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Treatment of diabetes mellitus in dogs using isophane insulin penfills and the use of serum fructosamine assays to diagnose and monitor the disease.

The objectives of the study were to test the use of a prefilled insulin syringe (Insulatard Novolet, isophane insulin, 100 IU/mL) in treating diabetic dogs and to test the clinical usefulness of serum fructosamine measurements in diagnosing and monitoring diabetes mellitus in dogs. For this study 15 dogs from throughout Norway with newly diagnosed diabetes mellitus were included and treated over a period of 180 days. All 15 dogs showed pretreatment hyperglycaemia. Of the 13 dogs tested, all showed elevated pretreatment serum fructosamine values. Within 2 weeks, 3 of the 15 included dogs had dropped out of the study. In 8 of the 12 remaining dogs, the clinical signs ceased within this period. Within a month, another dog was euthanised and one had died. Seven of the 10 remaining dogs were clinically normal. Three dogs had normal serum fructosamine concentrations, while in 6 dogs moderately or highly elevated serum fructosamine concentrations persisted. In one case serum fructosamine was not measured at this time. Increase in serum fructosamine concentration seemed to reflect hyperglycaemia and deteriorated clinical condition. Decrease in serum fructosamine concentration seemed to reflect improved glycaemic status and clinical condition. During the study period the owners did a total of approximately 3500 injections on their dogs. No reports of injection difficulties were received. This study documents that Insulatard Novolet is easy and safe to use in treating diabetic dogs and that serum fructosamine reflects long-term glucose concentrations in dogs. Serum fructosamine measurements provided a simple and easy way to diagnose persistent hyperglycaemia and monitor the treatment in diabetic patients.

Alkaline Phosphatase↗

Fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes.

Fructosamine 3-kinase, which phosphorylates low-molecular-mass and protein-bound fructosamines on the third carbon of their deoxyfructose moiety, is quite active in erythrocytes, and was proposed to initiate a process removing fructosamine residues from proteins. In the present study, we show that incubation of human erythrocytes with 200 mM glucose not only caused the progressive formation of glycated haemoglobin, but also increased the level of an anionic form of haemoglobin containing alkali-labile phosphate, to approx. 5% of total haemoglobin. 1-Deoxy-1-morpholinofructose (DMF), a substrate and competitive inhibitor of fructosamine 3-kinase, doubled the rate of accumulation of glycated haemoglobin, but markedly decreased the amount of haemoglobin containing alkali-labile phosphate. The latter corresponds therefore to haemoglobin bound to a fructosamine 3-phosphate group (FN3P-Hb). Returning erythrocytes incubated with 200 mM glucose and DMF to a low-glucose medium devoid of DMF caused a decrease in the amount of glycated haemoglobin, a transient increase in FN3P-Hb and a net decrease in the sum (glycated haemoglobin+FN3P-Hb). These effects were prevented by DMF, indicating that fructosamine 3-kinase is involved in the removal of fructosamine residues. The second step of this 'deglycation' process is most likely a spontaneous decomposition of the fructosamine 3-phosphate residues to a free amine, 3-deoxyglucosone and P(i). This is consistent with the findings that 2-oxo-3-deoxygluconate, the product of 3-deoxyglucosone oxidation, is formed in erythrocytes incubated for 2 days with 200 mM glucose in a sufficient amount to account for the removal of fructosamine residues from proteins, and that DMF appears to inhibit the formation of 2-oxo-3-deoxygluconate from elevated glucose concentrations.

Erythrocytes↗

Fructosamine levels demonstrate improved glycemic control for some children attending a diabetes summer camp.

Residential summer camps for youths with diabetes may have a positive effect on glycemic control. Hemoglobin A1c (HbA1c) is considered the best measure of control, but it reflects too long a period to evaluate a camp session. The fructosamine test reflects control over a period of 2-3 wk and may be ideal for this purpose. A portable device was used to examine the relationship between 2 wk of glycemic control and the change in fructosamine in order to determine whether control improved at camp. Thirty children, 8-12 yr old, were studied during a 2-wk session of a diabetes summer camp. Pre-camp HbA1c levels were obtained from the childrens' physicians. Each camper measured his/her blood glucose four times daily. Insulin doses were readjusted frequently by camp physicians. Each child's fructosamine was measured at the beginning and end of camp. The baseline fructosamine correlated with HbA1c. The final fructosamine correlated with the 2-wk mean glucose. The subgroup who started camp in below average glycemic control improved their fructosamine levels by the end of camp. Those who started camp in better control did not change. Without continuous glucose monitoring, it is impossible to accurately determine how well fructosamine reflects glucose levels. In this study, fructosamine correlated with the mean glucoses and with an HbA1c obtained prior to camp. Fructosamine appears to be a valid measure of glycemic control and being at camp was at least transiently beneficial to the children who needed it most.

Journal Article↗

Fructosamine: structure, analysis, and clinical usefulness.

Glucose molecules are joined to protein molecules to form stable ketoamines, or fructosamines, through glycation, a nonenzymatic mechanism involving a labile Schiff base intermediate and the Amadori rearrangement. The amount of fructosamine in serum is increased in diabetes mellitus owing to the abnormally high concentration of sugar in blood. The concentration of fructosamine in serum thus reflects the degree of glycemic control attained by the diabetic patient and is useful in monitoring the effectiveness of therapy in diabetes over a period of several weeks, in a manner analogous to the determination of glycated hemoglobin. Of the analytical approaches used to measure fructosamine, affinity chromatography with m-aminophenylboronic acid and the nitroblue tetrazolium reduction method appear to be the most practical means for clinical chemists to assay fructosamine quickly, economically, and accurately. Fructosamine values can readily distinguish normal individuals and diabetic patients in good glycemic control from diabetics in poor control. Unlike glycated hemoglobin, which reflects the average blood sugar concentration over the past six to eight weeks, fructosamine reflects the average blood sugar concentration over the past two to three weeks. Thus a clinical advantage is that fructosamine responds more quickly to changes in therapy, thereby allowing for improved glycemic control. Used in conjunction with determinations of blood sugar and (or) of glycated hemoglobin, or by itself, the fructosamine assay can provide clinically useful information for the detection and control of diabetes.

Blood Proteins↗

Serum fructosamine in canine diabetes mellitus. An initial study.

This study reports on a spectrophotometric assay for the determination of serum fructosamine concentration. The assay was evaluated for use in canine serum samples by assessment of the precision, accuracy, detectability and stability of serum fructosamine during storage. To evaluate the diagnostic usefulness of the assay, both the effect of acute changes in blood glucose on serum fructosamine concentration and the serum fructosamine concentration in canine diabetes mellitus and other canine diseases were studied. The main conclusions can be summarized as follows: Determination of canine serum fructosamines may be achieved by a precise and accurate assay with a detection limit well below the serum fructosamine concentration normally found in canine sera. Storage for 5 days at +4 degrees C or +25 degrees C, or for 28 days at -20 degrees C caused no significant change in serum fructosamine concentration. The concentration is not affected by acute changes in blood glucose. In diabetic dogs, serum fructosamine concentration is significantly greater than in dogs with other diseases.

Animals↗

The effect of altered thyroid function on serum fructosamine concentrations.

The effect of altered thyroid function on serum fructosamine concentrations was investigated in 31 untreated hyperthyroid patients, 18 short-term hypothyroid patients (i.e., 20 days after withdrawal of thyroid hormone suppressive therapy for thyroid cancer), 7 untreated long-term hypothyroid patients, and 25 age-matched normal controls. No differences in serum fructosamine concentrations were observed between hyperthyroid patients and normal controls; conversely, serum fructosamine concentrations were significantly higher both in short-term and in long-term hypothyroid patients than those found in normal controls. Furthermore, long-term hypothyroid patients showed significantly higher serum fructosamine concentrations than short-term hypothyroid patients. L-Thyroxine (L-T4), replacement therapy in two hypothyroid patients, resulted in a marked decrease in serum fructosamine concentrations. In seven hyperthyroid patients, the restoration of euthyroidism with antithyroid drug therapy was associated with no significant changes in serum fructosamine concentrations. The results of the present study indicate that hypothyroidism is associated with a marked increase in serum fructosamine concentrations. This alteration does not appear to be the consequence of gross abnormalities in plasma protein or glucose metabolism. The duration of hypothyroidism seems to be an important factor, even though the mechanism underlying this alteration remains at present unexplained. These results also suggest that caution must be used in the interpretation of elevated serum fructosamine concentrations as an index of the metabolic control of diabetes mellitus in the presence of hypothyroidism.

Adolescent↗

Serum fructosamine level and the risk of hip fracture in elderly women: a case-cohort study within the study of osteoporotic fractures.

PURPOSE: While a high serum fructosamine level may be an indicator of undiagnosed diabetes, a low level may be indicative of poor nutrition or frailty. As malnutrition is a risk factor for osteoporosis, low serum fructosamine levels may be associated with an increased risk of osteoporotic fracture. We examined the association between serum fructosamine levels and the risk of subsequent hip and vertebral fracture. SUBJECTS AND METHODS: We performed a case-cohort study within the Study of Osteoporotic Fractures. Subjects were elderly, ambulatory, community-dwelling, Caucasian, women. Fructosamine levels were measured in baseline serum. Incident vertebral fractures were identified by comparing baseline spinal radiographs to those obtained an average of 3.5 years later. Hip fractures were confirmed by radiograph. We randomly selected 101 women who suffered a hip fracture, 100 women who developed a vertebral fracture, and 276 controls. We compared fructosamine levels in women with subsequent osteoporotic fractures to controls. All analyses were adjusted for age, weight, and use of estrogens. RESULTS: Women with fructosamine levels in the lowest decile (< or = 223 micromol/L) had a three-fold increase in the risk of hip fracture (95% confidence interval 1.4-6.4), compared with all other women. Adjustment for markers of frailty, including smoking, functional status, and serum albumin levels, reduced the strength of this association. No clear association was observed between serum fructosamine level and the risk of vertebral fracture. CONCLUSION: Low serum fructosamine levels, which likely reflect frailty or malnutrition, may be a useful clinical tool to identify women at risk for hip fracture.

Aged↗

Fructosamine concentration and resistance to natural, predominantly Teladorsagia circumcincta infection.

Fructosamine concentrations reflect protein status and because infection with Teladorsagia circumcincta can induce a relative protein deficiency, we examined the usefulness of fructosamine concentrations as markers of the intensity of infection in naturally infected lambs. Fructosamine concentration was a heritable trait and variation in fructosamine concerntrations was associated with differences in body weight, and a variety of parasitological variables; animals with increased fructosamine concentrations grew more quickly, had increased faecal egg counts in one of the three study years, had decreased pepsinogen concentrations and decreased IgA activity against 4th-stage larvae of T. circumcincta. Fructosamine concentrations were also associated with variation in the subsequent acquisition of nematodes and in the length of adult female T. circumcincta; lambs with increased fructosamine concentrations had fewer nematodes but the mean length of adult female T. circumcincta was longer. Therefore fructosamine concentrations are potentially useful indicators of the severity of nematode infection and may predict magnitude of subsequent infection.

Abomasum↗

A prospective, randomized, multicentered controlled trial to compare the annual glycemic and quality outcomes of patients with diabetes mellitus monitored with weekly fructosamine testing versus usual care.

Fructosamine is an indicator of overall glycemic control for a 10-14-day time frame, medium-term marker, versus the 90-day average indicated by the hemoglobin A1c (A1C) test. The utility of the home fructosamine test for management of persons with diabetes remains undefined. The primary objectives of this study were (1) to compare the annual A1C results of subjects monitoring weekly fructosamine with those receiving usual care, (2) to identify the number of subjects achieving goal A1C, and (3) to determine if the addition of a weekly fructosamine test changed a subject's quality of life. This was a prospective, randomized, multicenter, controlled trial. Subjects were recruited from three sites and randomly assigned to collect weekly fructosamine in addition to daily glucose (Group 1) or to receive usual care of daily glucose collection (Group 2). Follow-up occurred at 3-month intervals for a year. Baseline and quarterly A1C tests were collected. Quality of life assessment was conducted at baseline and at the final study visit. Seventy-two subjects were randomized. Demographic and whole blood assessments were similar between the two groups at baseline. The mean percent change of A1C from baseline to final study visit in Group 1 (-0.52 +/- 1.5) was not statistically different than Group 2 (-0.86 +/- 1.4) (P = 0.320). Seven subjects in each group achieved A1C of less than 7% (P = 0.532). No change in quality of life between or within the two groups was observed (P > 0.05) for each area of concern. Blood glucose monitoring alone was shown to be superior to the additional fructosamine testing after 1 year of treatment; however, weekly fructosamine testing demonstrated a decrease in A1C earlier and more consistently throughout the study. Despite glycemic improvement, the number of subjects attaining American Diabetes Association-defined A1C goals was not different between the treatment groups. Quality of life did not change with the addition of a weekly fructosamine test.

Alcohol Drinking↗

Usefulness of fructosamine for monitoring outpatients with diabetes.

BACKGROUND: Measurements of total glycohemoglobin (glycoHb) or hemoglobin A1c are routinely used to evaluate intermediate-to-long term glycemic control in patients with diabetes. However, despite the recent availability of more rapid methods for glycohemoglobin determination, it remains difficult in many institutions to obtain same-day glycoHb determinations in time to assist physicians with management of outpatients with diabetes. Hence, we investigated whether fructosamine, which reflects very recent (2 to 3 weeks) glycemic control and which can be assayed more rapidly in our laboratory, could serve as a useful adjunct to glycoHb for management of these patients. METHODS: Diabetes control in outpatients managed using fructosamine, fasting serum glucose, and glycoHb (concentrations from the prior visit) was compared with that for outpatients monitored using fasting serum glucose and prior glycoHb alone. The relative usefulness of fructosamine, current and prior glycoHb, and "fasting" serum glucose for evaluation and management of outpatients with diabetes was compared. In addition, the acceptance of fructosamine by physicians was evaluated by a questionnaire. RESULTS: Same-day fructosamine concentrations correlated better with current glycoHb than did either prior glycoHb or current fasting serum glucose concentrations. However, the availability of same-day fructosamine results did not objectively improve diabetes control compared with that obtained using only fasting serum glucose values and prior glycoHb concentrations. Nonetheless, most examining physicians stated that same-day fructosamine concentrations helped them significantly with diabetes management, primarily because many patients do not adequately monitor home blood glucose levels. CONCLUSIONS: Fructosamine may be a useful adjunctive test for management of outpatients with diabetes in situations where it is not practical to obtain same-day glycoHb concentrations, for patients less compliant with home glucose monitoring, or where recent changes in insulin dose or clinical presentation might not be reflected in the glycoHb levels.

Blood Glucose↗

Determination of the fructosamine concentration in bovine serum samples.

The study reports on a spectrophotometric assay for the determination of serum fructosamine concentration. The assay was evaluated for use in bovine serum samples by assessment of the precision, accuracy and detectability. A reference interval for the bovine serum fructosamine concentration was also established. Further, the effect of acute changes in blood glucose on serum fructosamine concentration as well as the diurnal variations of the serum fructosamine concentration were investigated. The main conclusions can be summarized as follows: Determination of bovine serum fructosamines may be achieved by a precise and accurate assay with a detection limit well below the serum fructosamine concentration normally found in bovine sera. As a reference interval for the bovine serum fructosamine concentration 213.4 mumol/l to 265.0 mumol/l may be used. Serum fructosamine concentration is not affected by acute changes in blood glucose, and it displays no significant diurnal variation in cows.

Animals↗

Clinical evaluation of serum fructosamine in monitoring elderly outpatient diabetics.

Recently, new serum glycated protein assays (ie, serum fructosamine) have been developed. Fructosamine assays objectively monitor short-term glycemic control and, when used in conjunction with HgA1C, enhance the clinical information obtained and greatly aid in the clinical management of diabetes. Because they rely on glycation of serum proteins, the clinical utility of these assays in the elderly may be altered secondary to the hypoproteinemia that often is seen in these states. Therefore, we investigated the role of glycated serum proteins (ie, fructosamine level) in monitoring elderly diabetics over a 4-month period of observation. We found that the fasting blood glucose over the 4-month period correlated well with the serum fructosamine activity (r = 0.79, P less than .001) and HgA1C (r = 0.78, P less than .001). In addition, we found that the mean daily glucose, as determined by outpatient monitoring, correlated well to both the fructosamine activity (r = 0.66, P less than .001) and HgA1C (r = 0.74, P less than .001). We found no effect on the measurement of the fructosamine assay by the level of albumin seen in these patients. Our study suggests that serum fructosamine and HgA1C are equally effective in monitoring the elderly patient, as has been established in the younger diabetic, and no correction need be made in the fructosamine assay to compensate for variable serum protein levels seen clinically in the elderly.

Aged↗

Fructosamine. A new parameter for diagnosis and metabolic control in diabetic dogs and cats.

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 auto analysis appeared to be a practical means to assay fructosamine quickly, economically, and accurately. The upper limit of the reference range is 374 mumol/L in dogs (95% percentile) and 340 mumol/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 mumol/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.

Animals↗

Serum fructosamine in uraemia, myeloma and acute inflammatory disorders--relationship to serum glucose and albumin levels.

There has been considerable interest in the serum fructosamine assay as a measure of glycated serum proteins. We have measured serum fructosamine in three groups of patients--those with uraemia; those with multiple myeloma; and those with acute inflammatory conditions--none of whom were known to have diabetes. Serum fructosamine was significantly higher in the uraemic group than in the other two, and also than in a control group. When allowance was made for prevailing serum albumin levels fructosamine was shown to be increased in the acute inflammatory group also. There was a significant correlation between random plasma glucose and serum fructosamine only when fructosamine was adjusted for prevailing albumin levels. In control and uraemic subjects there was a significant positive correlation between serum fructosamine and albumin levels, whereas in the myeloma group there was a negative correlation with serum protein. These data would suggest the need to take into account serum albumin levels and protein composition if serum fructosamine is accurately to reflect short-term integrated glycaemia.

Adult↗

Increased fructosamine in non-diabetic rheumatoid arthritis patients: role of lipid peroxides and glutathione.

Modification of proteins by non-enzymatic glycation is one of the underlying factors known to play a major role in the pathogenesis of many clinical disorders. Glycation of plasma proteins is enhanced by elevated glucose concentrations. However, increased fructosamine has been documented in rheumatoid arthritis patients without any history of diabetes. Collective evidence reveals that malondialdehyde and reduced glutathione can modulate the glycation process. This study was undertaken to unravel the possible association of malondialdehyde and glutathione with fructosamine in rheumatoid arthritis patients. A case-control study was performed on 15 rheumatoid arthritis patients and 15 control subjects. Whole blood glutathione, plasma malondialdehyde, fructosamine and fasting glucose were analyzed in both groups. Partial correlation analysis was performed to predict the independent association of malondialdehyde, glutathione and fasting glucose on fructosamine. In rheumatoid arthritis patients, while fructosamine and malondialdehyde levels were significantly increased, glutathione levels were significantly decreased compared with controls. With partial correlation analysis, fructosamine was found to have a significant positive correlation with malondialdehyde and a negative correlation with glutathione. These data suggest that plasma fructosamine levels are closely associated with malondialdehyde and glutathione in rheumatoid arthritis patients, warranting extra precaution in interpreting fructosamine as a measure of glycemic control in these patients.

Adult↗

[Evaluation of the measurement of plasma fructosamine concentration in aged subjects].

Recently, plasma fructosamine concentration has been used as an indication of mean plasma glucose level preceding at last 1 to 2 weeks. In the present study, to characterize the clinical significance and problems of plasma fructosamine concentration in aged subjects (greater than or equal to 65 yrs), we determined plasma fructosamine concentration as well as serum albumin, total protein, HbA1, AbA1c and fasting plasma glucose concentrations in 81 (less than 65 yrs) non-diabetic subjects (group A), 161 aged (greater than or equal to 65 yrs) non-diabetic subjects and 26 aged diabetics (group D). Aged non-diabetic subjects were further classified into 75 subjects with good ADL (group B) and 86 with poor ADL (group C). The normal limit of plasma fructosamine concentration (mean +/- 2SD) in group A was 24% higher (3.1 mmol/l) than that in group B (2.5 mmol/l) but the plasma fructosamine/serum albumin ratio (F/ALB) was similar in these two groups. Plasma fructosamine correlated negatively (p less than 0.01) with age. This aging effect was explained by the reduced serum albumin in aged subjects. However, in group C, reduced plasma albumin was not associated with reduced plasma fructosamine. Plasma fructosamine corrected by albumin (F/ALB) is a useful parameter of blood glucose control in aged subjects. In aged subjects with poor ADL, HbA1, HbA1c and plasma glucose should be determined with fructosamine.

Aged↗

Can fructosamine be a surrogate for HbA(1c) in evaluating the achievement of therapeutic goals in diabetes?

OBJECTIVE: To determine if fructosamine can be used as a surrogate for HbA(1c) to monitor whether therapeutic goals in diabetes mellitus are achieved when HbA(1c) cannot be used for this purpose (hemoglobinopathies, anemia...). MATERIAL AND METHODS: Blood samples of 76 diabetic patients and 30 healthy subjects characterized by the absence of any risk of interference in the interpretations of HbA(1c) and fructosamine were studied in order to, first, deduce from the correlation a prediction of HbA(1c) from the fructosamine values, second, to evaluate the predictive value of such predicted HbA(1c) in the determination of poor metabolic control as defined by UKPDS and DCCT studies. RESULTS: The correlation between predicted HbA(1c) and actual fructosamine was fair (r=0.88) in diabetic patients but not in control subjects (r=0.01). It was therefore only possible to estimate HbA(1c) from fructosamine in diabetic patients. Nevertheless, the range of positive and negative predictive values of estimated HbA(1c) to detect a poor metabolic control defined by two thresholds of HbA(1c) (7%, 7.5%) was 91-93% and 86-87%, respectively. Then, even in this highly selected population, the risk of misclassification was around 10% when fructosamine was used to estimate HbA(1c). These results were unchanged when fructosamine was corrected by plasma protein level. CONCLUSIONS: This study shows the limitations to use fructosamine in place of HbA(1c) to evaluate the efficacy of antidiabetic treatments, even in a selected population.

Adult↗

Serum fructosamine: a parameter for monitoring metabolic control in diabetes.

The aim of this study was to determine serum fructosamine in a non-diabetic population and to evaluate the usefulness of fructosamine in the routine management of diabetic patients. The range of serum fructosamine in the non-diabetic population was 2.00-3.08 mmol/l (n = 300, mean 2.54 +/- 0.27). The mean level of fructosamine in the diabetic patients was 5.4 +/- 1.1 mmol/l at the beginning of the study and 3.5 +/- 0.4 mmol on the 12th week visit of the study. Significant differences in serum fructosamine levels were observed during the first visit and the 12th week visit p < 0.002. Serum fructosamine concentrations were significantly correlated with glycosylated haemoglobin at each subsequent visit (p < 0.001). No significant correlation between plasma glucose and fructosamine was found, suggesting the two parameters are markets for different time metabolic control. Routine use of serum fructosamine in management of diabetes is recommend.

Adult↗