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PubMed1989

The relative value of glycated albumin, hemoglobin A1c and fructosamine when screening for diabetes mellitus.

We compared the usefulness of three glycated serum proteins, glycated albumin (GA), glycated hemoglobin (HBA1c) and fructosamine (FA), for diabetic screening purposes. We measured these indices in 302 adults, most of whom underwent yearly physical examinations. We measured GA and HbA1c with high precision using high-performance liquid chromatography (interassay coefficients of variation 4.9 and 4.0%, respectively) and FA using commercial reagents (interassay coefficient of variation 1.65%). All the individuals underwent a 75-g oral glucose tolerance test, which revealed significant correlations between the values of the three glycated proteins and the four plasma glucose concentrations measured as well as the sum of these glucose concentrations, sigma BS (GA, r = 0.80; HbA1c, r = 0.80; FA, r = 0.65). On the basis of the test, 130 of the subjects were classified as normal (N), 123 as borderline and 49 as having diabetes mellitus (D) according to the criteria of the Japan Diabetes Society. Of the 123 borderline cases, 26 showed impaired glucose tolerance (IGT) according to the WHO criteria. The normal group values of GA, HbA1c and FA were 17.8 +/- 0.17% (mean +/- SEM), 5.02 +/- 0.03%, and 2.55 +/- 0.02 mM/l, respectively. Borderline and IGT subjects had significantly more GA and HbA1c than normal but not more FA (P less than 0.01). We divided the subjects into 10 groups on the basis of their sigma BS values; those with values higher than 671 +/- 4.7 mg/dl had significantly more GA and HbA1c than normal, while those with values higher than 1068 +/- 40.9 mg/dl (the most extreme cases) had significantly more FA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Is examination of fructosamine levels valuable as a diagnostic test for diabetes mellitus?

In order to develop a simple, one-point diagnostic test for diabetes mellitus in a mass population surveys, we measured levels of fructosamine (FRA), one of the glycated proteins. Seven hundred and thirty-eight people had their levels of fasting plasma glucose (FPG), FRA and hemoglobin A1c (HbA1c) examined before taking 75 g oral glucose tolerance tests (OGTT). The results of OGTT distinguished a diabetic group (DM) of 143 from a non-diabetic group (non-DM) of 595 subjects. Since there was a significant correlation between FRA levels and plasma glucose levels 2 h after OGTT (PG-2h), as well as between FPG and PG-2h, a discriminant analysis using FPG and FRA was carried out in order to separate the DM group from the non-DM group. According to this analysis, a positive f, where f = FPG-(mg/dl) + 12.0 FRA(mmol/l) - 150, would determine a subject to be a diabetic. However, the sensitivity of this analysis was only 0.521. It can be concluded that the sensitivity of a simple, one-point determination for diabetes mellitus using measured levels of FRA was insufficient, even by application of discriminant analysis, and that the OGTT is still needed for a diagnostic test for diabetes mellitus in mass population surveys.

Biomarkers↗
PubMed1991

Correction of fructosamine value for serum albumin and globulin concentrations.

Using the data of 131 patients with non-insulin dependent diabetes mellitus (NIDDM), the correction formulas of fructosamine value ([FRA]) were devised to standardize the uncorrected [FRA] to serum albumin concentrations ([ALB]) of 4 g/dl, globulin concentrations ([GLB]) of 3 g/dl, and total protein concentrations ([TP]) of 7 g/dl. The following formula was derived for its maximum correlation coefficient (r) between corrected [FRA] ([FRAc]) and fasting blood glucose concentration ([G]); [FRAc] = [FRA]x33.3/(7.6 [ALB]+[GLB]). In these 131 diabetic patients, r between uncorrected [FRA] and [G] at 2 weeks ago was 0.562. When corrected by [FRA]x33.3/(7.6 [ALB]+[GLB]), [FRA]x4/[ALB], [FRA]+30 (4-[ALB]), [FRA]+23 (4-[ALB]), [FRA]+30 (7-[TP]), [FRA]x7/[TP], and [FRA]x3/[GLB], r was, respectively, 0.616, 0.612, 0.595, 0.589, 0.582, 0.581 and 0.478. In 24 patients with NIDDM whose [ALB] is either above 4.5 g/dl or below 3.5 g/dl, r between uncorrected [FRA] and [G] was as low as 0.389 without positive correlation. By using our correction formulas of [FRA]x33.3/(7.6 [ALB]+[GLB]) or [FRA] x 4/[ALB], r was statistically increased, respectively, to 0.769 or 0.788 (P less than 0.05 in both cases) in contrast to no significant increase of r by other formulas being at 0.598, 0.556, 0.540, 0.562 and 0.121. Based on these analyses, it is concluded that our correction formula of [FRA] by [FRAc]=[FRA]x33.3/(7.6 [ALB]+[GLB]) accurately reflects [G] in NIDDM even with hypo- or hyper-albuminemia, and [FRAc]=[FRA]x4/[ALB] is useful for practical application for its simplicity.

Diabetes Mellitus, Type 2↗
PubMed1992

Physiologic concentrations of inorganic phosphate accelerate fructosamine synthesis.

The effect of physiologic concentrations of inorganic phosphate (Pi) on fructosamine (FRA) synthesis was studied. After 75 g oral glucose administration (OGTT), 'delta FRA/24 h', defined as delta FRA after incubating serum or other specimens at 37 degrees C for 24 h after adding 1000 mg/dl glucose, was significantly decreased in parallel to the decrease of plasma Pi concentrations. 'The FRA index', defined as the FRA value divided by the corresponding glucose concentration, both at fasting, correlated significantly with plasma Pi concentrations. In vitro incubation of serum total protein (TP), albumin (ALB), gamma-globulin (GLB), free lysine (Lys), and free valine (Val) with glucose at different concentrations of Pi showed a Pi-dependent increase of FRA synthesis throughout 48 h of incubation. The accelerating effect of 5 mg/dl Pi on FRA synthesis from TP, ALB, GLB, Lys, and Val at pH 7.4 was, respectively, as great as 48, 20, 24, 13 or 25% of those without Pi. Increase of pH from 6 to 10 logarithmically increased delta FRA/24 h in contrast to a logarithmic decrease of the accelerating effect of Pi on delta FRA/24 h. These data show that physiologic concentrations of Pi accelerate protein glycation by accelerating dehydrogenation during the Amadori rearrangement through the negative charge of Pi. Because this accelerating effect of physiologic Pi presumably exists in vivo, Pi concentration must be taken into account as an accelerating factor for FRA synthesis in evaluating diabetic control, and further studies must be carried out to elucidate whether hyperphosphatemia accelerates glycation-induced diabetic complications.

Adult↗
PubMed1988

Postmortem diagnosis of diabetes mellitus. Quantitation of fructosamine and glycated hemoglobin.

Fructosamine and glycated hemoglobin were determined in samples from 52 cadavers autopsied in the Forensic Pathology Institute of the University of Copenhagen (Denmark). The population studied comprised 15 adult subjects with history of diabetes mellitus and 37 adult non-diabetic subjects. The fructosamine/total protein ratio was 1.7 times higher in diabetic than in non-diabetic subjects, as was the case for glycated hemoglobin. Measurement of glycated serum protein appears to be a useful tool for the postmortem diagnosis of fatal diabetic coma and glucose concentration before death.

Adult↗
PubMed2005

Intrinsic toxicity of glucose, due to non-enzymatic glycation, is controlled in-vivo by deglycation systems including: FN3K-mediated deglycation of fructosamines and transglycation of aldosamines.

Along with oxygen, glucose is an essential macronutrient for most cells, a source of carbons for biosynthesis and energy. However, alongside this indispensable role for cell survival and growth, glucose is intrinsically toxic by reacting with primary amines such as lysine in proteins in a non-enzymatic glycation process (a.k.a. Maillard reaction) especially important in long-lived, homeothermic organisms where temperatures of 37-44 degrees C accelerate its rate. Products of Maillard reactions are known to have adverse effects on protein function and have been implicated in the development of diabetic complications and possibly in neurodegenerative diseases. Because of the unavoidable nature of non-enzymatic glycation and its deleterious effects, we propose that glucose-utilizing organisms, especially the homeothermic ones, possess mechanisms to control this process at its earliest stages. In the intracellular milieu two such mechanisms are apparent at present; a fructosamine-3-kinase(FN3K)-dependent process which is ubiquitous in all warm-blooded animals and a FN3K-independent deglycation pathway present in all animals, including ones which do not have FN3K, such as insects. We propose that of the two pathways, the FN3K-independent mechanism is more important due to the fact that it breaks down the very first intermediate of the Maillard reaction, the Schiff base (a.k.a aldosamine). We postulate that this, FN3K-independent, deglycation occurs by transglycation, in which carbohydrate moieties of glycated amines, such as glucoselysines on proteins, are removed by intracellular nucleophiles including free amino acids and peptides such as glutathione, carnosine and anserine. Furthermore, we hypothesize that one or more of these nucleophile-aldose adducts, formed as by-products of transglycation, are actively removed from cells by one or more of the multi-drug-resistance [MDR] proteins or similar pumps. In the extracellular space, non-enzymatic glycation and deglycation occur as well. We also postulate that, in that setting, transglycation products are removed from the system by the kidneys or similar excretory organs. Our hypothesis leads to several testable predictions including: The deglycation hypothesis offers new paradigm for thinking about non-enzymatic glycation and diabetic complications and offers possible strategies for intervention in this and possibly other degenerative conditions.

Amines↗
PubMedDate not supplied

Reliability of biomarkers of iron status, blood lipids, oxidative stress, vitamin D, C-reactive protein and fructosamine in two Dutch cohorts.

Biomarkers are widely used in epidemiology, yet there are few reliability studies to assess the appropriateness of using these biomarkers for the assessment of exposure-disease relationships. The aim of the study was to assess the reliability of 20 biomarkers in serum collected from two Dutch centres (Utrecht and Bilthoven) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) at two points several years apart. Blood samples were collected from 30 men from Bilthoven and 35 women from Utrecht. Ferritin, total iron, total iron-binding capacity, transferrin saturation, transferrin, C-reactive protein, bilirubin, cholesterol, triglycerides, apo lipoprotein-A, apo lipoprotein-B, high-density lipoproteins, low-density lipoproteins, uric acid, creatinine, reactive oxygen metabolites, the ferric-reducing ability of plasma, protein thiol oxidation, fructosamine, and vitamin D biomarkers in serum were analysed from the blood samples at the two points of time. For all biomarkers, except C-reactive protein, there were no substantial changes in the mean levels over time. Uric acid, ferritin, creatinine, HDL, and apo lipoprotein-B levels consistently showed the highest reliability for men and women (intra-class correlation = 0.69-0.86). Among women, the ferric-reducing ability of plasma, and protein thiol oxidation had poor reliability; and among men iron-related biomarkers (except serum ferritin) had poor reliability. With the exception of a few gender-specific differences, most of the 20 biomarkers performed well and can be considered to have sufficient reliability to be used in future cohort studies.

Biomarkers↗
PubMed1999

Determination of reference values for a novel ketoamine-specific fructosamine assay for assessment of diabetic glycemic control.

BACKGROUND: Intensive monitoring to improve glycemic control is essential for effective management of diabetes and reduction of long-term morbidity and pathology. Measurement of glycated serum proteins (fructosamine) allows more frequent assessment (monthly) of glycemic control than the 2- to 3-month window of the traditional glycated hemoglobin (HbA1c) assay. In response to concerns about assays designed to measure glycated serum proteins based on the nitroblue tetrazolium (NBT) methodology, a novel assay to measure glycated serum proteins has been developed based on the specific oxidation of the ketoamine bonds within the glycated proteins. METHODS: Reference range values for this new, enzymatic glycated-serum-protein assay (GlyPro; Genzyme Corporation, Cambridge, MA) are reported. RESULTS: The GlyPro reference range is lower and shows close correlation with ranges reported for the NBT assay. The 95% overall reference range was 122 to 236 mumol/L. CONCLUSIONS: GlyPro is a reliable, accurate assay and correlates well with the NBT assay for the measurement of glycated serum proteins. The assay may be useful in the short-term assessment of diabetes control, a necessary complement to long-term control as assessed by hemoglobin A1c (HbA1c) assays.

Adult↗
PubMed1990

Serum fructosamine and lipid profile in children with malignant diseases.

Serum levels of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and fructosamine (FA) were determined in thirty-three children with malignant diseases and twenty healthy controls aged 1-14 years. Of them, FA was the parameter measured in children with malignancy for the first time. Mean serum TC, HDL-C, LDL-C and FA showed statistically significant decreases in malignancy compared to healthy children, whereas a statistically significant increase was observed for TG concentrations in serum. From these data, we conclude that significant relations between serum lipids and lipoproteins and the state of malignancy exist in the children studied, and it should be remembered that serum FA concentrations are affected by abnormal serum protein turnover when one deals with any type of neoplastic disease.

Adolescent↗
PubMed1998

Clinical value of glycated hemoglobin and fructosamine in the long-term glycemic control of children with acute lymphoblastic leukemia.

Hyperglycemia in children with acute lymphoblastic leukemia (ALL) has been well documented in the literature. The purpose of the present study was to evaluate the clinical value of glycated hemoglobin (GHb) and fructosamine (Frc) in the long-term glycemic control of ALL patients. An attempt was made to identify the risk factors for hyperglycemia in ALL patients. The study group comprised 26 newly diagnosed ALL patients admitted to hospital during 1995-96. Patients with a history of blood transfusion or infection within the past 3 months were excluded from the study. White blood cell (WBC) counts, fasting blood glucose (FBG), GHb and Frc levels were analyzed in venous blood on screening day 0, before induction of chemotherapy. Frc analysis was repeated on the 21st day and GHb level on the 60th day of chemotherapy. FBG tests were performed before each dose of L-asparaginase, on days 21 and 60. None of the patients was obese. Although six children (23%) had hyperglycemia during the induction therapy, four of them had a GHb level higher than normal on admission. Only one patient who developed hyperglycemia had a family history of diabetes mellitus. Patients with a high initial WBC count (> 20 x 10(9)/L) had a significantly higher baseline GHb than patients with a WBC count below this level. GHb values returned to normal after achievement of complete remission. It is suggested that the leukemic process could impair glucose metabolism and baseline GHb may be used to monitor possible small changes in glucose homeostasis of ALL patients, prior to chemotherapy.

Adolescent↗
PubMed1995

An evaluation of fructosamine estimation in screening for gestational diabetes mellitus.

Although persuasive arguments against routine screening for gestational diabetes mellitus (GDM) have been made, it is widely but not universally performed as a part of antenatal care. There is no international agreement on methods or criteria used for screening (or for diagnosis), and administered glucose-load methods have significant practical difficulties in a busy antenatal clinic setting. However, recent evidence supports the concept of an increased level of importance being given to a diagnosis of GDM, with interest in the fetal and neonatal origins of adult disease being added to the short-term obstetric and fetal concern during pregnancy. A second generation fructosamine test, corrected for total protein, has been evaluated as a practical alternative to glucose screening for GDM in a busy, multi-ethnic antenatal clinic. This achieved a 79.4% sensitivity and a 77.3% specificity for a diagnosis of GDM confirmed by a glucose tolerance test using Carpenter's modified criteria. In view of the organizational simplicity of this sample/test requirement, a wider evaluation is suggested together with a re-evaluation of clinical outcome criteria rather than blood glucose levels alone.

Adult↗
PubMed1989

Alterations in fructosamine and glycated albumin levels during childhood.

Age-related changes in the blood concentrations of glycated proteins during childhood and adolescence were examined by measuring the blood fructosamine (FA), glycated albumin (GA), glucose levels and total serum protein levels in 611 healthy children (325 boys and 286 girls) aged 0-18 years old. These levels were compared with those of 130 healthy adults. GA was measured by a newly developed, highly precise method of high-performance liquid chromatography (inter-assay coefficient of variation, 4.9%). The FA values of all groups of up to 15 years old (grouped in two year age brackets) were significantly lower than those of adults. The mean serum concentrations of GA in infants up to four years old were also significantly lower than in adults. A slight but statistically significant positive correlation was found between age and values of FA (r = 0.36, P less than 0.001), but not of GA (r = 0.04). Levels of total serum proteins showed a positive correlation with those of FA (r = 0.47, P less than 0.001) but a weak correlation with those of GA (r = 0.29). These results suggest that age should be taken into account when the FA levels of children and the GA values of infants are evaluated.

Adolescent↗
PubMed2000

A new, modern, cost-saving micro/macro method for the determination of serum fructosamine.

Serum/plasma fructosamine (SeFa) concentration is a reliable indicator used in human diabetic control. Tests for monitoring the carbohydrate/energy metabolism of (farm) animals are less commonly performed in veterinary laboratories, since most of the reliable determinations, both automated and manual, are relatively expensive. The aim of this study was to develop a precise, money- (and time-) saving automated micro method for measuring SeFa. ELISA microplates (20 microL samples and 200 microL reagents) and an automatic microplate autoreader were used. The classical nitroblue tetrazolium (NBT) stain reagent solution of Johnson et al. (1982) was modified using a SIGMA reagent to render it stable for up to one year. SeFa concentrations measured by the new method in 30 human blood plasma samples were compared with values obtained by the standard (generally used) LaRoche kit procedure. Fifteen cow, 13 dog and 18 chicken plasma samples were assayed by the new automated 'micro' method as well as by the manual test tube 'macro' method commonly used earlier. The modified reagent was applied for both methods. The coefficient of correlation (r) between the results obtained by the two methods was consistently between 0.94 and 0.98 (p < 0.001).

Animals↗
PubMed1991

Comparison of 1,5-anhydroglucitol, HbA1c, and fructosamine for detection of diabetes mellitus.

To evaluate the use of serum 1,5-anhydroglucitol (AG) levels in screening for diabetes mellitus, we compared the sensitivity and specificity of HbA1c, fructosamine (FA), and AG in 1620 randomly selected subjects in 11 institutions throughout Japan. Most individuals were receiving diet and/or drug therapy for diabetes. Subjects were separated into four groups based on World Health Organization criteria: nondiabetic control subjects, subjects with impaired glucose tolerance (IGT), patients with diabetes, and patients with other disorders without IGT. The overlap of AG values between each group was less than that of HbA1c or FA values. AG levels were significantly correlated with fasting plasma glucose (r = -0.627), HbA1c (r = -0.629), and FA (r = -0.590) levels. If we took 14 micrograms/ml as the normal lower limit, AG level was highly specific (93.1%), and a decreased AG level indicated diabetes mellitus (84.2% sensitivity). According to the selectivity index (sensitivity value times specificity value), AG determinations were superior to both HbA1c and FA measurements for diabetes screening. When combinations of these tests were used, only AG and HbA1c together were slightly better than AG alone. Thus, together with other advantages of AG, e.g., its wide variance with relatively fair glycemic control and the negligible influence of the sampling conditions, AG level has more potential than HbA1c or FA level as a screening criterion for diabetes.

Biomarkers↗
PubMed1995

Kinetics of HbA1c, glycated albumin, and fructosamine and analysis of their weight functions against preceding plasma glucose level.

OBJECTIVE: To examine the kinetics of HbA1c, glycated albumin (GA), and fructosamine (FA) levels in response to plasma glucose change and their relationship with the preceding plasma glucose level. RESEARCH DESIGN AND METHODS: The time courses of HbA1c, GA, and FA after acute glycemic normalization were observed in nine patients with newly diagnosed non-insulin-dependent diabetes mellitus and compared with theoretical ones. Their weight functions against preceding plasma glucose level were analyzed assuming a stepwise plasma glucose change and compared with the theoretical prediction. RESULTS: The fasting plasma glucose level was acutely normalized after admission with a half-time of 6.3 +/- 2.4 days (mean +/- SD). The HbA1c level decreased linearly during the initial 2 months with a half-time of 34.6 +/- 10.1 days, followed by a gradual decrease thereafter. GA and FA levels decreased very rapidly during the initial 2-3 weeks with half-times of 17.1 +/- 2.8 and 12.2 +/- 4.8 days, respectively, followed by a gradual decrease thereafter. The time courses of HbA1c, GA, and FA agreed well with theoretically estimated decay curves. Experimental values of weight functions against the preceding plasma glucose level agreed well with the theoretical prediction. The weight functions for glycated proteins had maximum values on the days just before the measurement of glycated proteins and gradually decreased with an increasing time interval. The lengths of the periods over which the weight functions for HbA1c, GA, and FA extend back were estimated to be roughly 100, 40, and 30 days, respectively. CONCLUSIONS: The levels of HbA1c, GA, and FA do not reflect the simple mean but reflect the weighted mean of the preceding plasma glucose level over a considerably longer period than was previously speculated.

Adult↗
PubMed2003

Discordance between HbA1c and fructosamine: evidence for a glycosylation gap and its relation to diabetic nephropathy.

OBJECTIVE: Discordances between HbA1c and other measures of glycemic control are common in clinical practice and remain unexplained. We developed a measure of discordance between HbA1c and fructosamine (FA) (glycosylated serum proteins) to conduct a systematic evaluation. We termed this the glycosylation gap (GG) and sought to determine its relationship to diabetic nephropathy. RESEARCH DESIGN AND METHODS: Measurements of HbA1c and FA on the same sample in 153 people were used to calculate GG, defined as the difference between measured HbA1c and HbA1c predicted from FA based on the population regression of HbA1c on FA. RESULTS: GG had a broad distribution (range, -3.2% to 5.5%); 40% of samples had values indicating major differences in prediction of complications risk by the measured versus predicted HbA1c. GG was highly correlated (r = 0.81) between measurements repeated in 65 patients 23 +/- 2 weeks apart, indicating that the discordances are reliable and not explained by differences in turnover of underlying proteins. In 40 patients with type 1 diabetes of >or = 15 years' duration, an increase in GG by 1% was associated with a 2.9-fold greater frequency of increasing nephropathy stage (P = 0.0014). GG was -0.8 +/- 0.2% in subjects with no nephropathy, -0.3 +/- 0.2% with microalbuminuria/hypertension, and 0.7 +/- 0.3% in subjects with proteinuria or renal dysfunction (P < 0.05). GG correlated better with nephropathy than did either HbA1c or FA alone in this population. CONCLUSIONS: The glycosylation gap may be a useful clinical research tool for evaluating physiologic sources of variation in diabetic complications beyond glycemic control.

Adult↗
PubMed1992

Blood glycated haemoglobin, serum fructosamine, serum glycated albumin and serum glycated total protein as measures of glycaemia in diabetes mellitus.

Blood glycated haemoglobin (HbAlc), serum fructosamine (FA), serum glycated albumin (GA), and serum glycated total protein (GTP) were determined in 61 subjects (19 pregnant women with gestational diabetes, 24 pregnant women with insulin-dependent diabetes mellitus [IDDM] and 18 nonpregnant subjects with IDDM). FA, GA, and GTP correlated with HbAlc similarly (r = 0.791, 0.816, and 0.794, respectively, p < 0.001). In a subgroup of 22 subjects data on blood glucose home monitoring was recorded and used for calculating mean blood glucose as an index of average glycaemia preceding sampling of the glycation products. Mean blood glucose levels preceding sampling of HbAlc by 2 months and FA, GA, or GTP by three weeks correlated significantly with HbAlc (r = 0.668, p < 0.001) and GA (r = 0.441, p < 0.05) whereas no significant correlation was found between mean blood glucose and FA (r = 0.003) or GTP (r = 0.252). In conclusion, such methods which measure specifically the non-enzymatic glycation of a single species of protein (i.e. FPLC for HbAlc and affinity chromatography for GA) are to be preferred for assessing glycaemia.

Adult↗
PubMed1991

[The usefulness of measuring fructosamine in the cord blood of the newborn infants of diabetic mothers].

The aim of our study was to evaluate the usefulness of fructosamine measurement (Fram) in cord blood as an index of glucose metabolism in the last week of pregnancy in infants of diabetic mothers. In newborns and their respective mothers Fram values were surprisingly greater in N than in IDM and IGDM and neonatal and maternal values appeared to be strictly related. While intrauterine growth was associated with metabolic control indexes of 2nd and 3rd trimester gestation. Fram value appeared positively correlated to cord insulin. In conclusion Fram level appears as a good index of glucose metabolic control of the last week of pregnancy and it is associated to cord insulin level and to neonatal hypoglycemia.

Blood Glucose↗