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.     

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.     

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.     

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.     

Blood glycated hemoglobin evaluation in sick dogs.

Blood glycated hemoglobin concentration reflects long-term serum glucose levels in dogs. In this study, the effects of several diseases on blood glycated hemoglobin levels have been evaluated. For this study, blood samples were drawn from 93 unhealthy dogs. The animals were distributed into 10 groups according to pathological process (group 1, digestive problems; group 2, leishmaniasis; group 3, anemia; group 4, dermatological disorders; group 5, urinary problems; group 6, cardiorespiratory problems; group 7, diabetes mellitus; group 8, insulinoma; group 9, general diseases; group 10, control group). Blood glucose and glycated hemoglobin concentrations and hemoglobin and hematocrit values were analyzed in all the animals. In diabetic dogs, a strong increase in blood glycated hemoglobin was observed when compared with the other groups (P < 0.01). In contrast, dogs with insulinoma showed a decrease in blood glycated hemoglobin, though significant differences were not reported in all cases. No change in blood glycated hemoglobin concentrations were reported in dogs affected by other diseases. So, we can suppose that only the chronic alterations in glucose metabolism (chronic hyper- or hypoglycemia) can induce significant changes on the blood glycated hemoglobin concentrations in dogs.     

Ciclosporin A therapy is associated with disturbances in glucose metabolism in dogs with atopic dermatitis

The effect of ciclosporin A (CsA) on glucose homeostasis was investigated in 16 dogs with atopic dermatitis by determining plasma glucose, serum fructosamine and insulin concentrations, and serial insulin and glucose concentrations following a glucagon stimulation test, before and 6 weeks after CsA therapy at 5 mg/kg once daily. All dogs completed the study. Following CsA treatment, the median serum fructosamine concentrations were significantly higher (pretreatment 227.5 μmol/L; post-treatment 246.5 μmol/L; P = 0.001; reference range 162-310 μmol/L). Based on analyses of the areas under concentration-time curves (AUC) pre- and post-CsA treatment, plasma glucose concentrations were significantly higher (AUC without baseline correction 31.0 mmol/L/min greater; P = 0.021) and serum insulin concentrations were significantly lower (AUC without baseline correction 217.1 μIU/mL/min lower; P = 0.044) following CsA treatment. Peak glucose concentrations after glucagon stimulation test were significantly higher following CsA treatment (10.75 versus 12.05 mmol/L; P = 0.021), but there was no significant difference in peak serum insulin (52.0 versus 35.0 μIU/mL; P = 0.052). There was a negative correlation between baseline uncorrected insulin AUC and trough serum log CsA concentrations (r = -0.70, P = 0.005). The administration of CsA to dogs with atopic dermatitis leads to disturbances in glucose homeostasis. The clinical significance of this is unclear, but it should be taken into account when considering CsA treatment in dogs that already have such impairments.     

Effect of Acute Hyperglycaemia on the Serum Fructosamine and Blood Glycated Haemoglobin Concentrations in Canine Samples

The effect was studied of an acute and non-persistent hyperglycaemia on the serum fructosamine and blood glycated haemoglobin concentrations in canine samples. Five dogs were given glucose solution intravenously and blood samples were taken from each dog before and at 5, 15, 30, 60 and 120 min and 24 h after the infusion. There was an intense hyperglycaemia 5 min after the injection was given, but no statistically significant differences in the serum fructosamine and glycated haemoglobin were observed. It was concluded that an acute and transient hyperglycaemia does not cause significant changes in the glycated haemoglobin and fructosamine concentrations in healthy dogs.     

Reliability of history and physical examination findings for assessing control of glycemia in dogs with diabetes mellitus: 53 cases (1995-1998)

OBJECTIVE: To evaluate the reliability of history and physical examination findings for assessing control of glycemia in insulin-treated diabetic dogs. DESIGN: Retrospective study. ANIMALS: 53 insulin-treated dogs with diabetes mellitus. PROCEDURE: Medical records of insulin-treated diabetic dogs from June 1995 to June 1998 were reviewed, and information on owner perception of their dog's response to insulin treatment, physical examination findings, body weight, insulin dosage, and concentrations of food-withheld (i.e., fasting) blood glucose (FBG), mean blood glucose (MBG) during an 8-hour period, blood glycosylated hemoglobin (GHb), and serum fructosamine was obtained. Owner's perception of their dog's response to insulin treatment, physical examination findings, and changes in body weight were used to classify control of glycemia as good or poor for each dog. The FBG, MBG/8 h, blood GHb, and serum fructosamine concentrations were compared between well-controlled and poorly controlled insulin-treated diabetic dogs. RESULTS: Presence or absence of polyuria, polydipsia, polyphagia, lethargy, and weakness were most helpful in classifying control of glycemia. Mean FBG and MBG/8 h concentrations, blood GHb concentrations, and serum fructosamine concentrations were significantly decreased in 25 well-controlled diabetic dogs, compared with 28 poorly controlled diabetic dogs. Most well-controlled diabetic dogs had concentrations of FBG between 100 and 300 mg/dl, MBG/8 h < or = 250 mg/dl, blood GHb < or = 7.5%, and serum fructosamine < or = 525 mumol/L, whereas most poorly controlled diabetic dogs had results that were greater than these values. CONCLUSIONS AND CLINICAL RELEVANCE: Reliance on history, physical examination findings, and changes in body weight are effective for initially assessing control of glycemia in insulin-treated diabetic dogs.     

Glycated hemoglobin fractions in normal and diabetic dogs measured by high performance liquid chromatography.

We established a new analytical condition to measure the canine glycated hemoglobin by high performance liquid chromatography (HPLC) using cation exchange column. The canine hemoglobin gave five peaks consisting of 2 major and 3 minor hemoglobin fractions such as HbA1a, HbA1b and HbA1c. Measurement was done in 38 clinically normal dogs and 10 diabetic dogs. Mean HbA1c values (% of total Hb) in normal and diabetic dogs were 2.60 and 6.41%, respectively. And mean HbA1 values were 3.58 and 7.41%, respectively. The mean values of the canine HbA1c and HbA1 in diabetic dogs was higher than those in normal dogs, significantly (p less than 0.01). Advantages of the HPLC method and applicability for monitoring effectiveness of insulin therapy in the canine diabetes mellitus are discussed.     

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.     

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.     

Clinical usefulness of fructosamine measurements in diagnosing and monitoring feline diabetes mellitus

Fructosamines are glycated serum proteins that reflect long-term serum glucose concentrations in humans and several animal species. In the present study, blood samples were drawn from three populations of diabetic cats: untreated diabetic cats with clinical symptoms prevailing only a few days (n = 1), untreated diabetic cats with symptoms lasting more than two weeks (n = 6) and clinically well stabilised diabetic cats receiving insulin twice daily which showed no signs of disease (n = 4). All untreated diabetic cats showed elevated fructosamine measurements. Based on fructosamine measurements, clinically well stabilised diabetic cats could be subdivided further according to the degree of glycaemic control. Diabetic cats with satisfactory glycaemic control revealed fructosamine concentrations within or close to the reference range (146 to 271 umol/litre), whereas fructosamine concentrations above 400 umol/litre indicated insufficient glycaemic control. This study suggests that the fructosamine assay reflects persistently elevated serum glucose concentrations in cats and is a useful parameter for diagnosing and monitoring diabetes mellitus in cats.     

Evaluation of two point-of-care analysers for measurement of fructosamine or haemoglobin A1c in dogs

Measurement of glycosylated proteins such as fructosamine and haemoglobin A1c (HbA1c) can be used to assess glycaemic control in canine diabetic patients. Two point-of-care analysers, designed for human diabetics, were evaluated for use in dogs. Blood samples were collected from 50 normoglycaemic dogs, 100 diabetic patients and five dogs with insulinoma and tested using the In Charge fructosamine meter and the Haemaquant/Glycosal HbA1c meter. Readings were obtained in all cases except for 21 of 50 diabetics, which were above the upper limit of the In Charge meter. Diabetic dogs had higher fructosamine and HbA1c concentrations compared to controls. However, there was poor agreement between the In Charge meter readings and serum fructosamine concentrations, suggesting that there are problems associated with the use of this device in dogs. HbA1c concentrations showed a high degree of correlation with glycosylated haemoglobin measured at an external laboratory, suggesting that the Haemaquant/Glycosal meter warrants further evaluation for veterinary use.     

The response of the pituitary-adrenal and pituitary-thyroidal axes to the plasma glucose perturbations in Babesia canis rossi babesiosis

This prospective, cross-sectional, interventional study was designed to determine the association between the hormones of the pituitary-adrenal and pituitary-thyroid axes and other clinical parameters with the blood glucose perturbations in dogs with naturally occurring Babesia canis rossi babesiosis. Thirty-six dogs with canine babesiosis were studied. Blood samples were obtained from the jugular vein in each dog prior to treatment at admission to hospital and serum endogenous adrenocorticotrophic hormone (ACTH), pre-ACTH cortisol, thyroxine, free thyroxine and TSH concentrations were measured. Immediately thereafter each dog was injected intravenously with 5 microg/kg of ACTH (tetracosactrin). A 2nd blood sample was taken 1 hour later for serum post-ACTH cortisol measurement. Three patient groups were recruited: hypoglycaemic dogs (glucose < 3.3 mmol/l, n = 12); normoglycaemic dogs (glucose 3.3-5.5 mmol/l, n = 12); hyperglycaemic dogs (glucose > 5.5 mmol/l, n = 12). Basal and post-ACTH serum cortisol concentrations were significantly higher in hypoglycaemic dogs, whereas body temperature, serum thyroxine and free thyroxine were significantly lower in hypoglycaemic dogs. Haematocrit was significantly lower in both hypo-and hyperglycaemic dogs compared with normoglycaemic dogs. Low blood glucose concentrations were significantly associated with high basal and post-ACTH cortisol concentrations and with low serum thyroxine and free thyroxine concentrations in dogs suffering from B. canis rossi babesiosis.     

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.     

Association of canine obesity with reduced serum levels of C-reactive protein.

The prevalence of obesity is increasing in dogs as well as in humans. C-reactive protein (CRP) is an important tool for the detection of inflammation and/or early tissue damage and is linked to obesity in humans. The objective of the present study was to determine if serum CRP levels are altered in obese dogs. Fifteen lean (control group) and 16 overweight (obese group) dogs were examined. Blood samples were collected under fasted conditions for serum determination of CRP, glucose, insulin, cholesterol, triglyceride, and fructosamine. Results indicated that obese dogs were insulin resistant because serum insulin and insulin/glucose ratios were higher than in lean dogs (P < or = 0.05). Serum CRP concentrations were lower in obese dogs than in controls (P < or = 0.001). C-reactive protein was negatively correlated with insulin/glucose ratio (R = -0.42) and cholesterol (R = -0.39; P < or = 0.05). Furthermore, levels of cholesterol, triglycerides, and fructosamine were increased in the obese group compared with the control group. Based on these results, it can be postulated that CRP production is inhibited by obesity and insulin resistance in dogs.     

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.     

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.     

Effect of the alpha-glucosidase inhibitor acarbose on control of glycemia in dogs with naturally acquired diabetes mellitus

OBJECTIVE: To evaluate effect of acarbose on control of glycemia in dogs with diabetes mellitus. DESIGN: Prospective randomized crossover controlled trial. ANIMALS: 5 dogs with naturally acquired diabetes mellitus. PROCEDURE: Dogs were treated with acarbose and placebo for 2 months each: in 1 of 2 randomly assigned treatment sequences. Dogs that weighed < or = 10 kg (22 lb; n = 3) or > 10 kg (2) were given 25 or 50 mg of acarbose, respectively, at each meal for 2 weeks, then 50 or 100 mg of acarbose, respectively, at each meal for 6 weeks, with a 1-month interval between treatments. Caloric intake, type of insulin, and frequency of insulin administration were kept constant, and insulin dosage was adjusted as needed to maintain control of glycemia. Serum glucose concentrations, blood glycosylated hemoglobin concentration, and serum fructosamine concentration were determined. RESULTS: Significant differences in mean body weight and daily insulin dosage among dogs treated with acarbose and placebo were not found. Mean preprandial serum glucose concentration, 8-hour mean serum glucose concentration, and blood glycosylated hemoglobin concentration were significantly lower in dogs treated with insulin and acarbose, compared with insulin and placebo. Semisoft to watery feces developed in 3 dogs treated with acarbose. CONCLUSIONS AND CLINICAL RELEVANCE: Acarbose may be useful as an adjunctive treatment in diabetic dogs in which cause for poor glycemic control cannot be identified, and insulin treatment alone is ineffective.     

Corneal sensitivity in dogs with diabetes mellitus

OBJECTIVE: To compare aesthesiometer-determined corneal sensitivity between diabetic and nondiabetic dogs and to investigate the correlation between corneal sensitivity and duration of diabetes or status of glycemic control, as estimated by use of glycated blood protein concentrations. ANIMALS: 23 diabetic and 29 nondiabetic normoglycemic dogs. PROCEDURE: A Cochet-Bonnet aesthesiometer was used to measure corneal touch threshold (CTT) in 5 corneal regions of each dog. At the time of ocular examination, duration of diabetes mellitus was estimated from the history, and blood was drawn for assessment of blood glycosylated hemoglobin and serum fructosamine concentrations. RESULTS: Median CTT for central, nasal, dorsal, temporal, and ventral corneal regions in nondiabetic dogs (1.6, 2.3, 2.8, 2.8, and 5.1 g/mm2, respectively) was significantly lower than in diabetic dogs (2.8, 4.0, 5.1, 5.1, and 6.6 g/mm2, respectively). Median regional CTT in diabetic dogs was not significantly correlated with estimated duration of diabetes mellitus or blood glycated protein concentrations. No significant difference was found in regional CTT between eyes of normoglycemic dogs with unilateral cataracts. CONCLUSIONS AND CLINICAL RELEVANCE: Diabetic dogs have significantly reduced corneal sensitivity in all regions, compared with nondiabetic normoglycemic dogs. Regional variation in corneal sensitivity is similar in diabetic and normoglycemic dogs. Neither glycemic control nor duration of diabetes, as estimated, is significantly correlated with corneal hyposensitivity. Corneal nerve dysfunction may be associated with recurrent or nonhealing ulcers in diabetic dogs for which no other underlying cause can be found.