed distortion and fusion of podocyte foot processes and increased microvilli on podocytes. These morphologic changes were consistent with transient glomerular leakage of protein of a magnitude that would significantly contribute to hypoalbuminemia during acute E canis infection. An underlying immunologic mechanism was suggested by positive glomerular immunofluorescence and previously described histologic findings.     

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.