Carbohydrate-deficient transferrin as a marker of heavy drinking in Korean males

This study was performed to evaluate the usefulness of carbohydrate-deficient transferrin (CDT) as a marker of heavy drinking in Korean males. The subjects (143 Korean males) were classified into 2 groups according to the amount of drinking, moderate drinkers (72 individuals) who drank 14 drinks or less per week and heavy drinkers (71 individuals) who drank more than 14 drinks per week. Using %CDT, gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) as clinical markers for heavy drinking, sensitivity, specificity, positive and negative predictive values were investigated. Sensitivities of %CDT, GGT, AST, and ALT were 83.1%, 67.6%, 52.1% and 46.5%, respectively. Specificities were 63.9%, 45.8%, 72.2%, and 54.2%, respectively. Positive predictive values were 69.4%, 55.2%, 64.9%, and 50.0% respectively. Negative predictive values were 79.3%, 58.9%, 60.5%, and 50.6% respectively. The areas under the receiver operating characteristic curve (95% confidence interval) for %CDT, GGT, AST, and ALT were 0.823 (0.755-0.891), 0.578 (0.484-0.673), 0.622 (0.528-0.717), and 0.516 (0.420-0.613), respectively. CDT is considered as the most reliable marker for detecting heavy drinking in Korean males.     

Analyse de la CDT par électrophorèse capillaire : comparaison de deux analyseurs

Carbohydrate-deficient transferrin (CDT) seems nowadays to be an excellent biochemical marker of an excessive alcohol consumption. Capillary electrophoresis separates efficiently and rapidly the isoforms of transferrin and allows a good representation of different isoforms peaks. We decided to study the equipment influence within this method. We determined CDT values with 2 analysers (P/ACE 5500 et P/ACE MDQ) (Beckman Coulter) for a population of 224 persons including men and women from 1 to 89 years old. Analysis of CDT results for both analysers show a very good correlation. However an average bias can be observed with higher levels for P/ACE MDQ. This bias must be considered for low CDT levels or for normal values establishment.     

Multisite validation of CDT measurement by the %CDT TIA and the Tina Quant %CDT kits

The measurement of CDT (Carbohydrate Deficient Transferrin) is an essential biological tool in the diagnosis and follow-up of alcohol abuse. It is also employed as a marker of abstinence for the restitution of driving licences. However, the precision of measurement, and the between laboratory homogeneity of the results are still discussed. The ion exchange followed by immunodetermination of CDT is available in two products, the Tina Quant %CDT (Roche, Mannheim, Germany) and the %CDT TIA (Bio-Rad, Hercules, United States). This multicentre study was undertaken: 1) to evaluate the analytical characteristics of these kits and the homogeneity of the results from one laboratory to another, independently of the method used, 2) to validate the differences between the proposed normal values of both kits, 3) to study the possibility of using commercial control sera as external quality control. Four analytical systems were included in the study (Roche Modular/Hitachi 717, Beckman Coulter Immage and LX20, Dade Behring BNII). Determinations were carried out on pools of sera, commercial control sera, kit controls, and 30 serums of patients. These latter were also analyzed in capillary electrophoresis in order to establish correlations between the techniques. The calibrations were stable over one 2 weeks period. The repeatability of measurements spread out from 3,1% to 24,7%, for a mean value lower than 10%. The commercial control sera provided reliable results, with values adapted to a routine quality control use. The results of the Bio-Rad applications were lower by approximately 20% than those of the Roche application, which justifies the difference of the normal values (2,6% versus 3%), and an identical classification of the patients in at least 27 of the 30 samples. We conclude that the analytical quality of the compared techniques, even if it could be improved, is sufficient to guarantee a good reliability of the results. An external quality control could be proposed by using the control sera that we tested.     

Assessing prevalence of alcohol consumption in early pregnancy: Self-report compared to blood biomarker analysis

Providing appropriate antenatal and postnatal care for women who drink alcohol in pregnancy is only possible if those at risk can be identified. We aimed to compare the prevalence of alcohol consumption in the first trimester of pregnancy using self-report and blood biomarker analysis. Six-hundred routine blood samples from 2014, taken at the antenatal booking appointment, in the first trimester of pregnancy, were anonymously analysed for the presence of Carbohydrate Deficient Transferrin (CDT), a validated marker of chronic alcohol exposure (normalising 2–3 weeks from abstinence) and Gamma-glutamyltransferase (GGT), a liver enzyme elevated for up to 8 weeks after alcohol exposure. In a separate sample of women, from 2015, data taken during the antenatal visit, documenting women's self-reported alcohol consumption, were collected. The percentage of women who reported alcohol intake in the first trimester was 0.8%. This compared to 74.1% of women who reported consuming alcohol before pregnancy. CDT analysis revealed a prevalence rate of 1.4% and GGT a prevalence rate of 3.5% in the first trimester of pregnancy. Although those with elevated CDT generally had high levels of GGT, only one person was positive for CDT and GGT. Results from CDT analysis and self-report may underestimate prevalence for different reasons. GGT appeared to lack specificity, but it may have value in supporting findings from CDT analysis. Further studies using additional blood biomarkers, or a combination of blood biomarkers and self-report, may be beneficial in accurately detecting alcohol drinking history in pregnancy.     

Screening properties of questionnaires and laboratory tests for the detection of alcohol abuse or dependence in a general practice population.

BACKGROUND: Early identification of alcohol abuse or dependence is important in general practice because many diseases are influenced by alcohol. General practitioners, however, fail to recognise most patients with alcohol problems. AIM: To assess the diagnostic performance of the CAGE and AUDIT questionnaires, their derivatives, and laboratory tests in screening for alcohol abuse or dependence in a primary care population (male and female patients), attending their general practitioner (GP). DESIGN OF STUDY: A diagnostic cross-sectional study. SETTING: A random sample of patients who were over 18 years of age (n = 1992) attending 69 general practices situated in the same region in Belgium. METHOD: Alcohol questionnaires (CIDI 1.1, section I, CAGE, AUDIT, AUDIT-C, Five-Shot, and AUDIT Piccinelli) were completed, demographic information was recorded, and patients underwent conventional blood tests, including mean corpuscular volume, liver function tests, the gamma-glutamyl transferase test, and carbohydrate-deficient transferrin (CDT, estimated using %CDT). Calculations of sensitivity, specificity, positive predictive value, negative predictive value, odds ratios with their 95% CIs, and receiver operating characteristic (ROC) curves for different scores of the questionnaires and laboratory tests, using DSM-III-R as the reference standard. RESULTS: The past-year prevalence of alcohol abuse or dependence in this population was 8.9% (178/1992) of which there were 132 male and 45 female patients attending a general practice. The GPs identified 33.5% of patients with alcohol abuse or dependence. Among male patients, all questionnaires had reasonable sensitivities between 68% and 93% and hence at lower cut-points than recommended. Only the sensitivity of the CAGE, even at its lowest cut-point of > or = 1 was lower (62%). In female patients the sensitivities were lower; however, odds ratios were higher for different questionnaires. The receiver operating characteristic (ROC) curves did not differ between the questionnaires. The laboratory tests had low diagnostic accuracy with areas under the ROC curves (AUCs) between 0.60 and 0.67 for female patients and 0.57 and 0.65 for male patients. CONCLUSIONS: This is one of the largest known studies on alcohol abuse or dependence among family care practices. We confirm earlier results that the AUDIT questionnaire seems equally appropriate for males and females; however, screening properties among male patients are higher. Nevertheless, the Five-Shot questionnaire is shorter and easier to use in a general practice setting and has nearly the same diagnostic properties in male and female general practice patient populations. We confirm that conventional laboratory tests are of no use for detecting alcohol abuse or dependence in a primary care setting. Also, the %CDT cannot been used as a screening instrument in this general practice population.     

Sialic acid deficiency transferrin: a very promising biological marker, sensitive to chronic alcoholism]

Chronical alcohol ingestion may induce conformational molecular modifications of plasma transferrin: alcohol modifies the content of its carbohydrates. The abnormal transferrin contains reduced amounts of carbohydrates, especially sialic acid, constituting its terminal trisaccharides biantennary chains. Plasma levels of partly deficient or asialotransferrin increase in chronically drinkers. In English speaking countries, it is called carbohydrate deficient transferrin or CDT. A positive correlation is obtained between the plasmatic concentration of CDT and the amount of ingested alcohol. Positivity and sensitivity of CDT are superior to those other usual biological parameters. The CDT quantitation may be proposed for the detection and the follow-up of alcohol drinkers, in order to evaluate the degree of intoxication, and during the period of withdrawal.     

Carbohydrate deficient transferrin: what's new 20 years later?

The clinical diagnosis of alcohol abuse has frequently to be supported by biological data. These data help the practitioner to establish the diagnosis and to monitor the alcohol withdrawal and possible relapses. They also can help to demonstrate to the patient the existence of a denied alcohol abuse. CDT determination has been proposed for more than twenty years, but commercial kits are available since only 1990. A consensus has to be established concerning a reference method and the definition of the transferrin isoforms that should be included in the CDT. CDT is nevertheless considered in many studies as the best marker of alcohol abuse now available. Its sensitivity is at least equal to that of gamma glutamyltransferase (GGT), and its specificity remains very high even in the presence of other pathologies connected or not to the alcohol abuse. CDT is, despite the lack of standardisation and the cost of its determination, a basic marker of alcohol abuse more particularly in the circumstances of lack of efficiency of the other markers.     

The assessment of serum soluble transferrin receptor in alcoholics

The consumption of large amounts of alcohol disturbs body iron metabolism and leads to increase of body iron stores and may cause various hematologic changes. Both, iron overload and iron depletion could have effect on the metabolic, transit and storage pools. These pools and its indicators were evaluated previously in abusers, but there is no information concerning the serum soluble transferrin receptor (sTfR) as a new marker of transit compartment. Therefore, the aim of this study was to assess the sTfR and compare it to the other indicators of transit pool in alcoholics. sTfR was measured immunoturbidimetrically. The markers of alcohol abuse, metabolic, transport and storage pools and the other hematologic assays were determined by routine laboratory methods. The tested group consisted of 148 alcoholics. The abusers were not affected by anemia. Every second patient had increased iron storage pool. Serum iron level only tended to increase. The mean serum sTfR did not show any significant difference and the mean transferrin–ferritin index (sTfR/log ferritin ratio) was significantly decreased compared with the controls. None of the transit pool markers presented significant differences between subgroups classified according to liver enzyme activities. We suggest that the iron excess in alcoholics did not limit the cellular iron uptake by transferrin receptor-mediated endocytosis which was confirmed by the unchanged level of serum soluble transferrin receptor. Additionally, the serum sTfR in alcohol abusers is independent of the weekly alcohol intake, age of the patients, duration of dependence, time of abstinence, time of last drinking and the liver function tests.     

Détermination des valeurs de la transferrine carboxydéficiente par électrophorèse capillaire sur une population d'enfants âgés de 0 à 20 ans

Rationale and ObjectiveCarbohydrate-deficient transferrin (CDT) seems to be at the moment an excellent biochemical marker of an excessive alcohol consumption.Materials and MethodsIn this article, we describe CDT values within a population of children aged from several days to 20 years in the aim to compare our results with the already defined reference values.ResultsThe CDT mean rate (0,888%) in our population, which includes 185 subjects from 0 to 20 years, is slightly lower than the rate defined in an adult population (1,028%).ConclusionNew-born's electropherogram is different and a complete study of this last one could be usefull for a better follow-up of alcoholic mothers' children.     

Genome-wide association study identifies two loci strongly affecting transferrin glycosylation

Polysaccharide sidechains attached to proteins play important roles in cell-cell and receptor-ligand interactions. Variation in the carbohydrate component has been extensively studied for the iron transport protein transferrin, because serum levels of the transferrin isoforms asialotransferrin + disialotransferrin (carbohydrate-deficient transferrin, CDT) are used as biomarkers of excessive alcohol intake. We conducted a genome-wide association study to assess whether genetic factors affect CDT concentration in serum. CDT was measured in three population-based studies: one in Switzerland (CoLaus study, n = 5181) and two in Australia (n = 1509, n = 775). The first cohort was used as the discovery panel and the latter ones served as replication. Genome-wide single-nucleotide polymorphism (SNP) typing data were used to identify loci with significant associations with CDT as a percentage of total transferrin (CDT%). The top three SNPs in the discovery panel (rs2749097 near PGM1 on chromosome 1, and missense polymorphisms rs1049296, rs1799899 in TF on chromosome 3) were successfully replicated , yielding genome-wide significant combined association with CDT% (P = 1.9 × 10(-9), 4 × 10(-39), 5.5 × 10(-43), respectively) and explain 5.8% of the variation in CDT%. These allelic effects are postulated to be caused by variation in availability of glucose-1-phosphate as a precursor of the glycan (PGM1), and variation in transferrin (TF) structure.     

Drinking patterns in general practice patients

Patients from 47 group practices recruited from the Medical Research Council's general practice research framework participated in a study involving the collection of information about smoking, drinking, exercise and dieting and weight. This paper is concerned with the data on alcohol consumption obtained in the first stage of the study in which a self-administered questionnaire, the health survey questionnaire, was distributed by hand or by post to patients registered with the participating practices.

Of the 25496 men who completed the questionnaire, 83.6% stated that they had been drinking in the previous three months compared with 69.2% of the 36657 women. For both sexes, abstinence rates were significantly lower in the younger age groups (P<O.001). Of the men, 7.6% admitted to a weekly alcohol consumption of 35 units or more and 2.7% women were drinking 21 units per week or more.

Of the 1948 male excessive drinkers 45.9% expressed concern about their drinking through a positive CAGE response and/or self assessment of a drinking problem, while for the 989 female excessive drinkers the figure was 44.1%. A positive response to these questions was strongly related to alcohol consumption and was more frequent among women than men at most levels of consumption.

     

Sex-related differences in the haematological effects of excessive alcohol consumption.

Mean corpuscular volume (MCV) was measured at presentation in 320 hospital patients with a history of excessive alcohol consumption. The MCV of the 94 women thought to be actively drinking more than 80 g/day of alcohol was 101.3 fl compared with 96.7 fl in their male counterparts. Alcohol consumption, age, smoking habits, prevalence of inadequate diet, or serum and red cell folate levels did not differ significantly between men and women. It is suggested that MCV is a better indicator of excessive alcohol consumption in women than in men, and that women are more susceptible to the haematological toxicity of alcohol.     

Peripheral markers, future perspectives]

Four of the recently described peripheral markers of alcohol abuse have been reviewed. The acetaldehyde adducts allow to detect an alcohol abuse lasting for several weeks, even after a recent alcohol withdrawal. Inversely, 5-hydroxytryptophol (5-HTOL) reflects the alcohol consumption of the last 24 hours. Its detection is possible after the blood alcohol concentration has disappeared. Its measurement is run in urine samples, thus without invasive sampling. The hyaluronic acid and the activity of beta-hexosaminidase are markers of hepatobiliary alcohol induced disorders more than direct markers of alcohol intake. Acetaldehyde adducts could be used as markers of long term alcohol abuse, CDT as a marker of the recent alcohol abuse, and 5-HTOL the detection of alcohol abuse of the past day.     

Improved method for carbohydrate-deficient transferrin determination in human serum by capillary zone electrophoresis

Carbohydrate-deficient transferrin (CDT) is a reliable marker of chronic or repeated alcohol abuse. It indicates a group of isoforms of human transferrin (Tf), the main iron transport serum protein, deficient in sialic acid residues (asialo-, monosialo- and disialo-Tf) in comparison to the main isotransferrin which contains four sialic acid groups (tetrasialo-Tf). The aim of the present work was to develop a capillary electrophoretic method suitable for rapid determination of CDT components in serum. Serum samples (0.1 ml) were saturated with iron by incubation with 10 mM FeCl3 (2 microl) and 500 mM NaHCO3 (3 microl) for 30 min, then diluted 1:10 in water and injected by positive pressure (0.5 p.s.i. for 10 s). Separation was performed with a capillary zone electrophoretic method using bare fused-silica capillaries (57 cm x 20 microm I.D.) and a buffer composed of 100 mM sodium tetraborate adjusted with 6 M HCl to pH 8.3 added with 1.5 mM diaminobutane. Applied voltage was 20 kV and temperature 25 degrees C. Detection was by UV absorption at 200 nm wavelength. Under the described conditions, asialo-, monosialo-, disialo-, trisialo- and tetrasialo-transferrin were baseline separated. The limit of detection (signal-to-noise ratio of 2) was about 0.3% for disialo-Tf, and 0.5% of trisialo-Tf, expressed as percentages of the terasialo-Tf peak area. Day-to-day RSDs of relative migration times were < or = 0.2%. Quantitation showed day-to-day RDSs < or = 6.9% and < or = 10.9% for disialo- and trisialo-Tf, respectively. The results from 79 control subjects, including social drinkers, and 23 alcoholics showed disialo- and trisialo-Tf significantly increased in patients (P<0.0001 and <0.01, respectively). A clear interference from trisialo-Tf in an immunoassay for CDT was demonstrated. The present method is suitable for confirmation of CDT immunoassays by independent technique.     

Autobiographical memory predicts the course of depression during detoxification therapy in alcohol dependent men

BACKGROUND: Recall of autobiographical memories (AM) has shown to predict the course of depression during psychiatric treatment [British Journal of Psychiatry 162 (1993)]; therefore, we assume that AM also predicts the remissive course of depression during detoxification therapy in alcohol dependent men. METHODS: In a longitudinal study, 65 patients were assessed twice: at admission to a detoxification unit and about 3 weeks later for follow-up. AM scores at the beginning of the detoxification program were used as predictors in hierarchical regression analyses. RESULTS: After controlling for initial depression, mental status and degree of alcohol dependence, AM in response to positive and aggressive cue words significantly predicted affective change. These results validate the assumption that AM is a psychological depression marker. LIMITATIONS: No data are reported on depression prior to drinking onset. CONCLUSIONS: As a practical consequence, AM can assist the physician with the decision for concomittant antidepressive therapy during detoxification and rehabilitation of alcohol dependent men.     

Discriminating neuropsychological sequelae of head injury from alcohol-ABUSE-induced deficits: A review and analysis

Alcohol abuse is linked strongly with neuropsychological deficits that may resemble deficits seen in head-injured individuals. Heavy daily drinking appears more damaging than episodic abusive consumption. Cognitive deficits associated with alcohol include abstraction, perceptuospatial, and problem- solving skills. Verbal abilities are spared. For alcoholics younger than 40, abstinence is associated with improved functioning. For those over 40, deficits may be permanent. Intelligence tests are unlikely to pick up alcohol-induced deficits. Points for neuropsychologists to consider in differentiating between head injury and alcohol-induced deficits include abstinence from drinking prior to testing, intactness of remote memory and verbal functions, and changes in tolerance for alcohol.     

Gender differences in risk factors and consequences for alcohol use and problems

Women drink less alcohol and have fewer alcohol-related problems than men. Women appear to be less likely than men to manifest certain risk factors for alcohol use and problems and are more likely to have certain protective factors against these problems: women perceive greater social sanctions for drinking; women are less likely to have characteristics associated with excessive drinking including aggressiveness, drinking to reduce distress, behavioral undercontrol, sensation-seeking and antisociality; and women are more likely to have desirable feminine traits (e.g., nurturance) protective against excessive drinking. In addition, consequences of heavy alcohol use, or alcohol use disorders, appear to be more negative for women than men, at least in some domains: women suffer alcohol-related physical illnesses at lower levels of exposure to alcohol than men, and some studies suggest women suffer more cognitive and motor impairment due to alcohol than men; women may be more likely than men to suffer physical harm and sexual assault when they are using alcohol; heavy alcohol use in women is associated with a range of reproductive problems. Implications of these findings for future research and public health education campaigns are discussed.     

Effects of abstinence on the ability of clinical laboratory tests to identify male alcoholics

Quadratic discriminant analysis of 25 commonly ordered clinical laboratory tests resulted in correct classification of 100% of nonalcoholic inpatients (n = 41), 100% of medical ward alcoholics as alcoholic (n = 63), and 95% of alcoholism treatment program participants as alcoholic (n = 274). Admission laboratory values for a random sample of 138 additional alcoholism treatment program participants were used to correctly classify 96% of them as alcoholics. Repeat analysis of these same laboratory tests after some 27 days of hospitalization resulted in 94% of the 138 patients still being classified as alcoholic, even though significant improvements in individual hepatic and hematologic laboratory values were noted. Classification was not changed with reanalysis after long-term abstinence (7 or 24 months), suggesting widespread and persistent alcohol-related alterations in organ system functioning with chronic alcohol abuse. Quadratic discriminant analysis of laboratory tests is an effective means of identifying people with present or past alcohol abuse but is not yet of value in detecting compliance with a treatment goal of abstinence.     

Rhabdomyolysis: report of eleven cases.

This article reports the results of a retrospective study of 11 patients with rhabdomyolysis-induced acute renal failure. All patients had multiple risk factors for rhabdomyolysis, the most common of which were alcoholism, illicit drug abuse, compression, and trauma. Patients with combined alcohol/illicit drug abuse had more severe electrolyte imbalances than patients without alcohol/illicit drug abuse. Myoglobinuria was detected in only half the patients despite rhabdomyolysis and urine "hematest" positivity. The serum creatine phosphokinase level was elevated in all of the patients, which is a good marker for rhabdomyolysis. Rhabdomyolysis is a relatively common disorder in municipal hospitals. Routine serum creatine phosphokinase levels should be checked on patients at risk, especially alcoholics, illicit drug abusers, and older patients.     

Symptomatic correlates of alcohol abuse as a presenting problem

This investigation examined a large number of self-reported symptoms of psychopathology. Its specific purpose was to assess their relationship to alcohol abuse as a self-indicated problem behavior. Participants in the study were 72 adults of both sexes who sought mental health services at a Veterans Administration outpatient Mental Hygiene Clinic. The self-reporting instrument was a behavioral problem checklist that was administered as part of a routine psychological test battery given at the time of each client's intake assessment at the Clinic. A correlational analysis of these data revealed that several broad areas of psychopathology were related significantly to alcohol abuse: Social/interpersonal skill deficits, anxiety, addiction proneness, impulse dyscontrol, and self-destructive ideation. These findings support a social learning theory of alcohol abuse. The results also imply that future treatment approaches to excessive drinking should include social skill and relaxation training as well as attention to traditional clinical concerns with self-destructive thinking and impulse control.