Carbohydrate-deficient Transferrin Values Research Articles

Alcohol consumption and liver phenotype of individuals with alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin deficiency is an inherited disorder caused by alpha-1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver-related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non-carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate-deficient transferrin (CDT). In both cohorts, no/low alcohol intake was reported by >80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a <30% increased rate of elevated transaminases and ~50% increase in elevated gamma-glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease. Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption.

Defining trimester-specific reference intervals for carbohydrate deficient transferrin in pregnant women

ObjectivesExtensive consumption of alcohol during pregnancy can lead to severe complications for the unborn child. Carbohydrate-deficient transferrin (CDT) levels in serum have become a common biomarker for excessive alcohol intake. However, during pregnancy CDT levels can rise to levels above commonly used cut-off values, for reasons unrelated to alcohol intake. The aim of this study is to investigate the changes in CDT values during pregnancy and to determine accurate, trimester dependent reference intervals. Methods439 serum samples of 147 healthy pregnant women were obtained for trimester 1, 2, 3, and post-partum and were analysed by high-performance liquid chromatography (HPLC) and an N-Latex immunonephelometric assay. New trimester-specific reference intervals were established. ResultsThis study demonstrates there is a trimester-dependent increase of %CDT, as up to 39.4% of the population exceeded the previously established upper reference limit of 1.7%. In our study the estimated upper reference limit for %DST/%CDT were 1.55%, 1.96%, 2.05% and 1.35% for trimester 1, 2, 3 and post-partum for the HPLC-method and 2.02%, 2.19%, 2.19% and 1.96% for the N-Latex immunoassay. ConclusionsWe demonstrate that CDT levels rise during pregnancy. The magnitude of the increase is method-dependent and needs to be taken into account. We have established method- and trimester-specific reference intervals to prevent false-positive results in alcohol abuse screening tests during pregnancy.

Falsely low phosphatidylethanol may be associated with biomarkers of haemolytic disease.

Falsely lower or even negative phosphatidylethanol (PEth) levels may theoretically be seen in patients with haemolytic diseases, and the present study aimed to elucidate this hypothesis. PEth and carbohydrate-deficient transferrin (CDT) from 9893 serum and whole blood samples were included along with markers of haemolysis (i.e. haptoglobin, HbA1c, reticulocytes, LD and Hb). Cases showing discrepancy between PEth and CDT, that is, a low PEth value and a high CDT value, were considered to be possibly caused by falsely lowered PEth despite high alcohol consumption. These cases (N = 233) were compared to the control group without PEth and CDT mismatch. The levels of haptoglobin were significantly lower in the cases showing low PEth and high CDT (estimate = -0.62, p = 0.002). The levels of HbA1c (estimate = -3.26, p = 0.001) and Hb (estimate = -0.507, p < 0.001) were also significantly lower in this group. These findings indicate haemolytic diseases in the low PEth/high CDT group. There were no significant differences for reticulocytes and LD concentrations between the low PEth/high CDT group and the control group. These results indicate that falsely low PEth values could be associated with markers of haemolytic diseases, although more research is needed to highlight this further.

Evaluation of the diagnostic utility of carbohydrate-deficient transferrin in chronic alcoholism: Results from Southwest China.

Although recent gathered evidence indicates that obtaining the diagnostic value of serum carbohydrate-deficient transferrin might be more useful for identifying alcohol abuse than other widely available biochemical tests; however, its precise value as an indicator of chronic alcoholism is unclear. The main objective is to investigate the diagnostic significance of carbohydrate-deficient transferrin in chronic alcoholism in the Chinese population.In this study, we enrolled (1) 52 physically healthy subjects, (2) 20 patients with nonalcoholic liver disease, and (3) 70 alcoholics. Patients with liver injuries and a history of liver surgery were excluded. Serum gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, and mean corpuscular volume were determined by standard biochemical assays, and serum carbohydrate-deficient transferrin was estimated in each group using capillary electrophoresis. Subsequently, the diagnostic value of carbohydrate-deficient transferrin (CDT) in chronic alcoholism was determined based on differences between each indicator among the three groups.The CDT level in the alcoholic group was significantly higher than that of the non-alcoholic liver disease and healthy control groups (P < .05). The area under the curve for alcoholism diagnosis was the highest for CDT, at 0.922, whereas those for gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, and mean corpuscular volume were 0.860, 0.744, 0.615, and 0.754, respectively. When the cutoff value of CDT was set at 1.25%, the sensitivity and specificity were 85.5% and 89.6%, respectively. However, the correlation between CDT and daily alcohol consumption was weak (r = 0.175; P = .16).Compared with the other parameters evaluated, CDT was a better indicator of alcoholism. It should, therefore, be actively promoted in clinical practice. However, the correlation between CDT and daily alcohol consumption needs further evaluation.

Gelatinasas como marcadores de consumo crónico de alcohol: un estudio piloto en Uruguay

Chronic alcohol consumption in Uruguay is a growing problem, however, determinations of consensual biomarker are not performed systematically neither potential markers are explored. To validate the hypothesis that matrix metalloproteinases with gelatinase activity are biomarkers of chronic alcohol consumption, blood samples of 100 alcoholics that began medical treatment at the Unidad de TrastornosRelacionados con el Alcohol and 50 healthy non-alcoholic donors were evaluated. Alcoholic samples showed gelatinase activity that tripled that of controls and small but significant increases in levels of gamma-glutamyl transferase, aspartate-aminotransferase and mean cellular volume. Carbohydrate deficient transferrin values were lower in alcoholics than in controls. These results allow proposing gelatinases as the most sensitive indicators of sustained alcohol consumption in the population analyzed since hepatic enzymes and mean cellular volume showed a tendency consistent with the literature but did not reach values associated with thepathology. Since carbohydrate-deficient transferrin is considered the most sensitive and specific indirect biomarker of chronic alcohol consumption, lower values in alcoholics related to controls suggest methodological problems that could be solved by applying other measurement techniques or the presence of yet unknown interferences. Finally, these findings justify an extension of this pilot work, as well as additional studies focused on the participation of matrix metalloproteinases with gelatinase activity in the cascades of damage associated with chronic alcohol consumption.

A Proof-of-concept Analysis of Carbohydrate-deficient Transferrin by Imaged Capillary Isoelectric Focusing and In-capillary Immunodetection

Carbohydrate-deficient transferrin (CDT) is a reliable biomarker for chronic alcohol abuse. We developed a method for CDT analysis by capillary isoelectric focusing, followed by immunodetection directly in the capillary, in an automated fashion and on a single platform (Peggy Sue™; ProteinSimple, CA, USA). Transferrin glycoforms in serum samples, including disialo-transferrin, were separated and their apparent isoelectric points and relative percentages were determined. The relative CDT values (percent of total transferrin) matched expected values for both healthy and alcoholic samples. Because the method leveraged the sensitivity of an immunoassay, CDT was measured when serum samples were diluted up to 1200-fold, reducing the volume of serum required. Finally, the process is fully automated, with up to 96 samples analyzed per batch.

An Integrative Screening Tool of Alcohol Exposure During Early Pregnancy: Combining of the CDT Biomarker with Green Page Questionnaire.

In current clinical practice, prenatal alcohol exposure is usually assessed by interviewing the pregnant woman by applying questionnaires. An alternative method for detecting alcohol use is to measure the biomarker carbohydrate-deficient transferrin (CDT). However, few studies measure CDT during pregnancy. This study examines the utility of CDT biomarker in the screening of alcohol exposure during early pregnancy. A cohort of 91, first-trimester pregnant women assigned to a public reference maternity hospital, was screened using the Green Page (GP) questionnaire, an environmental exposure tool. CDT levels and other biomarkers of alcohol use were measured and compared with questionnaire data. About 70% of the mothers in the study consumed alcohol during early pregnancy and 22% met high-risk criteria for prenatal exposure to alcohol. CDT measurement showed a statistically significant area under the receiver operating characteristic curve with a value of 0.70. For a value of 0.95% of CDT, a specificity of 93% was observed. The most significant predictors of CDT were the number of binge drinking episodes, women's body mass index and European white race. Pregnant women with a CDT value >0.95% would be good candidates for the performance of the GP questionnaire during early pregnancy in order to detect potential high-risk pregnancy due to alcohol exposure.

Dose-Response Characteristics of the Alcohol Biomarker Phosphatidylethanol (PEth)-A Study of Outpatients in Treatment for Reduced Drinking.

Measurement of whole-blood phosphatidylethanol (PEth) offers high sensitivity and specificity as alcohol biomarker. A remaining issue of importance for the routine application is to better establish the relationship between PEth concentration and amount and duration of drinking. The study included 36 subjects (32-83years) voluntarily attending outpatient treatment for reduced drinking. At ~ 3- to 4-week intervals, they provided a diary on their daily alcohol intake and gave blood samples for measurement of PEth and carbohydrate-deficient transferrin (CDT). Whole-blood PEth 16:0/18:1 was measured by liquid chromatography-tandem mass spectrometry and serum CDT (%disialotransferrin) by high-performance liquid chromatography. At start, the self-reported past 2-week alcohol intake ranged 0-1260 (median 330) g ethanol, the PEth 16:0/18:1 concentration ranged 0.05-1.20 (median 0.23) μmol/L, and the CDT value ranged 0.7-13.0% (median 1.5%). At the final sampling after 5-20 (median 12) weeks, neither reported alcohol intake nor PEth and CDT levels differed significantly from the starting values. The PEth concentration showed best association with past 2-week drinking, followed by for intake in the next last week. The changes in PEth concentration vs past 2-week alcohol intake between two successive tests revealed that an increased ethanol intake by ~ 20g/day elevated the PEth concentration by on average ~ 0.10μmol/L, and vice versa for decreased drinking. The PEth concentration correlated well with past weeks alcohol intake, albeit with a large inter-individual scatter. This indicates that it is possible to make only approximate estimates of drinking based on a single PEth value, implying risk for misclassification between moderate and heavy drinking.

Detection and Quantification of Carbohydrate-Deficient Transferrin by MALDI-Compatible Protein Chips Prepared by Ambient Ion Soft Landing.

Transferrin is synthetized in the liver and is the most important iron-transport carrier in the human body. Severe alcohol consumption leads to alterations in glycosylation of transferrin. Mass spectrometry can provide fast detection and quantification of transferrin isoforms because they have different molecular masses. In this study, we used antibody chips in combination with MALDI-TOF MS for the detection and quantification of transferrin isoforms. Protein chips were prepared by functionalization of indium tin oxide glass using ambient ion soft landing of electrosprayed antitransferrin antibody. Two microliters of patient serum was applied on the antibody-modified spots, and after incubation, washing, and matrix deposition, transferrin isoforms were detected by MALDI-TOF MS. Peak intensities of each transferrin form were used to calculate total carbohydrate-deficient transferrin (CDT). The CDT values obtained by the MALDI chip method were compared with the results obtained by a standard capillary electrophoresis (CE). The chip-based MALDI-TOF MS method was used for enrichment and detection of CDT from human serum. A sample cohort from 186 patients was analyzed. Of these samples, 44 were positively identified as belonging to alcoholic patients, whereas 142 were negative by the MALDI chip approach. The correlation of the data obtained by the CE and the chip-based MALDI was r = 0.986, 95% CI. Functionalized MALDI chips modified by antitransferrin antibody prepared by ambient ion soft landing were successfully used for detection and quantification of CDT from human sera.

Infrared analysis of lipoproteins in the detection of alcohol biomarkers.

Alcoholism is a major public health problem. Alcohol causes modifications in the composition and concentration of lipoproteins and influences the enzymes and transfer proteins that transform lipoproteins in plasma. Alcohol is associated with the presence of alcohol biomarkers (fatty acid ethyl esters [FAEEs] and phosphatidylethanol [PEth]) in lipoproteins. We explore the possibilities of detecting alcohol biomarkers in non-high-density-lipoproteins (non-HDLs) precipitated from serum using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Analyzes were carried out on stored serum samples, with known % carbohydrate-deficient transferrin (CDT) values, included in a driver's license regranting program under the control of the Belgian Institute of Road Safety. The study consisted of 127 control samples (CDT≤1.3%) and 114 alcoholic samples (CDT>1.3%). Liver enzymes, CRP, triglycerides, total, HDL- and LDL-cholesterol values were determined. Non-HDLs were precipitated with sodium phosphotungstate and MgCl2 and analyzed using ATR-FTIR in the range from 4500 cm-1 to 450 cm-1 using a Perkin Elmer ATR-FTIR Spectrometer Two. The area under the curve of the 1130-990 cm-1 region (AUC1130-990 cm-1) was able to discriminate controls from alcoholics (p<0.0001) due to the presence of FAEEs in lipoproteins. Multiple regression analysis significantly predicted the AUC1130-990 cm-1 (adj. r2=0.13, p<0.0001). Significant correlations were found between AUC1130-990 cm-1 and CDT values (r=0.32, p<0.0001), AST/ALT ratio (r=0.21, p=0.001). GGT showed no significant correlation. Infrared analysis of lipoproteins is a potential tool in the detection of alcohol biomarkers.

Carbohydrate-Deficient Transferrin Determination in a Clinical Setting: Consistency Between Capillary Electrophoresis Assays and Utility of HPLC as a Confirmatory Test.

Carbohydrate-deficient transferrin (CDT) is used to assess chronic alcohol consumption in administrative and forensic context. The aim of the present study was the optimization of the diagnostic strategy for CDT determination in a clinical laboratory setting. Two capillary zone electrophoresis (CZE) assays, the CEofix CDT (Analis, Suarlée, Belgium) run on single capillary MDQ instrument and the muticapillary (Sebia, Lisses, France), were compared as screening methods and a commercial high-performance liquid chromatography (HPLC) assay (Recipe, Munich, Germany) was used for confirmation. In total, 367 serum samples were analyzed by both CZE assays with concordant classification in 92% of cases. All discordant samples were classified as negative by HPLC, as did 2/3 of those that could not be classified by either CZE assay. Classification of samples with CDT values close to cut-off by CZE was confirmed by HPLC in 95-100% of negative samples but only in 28.6-33.3% of positive samples. Both CZE assays proved suitable for CDT screening. HPLC was useful for discriminating CDT value in most of samples that could not be interpreted by CZE due to analytical interferences. Considering the implication of CDT testing, HPLC assay may also be helpful for the confirmation of positive results close to the cut-off value of CZE assays.

Asymptomatic phosphomannose isomerase deficiency (MPI-CDG) initially mistaken for excessive alcohol consumption

Case reportIn a routine company health check-up, a 32-year-old woman presented a highly elevated serum level of carbohydrate-deficient transferrin (CDT), a biomarker for excessive alcohol consumption. The test result (~17% disialotransferrin, reference interval <2.0%; ~3% asialotransferrin, reference 0%) was confirmed by analysis of a second sample, while another alcohol biomarker, phosphatidylethanol (PEth) in whole-blood, was negative. This suggested that her elevated CDT may be unrelated to heavy drinking. The abnormal “type-1” transferrin glycoform pattern indicated a defect in N-glycan assembly occurring in congenital disorders of glycosylation (CDG), a family of rare inherited metabolic disorders. Probing for the underlying enzyme defect(s) using cultured skin fibroblasts demonstrated normal activity of phosphomannomutase, whereas the activity of phosphomannose isomerase (MPI) was reduced (0.64mU/mg protein, reference 2.1–6.9), pointing to CDG of the MPI subtype (formerly called CDG-Ib). The diagnosis was confirmed by sequence analysis of the MPI gene revealing a homozygous missense mutation (c.656G>A) causing replacement of arginine by glutamine (p.R219Q). However, the woman had never experienced any clinical manifestations associated with MPI-CDG. Both parents, being distant relatives, were heterozygous mutation carriers with normal CDT values. Two of three siblings were not affected, whereas one brother was also homozygous for c.656G>A and had a highly elevated CDT and no clinical symptoms. ConclusionThe finding of MPI-CDG adults without clinical manifestations suggests that this type of the disorder may be underdiagnosed. If asymptomatic MPI-CDG subjects undergo CDT screening, their highly elevated test results may be wrongly interpreted as caused by excessive alcohol consumption.

Determination of carbohydrate‐deficient transferrin in human serum by capillary zone electrophoresis: Evaluation of assay performance and quality assurance over a 10‐year period in the routine arena

The performance of high-resolution CZE for determination of carbohydrate-deficient transferrin (CDT) in human serum based on internal and external quality data gathered over a 10-year period is reported. The assay comprises mixing of serum with a Fe(III) ion-containing solution prior to analysis of the iron saturated mixture in a dynamically double-coated capillary using a commercial buffer at alkaline pH. CDT values obtained with a human serum of a healthy individual and commercial quality control sera are shown to vary less than 10%. Values of a control from a specific lot were found to slowly decrease as function of time (less than 10% per year). Furthermore, due to unknown reasons, gradual changes in the monitored pattern around pentasialo-transferrin were detected, which limit the use of commercial control sera of the same lot to less than 2 years. Analysis of external quality control sera revealed correct classification of the samples over the entire 10-year period. Data obtained compare well with those of HPLC and CZE assays of other laboratories. The data gathered over a 10-year period demonstrate the robustness of the high-resolution CZE assay. This is the first account of a CZE-based CDT assay with complete internal and external quality assessment over an extended time period.

Effect of Transferrin Glycation on the Use of Carbohydrate-Deficient Transferrin as an Alcohol Biomarker

Measurement of an alcohol-induced shift in the serum transferrin glycosylation pattern, termed carbohydrate-deficient transferrin (CDT), is used as a biomarker for sustained high alcohol consumption. The present work examined whether non-enzymatic reaction of transferrin with glucose (glycation) might interfere with the use of CDT as an alcohol biomarker. The blood specimens were leftover volumes from the routine sample pool. Plasma and serum were collected among samples submitted for hemoglobin A1c (HbA1c) and CDT testing. Quantification of individual transferrin glycoforms in percentage of total transferrin was performed by an HPLC candidate CDT reference method. Incubating serum spiked with 20 or 200 mmol/l glucose caused time- and dose-dependent changes in the chromatographic profile of transferrin glycoforms, resulting in gradually wider peaks and reduced relative amounts of disialo- and trisialotransferrin. No similar chromatographic effects were seen in samples collected from diabetic patients with elevated HbA1c (>68 mmol/mol) values. These samples instead showed slightly higher mean %disialotransferrin levels (1.21%) compared with low HbA1c (<44 mmol/mol) samples (mean 1.06%; P = 0.023), pointing at a higher alcohol consumption level in the former group. Altogether ∼5% of the CDT values exceeded the cutoff. There was no significant difference in phosphatidylethanol (PEth) levels between the high and low HbA1c samples, but several (∼14%) showed elevated PEth concentrations. Glycation of serum transferrin in vivo was indicated to differ from that in vitro, and suggested not to interfere with %CDT testing by the HPLC method. The results indicated that CDT and PEth are useful as objective, complementary alcohol biomarkers to identify risky drinking also in diabetic subjects.

Microheterogeneity of Serum β‐Hexosaminidase in Chronic Alcohol Abusers in a Driver's License Regranting Program

Carbohydrate-deficient transferrin (CDT) is one of the best indicators for chronic alcohol abuse and detection of relapse. In this study, we explore the microheterogeneity of β-hexosaminidase (β-HEX) in chronic alcohol abusers in the framework of a driver's license regranting program. Studies have shown that increased serum activity of β-HEX B (isoforms P, I, and B) may be a sensitive marker for chronic alcohol abuse. Here, we describe methodology, limitations, and correlation of β-HEX isoforms with CDT. CDT was assayed at the central laboratory of the Ghent University Hospital by capillary zone electrophoresis, measured on the Capillarys 2™ system and was expressed as a percentage of total serum transferrin (%CDT). Serum of chronic alcohol abusers was compared to nonheavy drinkers using agarose gel isoelectric focusing (IEF). Total β-HEX activity was assayed fluorimetrically following preparative IEF in 81 subjects. β-HEX isoforms were investigated and compared between nonheavy drinkers and heavy drinkers. Agarose gel IEF shows additional cathodal bands in serum of chronic alcohol abusers. Mean total β-HEX activity between pH 6.8 and 7.7, designated as HEX-7, showed the highest correlation with %CDT (r = 0.70, p < 0.0001, n = 68). In a selected subgroup, where CDT could not be quantified (n = 13) because of an atypical electropherogram, HEX-7 was in concordance with either estimated %CDT value or liver enzyme activities. In this proof-of-concept study, we introduce a novel approach to quantify β-HEX isoforms using preparative IEF and fluorimetry. A highly significant correlation of HEX-7 and %CDT has been found. Because of exclusion of the P isoform, HEX-7 could be a useful supplementary marker for detecting chronic alcohol abuse.

Toward standardization of carbohydrate-deficient transferrin (CDT) measurements: III. Performance of native serum and serum spiked with disialotransferrin proves that harmonization of CDT assays is possible

Carbohydrate-deficient transferrin (CDT) is a generic term that refers to the transferrin glycoforms whose concentration in blood is temporarily increased by sustained alcohol consumption. Due to high clinical specificity, CDT was proposed as a biomarker of heavy alcohol use and has been available for about 20 years. A number of methods have been developed for CDT measurement based on different analytical techniques and principles and without any harmonization or calibration to a reference method. As a consequence, neither the reference limits nor the cut-off values have been similar across assays, hampering understanding of the diagnostic value of CDT and its routine use. This prompted the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) to initiate a Working Group on Standardization of CDT (WG-CDT). This third publication of the WG-CDT is devoted to testing the commutability of native and disialotransferrin-spiked serum panels as candidate secondary reference materials, in order to prove the harmonization potential of commercial CDT methods. The results showed that assay harmonization reduced the inter-laboratory imprecision in a network of reference laboratories running the HPLC candidate reference method. In the seven commercial methods evaluated in this study, the use of multi-level secondary calibrators of human serum origin significantly reduced the between-method imprecision. Thus, harmonization of CDT measurements by different methods can be achieved using this calibration system, opening the way for a full standardization of commercial methods against a reference method by use of certified reference materials.

Monitoring of the Alcohol Biomarkers PEth, CDT and EtG/EtS in an Outpatient Treatment Setting

To compare the sensitivity of whole blood phosphatidylethanol (PEth) with serum carbohydrate-deficient transferrin (CDT) as biomarkers of current regular alcohol consumption, during outpatient treatment for alcohol-related problems. Urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS), and clinical assessment, were used as complementary estimates of relapse to drinking. Biomarker results for 29 men and 11 women (aged 20-73 years) undergoing voluntary outpatient treatment for harmful alcohol use or dependence were utilized for this evaluation. In connection with visits to the unit, blood and/or urine were sampled for measurement of PEth, EtG and EtS (by liquid chromatography-mass spectrometry), and CDT (%disialotransferrin, by high-pressure liquid chromatography). The comparison included 326 whole blood, 319 serum (1-82 samples/patient) and 654 urine samples (1-178 samples/patient) collected over ~2 years. At the initial assessment, the total PEth value ranged between 0 and 16.5 µmol/l (mean 2.6) with 70% being above the quantification limit (0.1 µmol/l) and 55% above the reference interval (0.7 µmol/l). Initial CDT values were 0.87-6.9% (mean 2.1) with 35% above the applied reference interval (1.7%). At the final sampling (treatment period up to 21 months), the total PEth value had decreased to 0-5.9 µmol/l (mean 0.6; P = 0.0004) and CDT to 0.87-3.3% (mean 1.3; P = 0.0030). Relapses were detected by PEth alone (43% of cases), by PEth and CDT (38%) and the remainder by EtG/EtS. PEth was the most sensitive biomarker of current regular alcohol consumption. PEth-16:0/18:1, usually being the major subform, was as sensitive as total PEth. PEth, CDT and EtG/EtS are useful complementary tools for objective identification of current drinking and relapse detection.

Carbohydrate deficient transferrin in doping and non-doping sportsmen

The determination of carbohydrate deficient transferrin (CDT) concentration is primarily used in social security studies as a proof of regular alcohol consumption exceeding the amount of 60 grams per day. Aims: The present study was performed to investigate into how carbohydrate deficient transferrin CDT values in serum are affected by the so-called food supplements and chemicals included in doping lists. Methods: The investigation was carried out in 15 bodybuilders of two sport clubs and in 10 boxers. All sportsmen were males. In both groups serum carbohydrate deficient transferrin (CDT%), median red blood cell volume and (MCV) gamma-glutamyl-transpeptidase (GGT) values were measured. Results: The authors found a significant difference between the two groups only in carbohydrate deficient transferrin CDT% that was the CDT% value in bodybuilders was twice as high as in boxers. Conclusion: Not all the details of the specificity of carbohydrate deficient transferrin (CDT) concentration are known, however, the remarkably high sensitivity of the method makes it suitable and probably cost-financially effective for serving as a pre-screening tool in doping tests. Orv. Hetil., 2012, 153, 514–517.

Carbohydrate Deficient Transferrin in a Driver's License Regranting Program

Carbohydrate deficient transferrin (CDT) is a common diagnostic marker for detecting chronic alcohol abuse. For over 2.5 years, it has been used in traffic medicine among subjects applying for driver's license renewal or regranting in Belgium. We report on data collected during the program and provide an estimation of an applicable cut-off point in forensic situations. Using this cut-off, the success of the driver's license regranting program is evaluated. CDT was assayed at Ghent University Hospital by capillary zone electrophoresis, measured on the Capillarys 2™ system, in 3977 subjects applying for driver's license regranting. Determination of a cut-off was done by using Bhattacharya statistics and by adding a measurement uncertainty interval. The outcome of the program was evaluated by monitoring CDT values for 163 subjects during one entire year. In 3977 subjects (3481 males and 496 females), CDT values were significantly higher in men compared with women, but there is no need for a gender-specific cut-off value. Drunk drivers under the age of 30 have significantly lower CDT values than older subjects, and a separate cut-off could be calculated. A general cut-off of 2.3% CDT was calculated for the entire study population. Using this cut-off value for evaluating the outcome of the program for 163 subjects, the percentage offenders at the beginning (29%) decreased to 8% after 1 year. Applying a marker for chronic alcohol abuse such as CDT for driver's license renewal or regranting is a powerful tool. Analysis of data collected over 2.5 years reveals a favorable outcome of the program and a useful cut-off point could be determined.

Analysis of carbohydrate deficient transferrin serum levels during abstinence

An alcohol-associated change in the serum transferrin glycoform pattern, carbohydrate-deficient transferrin (CDT), is used as a biomarker of chronic moderate to heavy alcohol consumption. Furthermore, CDT is employed as a marker of abstinence. Here, we analyzed CDT in patients with chronic excessive alcohol abuse at the beginning and during abstinence. Twenty-nine alcohol dependent patients were recruited from an in-patient abstention program. Reported drinking levels were at least 100g/d (range up to 450g/d; mean: 248.9±94.7g/d) within the last month before study entry. Blood samples were drawn at the beginning and during the abstention program and the relative concentration (%CDT) of CDT was determined using ion exchange followed by immunodetermination of CDT. At study entry, 25/29 patients had a %CDT level above the established cutoff. Although CDT levels declined during abstinence in most patients, in ten patients with %CDT levels just above the cutoff at the start of the program, the CDT values remained elevated 6weeks after cessation of drinking. Our data indicate that %CDT levels below the cutoff cannot even rule out long lasting excessive alcohol abuse. Further, measurement of %CDT should be interpreted with special care when used as a marker of alcohol abstinence.