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Effect of fluctuations in albumin on serum fructosamine assay.

Serum fructosamine, albumin and plasma glucose were studied in eight patients during recovery from diabetic ketoacidosis, and in eight patients with "decompensated" diabetes without acidosis. In the ketoacidotic group, serum fructosamine had fallen significantly by a mean of 12% by 8h, and fell further during the remainder of the study. A smaller but significant fall in fructosamine (mean 6.1%) was seen in the decompensated group after only 18 h, with again a further fall thereafter. These changes in serum fructosamine were accompanied by decreases in serum albumin. However, when fructosamine was corrected by calculating a fructosamine/albumin index (FAI) (fructosamine X 100/albumin), the FAI did not change significantly in either group until a small reduction was noted in the ketoacidotic group at 5 days, which might reasonably be expected as an index of intermediate-term glycaemia. Therefore minor fluctuations in albumin levels seen in diabetic patients can affect fructosamine, and correction may be be advisable for the test to be a valid measure of glycosylated serum proteins.

Acidosis↗

Use of fructosamine and glycated haemoglobin to verify self blood glucose monitoring data in diabetic pregnancy.

Relationships between fructosamine and HbA1, and mean blood glucose over the previous 1-8 weeks, determined from self blood glucose monitoring with memory meters, were studied prospectively throughout 16 pregnancies in Type 1 diabetic women. Fructosamine correlated best (Spearman rank) with mean blood glucose over the previous 2 weeks in the first and second trimesters (0.5) and over the previous 1 week in the third trimester (0.39). HbA1 correlated best with mean blood glucose over the previous 8 weeks in the first and second trimesters (0.56), but over the previous 2 weeks in the third trimester (0.524) probably because of increased erythropoiesis in late pregnancy. From Deming regression models, 95% prediction intervals for mean blood glucose for fructosamine and HbA1 values were calculated, showing that fructosamine predicted levels of mean blood glucose more precisely than HbA1. These intervals can be used to estimate an individual pregnant diabetic woman's mean blood glucose from her fructosamine or HbA1 results and to verify self blood glucose monitoring data. In well-controlled diabetic pregnancy, both fructosamine and HbA1 reliably indicated trends in blood glucose but fructosamine estimated blood glucose levels more precisely.

Adult↗

Clinical availability of serum fructosamine measurement in diabetic patients with uremia. Use as a glycemic index in uremic diabetes.

Serum fructosamine levels were investigated in patients with uremia undergoing various modes of treatment. The serum fructosamine levels correlated positively with the blood glucose levels determined a week or two earlier. The fructosamine levels were significantly affected by the protein concentration, and those corrected for protein concentrations had a closer correlation to the blood glucose levels than did the uncorrected levels. The corrected fructosamine levels were not significantly different between healthy volunteers and nondiabetic patients with uremia on conservative treatment. In an in vitro system, fructosamine concentrations were hardly affected by urea, which is known to influence the level of hemoglobin A1. These results suggest that serum fructosamine measurement can provide us with reliable information on a short-term glycemic condition, even in azotemic patients. To be more precise, the serum level of fructosamine corrected for protein concentration can be an excellent glycemic index which is not susceptible to over- or dehydration and is of high clinical value, especially in the management of diabetic patients with chronic renal failure.

Adult↗

Serum fructosamine concentration in patients with nephrotic syndrome and with cirrhosis of the liver: the influence of hypoalbuminaemia and hypergammaglobulinaemia.

We have investigated the influence of variation of the concentrations of serum albumin and immunoglobulins on serum fructosamine concentration in 33 patients with nephrotic syndrome, and 18 patients with cirrhosis of the liver. Protein alterations were evident in these patients and they were compared with 109 normal subjects, 43 patients with type II diabetes mellitus and nine diabetic patients with nephrotic syndrome. The mean serum fructosamine concentration in diabetic patients (2.76 +/- 0.53 mmol/L) was significantly increased (P less than 0.001) by comparison with normal subjects (1.93 +/- 0.20 mmol/L) and the other patients studied. Patients with diabetic nephropathy had higher (P less than 0.01) serum fructosamine concentrations (2.23 +/- 0.54 mmol/L) than non-diabetic patients with the nephrotic syndrome (1.57 +/- 0.37 mmol/L) but remained with the normal range. Positive correlations were observed between fructosamine and immunoglobulins G and M in nephrotic and cirrhotic patients. Serum immunoglobulin A was also directly correlated with serum fructosamine in patients with cirrhosis of the liver. An inverse correlation between albumin and fructosamine in serum of patients with cirrhosis of the liver was also noted. We conclude that the fructosamine assay is not useful in the assessment of glycemic control in patients with cirrhosis of the liver, nephrotic syndrome or in any other clinical situation in which protein metabolism is altered.

Adult↗

Fructosamine assay using albumin extracted from serum.

Albumin extracted from serum by a simple technique using trichloroacetic acid and ethanol has been applied to a fructosamine assay using nitroblue tetrazolium. A fructosamine assay using extracted albumin sample was carried out without interference from low molecular weight substances with reducing activities and other proteins with varying concentrations, half-lives and reducing activities. 1-Deoxy-1-p-toluidino-D-fructose (DTF) was selected as a calibrator for the assay because it is a stable Amadori reaction product with a constant glycation rate. Albumin fructosamine value was calculated using the calibration curve of DTF. The corrected albumin fructosamine value was expressed as the amount of albumin fructosamine per gram of extracted albumin taking into consideration the variation in albumin concentrations in sera from patients. The corrected albumin fructosamine values correlated more closely with the fasting blood glucose levels (r=0.735) than the serum fructosamine values corrected for albumin concentrations (r=0.514) (p<0.05).

Fructosamine↗

[The significance of serum fructosamine measurement in patients with thyroid diseases].

Serum fructosamine was measured in patients with Graves' disease and primary hypothyroidism. Fructosamine levels and fructosamine per albumin ratio were significantly lower in patients with Graves' disease than in normal subjects, while they were significantly higher in patients with primary hypothyroidism. Fructosamine levels were normalized by treatment in the euthyroid state in patients with Graves' disease. Along with the normalization of thyroid stimulating hormone levels, fructosamine levels returned to the normal range in patients with primary hypothyroidism with treatment. There were significant correlations between fructosamine levels and free triiodothyronine levels, free thyroxine levels, thyroid stimulating hormone levels, hemoglobin A1C levels, albumin levels, and creatine phosphokinase levels. We concluded that it was useful to measure serum fructosamine as an indicator of peripheral metabolic function in patients with thyroid diseases.

Creatine Kinase↗

The clinical usefulness of serum fructosamine and HbAlc in patients with NIDDM.

To evaluate the clinical values of serum fructosamine and HbAlc, serum fructosamine and HbAlc were assessed in 50 normal controls and 36 patients with NIDDM (non-insulin-dependent diabetes mellitus). And we studied 10 patients selected at random among the 36 patients with NIDDM. The values of serum fructosamine and HbAlc in controls were 2.1 mmol/L and 5.3%, respectively. The levels of serum fructosamine and HbAlc were significantly higher in NIDDM patients (3.27 mmol/L and 8.8%, respectively, p less than 0.005) compared with those in the controls. The serum fructosamine was significantly correlated with fasting plasma glucose and HbAlc (r = 0.78, p less than 0.78, p less than 0.001; r = 0.76, p less than 0.005, respectively). Also, in retrograde study, serum fructosamine concentration had a significant correlation to fasting plasma glucose determined 2 weeks before (r = 0.72, p less than 0.002), and 4 weeks before (r = 0.54, p less than 0.005). It is concluded that serum fructosamine measurement may be useful in monitoring short-term control of plasma glucose in patients with NIDDM.

Adult↗

Home testing of fructosamine improves glycemic control in patients with diabetes.

OBJECTIVE: To determine whether weekly fructosamine testing at home by patients with type 2 diabetes, combined with therapeutic intervention when necessary on the basis of the results, would lead to improved glycemic control in comparison with usual care during a 3-month period. METHODS: In a prospective study, 25 patients with glycosylated hemoglobin (HbA1c) values above 8.0% were randomized into 2 groups. Both groups, a glucose-only testing group (14 patients with an initial mean HbA1c of 9.4 +/- 0.9%) and a combined glucose plus fructosamine testing group (11 patients with an initial mean HbA1c of 9.2 +/- 0.7%), received therapeutic intervention at the time of randomization. Both groups were instructed to perform blood glucose testing up to four times per day. The combined glucose plus fructosamine testing group was also instructed to perform weekly fructosamine testing in addition to the glucose testing and to telephone the investigator if their home-testing fructosamine value exceeded 350 mmol/L (approximately equivalent to HbA1c of 7.8%), whereupon the investigator implemented further interventions. Both groups returned in 3 months, at which time HbA1c testing was repeated in order to determine whether glycemic control had changed. RESULTS: The study results after 3 months showed that the HbA1c values in the combined glucose plus fructosamine testing group decreased from 9.2 +/- 0.7% to 8.0 +/- 0.5% (P<0.0001). In contrast, the HbA1c values in the glucose-only testing group declined from 9.4 +/- 0.9% to 9.1 +/- 1.3%, a difference that was not significant. CONCLUSION: In the 3 months after a change in therapy for type 2 diabetes, weekly home testing of fructosamine, combined with therapeutic interventions based on the results, led to a more rapid and significant improvement in glycemic control than did the usual regimen of glucose-only testing.

Blood Glucose Self-Monitoring↗

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.

Animals↗

[Effect of bilirubin on serum fructosamine value, and the elimination of bilirubin by bilirubin oxidase].

Fructosamine is examined as the index of past mean blood glucose levels. However, the fructosamine value appears to be influenced by the bilirubin. Therefore, we examined patients with hyperbilirubinemia showing suspected and definite jaundice. Abnormal fructosamine values were noted in 9 out of the 50 cases (18%) with suspected jaundice and 40 out of the 55 cases (72.2%) with definite jaundice. An experiment in which bilirubin was removed by bilirubin oxidase revealed that fructosamine levels in hyperbilirubinemia correlated with the values of bilirubin and increased fructosamine values were expressed as the values of bilirubin x 6.5. These results demonstrate abnormal fructosamine values not only in jaundice patients but also in those with suspected jaundice. These cases must be taken in the examination of fructosamine in patients with hyperbilirubinemia.

Bilirubin↗

Comparison of serum fructosamine and blood glucose concentrations as indices of glycaemic control in non-insulin dependent diabetic out-patients.

The usefulness and validity of blood glucose measurement as an index of diabetic control were assessed with reference to serum fructosamine. Two hundred and twenty-eight non-insulin dependent diabetic out-patients were studied in the usual clinical setting. Fasting blood glucose (FBG) concentration was positively correlated with serum fructosamine (r = 0.42, t = 6.78 p less than 0.01). On the basis of their serum fructosamine concentrations, patients were divided into 3 groups. They were good control (fructosamine less than or equal to 288 umol/l), acceptable control (fructosamine less than or equal to 320 umol/l) and poor control groups (fructosamine greater than 320 umol/l). The mean fasting blood glucose concentration was significantly higher in the latter than the former 2 groups. However, at each level of control, there was a wide range of FBG concentrations. Thus, the value of FBG in predicting glycaemic control is limited. Its positive predictive value was only 32%, and its overall accuracy as an index of diabetic control was only 58% though its negative predictive value was high (93%). In 162 patients with poor diabetic control as indicated by their serum fructosamine concentrations, 81 (50%) of them had FBG less than 10 mmol/l on their clinic visit day. Fasting blood glucose is therefore not a reliable measure of good diabetic control, though it is useful in predicting poor control. FBG is simple to measure, cheap and rapidly available on clinic day, thus ensuring its continuing use. Doctors should be aware of its limitations and should not rely solely on FBG to assess diabetic control.

Adult↗

Correlation between fasting plasma glucose, post prandial glucose and glycated haemoglobin and fructosamine.

This study was done to determine the correlation between glucose monitoring by fasting blood glucose or 2 hours postprandial blood glucose with HbA1c and fructosamine in type 2 diabetic patients. A total of 82 patients from the Primary Care Clinic were enrolled in the study. Fasting blood was drawn for fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) and fructosamine. Two hours after a standard breakfast, blood was again drawn for prandial plasma glucose (PPG). Both PPG and FPG significantly correlated with both HbA1c and fructosamine but PPG showed better correlation to HbA1c than FPG (r= 0.604 vs.0.575) whereas that of FPG and PPG were equally correlated to fructosamine (r= 0.566 vs. 0.551). In predicting good glycaemic control (HbA1c < 7.0%), the sensitivity, specificity and positive predictive value of PPG were 75.0%, 80.6% and 82.5% whereas FPG were 81.8%, 58.3% and 70.6% respectively. These results show that PPG correlated better than FPG to HbA1c and both equally correlated to fructosamine levels. Thus, PPG predicted overall glycaemic control better than FPG. Compared to HbA1c, fructosamine correlated least well with mean glucose profiles. Hence, using HbAlc in monitoring overall glycaemic control is better than fructosamine.

Adult↗

Serum fructosamine in the assessment of glycaemic status in patients with sickle cell anaemia.

AIM: To assess the usefulness of fructosamine in evaluating the glycaemic status in patients with sickle cell anaemia. METHOD: Serum fructosamine, glucose, albumin and bilirubin were measured in one hundred and fifty patients with sickle cell anaemia (HbSS), fifty poorly controlled diabetics and one hundred healthy control subjects. Fructosamine was assayed using the method of Johnson et al. RESULTS: None of the HbSS patients had hyperglycaemia. Serum fructosamine was significantly higher in the poorly controlled Diabetics compared to the HbSS patients and the Controls. The mean serum albumin levels were within the laboratory's reference interval in the three groups of subjects studied. There was no significant correlation between fructosamine and normal serum albumin in the three groups of subjects. Moderately raised serum bilirubin concentrations in the HbSS patients did not cause any significant interference in the assay of fructosamine in the patients. CONCLUSION: Serum fructosamine could be reliably employed as a measure of glycaemic status of patients with sickle cell anaemia with moderate hyperbilirubinaemia.

Adolescent↗

An improved colorimetric assay for fructosamine.

With the commercial availability of the improved colorimetric assay for fructosamine, we established the fructosamine values for non-diabetic healthy persons. This improved assay incorporates detergent and uricase in a more concentrated nitroblue-tetrazolium reagent base compared to the earlier reagent (Johnson & Baker assay), including a new serum calibrator. An evaluation of the assay showed that fructosamine values obtained with serum, EDTA-plasma and heparin-plasma were comparable to each other. There was no apparent effect on fructosamine by lipids. Within-run precision variations for each specimen type (fructosamine 248-592 mumol/l), determined with a mechanised analyser were less than 3% (0.9-3%). Between-run precision for serum and EDTA-plasma ranged from 2.5% to 5.6%. This fructosamine assay also showed a positive correlation with the Johnson and Baker assay. Based on 48 healthy adults (20 males, 28 females) of mean age 32.9 +/- 9.2 years, the fructosamines ranged from 195 to 304 mumol/l, with a mean 250 +/- 24.3 mumol/l. The 2.5 and 97.5 percentiles were 196.4 mumol/l and 301.8 mumol/l respectively.

Adult↗

Automated fructosamine assay with improved accuracy used to quantify nonenzymatic glycation of serum proteins in diabetes mellitus and chronic renal failure.

We optimally solubilized the diformazan that forms during the fructosamine reaction with a nonionic detergent; we then automated the assay. After optimal solubilization of diformazan, we found that serum urate contributed significantly to the color formation in fructosamine reaction. When the error introduced by urate was corrected mathematically by use of an experimental determined factor, the serum fructosamine concentrations obtained were comparable with those of a more specific test of the nonenzymatic glycation (HPLC of hydrolyzed proteins). We found that concentrations of fructosamine in serum increased with increasing age of subjects. In diabetic patients the average concentration of fructosamine in serum exceeded that in nondiabetic subjects and correlated with the preprandial serum glucose and with other measures of deteriorating glycemic control (e.g., increased need for insulin therapy). Serum fructosamine normalized for albumin content was also increased in patients with chronic renal failure. Multiple mechanisms (including exposure of patients to hypertonic glucose during dialysis) appear to be involved in the increase of serum fructosamine in patients with chronic renal failure.

Adult↗

Evaluation of diabetic control by using hemoglobin A1 and fructosamine.

Evaluation of diabetic control was performed by using fasting plasma glucose, hemoglobin A1 and fructosamine in 139 patients with diabetes mellitus, and 36 normal controls. A linear correlation of fasting plasma glucose with fructosamine and hemoglobin A1 was found. Using fasting plasma glucose alone was found to be inadequate to define good control. HbA1 and fructosamine had an acceptable sensitivity and specificity in assessment of diabetic control, although fructosamine was slightly less sensitive than HbA1. In patients with thalassemia, hemoglobin A1 levels were elevated in 18 of 19 patients. Fructosamine levels also gave misleading results since 6 to 19 patients had an elevated level and one patient had a decreased level. Patients with hypoproteinemia had a decreased fructosamine and hemoglobin A1 level compared to normal control. HbA1 and fructosamine should be cautiously interpreted in patients with thalassemia and hypoproteinemic states. Using these methods in combination with other measure such as home monitoring of blood glucose would be more precise particularly in diabetic patients with hypoproteinemia, abnormal hemoglobin and other hemolytic disorders.

Adolescent↗

Serum fructosamine determination as an index of glycaemic control: comparison between an automated and manual method, and the effect of serum storage.

The measurement of glycated serum proteins was recently introduced as an alternative index of diabetic control of glycated haemoglobin. Manual and automated serum fructosamine colorimetric assays are available for glycated serum proteins determination. We have assessed two serum fructosamine assays, an automated and a manual method, and compared them with a glycated haemoglobin assay. We also studied the effect of serum storage on serum fructosamine concentrations. Serum fructosamine at four different concentrations measured by automated method gave an inner-assay of a 2% (range 1.29 - 1.56%) and an inter-assay variation of 3% (range 1.63-2.92%). There was a good correlation between the automated and manual methods, with a coefficient of r = 0.944. Serum fructosamine by either method is a sample assay to perform and is relatively inexpensive. With automated analysis, a large number of tests can be performed more rapidly. Comparing serum fructosamine with glycated haemoglobin, coefficients = 0.54 (automated) and r = 0.50 (manual) were obtained. An increase in serum fructosamine by 5-20% occurred when the assay is performed on serum samples stored for more than two weeks. It is recommended therefore that test should be performed soon after blood collection, preferably within one week.

Blood Glucose↗

Fructosamine: an alternative assessment of past glycaemic control in developing countries.

Fructosamine assay determines glycaemic control in diabetic patients by measuring glycosylated plasma protein. This study was done to assess the value of fructosamine as an alternative test to HbA1c as a measure of glycaemia. Sixty patients (both insulin dependent diabetes mellitus and non insulin dependent diabetes mellitus) were selected from the diabetic clinic and fasting blood samples were collected for estimation of glucose, HbA1c and fructosamine levels. The results were compared by correlation analysis and major discrepancies/discordance was detected by dividing the results into 3 clinical categories and detecting the cases in which the values fell in opposite clinical categories. Fructosamine correlated well with HbA1c (r = 0.41, p < 0.01) and with fasting blood glucose (r = 0.45 p < 0.01). Major discordance was detected in the results of only 7 patients which can partly be attributed to different periods over which HbA1c and fructosamine reflect average glycaemia. Fructosamine measures glycaemia over the past 2-3 weeks and HbA1c over 8 weeks. As fructosamine assay is relatively inexpensive, reliable and simple to perform; it can be used as an alternative to HbA1c and is particularly suited for developing countries.

Blood Glucose↗