ABSTRACT
BACKGROUND: There is growing interest in fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG) as alternative measures of hyperglycemia, particularly for use in settings where traditional measures (glucose and HbA1c) are problematic or where intermediate (2-4 weeks) glycemic control is of interest. However, reference intervals for these alternative biomarkers are not established. METHODS: We measured fructosamine, glycated albumin, and 1,5-AG in a community-based sample of US black and white adults who participated in the Atherosclerosis Risk in Communities (ARIC) Study. We calculated reference intervals, evaluated demographic differences, and derived cutoffs aligned with current diagnostic cutpoints for HbA1c and fasting glucose. RESULTS: In a healthy reference population of 1799 individuals (mean age, 55 years; 51% women; 15% black), the 2.5 and 97.5 percentiles, respectively, were 194.8 and 258.0 µmol/L for fructosamine, 10.7% and 15.1% for glycated albumin, and 8.4 and 28.7 µg/mL for 1,5-AG. Distributions differed by race, sex, and body mass index. Equivalent concentrations of fructosamine and glycated albumin corresponding to an HbA1c of 6.5% (96.5 percentile) were 270.2 µmol/L and 15.6%, respectively. Equivalent concentrations of fructosamine and glycated albumin corresponding to a fasting glucose of 126 mg/dL (93.9 percentile) were 261.7 µmol/L and 15.0%, respectively. CONCLUSIONS: The reference intervals for these biomarkers should inform their clinical use. Diagnostic cutpoint equivalents for fructosamine and glycated albumin could be useful to identify persons with hyperglycemia in settings where fasting glucose or HbA1c are not available or where the interpretation of these traditional measures is problematic.
Subject(s)
Deoxyglucose/blood , Fructosamine/blood , Serum Albumin/metabolism , Deoxyglucose/standards , Female , Fructosamine/standards , Glycated Hemoglobin/analysis , Glycation End Products, Advanced , Humans , Male , Reference Standards , Serum Albumin/standards , Glycated Serum AlbuminABSTRACT
BACKGROUND: The reactive α-oxoaldehydes glyoxal (GO), methylglyoxal (MGO) and 3-deoxyglucosone (3-DG) have been linked to diabetic complications and other age-related diseases. Numerous techniques have been described for the quantification of α-oxoaldehydes in blood or plasma, although with several shortcomings such as the need of large sample volume, elaborate extraction steps or long run-times during analysis. Therefore, we developed and evaluated an improved method including sample preparation, for the quantification of these α-oxoaldehydes in blood and plasma with ultra performance liquid chromatography tandem mass spectrometry (UPLC MS/MS). METHODS: EDTA plasma and whole blood samples were deproteinized using perchloric acid (PCA) and subsequently derivatized with o-phenylenediamine (oPD). GO, MGO and 3-DG concentrations were determined using stable isotope dilution UPLC MS/MS with a run-to-run time of 8 min. Stability of α-oxoaldehyde concentrations in plasma and whole blood during storage was tested. The concentration of GO, MGO and 3-DG was measured in EDTA plasma of non-diabetic controls and patients with type 2 diabetes (T2DM). RESULTS: Calibration curves of GO, MGO and 3-DG were linear throughout selected ranges. Recoveries of these α-oxoaldehydes were between 95% and 104%. Intra- and inter-assay CVs were between 2% and 14%. CONCLUSIONS: To obtain stable and reliable α-oxoaldehyde concentrations, immediate centrifugation of blood after blood sampling is essential and the use of EDTA as anticoagulant is preferable. Moreover, immediate precipitation of plasma protein with PCA stabilized α-oxoaldehyde concentrations for at least 120 min. With the use of the developed method, we found increased plasma concentrations of GO, MGO and 3-DG in T2DM as compared with non-diabetic controls.
Subject(s)
Blood Chemical Analysis/methods , Chromatography, High Pressure Liquid , Deoxyglucose/analogs & derivatives , Glyoxal/blood , Pyruvaldehyde/blood , Tandem Mass Spectrometry , Blood Chemical Analysis/standards , Calibration , Chromatography, High Pressure Liquid/standards , Deoxyglucose/blood , Deoxyglucose/standards , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/pathology , Glyoxal/standards , Humans , Isotope Labeling , Perchlorates/chemistry , Phenylenediamines/chemistry , Phenylenediamines/metabolism , Pyruvaldehyde/standards , Tandem Mass Spectrometry/standards , Time FactorsABSTRACT
A color spot test is described that can confirm the absence of Kryptofix 2.2.2 in 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) in less than 5 min. Pretreated strips of plastic-backed silica gel 60 thin-layer chromatographic medium, saturated with iodoplatinate reagent, are over-spotted with separate droplets of final product [18F]FDG and Kryptofix standard solutions. A blue-black circular spot is clearly visible at Kryptofix concentrations as low as 2 micrograms/mL.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/analysis , Deoxyglucose/analogs & derivatives , Fluorine Radioisotopes , Chelating Agents/analysis , Chromatography, Thin Layer/methods , Colorimetry/methods , Deoxyglucose/chemistry , Deoxyglucose/standards , Fluorodeoxyglucose F18 , Indicators and Reagents , Reagent StripsABSTRACT
Described is an efficient method for the synthesis of the sixteen positional isomers of methylated and acetylated or benzoylated 1,5-anhydro-D-glucitol. The compounds are generated simultaneously by partial methylation of 1,5-anhydro-D-glucitol and subsequent benzoylation, and the individual isomers are obtained in pure form by high-performance liquid chromatography. Debenzoylation of the latter and acetylation yielded the desired acetates. Reported are the 1H NMR spectra of the benzoates and the electron-ionization mass spectra of the acetates and the tetra-O-methyl derivative. Also reported for the acetates and the tetra-O-methyl derivative are their linear temperature programmed gas-liquid chromatography retention indices on three different capillary columns.