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Can plasma fructosamine substitute for glycated haemoglobin (HbA1c) estimation in the assessment of diabetic control?

The 'gold standard' marker of overall glycaemic control in diabetes mellitus is the level of glycated haemoglobin (HbA1c). It is, however, an expensive and technically difficult assay and is rarely appropriate to tropical laboratories. Plasma fructosamine measurement is cheaper and easier, though it reflects shorter-term glycaemia. We have measured both indices of control in a group of 154 diabetic patients. There was close correlation between the two measurements (r = 0.6506, P < 0.001), but many patients with abnormal HbA1c levels had normal fructosamine levels. This resulted in an assay sensitivity (compared with HbA1c as gold standard) of only 30%, though specificity was 98%. We conclude that fructosamine measurement cannot be regarded as a substitute for HbA1c determination.

Adolescent↗

Relation with preoperative fructosamine and autonomic nerve function and blood pressure during anesthesia in diabetics: a retrospective study.

Many diabetics may have a high risk involving the cardiovascular system. In an attempt to predict the intraoperative risks of diabetics during anesthesia, we evaluated retrospectively the relationship among the biochemical assay or autonomic nerve function obtained as parts of the preoperative examination, and the blood pressure changes relating to the stimulation of intubation and extubation for anesthesia. In 40 diabetic surgical patients examined the biochemical assay (HbA1c, fructosamine level and blood glucose level) beforehand, the autonomic nerve function was quantified preoperatively by analysis of ECG R-R variability recorded in supine and subsequent standing position using an HRV analyzer, and some parameters of autonomic nerve function especially responsive sympathetic nerve activities were obtained. We assessed the correlation with systolic blood pressure changes in these cases at intubation for general anesthesia comparing to similar conditioned 40 non-diabetics. A diabetics with low vagal activity became larger systolic blood pressure afterdrop at tracheal intubation for anesthesia (r=0.513, p<0.001). Otherwise the blood pressure afterdrop at extubation became larger in a non-diabetics with high sympathetic activity (r=0.502, p<0.001). The preoperative fructosamine concentration in diabetics correlated positively with the responsive sympathetic nerve irritability index; "mRR(sup)-RRmin(std)" (r=0.432, p<0.05) and the responsive sympathetic nerve excitability index; "mRR(sup-std)" (r=0.448, p<0.05). However HbA1c had no correlation with these parameters of autonomic nerve function and blood pressure rise at tracheal intubation. Because of above correlation with blood pressure rise at intubation for anesthesia induction, the preoperative fructosamine examination and the responsive sympathetic nerve function test must be useful preoperative examination for detection of the unexpected heart events of diabetic patients during operation.

Aged↗

Oral glucose tolerance test and determination of serum fructosamine level in beagle dogs.

The present communication deals with information regarding the practice of the oral glucose tolerance test and determination of serum fructosamine in laboratory beagles. In the oral glucose tolerance test, a 180-min level was found to be crucial following a gavage administration of 50% glucose solution at 5 mL/kg per body weight under fasting conditions. Serum fructosamine concentration as 'determined by enzymatic assay ranged between 82 and 123 micromol/L (mean of 104 micromol/L), which was about 0.285 to 0.25 times the value obtained by the chemical method described by Johnson and colleagues. Reasons for differences are ascribed to the presence of substances with reducing potential other than fructosamine in the serum.

Administration, Oral↗

Receiver operating characteristic analysis on fasting plasma glucose, HbA1c, and fructosamine on diabetes screening.

OBJECTIVE: To determine the efficacy of HbA1c and fructosamine as alternatives to fasting plasma glucose (FPG) for diabetes screening. RESEARCH DESIGN AND METHODS: Receiver operating characteristic (ROC) analysis was conducted on the above tests. Comparison among tests was based on the area under ROC curve of a test. World Health Organization criteria for classifying glucose tolerance status of the subjects was used. The study consisted of subjects (n = 583) who visited the clinic from September to October 1989 and all diabetic cases (n = 36) from November 1989 to March 1990, after excluding those less than 40 yr of age or with hypoglycemic therapies (469 were normal, 88 with impaired glucose tolerance ( IGT], and 62 with diabetes). RESULTS: Area under ROC curve of HbA1c was not different from that of FPG. Area under curve of fructosamine was significantly smaller than that of FPG. For all tests, overall efficacy of a test to detect IGT and diabetes was considerably diminished compared with detection of diabetes alone. CONCLUSIONS: The discriminating ability of HbA1c is almost the same as that of FPG, therefore HbA1c is a good alternative to FPG. Fructosamine is not suitable for diabetes screening.

Analysis of Variance↗

Conversion of a synthetic fructosamine into its 3-phospho derivative in human erythrocytes.

Intact human erythrocytes catalyse the conversion of fructose into fructose 3-phosphate with an apparent K(m) of 30 mM [Petersen, Kappler, Szwergold and Brown (1992) Biochem. J. 284, 363-366]. The physiological significance of this process is still unknown. In the present study we report that the formation of fructose 3-phosphate from 50 mM fructose in intact erythrocytes is inhibited by 1-deoxy-1-morpholinofructose (DMF), a synthetic fructosamine, with an apparent K(i) of 100 microM. (31)P NMR analysis of cell extracts incubated with DMF indicated the presence of an additional phosphorylated compound, which was partially purified and shown to be DMF 3-phosphate by tandem MS. Radiolabelled DMF was phosphorylated by intact erythrocytes with an apparent K(m) ( approximately 100 microM) approx. 300-fold lower than the value reported for fructose phosphorylation on its third carbon. These results indicate that the physiological function of the enzyme that is able to convert fructose into fructose 3-phosphate in intact erythrocytes is probably to phosphorylate fructosamines. This suggests that fructosamines, which are produced non-enzymically from glucose and amino compounds, may be metabolized in human erythrocytes.

Erythrocytes↗

The relation between the results of determination of fructosamine and glycosylated proteins of blood serum.

Fructosamine concentration (measured by NBT reduction method) and the concentration of glycosylated proteins (measured by a direct UV spectrophotometry upon separation from nonglycosylated proteins by means of affinity chromatography, have been determined simultaneously in 52 samples of blood serum obtained from 42 children with diabetes mellitus and 10 children without metabolic disorders. A highly significant positive correlation (r = 0.96, p < 0.001) was found between the two parameters. It was concluded that fructosamine determination by NBT reduction test reflects the true concentration of glycosylated proteins of blood serum, provided that the proper correction factor derived from the equation of linear regression is used as shown in the following equation: Concentration of glycosylated proteins of blood serum in milligram = 2.78 x (fructosamine concentration in mmol/l + 1.26).

Blood Proteins↗

Value of fasting blood glucose and serum fructosamine as a measure of diabetic control in non-insulin-dependent diabetes mellitus.

The predictive values of fasting blood glucose and serum fructosamine for monitoring longterm diabetic control were investigated in 98 non-insulin dependent diabetic patients. The HbA1c percentage was taken as standard in this study. Despite a significant correlation, the predictive values of the parameters studied for an acceptable HbA1c-value appeared to be low (37% and 44% respectively), possibly due to differences in periods of time in which these parameters can change during variable metabolic control. In addition, the serum fructosamine value may vary due to variations in serum albumin and lipid content. It is concluded that the fasting blood glucose and serum fructosamine values cannot replace HbA1c measurement for monitoring diabetic control, but are additional for assessment of this control over short-and longterm periods of time.

Adult↗

[Postpartum diabetes screening: value of fructosamine determination].

After birth of an infant with a birthweight of 4000 g or more maternal glucose tolerance should be examined. We measured blood glucose values after a 100 g oral glucose challenge and compared them with serum fructosamine values of the same subjects. 40 women who had given birth to an infant with macrosomia (group I) were matched with 40 women who had delivered babies with normal birthweight (group II). Impaired glucose tolerance was found in 6 women (15%) of group I, and in one woman (2.5%) of group II. Fructosamine values were within the normal range in each of the seven women (1.74 + 0.2 mmol/l vs 1.73 + 0.2 mmol/l). Thus, fructosamine determination is not sensitive enough to detect impaired glucose tolerance in asymptomatic women post partum. It is not feasible to replace the oral glucose tolerance test in screening for gestational diabetes mellitus.

Birth Weight↗

Glycosylated hemoglobin and fructosamine. Indicators of glycemic control in pregnancies complicated by diabetes mellitus.

In 50 gravidas with insulin-dependent diabetes mellitus, mean preprandial whole blood glucose levels over a two-week period were compared with serum glycosylated hemoglobin (HbA1c) and fructosamine values. Although there was a statistically significant correlation between mean glucose levels and both HbA1c (r = .44, P less than .01) and fructosamine (r = .37, P less than .01), the wide range of HbA1c and fructosamine observed at all levels of mean blood glucose limited the usefulness of those assays in the management of pregnant diabetics.

Blood Glucose↗

A comparison of home glucose monitoring with determinations of hemoglobin A1c, total glycated hemoglobin, fructosamine, and random serum glucose in diabetic patients.

We compared four objective measures of glycemic control (fructosamine, total glycated hemoglobin, hemoglobin A1c, and random serum glucose) with home glucose monitoring records in 17 diabetic patients followed up prospectively for 4 months. There was good overall correlation between all of these objective measures and weekly mean capillary glucose values. However, considerable scatter was seen in the data such that none of the glycated protein measurements was an ideal predictor of home glucose values. For example, all markedly elevated home glucose levels (greater than 11.1 mmol/L) were associated with elevated glycated protein levels, but moderately high blood glucose levels (8.3 to 11.1 mmol/L) were associated with one or more normal glycated protein values in some patients. Similar correlations were obtained whether glycemia was estimated by 1-week or 6-week home averages. Random serum glucose level also correlated with average home glucose level; however, there was wide fluctuation within individual subjects. All three glycated protein measurements (hemoglobin A1c, glycated hemoglobin, and fructosamine) appear equally useful as a supplement to home glucose monitoring in the assessment of glycemic control. Of the three types of glycated protein assays, fructosamine, with its advantage of speed and simplicity, may offer a more cost-effective alternative.

Adolescent↗

[A new fructosamine test--as a routine parameter in the control of diabetes].

Measurement of protein glycation (fructosamine) has become an accepted tool in diabetes diagnostics. Among different methods available, the serum fructosamine test published by Johnson and Baker in 1983 has gained wide acceptance due to a simple and easily automated assay procedure providing clinically meaningful results. A recent modification of the Nitroblue Tetrazolium (NBT) reagent, improved by addition of tensides and uricase, exhibits lower interference by lipaemia and urate. It is also less affected by the sample matrix and yields results closer to the physiological range of glycated proteins. Furthermore, a completely new standardization protocol was used in the preparation of calibration material. The new colorimetric method for the determination of fructosamine was evaluated in 12 European clinical laboratories.

Blood Glucose↗

[Fructosamine as a valuable criterion for the evaluation of diabetic animals and its photometric determination].

The new photometrical kit fructosamine is tested for its use with canine, feline and equine blood. Normal values of fructosamine in nondiabetic animals as well as adequately and inadequately stabilized patients are given. The measurement of fructosamine is an excellent new tool for diagnosis and treatment of diabetes mellitus and should become an essential part of the control of the course of diabetes mellitus in animals.

Animals↗

[Fructosamine values in venous and capillary blood].

The determination of fructosamine could also be performed in serum obtained from capillary blood. The sample taking using micro sample carriers for capillary blood is more convenient for the patients. The described procedure is an alternative way suitable for the determination of fructosamine in ambulance and in doctor's office. Results obtained with uncoated micro carriers and capillary blood are in good agreement with fructosamine values from venous blood. However, the use of sample carriers coated with EDTA or heparin produced discrepant results.

Blood Specimen Collection↗

[The effect of orthostasis on the fructosamine value].

With the introduction of an improved method for the determination of fructosamine a new tool is available for the monitoring of diabetes. This method provides a good reproducibility together with a standardized quality control and is easily applicated to automated clinical chemistry analyzers. Besides the analytical performance in general the impact of preanalysis on fructosamine values is important for routine work. In a study with 20 volunteers the impact of orthostasis has been investigated. Changes in fructosamine concentration correspond to a shift in the concentration of other analytical parameters related to serum proteins.

Adult↗

[Age dependence, sex independence and reference values of serum fructosamine determined using a new colorimetry method].

Reference ranges were evaluated for a new colorimetric method for the determination of fructosamine in serum. The reference group was composed of 1114 non-diabetics of both sexes including children. Reference values are only slightly affected by age and sex. In the course of childhood to adolescence fructosamine values raise and finally stabilize in adults. The small differences between both sexes have no effect on the interpretation of clinical results. Relating fructosamine values to albumin or total protein has little impact on the distribution of the values when protein values were within the reference range.

Adolescent↗

[Importance of the determination of fructosamine in monitoring diabetic patients].

Protein glycosylation plays a role in the metabolic control and in the pathogenesis of diabetic complications; indeed it has an important role in the process leading to micro- and macroangiography in diabetes. In an attempt to determine the clinical value of fructosamine assay for monitoring type II diabetic patients, the correlation of fructosamine and HbA1c, glycemia, cholesterol and triglycerides was studied. The results show that fructosamine is a good index for short-term metabolic control of diabetic patients.

Blood Glucose↗

Glycated proteins in serum: effect of their relative proportions on their alkaline reducing activity in the fructosamine test.

The fructosamine test is considered clinically useful for assessing short-term integrated control of blood glucose, but there are few published data to support this hypothesis. We fractionated glycated and nonglycated proteins by affinity chromatography on phenylboronate columns and, with specific immunochemical methods, determined in the eluted fractions the following proteins, selected according to their biological half-lives and relative concentrations in serum: albumin, IgA, IgG, IgM, apolipoprotein B, haptoglobin, transferrin, alpha 1-antitrypsin, and alpha 2-macroglobulin. We found the following correlations between fructosamine (mmol/L) and, respectively, glycated albumin, IgG, and (albumin + IgG) (each in grams per liter): r = 0.901, 0.702, 0.878. IgM had the highest percentage of glycated molecules (range 11.1-37.5%, mean 22.4%), haptoglobin and alpha 1-antitrypsin the least. This result was almost independent of the proteins' molecular masses and fractional catabolic rate. Albumin evidently contributes most to results of the fructosamine test, confirming conclusions obtained in different ways by others.

Apolipoproteins B↗

Correlation of HbA1C, glycated serum proteins and albumin, and fructosamine with the 24-h glucose profile of insulin-dependent pregnant diabetics.

To assess the value of various methods for long-term follow-up of diabetic patients, we compared the concentrations of fructosamine in serum with those of various glycated proteins: hemoglobin (HbA1C), total serum proteins (G-prot), and albumin (G-alb), assayed in 30 pregnant insulin-dependent diabetics every two weeks after initial determination of a 24-h blood glucose profile. HbA1C correlated best with the 24-h glucose profile during the succeeding 10-35 days (r = 0.65-0.68, P less than 0.001). G-prot and G-alb correlated nearly as well as HbA1C 10-20 days after the glucose profile (r = 0.54-0.64, P less than 0.01-0.001), but only weakly after 25-35 days. Values for fructosamine did not correlate significantly with the glucose profile 10-35 days after it (r = 0.23-0.36). Evidently the fructosamine assay is not an adequate alternative to HbA1C, G-alb, or G-prot as an index to long-term control of blood glucose in such patients.

Blood Glucose↗