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Combined use of a fasting plasma glucose concentration and HbA1c or fructosamine predicts the likelihood of having diabetes in high-risk subjects.

OBJECTIVE: To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS: In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity. RESULTS: Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG > or = 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) > or = 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG > or = 5.6 mmol/l and an HbA1c > or = 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG > or = 5.4 mmol/l and a fructosamine > or = 235 mumol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG > or = 5.6 mmol/l and < 7.8 mmol/l and an HbA1c > or = 5.5% (n = 642) required an OGTT to confirm diabetes, thereby saving 77.7% [(2,877-642)/2,877] of the OGTTs performed. Similarly, only subjects who had an FPG > or = 5.4 mmol/l and < 7.8 mmol/l and a fructosamine > or = 235 mumol/l (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408-526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/l, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively. CONCLUSIONS: The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach approximately 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG.

Adult↗

Rapid and inexpensive microdetermination of serum fructosamine results in diabetics, uraemics, diabetics with uraemia and healthy subjects.

This paper describes a simple, reliable and inexpensive method for rapid determination of serum fructosamine. The assay is based on commercially available reagents and utilizes equipment accessible in most laboratories (i.e. an automated ELISA-reader interfaced with an IBM computer). In contrast to HbA1c determination, the fructosamine method presented can be used in diabetes complicated by uraemia. In the clinically relevant measuring range, fructosamine is uninfluenced by serum albumin concentration in diabetics with or without uraemia. Eighty microlitres of non-haemolysed capillary serum suffices for a duplicate determination. One year's storage of normal serum induced no change in serum fructosamine estimates. s-Fructosamine in 18 healthy subjects was 2.1 +/- 0.3 mmol/l (mean +/- SD) in venous blood and 2.2 +/- 0.4 mmol/l in capillary blood. In diabetics 3.4 +/- 0.6 mmol/l and 3.3 +/- 0.6 mmol/l (n = 38) were found. The method is well-suited for routine use in the diabetic out-patient clinic.

Adult↗

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.

Animals↗

Randomized trial of fructosamine home monitoring in patients with diabetes.

CONTEXT: Recognition of the importance of glycemic control in type 2 diabetes has generated interest in developing ways to improve such control. Levels of fructosamine, 1-amino-1-deoxyfructose, are highly correlated with those of hemoglobin A1c (HbA1c) and can be monitored in the home. DESIGN: Randomized trial. PARTICIPANTS: 140 adult patients with HbA1c values of 8% or greater were recruited to the trial through referral from physicians and a direct mailing to potentially eligible persons. INTERVENTION: Weekly home fructosamine monitoring in addition to daily glucose monitoring. Control patients monitored daily glucose only. Both groups of patients were contacted regularly by telephone and were given the same instructions on diet and exercise. OUTCOME: Measures of glycemic control 3 and 6 months after randomization. RESULTS: No significant difference was found between the two groups in the mean absolute decrease of HbA1c levels at 3 months (0.5% in the fructosamine group vs. 0.8% in the control group; P > 0.2), and the difference favored the control group at 6 months (0.7% fructosamine vs. 1.2% control; P = 0.04). Both groups had a statistically significant improvement in glycemic control. CONCLUSIONS: The addition of home fructosamine monitoring to routine glucose monitoring did not improve glycemic control.

Adolescent↗

Serum fructosamine and subsequent breast cancer risk: a nested case-control study in the ORDET prospective cohort study.

There is evidence that abnormal glucose metabolism may contribute to the risk of breast cancer. The measurement of markers of glucose metabolism could help to identify women at risk for breast cancer. Serum fructosamine is one such marker. In this study, we investigated whether prediagnostic serum fructosamine was associated with breast cancer. Between 1987 and 1992, 10,786 women ages 35 to 69 were recruited in Italy for a prospective study. Women with a history of cancer or on hormone therapy were excluded at baseline. Blood samples were collected after 12 hours fasting from all participants at recruitment. After 5.5 years of follow-up, 144 breast cancer cases were identified and four matched controls were selected from the cohort; serum fructosamine levels were measured in both groups at baseline. Adjusted odds ratios (OR) for the highest tertile of serum fructosamine compared to the lowest was 1.60 [95% confidence interval (CI), 0.95-2.73]. In premenopausal women, the OR was 1.58 (95% CI, 0.76-3.40) and in postmenopausal women, the OR was 1.60 (95% CI, 0.76-3.48). Serum fructosamine levels tended to be positively associated with breast cancer risk independent of menopausal status.

Adult↗

Comparison of fructosamine with glycated hemoglobin as an index of glycemic control in diabetic patients.

Fasting and postprandial (or post-glucose load) plasma glucose, total HbA1 and fructosamine (F) were simultaneously assessed in 371 diabetic patients (125 insulin dependent and 246 non-insulin dependent) and in 122 nondiabetic subjects, (98 with normal glucose tolerance and 24 with impaired glucose tolerance). Fructosamine yielded nearly similar information as HbA1 about glycemic control, since similar relationships were observed between plasma glucose values and HbA1 or fructosamine levels in the different groups. A longitudinal study performed during a three-month follow-up in 74 diabetic patients and extended to six months in 19 of them, without any modification of treatment, indicated that reproducibility of HbA1 and fructosamine was nearly the same with a slight advantage for HbA1. The only clinically significant difference results from the longer half-life of hemoglobin when compared to serum proteins. Fructosamine assay should be proposed as a complement of HbA1 in the management of diabetic patients when detection of recent metabolic changes is needed.

Adult↗

Serum fructosamine concentrations in Singapore pregnant women.

Serum fructosamine levels in women at pregnancy (28 weeks' gestation) were determined. The women (n = 99) also participated in an oral glucose tolerance test (OGTT) with a 75g liquid glucose load, to determine their glucose tolerance. At 32 weeks' gestation, seventy-nine of them repeated the oral glucose tolerance test and fructosamine measurement. Results showed that fructosamine levels in pregnant women with normal glucose tolerance (2.20 +/- 0.19 mmol/l, n = 76), were not statistically different from those with glucose intolerance (gestational diabetes: 2.19 +/- 0.22 mmol/l, n = 23) at 28 weeks' and also 32 weeks' gestation. However, serum fructosamine levels in pregnant women were lower than those in non-pregnant subjects. Serum fructosamine measurement is not a sufficiently sensitive test for diagnosis of gestational diabetes.

Adult↗

[Fructosamine values in hyperthyroidism, hypothyroidism and gammopathy].

Fructosamine values in two groups of hypo- and hyperthyroid patients were compared with the values in a reference group of non-diabetics. In hyperthyroid patients the fructosamine values were significantly lower than in the reference group. Also the mean concentrations of albumin and total protein in serum are significantly lower for hyperthyroid patients compared to hypothyroid patients. The results do not provide evidence for a simple relationship between fructosamine and protein values in these patient groups. Therefore we do not recommend to relate fructosamine to protein or albumin using correction factors. Under conditions of thyrotoxicosis fructosamine is no reliable indicator of previous serum glucose concentrations. The test is not affected by monoclonal IgG gammopathy.

Adult↗

[Effect of a change in posture on the diurnal variations of fructosamine concentration in diabetic patients].

Daily profiles of blood glucose, HbA1c, total protein and fructosamine were measured in 10 diabetic patients and the factor fructosamine x 7/g total protein was calculated. Measurements were done at 4 a.m. to be sure that the patients were sleeping for some time, during the day and the following evening at 11 p.m., when the patients were lying again, so that the influence of orthostasis, the difference between bed rest and walking could be demonstrated. The blood glucose profile was typical whereas the HbA1c concentration was very stable and constant. Total protein and fructosamine increased significantly by orthostasis; the correction of fructosamine by total protein diminished the differences, but did not completely eliminate the effect of orthostasis. However, fructosamine should be corrected by the total protein concentration in order to increase the diagnostic value of the parameter.

Adolescent↗

[Diagnosis of the diabetic metabolic status using fructosamine (and HbA1c) determination. The glycation quotient Glyc-Q, the glycation nomogram].

The determination of fructosamine in serum is an accepted tool for the metabolic monitoring of diabetic patients. It provides an estimation of the glycemia state during the preceding 10 to 20 days. The turn-over of serum proteins is in general faster than that of hemoglobin. Therefore, fructosamine is faster responding than HbA1c to recompensation or fluctuations in glycemic control as observed in labile metabolic situations. On the other hand, under conditions of stable metabolic control fructosamine values correlate closely to HbA1c. The relation between the two parameters can be visualized in a nomogram of HbA1c, fructosamine and glucose or be expressed by a quotient (Glyc-Q = Fructosamine*2.2/HbA1c). A deviation from the stable metabolic situation (Glyc-Q = 100) reflects a trend in the recent development of glycemia: a Glyc-Q of greater than 120 is obtained in the state of decompensation, whereas in recompensation the Glyc-Q decreases significantly to values below 80. We propose to use the Glyc-Q in situations where a fast assessment of the glycemic state or an estimation of the development of glycemia within short intervals of observation are required.

Blood Glucose↗

[Changes in the plasma protein concentration as a factor influencing the fructosamine value].

Fructosamine values are notably influenced by plasma protein concentration. Total protein concentration in addition to variations in the plasma protein concentrations (Dysproteinemia) play a role here. This is a result of the various glycosylation of the different plasma proteins. Since fructosamine behaves similar to total protein for hypo- and hyperproteinemia, a good relationship with the total protein is expected for normoproteinemia. Hence, no erroneous high nor low fructosamine values are obtained. Dysproteinemia at normal total protein concentration causes no erroneous fructosamine values with the exception of some illnesses. Therefore, a direct relationship between protein and fructosamine at normoproteinemia is not generally necessary.

Blood Proteins↗

Sensitivity of serum fructosamine in short term glycemic control.

The serum fructosamine concentrations measured in 64 diabetic patients correlated (r = 0.73) with glycated hemoglobins (HbA1c). However, 23 percent of the diabetic patients had normal fructosamine and abnormal HbA1c levels. In order to determine whether or not the discrepant values were the result of recent glycemic regulation by the diabetic patient, fructosamine levels of patients suffering from diabetic ketoacidosis (along with beta-hydroxybutyrate levels) were closely monitored. It was shown that short term alterations (one to three days) in serum glucose did not significantly affect fructosamine levels. Therefore, disagreements between fructosamine and HbA1c are most likely due to longer term improvement in glucose control by the diabetic or the result of the higher imprecision of the HbA1c assay.

3-Hydroxybutyric Acid↗

Serum fructosamine in diabetic pregnancy.

Serum fructosamine was measured in 275 blood donors, in 559 subjects with a normal pregnancy, in 32 gestational diabetics being treated with insulin and 69 being treated by diet only, and in 53 pregnant subjects with established diabetes. In none of the pregnant subgroups did the mean fructosamine concentration exceed that of the donor group. The concentration in normal pregnant subjects showed a modest but significant decrease with gestational age and an increase with maternal age. Hyperglycemic non-pregnant subjects (n = 24) had significantly increased serum fructosamine concentrations, and 96% of these subjects exceeded the upper 95% confidence limit for fructosamine in the donor group. A highly significant correlation was demonstrated between serum fructosamine and preprandial plasma glucose in the hyperglycemic subjects. A weak, but significant, correlation was shown for the entire population sample of antenatal patients, while this was non-significant within each of the sub-groups comprising established diabetics and gestational diabetics, respectively.

Adult↗

[Usefulness of fructosamine determination in short-term monitoring of metabolic control in children with insulin-dependent diabetes mellitus at onset].

The present study was undertaken to determine the clinical usefulness of fructosamine estimations in monitoring the short term changing in metabolic control in 5 newly diagnosed type 1 diabetic children (3 boys, 2 girls, aged 3-13 years). Mean glycaemic values, HbAlc (normal range: 4.77 +/- 0.67%), fructosamine (normal range: 2.65 +/- 0.65 mmol/l) were determined at the admission and after 1, 2, 3, 4 weeks. Normoglycaemia was achieved within 1 week (mean values: 232 +/- 107 mg% at admission; 98 +/- 39 mg% after 1 week of insulin therapy), HbAlc slightly decreased from 12 +/- 0.71 at admission to 9.90 +/- 1.81 after 4 weeks, but not reached normal values. Fructosamine decreased from 5.49 mmol/l to near normal values (3.02 +/- 0.67) after 4 weeks. The validity of the method was confirmed by the comparison of HbAlc and fructosamine in 22 stable long-standing diabetic children (r = 0.77, p less than 0.01). Compared with HbAlc, fructosamine appeared more useful in monitoring short term (3 weeks) changes in metabolic control. Additional advantages were lower cost and technical simplicity of measurement.

Adolescent↗

[Significance of serum fructosamine in the metabolic control of children and adolescents with type I diabetes mellitus].

In 1982 Johnson et al. described a simple colorimetric assay for measuring glycated proteins, termed fructosamine, in the serum of adults with diabetes mellitus and demonstrated this to be a useful index of intermediate glucose control (1-3 weeks). Our study was designed to show this as well in children and adolescents with type I diabetes mellitus. Serum fructosamine was determined in 76 children and adolescents with diabetes mellitus, and 111 age-matched controls. In the controls an age-dependency but not sex-dependency could be demonstrated. In the diabetic patients we found a significant correlation between serum fructosamine and HbA1 values (r = 0.87, p less than 0.001). In 6 patients with newly diagnosed diabetes mellitus serum fructosamine concentrations decreased at a faster rate than HbA1 values. The fructosamine assay is rapid, technically simple and inexpensive, and is at least a useful addition or perhaps an alternative to HbA1 estimation.

Adolescent↗

[Determination of postpartum fructosamine for assessment of gestational diabetes--a suitable method?].

Postpartal screening of undetected gestational diabetes has proven to be difficult. Rapid decrease in diabetogenic hormones and normalisation of the former delayed insulin-response make it difficult to detect disturbed glucose tolerance in the puerperium. Therefore, glycolysated serum proteins offer the opportunity for retrospective diagnosis. They allow an evaluation of the patient's carbohydrate metabolism, retrospectively over several weeks. In this context, we were most interested in the significance of fructosamine. In a prospective study covering 12 months, 123 patients with several risk factors for gestational diabetes underwent a 100 g glucose tolerance test in the puerperium. Furthermore, we measured fructosamine and glycolysated hemoglobin. A carbohydrate intolerance could be detected by the oral glucose tolerance test in 22.7%. In 12.2% of the cases, glycolysated hemoglobin was found to be higher than 5.5%. Fructosamine levels were normal for all patients, with a mean value of 1.84 mmol/l. Even though fructosamine concentration was significantly higher (p < 0.05) in patients with a pathologic glucose tolerance, our study showed the oral glucose tolerance test to be better to detect unknown gestational diabetes than measurement of serum fructosamine.

Adult↗

Chemistry of the fructosamine assay: D-glucosone is the product of oxidation of Amadori compounds.

The chemistry of the fructosamine assay was studied by using the Amadori compound, N alpha-formyl-N epsilon-fructose-lysine (fFL), an analog of glycated lysine residues in protein. Previously (Clin Chem 1993;39:2460-5), we reported that free lysine was formed from fFL at 70% yield during incubation with alkaline nitroblue tetrazolium (NBT) under the conditions routinely used for the fructosamine assay (sodium carbonate buffer, pH 10.35 at 37 degrees C). Here, we show that D-glucosone is the primary carbohydrate oxidation product formed from Amadori compounds in the fructosamine assay. Glucosone, which decomposes under alkaline assay conditions with a half-life of < 30 min, reaches a maximum concentration of approximately 50% of the initial fFL concentration after 10 min of incubation. Like fFL, glucosone reduces NBT to the purple monoformazan dye, but its decomposition is not accelerated by the presence of NBT. The dicarbonyl-trapping reagent, aminoguanidine, inhibits the fructosamine assay by approximately 25% when fFL is the substrate, but by nearly 100% with glucosone as substrate. Studies with serum samples from diabetics and nondiabetics indicate that glucosone formation does not have a significant effect on the clinical usefulness of the fructosamine assay; however, corrections for glucosone formation may be required when the assay is used for estimating the extent of glycation of proteins.

Borohydrides↗

[Value of fructosamine test in monitoring of diabetes complicated by proteinuria].

The aim of study was evaluation of fructosamine test in monitoring of diabetes mellitus complicated by proteinuria. Twenty patients with type 1 diabetes mellitus without proteinuria and 20 diabetic (type 1) patients with proteinuria were examined. Absent-present proteinuria was alone differential parameter between these groups. Correlations between past-glycaemia and other indices of diabetes balance as fructosamine, glycated haemoglobin and fructosamine: albumin molal ratio were examined. Results of study suggest that fructosamine test is useless in monitoring diabetes with proteinuria, but fructosamine: albumin molal ratio is a good parameter in monitoring of either: diabetes mellitus without proteinuria and with proteinuria.

Adult↗