Carbohydrate-deficient Transferrin Levels Research Articles

The efficacy of high pressure liquid chromatography (HPLC) in detecting congenital glycosylation disorders (CDG)

Abstract Objectives Congenital disorders of glycosylation (CDG) are a family of rare inherited metabolic disorders. This study aimed to examine the carbohydrate-deficient transferrin (CDT) screening results of 1,328 patients with suspected CDG by using transferrin- high pressure liquid chromatography (Tf- HPLC) method and to evaluate the performance of the method as a reference diagnostic tool. Methods Relative CDT levels (CDT concentrations expressed as percent of total transferrin) were determined in serum samples by HPLC. The method sensitivity, specificity and positive predictive value (PPV) were further calculated. Results Abnormal transferrin isoform profile consistent with CDG Type-I and CDG Type-II were determined in 50 cases; in 44 cases asiolo-Tf (7.63 ± 5.44 %) and disialo-Tf (36.29 ± 9.04 %), in six cases monosialo-Tf (3.95 ± 0.95 %) and trisialo-Tf (25.05 ± 4.46 %) were determined and decreased tetrasialo-Tf (49.75 ± 11.59 %) was identified in all cases. Two cases having abnormal CDT pattern were molecularly diagnosed with hereditary fructose intolerance and galactosemia and 11 cases diagnosed with CDG based on clinical and molecular analysis showed a normal pattern. The sensitivity, specificity and positive predictive values of Tf-HPLC method were 81.96 %, 99% and 96 %, respectively. Conclusions Tf-HPLC is a useful, highly sensitive, cost-advantageous and reliable method for the detection and preliminary diagnosis of CDG for laboratories working with large sample series.

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.

Acute pancreatitis in a patient with normal lipase: a case report

This case report highlights the rare occurrence of acute pancreatitis in a patient exhibiting normal lipase levels. The patient presented to the emergency department with abdominal pain and fever. Laboratory tests indicated an acute inflammatory process but a negative lipase value. The diagnosis was established by a CT scan showing necrotizing pancreatic changes with elevated carbohydrate-deficient transferrin (CDT) levels, suggesting alcohol as the etiology. Management involved supportive care, aggressive fluid resuscitation, nutritional support, and empirical antibiotic therapy, which led to clinical improvement. This case emphasizes the importance of a comprehensive clinical assessment beyond standard biochemical markers in diagnosing and managing pancreatitis.

C60 Fullerene Reduces the Level of Liver Damage in Chronic Alcohol Intoxication of Rats.

The liver is the main organ responsible for the metabolism of ethanol, which suffers significantly as a result of tissue damage due to oxidative stress. It is known that C60 fullerenes are able to efficiently capture and inactivate reactive oxygen species in in vivo and in vitro systems. Therefore, the purpose of this study is to determine whether water-soluble C60 fullerene reduces the level of pathological process development in the liver of rats induced by chronic alcohol intoxication for 3, 6, and 9 months, depending on the daily dose (oral administration; 0.5, 1, and 2 mg/kg) of C60 fullerene throughout the experiment. In this context, the morphology of the C60 fullerene nanoparticles in aqueous solution was studied using atomic force microscopy. Such biochemical parameters of experimental animal blood as ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma-glutamyl transferase) and ALP (alkaline phosphatase) enzyme activities, CDT (carbohydrate-deficient transferrin) level, values of pro-antioxidant balance indicators (concentrations of H2O2 (hydrogen peroxide) and GSH (reduced glutathione), activities of CAT (catalase), SOD (superoxide dismutase) and GPx (selenium-dependent glutathione peroxidase)), and pathohistological and morphometric features of liver damage were analyzed. The most significant positive change in the studied biochemical parameters (up to 29 ± 2% relative to the control), as markers of liver damage, was recorded at the combined administration of alcohol (40% ethanol in drinking water) and water-soluble C60 fullerenes in the optimal dose of 1 mg/kg, which was confirmed by small histopathological changes in the liver of rats. The obtained results prove the prospective use of C60 fullerenes as powerful antioxidants for the mitigation of pathological conditions of the liver arising under prolonged alcohol intoxication.

Preclinical Online Sсreening for Stress-Associated Disorders in Combatants

Background: the need to improve standards, organizational methods and practical scientific approaches to the prevention and treatment of mental pathology and the restoration of mental health of military personnel involved in combat operations determines the importance of developing and implementing effective strategies for correcting the mental state of combatants. The aim: to analyze the results of preclinical online screening of stress-associated disorders in combatants to assess its effectiveness in conducting routine psychoprophylactic examinations of military personnel after returning from the combat zone. Subjects and methods: 176 male employees of the Russian Guard who returned after a business trip of up to 90 days in the combat zone were examined. All combatants underwent preclinical online screening for the detection of stress-associated mental disorders, including methods regulated by the Ministry of Health of the Russian Federation. After testing, the obtained data were processed using cluster analysis by the K-means method. Clinical and psychopathological examination and laboratory studies were conducted, including: the content of carbohydrate-deficient transferrin (CDT), testosterone and cortisol levels, processing of the data obtained using statistical methods. Results: the combination of high levels of evening cortisol and CDT in combatants may indicate a complex interaction of physical stress, psychological trauma and possible alcohol abuse, which may be the result of both specific conditions of military service and a way to cope with post-war stress and trauma. Conclusions: it was found that the data of preclinical screening testing are consistent with clinical and laboratory results. Online screening testing for the detection of stress-associated disorders in combatants, combined with the determination of testosterone, evening cortisol and CDT levels, can serve as markers of the presence of stress-associated disorders.

Detection of Fluorescently Labeled Carbohydrate-Deficient Transferrin, a Marker of Alcohol Dependence, in Dried Blood Spots

A fluorescence-based (HPLC-FLD) method was developed for the detection of carbohydrate-deficient transferrin (CDT), a marker of alcohol dependence, in dried blood spots (DBS). Dried blood spots were cut and immersed in hydrochloric acid to leach out proteins, labeled with terbium ions, and then sent to high-performance liquid chromatography coupled with a fluorescence detector for detection. The levels of CDT in the dried blood spot samples of 10 clinically alcohol-dependent individuals were in general agreement with the results of the assayed levels of CDT in serum samples from the same source. The method can effectively amplify the detection signal of micro samples with high sensitivity and specificity, and the sampling method is simple and convenient to ensure the accuracy of the results, which is suitable for the qualitative and quantitative analysis of CDT in clinical micro samples.

ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome

ABSTRACT Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 (ZSCAN25) and CDT strongly predicted severe AWS with ATS (p < 0.007) and cg07375256 (p < 6 × 10–5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.

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.

Biomarkers of alcohol abuse potentially predict delirium, delirium duration and mortality in critically ill patients

Carbohydrate-deficient transferrin (CDT) and the γ-glutamyltransferase-CDT derived Anttila-Index are established biomarkers for sustained heavy alcohol consumption and their potential role to predict delirium and mortality in critically ill patients is not clear. In our prospective observational study, we included 343 consecutive patients admitted to our ICU, assessed the occurrence of delirium and investigated its association with biomarkers of alcohol abuse measured on the day of ICU admission. 35% of patients developed delirium during ICU stay. We found significantly higher CDT levels (p= 0.011) and Anttila-Index (p= 0.001) in patients with delirium. CDT above 1.7% (OR 2.06), CDT per percent increase (OR 1.26, AUROC 0.75), and Anttila-Index per unit increase (OR 1.28, AUROC 0.74) were associated with delirium development in adjusted regression models. Anttila-Index and CDT also correlated with delirium duration exceeding 5days. Additionally, Anttila-Index above 4, Anttila-Index per unit increase, and CDT per percent increase were independently associated with hospital mortality.

Alcohol consumption in healthcare workers and risk of workplace injury: a case-control study

Medical surveillance for alcohol abuse and dependency at work is mandatory for a list of high-risk occupations. The occupational physician is the only figure entitled to perform alcohol and laboratory tests on employees. This study aims to investigate alcohol-induced injuries in healthcare workers, by using Carbohydrate-Deficient Transferrin (CDT) as a marker during medical surveillance visits. A retrospective study was carried out in an Italian healthcare unit. The sample consisted in 75 healthcare workers who sustained an occupational injury. To assess alcohol consumption, CDT levels were tested as well as serum alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), mean corpuscular volume (MCV). No worker had positive CDT levels (cut-off 2%); 12% of cases (5 male and 4 female workers) had γ-GT level higher than normal range (cut-off: 36 U/L). Most injuries (53.33%) occurred during morning shifts, 33.33% during afternoon shifts and 13.33% during night shifts. Female workers had a higher injury rate (73%); biological injuries were the most frequent (36%), followed by slipping and falling 33%. This study seems to indicate that alcohol does not represent an important cause of occupational injuries, as no cases of workplace injury were found positive for CDT. CDT as a biomarker in health surveillance programs could be used to assess alcohol consumption when used alongside other biochemical parameters, and its routine use during medical surveillance could act as a deterrent.

Driving license regranting: Hair EtG, serum CDT, and the role of sociodemographic and medicolegal variables.

Driving under the influence (DUI) of alcohol is a road safety problem. Driving license regranting is based on the evaluation of medicolegal and toxicological variables that may include serum carbohydrate-deficient transferrin (CDT) and hair ethyl glucuronide (hEtG). The aim of the study was to compare the diagnostic performance of CDT and hEtG in a population of DUI offenders. Other factors potentially associated with heavy alcohol use were explored. The population included DUI offenders examined during the period of January 1, 2019, through June 30, 2022. Sociodemographic, medicolegal, and toxicological variables were collected. CDT in serum and EtG in head hair were determined in all subjects. Excessive alcohol intake (hEtG ≥30 pg/mg) was considered cause for unfitness to drive. Cohen's kappa coefficient was calculated. Descriptive analyses were performed using chi-square and Mann-Whitney tests. Variables significantly different between the groups were included in a multivariate binary logistic regression model. The sample encompassed 838 subjects (case group: 179, comparison group: 689). CDT exhibited poor agreement (κ = 0.053) with hEtG as the reference test. Lower education, age at DUI, heavy smoking, and GGT levels associated with heavy alcohol consumption differentiated the two groups. For DUI offenders, the use of CDT to assess heavy alcohol consumption is limited, possibly due to the time-window assessed, the time required for normalization, and the different amount of ethanol needed to reach higher CDT levels, in comparison to hEtG; thus, hEtG assessment is strongly recommended for this population. Heavy smoking, GGT, education, and age could be related to heavy alcohol consumption and higher risk of DUI.

Self-reported alcohol consumption, carbohydrate deficient transferrin and risk of cardiovascular disease: The PREVEND prospective cohort study

BackgroundSelf-reported alcohol consumption is an established risk factor for cardiovascular disease (CVD). Carbohydrate deficient transferrin (CDT) is an established objective marker of excessive alcohol consumption, but data on its prospective association with CVD are lacking. We aimed to evaluate the associations of self-reported alcohol consumption and CDT (expressed as %CDT, a more reliable marker than absolute CDT levels) with CVD risk. Materials and methodsIn the PREVEND prospective study of 5,206 participants (mean age, 53 years; 47.7% males), alcohol consumption by self-reports, absolute CDT measured using the Siemens nephelometric assay and %CDT calculated as the percentage of total transferrin concentrations, were assessed at baseline. Alcohol consumption was classified into 5 categories: abstention (reference), light, light–moderate, moderate and heavy alcohol consumption.Hazard ratios (HRs) (95% confidence intervals [CI]) for first CVD events were estimated. ResultsMean (SD) of %CDT was 1.59 (0.54) %. During a median follow-up of 8.3 years, 326 first CVD events were recorded. Compared with abstainers, the multivariable-adjusted HRs (95% CIs) of CVD for light, light–moderate, moderate and heavy alcohol consumption were 0.66 (0.46–0.95), 0.83 (0.62–1.11), 0.83 (0.61–1.14) and 0.80 (0.48–1.36), respectively. Light alcohol consumption was associated with reduced coronary heart disease risk 0.62 (0.40–0.96), whereas light-moderate alcohol consumption was associated with reduced stroke risk 0.45 (0.24–0.83). The association of %CDT with CVD risk was not significant. ConclusionsOur findings confirm the established association between self-reported light to moderate alcohol consumption and reduced CVD risk. However, %CDT within the normal reference range may not be a risk indicator for CVD.

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.

A Comparison of the Predictive Power of DNA Methylation with Carbohydrate Deficient Transferrin for Heavy Alcohol Consumption

ABSTRACT Currently, the most commonly used biomarker of alcohol consumption patterns is carbohydrate-deficient transferrin (CDT). However, the CDT has limited sensitivity and requires the use of blood. Recently, we have shown that digital DNA methylation techniques can both sensitively and specifically detect heavy alcohol consumption (HAC) using DNA from blood or saliva. In order to better understand the relative performance characteristics of these two tests, we compared an Alcohol T-Score (ATS) derived from our prior study and serum CDT levels in 313 (182 controls and 131 HAC cases) subjects discordant for HAC. Overall, the Receiver Operating Characteristic (ROC) area under the curve (AUC) analyses showed that DNA methylation predicted HAC status better than CDT with AUCs of 0.96 and 0.87, respectively (p < 0.0001). The performance of the CDT was affected by gender while the ATS was not, while both were affected by age. We conclude that DNA methylation is a promising method for quantifying HAC and that further studies to better refine its strengths and limitations are in order.

The Utility of Carbohydrate-Deficient Transferrin in Identifying Chronic Alcohol Users in the Injured Patient: Expanding the Toolkit

BackgroundAlcohol use remains abundant in patients with traumatic injury. Previous studies have suggested that serum carbohydrate-deficient transferrin (%dCDT) levels, relative to blood alcohol levels (BALs), may better differentiate episodic binge drinkers from sustained heavy consumers in admitted patients with traumatic injury. We characterized %dCDT levels and BAL levels to differentiate binge drinkers from sustained heavy consumers in admitted trauma patients and their associations with outcomes. MethodsThis prospective, cross-sectional, observational study assessed %dCDT and BAL levels in admitted male and female patients with traumatic injury (≥18 y) at an American College of Surgeons Committee on Trauma level-1 center from July 2014 to June 2016. We designated patients with %dCDT levels ≥1.7% (CDT+) as chronic alcohol users and dichotomized acutely intoxicated patients using three different BAL-level thresholds. Primary outcomes included in-hospital complications, along with prolonged ventilation and intensive care unit length of stay, both defined as the top decile. Secondary outcomes included rates of drug or alcohol withdrawal and all-cause mortality. Analyses were adjusted for clinical factors. ResultsWe studied 715 patients (77.5% men, 60.6% ≤ 40 y of age, median Injury Severity Score: 14, 41.7% motor vehicle crashes, 17.9% gunshot wounds, 11.1% falls). While 31.0% were CDT+, 48.7% were BAL>0. After adjusting for CDT levels, BAL levels >0, >100, or >200 were not associated with adverse outcomes. However, CDT+ relative to patients with CDT were associated with complications (adjusted odds ratio: 1.96 [1.24-3.09]), prolonged ventilation days (3.23 [1.08-9.65]), and prolonged intensive care unit stays (2.83 [1.20-6.68]). ConclusionsIn this 2-year prospective, cross-sectional, and observational study, we found that %dCDT levels, relative to BAL levels, may better stratify admitted patients with traumatic injury into acute versus chronic alcohol users, identifying those at higher risk for in-hospital complications.

Serum lipids, leptin, and soluble leptin receptor in alcohol dependence: A cross-sectional and longitudinal study

ObjectiveAlcohol dependence affects metabolic processes. Further research is needed to apply this knowledge clinically. In this study, possible differences in serum lipids and/or leptin activities between alcohol-dependent in-patients and healthy controls and possible associations with alcohol-related blood parameters and with prospective outcomes in alcohol dependence were assessed sex-specifically. MethodWe measured and compared (median) serum lipids (triglycerides and total, HDL, and LDL cholesterol) and leptin activities (leptin, soluble leptin receptor [ObRe], and free leptin index) in 200 (males 56.5 %) early-abstinent alcohol-dependent in-patients and 240 (males 55.4 %) healthy controls and assessed alcohol-related readmissions during a 24 -month post-inclusion period. ResultsMale patients showed higher HDL cholesterol (61 versus 48 mg/dl), lower LDL/HDL ratios (2.06 versus 3.04), and lower free leptin index (0.30 versus 0.59) at study inclusion compared to healthy controls. In patients, ObRe levels were higher than in controls and decreased from inclusion to the second study-visit (at median 5 days later; males: 16.7–13.8 versus 11.0 ng/ml; females: 17.0–13.4 versus 12.1 ng/ml). The free leptin index increased between the two time points in females (0.80 versus 1.20). Lipids and leptin activities correlated with carbohydrate-deficient transferrin levels and liver enzyme activities. None of the serum parameters were significantly associated with alcohol-related readmissions. ConclusionOur data support that serum lipid levels and leptin activities are involved in alcohol dependence. The parameters appear as possible indirect biomarkers for alcohol dependence.

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.

Carbohydrate deficient transferrin (CDT) predicts heavy drinking in adolescents with alcohol dependence.

A biomarker that could indicate problematic drinking in adolescents and/or reflect changes in heavy drinking would be a valuable addition to prevention, treatment, and research efforts. Carbohydrate deficient transferrin (CDT) is a valid biomarker of heavy drinking in adults; however, it is not well examined in adolescents. Adolescents with alcohol dependence (AD) (n=21; 9 females) and non-dependent controls (ND) (n=6; 3 females), ages 14-20, were interviewed to determine drinks per drinking day, peak number of drinks, and percent days heavy drinking (≥4 standard drinks/day). Blood samples from participants were assayed for percent of transferrin that was carbohydrate deficient (%CDT). Analyses compared groups on drinking and %CDT, examined the relationship between %CDT and indices of drinking, and provided preliminary estimates of the test validity of %CDT for heavy drinking in adolescents. Among adolescents with AD, %CDT was significantly and strongly correlated (r=.54) with percent heavy drinking days, and this relationship was consistent for both males and females. AD adolescents did not differ from ND on mean %CDT levels, despite significantly greater alcohol use. Indicators of test validity showed that %CDT had low sensitivity (33%) but adequate specificity (83%) for heavy drinking. Results provide proof of concept that %CDT is a potentially valuable tool to use in alcohol treatment and research in adolescents. Even if %CDT does not discriminate between adolescents with and without alcohol dependence, it could be an effective monitoring tool to indicate changes over time in binge drinking. Improved %CDT measurement methods might enhance its utility.

Social and age-related aspects of informativeness of indirect laboratory markers of alcohol consumption

Aim. To compare the diagnostic capabilities of indirect laboratory markers of alcohol consumption - alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltranspeptidase and carbohydrate-deficient transferrin, depending on the social status and age group of the subjects. Methods. The activity of enzymes were assessed in the blood serum of socially adapted young subjects (18-25 years, 201 people) and adults (35-50 years, 121 people) by standard biochemical methods, and the level of carbohydrate-deficient transferrin was determined by capillary electrophoresis. With the use of questionnaires, the subjects were tested for alcohol abuse. Non-parametric criteria of statistical significance were used to evaluate the difference. Results. No differences in the activity of enzymes associated with the level of alcohol consumption were found in the youth group (p = 0.911 for alanine aminotransferase, p = 0.669 for aspartate aminotransferase, p = 0.303 for gamma-glutamyltranspeptidase). Activity of gamma-glutamyltranspeptidase was significantly higher in adult group of alcohol abuse (p = 0.021), but individual values of enzyme activity of some subjects from this group fit into the population reference interval. Differences in the level of carbohydrate-deficient transferrin in the youth group, associated with the volume and frequency of alcohol consumption, were not revealed (p = 0.348), and all individual values were within the reference interval. In the adult group, values of this parameter were higher in high-dose alcohol drinkers (p = 0.019) but the diagnostic threshold of alcohol abuse was reached only in 2 subjects. Conclusion. Indirect laboratory markers do not have sufficient diagnostic significance for screening of alcohol abuse among socially adapted young people and adults. Informativeness of carbohydrate-deficient transferrin may be sufficient if the diagnostic threshold corresponding to a definite social and age group replaces the standard population-established concentration limit.