Carbohydrate-deficient Transferrin Research Articles

Serum Carbohydrate Deficient Transferrin: A Sensitive Marker in Diagnosing Alcohol Abuse

Introduction: Alcohol is a psychoactive substance with dependence producing properties and the burden of disease and death related to alcohol consumption remains significant in most countries. Early detection and proper medication with counselling can restore the alcoholics to normalcy. There is a need for a specific assay procedure to detect alcoholics early, so that proper therapy can be instituted. The traditional biomarkers in liver function test (LFT) are more frequently used for diagnosing alcohol abuse but they have variable and limited sensitivity and specificity. Carbohydrate Deficient Transferrin (CDT) can be considered as a more sensitive and specific marker for diagnosing alcohol abuse. The aim of this study is to determine % CDT in alcoholics and compare it with other alcohol markers in respect with sensitivity and specificity. The results of the study will be helpful in assessment of the alcohol dependence patients and therefore in their early detection and management. Materials and Methods: This is a hospital based comparative cross-sectional study carried out in Dharan. A total of 40 cases of alcohol abuse with ≥2 score in CAGE questionnaire and matched 40 subjects with no history of alcohol intake were enrolled in the study. Informed written consent and ethical approval were taken. Result: Serum %CDT has the highest diagnostic efficacy followed by serum gamma glutamyl transferase (GGT), Aspartate Transaminase (AST), Alanine Transaminase (ALT), AST/AL, and ALP as a biomarker for diagnosing alcohol abuse. Serum %CDT has the highest sensitivity with 97.5% and specificity of 73% at a cut off value of 3.5% compared to serum GGT with the sensitivity and specificity of 87% and 73%, respectively at a cut off value of 33.5 U/L. Conclusion: Serum %CDT is a better marker both in terms of sensitivity and specificity compared to other conventional markers and thus can be used as a tool to early diagnose the alcoholic cases and monitor the therapy and for early identification of the relapses in alcoholics during treatment.

Risk Analysis for Quality Control Part 3: Practical Application of the Precision Quality Control Model.

We developed a theoretical framework (Precision Quality Control [PQC]) to minimize the cost of quality, but it is not known whether the method can be applied in practice. We used data for 2 analytes, cadmium and carbohydrate-deficient transferrin (CDT), and applied the PQC framework to find the optimal control limits. These analytes were selected because they differed with respect to sigma values that are major determinants of control limits. We explored different ways to visualize the results: (a) risk trade-off (false-positive risk vs false-negative risk), (b) cost-risk trade-off (false-positive cost vs false-negative risk), and (c) cost minimization. We were able to use the PQC limit to produce 3 different visualizations to suggest control limits. The risk-based analysis was the simplest to apply, but the most difficult to interpret. The cost vs risk method was easy to apply but was still difficult to interpret. The cost minimization method was easy to interpret but required users to declare a willingness to pay that may be difficult to estimate. The PQC method can be used to find control limits that minimize the cost of quality.

A BRIEF HISTORY OF THE ALCOHOL BIOMARKER CDT AND ITS APPLICATION IN FORENSIC MEDICAL EXPERTISE IN ROAD ACCIDENT INVESTIGATIONS"

It is well known that large-scale binge drinking is one of the leading risk factors for poor public health around the world. This is why an objective assessment of the current state of alcohol abuse is critical to protecting public health and safety, especially in clinical, professional context and in the context of road traffic. The article is devoted to the current problem of the history of the formation of the process of one of the most commonly used biostandards of consumed alcohol, namely carbohydrate-deficient transferrin. Taking into account the observed increase in road accidents while intoxicated, the article substantiates the importance of the CDT biomarker when conducting medical expertise. Keywords: CDT biomarker, road accident, forensic medical expertise, alcohol intoxication, public health protection.

Predictive risk markers in alcoholism.

The medical disorders of alcoholism rank among the leading public health problems worldwide and the need for predictive and prognostic risk markers for assessing alcohol use disorders (AUD) has been widely acknowledged. Early-phase detection of problem drinking and associated tissue toxicity are important prerequisites for timely initiations of appropriate treatments and improving patient's committing to the objective of reducing drinking. Recent advances in clinical chemistry have provided novel approaches for a specific detection of heavy drinking through assays of unique ethanol metabolites, phosphatidylethanol (PEth) or ethyl glucuronide (EtG). Carbohydrate-deficient transferrin (CDT) measurements can be used to indicate severe alcohol problems. Hazardous drinking frequently manifests as heavy episodic drinking or in combinations with other unfavorable lifestyle factors, such as smoking, physical inactivity, poor diet or adiposity, which aggravate the metabolic consequences of alcohol intake in a supra-additive manner. Such interactions are also reflected in multiple disease outcomes and distinct abnormalities in biomarkers of liver function, inflammation and oxidative stress. Use of predictive biomarkers either alone or as part of specifically designed biological algorithms helps to predict both hepatic and extrahepatic morbidity in individuals with such risk factors. Novel approaches for assessing progression of fibrosis, a major determinant of prognosis in AUD, have also been made available. Predictive algorithms based on the combined use of biomarkers and clinical observations may prove to have a major impact on clinical decisions to detect AUD in early pre-symptomatic stages, stratify patients according to their substantially different disease risks and predict individual responses to treatment.

The carbohydrate-deficient transferrin as a marker of chronic alcohol consumption and assessment of its usefulness in patients with cardiovascular diseases – a pilot study

Abstract Introduction Cardiovascular diseases (CVDs) are the leading cause of death in the world. The dose of 60 g of alcohol / day has been estimated to significantly increase the risk of developing high blood pressure, arrhythmias, hemorrhagic stroke, and cardiomyopathy. The aim of the study was to evaluate the diagnostic value of CDT when compared with gammaglutamyltransferase (GGT), alkaline phosphatase (ALP), N-terminal fragment brain natriuretic peptide (NT pro-BNP) and troponin T biomarkers in patients with heart failure. Materials and Methods The study was conducted on 59 patients with advanced heart failure with reduced ejection fraction (EF<40%). CDT serum levels were measured using CDT kit, Chromsystems Instruments & Chemicals GmbH, Germany and were expressed as a percentage of total transferrin using high-performance liquid chromatography (HPLC). Results Nineteen patients (n = 19) expressed a normal level of carbohydrate deficiency transferrin <1.2% of the total transferrin found in plasma. The results are obtained from 34 patients (n = 34) were within the range doubtful for the test (1.2–2.5%). In 6 Patients (n = 6) the results of more than 2.5% of CDT content were observed, which could indicate chronic alcohol consumption. Conclusions No statistically significant correlations between CDT and troponin T or NT pro-BNP were identified.

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.

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.

Epigenetic and Proteomic Biomarkers of Elevated Alcohol Use Predict Epigenetic Aging and Cell-Type variation Better Than Self-Report.

Excessive alcohol consumption (EAC) has a generally accepted effect on morbidity and mortality, outcomes thought to be reflected in measures of epigenetic aging (EA). As the association of self-reported EAC with EA has not been consistent with these expectations, underscoring the need for readily employable non-self-report tools for accurately assessing and monitoring the contribution of EAC to accelerated EA, newly developed alcohol consumption DNA methylation indices, such as the Alcohol T Score (ATS) and Methyl DetectR (MDR), may be helpful. To test that hypothesis, we used these new indices along with the carbohydrate deficient transferrin (CDT), concurrent as well as past self-reports of EAC, and well-established measures of cigarette smoking to examine the relationship of EAC to both accelerated EA and immune cell counts in a cohort of 437 young Black American adults. We found that MDR, CDT, and ATS were intercorrelated, even after controlling for gender and cotinine effects. Correlations between EA and self-reported EAC were low or non-significant, replicating prior research, whereas correlations with non-self-report indices were significant and more substantial. Comparing non-self-report indices showed that the ATS predicted more than four times as much variance in EA, CDT4 cells and B-cells as for both the MDR and CDT, and better predicted indices of accelerated EA. We conclude that each of the non-self-report indices have differing predictive capacities with respect to key alcohol-related health outcomes, and that the ATS may be particularly useful for clinicians seeking to understand and prevent accelerated EA. The results also underscore the likelihood of substantial underestimates of problematic use when self-report is used and a reduction in correlations with EA and variance in cell-types.

Clinical and diagnostic value of alcohol biomarkers

Alcohol abuse is a socially significant problem that makes a significant negative contribution to the world health statistics. Alcohol is one of the main factors of mortality in Russia. Despite the current situation, the existing diagnostic approaches to patients with possible alcohol abuse and alcohol-associated diseases do not always allow us to determine the direct contribution of alcohol to the severity and prognosis of the course of these diseases. Objective diagnostic tools for identifying and monitoring the fact of alcohol consumption and its pattern in clinical practice can be useful from the point of view of managing the patient’s disease. In addition, informing the patients about the possibilities of such a diagnosis can motivate them to refuse to take alcohol during further treatment, thereby improving the prognosis of the disease. Currently, various approaches have been developed to assess the fact and nature of alcohol consumption, including the direct determination of ethanol in the blood, but not all of them have found their wide application in clinical practice. In this review, we presented information about the main alcohol biomarkers currently developed: alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltranspeptidase, mean corpuscular volume, carbohydrate-deficient transferrin, ethylglucuronide and ethylsulfate, phosphatidylethanol, ethyl esters of fatty acids, described their disadvantages and advantages in terms of application in clinical practice. Despite the high sensitivity and specificity of some alcohol biomarkers, for example, phosphatidylethanol, the results of laboratory assessment of the content of alcohol biomarkers should be interpreted only in the context of all relevant factors, including the clinical presentation, medical history, mental and physical health of the patient

Ethyl glucuronide in hair detects a high rate of harmful alcohol consumption in presumed non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) cannot reliably be distinguished by routine diagnostics, and the role of alcohol consumption in metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. We investigated alcohol consumption in patients with presumed NAFLD and ALD using novel objective alcohol markers. In total, 184 consecutive patients were included in this prospective observational study. Alcohol intake was assessed by ethylglucuronide in hair (hEtG) and urine (uEtG); the utility of these measures for alcohol detection was compared to Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), carbohydrate deficient transferrin (CDT), mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), and ALD/NAFLD index (ANI). Clinical characteristics of patients with NAFLD and ALD were re-assessed after reclassification based on repeated moderate (≥10 g <60 g EtOH/day) and excessive (≥60 g EtOH/day) alcohol consumption, and patients were retrospectively reclassified based on MAFLD criteria. Repeated moderate to excessive alcohol consumption was detected in 28.6%, 28.5%, and 25.0% of patients with presumed NAFLD, ALD or MAFLD, respectively. ANI score, AUDIT-C, uEtG, and hEtG showed AUCs of 0.628, 0.733, 0.754, and 0.927 for the detection of repeated moderate to excessive alcohol consumption, respectively. The indirect markers CDT, MCV and GGT were not reliable. Patients with repeated moderate or excessive alcohol consumption were significantly more often male, had a significantly lower BMI, and suffered significantly less often from type 2 diabetes or impaired glucose tolerance. In total, 28.6% of patients with presumed NAFLD, and 25.0% with MAFLD are at risk of alcohol-related liver damage. AUDIT-C, uEtG and hEtG should be used to screen for alcohol consumption in patients with fatty liver disease. Fatty liver disease can be caused by metabolic factors and/or alcohol consumption. The diagnosis of non-alcoholic fatty liver disease (NAFLD) is based on the exclusion of harmful alcohol consumption, while metabolic dysfunction-associated fatty liver disease (MAFLD), which has been proposed as a new name for NAFLD, is based on the presence of metabolic comorbidities and allows for alcohol consumption. Herein, we show that up to 29% of patients diagnosed with NAFLD and 25% with MAFLD are at risk of alcohol-related liver damage. We show that ethyl glucuronide (a metabolite of alcohol) in the hair and urine can accurately detect potentially harmful alcohol consumption in these patients - as such, these tests should be integrated into routine diagnostic work-up for patients with fatty liver disease.

New evidence of high association between carbohydrate deficient transferrin (CDT) and alcohol-related road traffic accidents. A retrospective study on 929 injured drivers

BackgroundIt is well known that traffic injuries still represent one of the main causes of death and that high blood alcohol concentrations while driving significantly increase the occurrence of accidents. However, only limited literature on the correlation between chronic alcohol abuse and accident risk is available. The aim of the present study was to investigate the hypothesis of an association between elevated concentrations of carbohydrate deficient transferrin (CDT) and the occurrence of alcohol-related traffic accidents. MethodsThe analytical determinations of BAC and CDT were performed following certified methods in HS-GC-FID and HPLC, respectively. For BAC, 0.50 g/L was used as cut-off, whereas 2.0% was used for CDT, according to the standardisation proposed by IFCC. A total of 929 drivers, tested for BAC at the time of hospital admission after a traffic accident, were classified into two groups: InjDr 1 (BAC ≤ 0.50 g/L) and InjDr 2 (BAC>0.50 g/L); all drivers were also tested for CDT. ResultsInjDr 1 included 674 individuals, only 2.5% showing a CDT above the cutoff, whereas InjDr 2 group consisted of 255 subjects, 28.6% testing positive for CDT (Odds Ratio 15.5). When subdividing the InjDr group into increasing classes of CDT, a steady increase in the percentage of BAC-positive drivers was appreciated. Moreover, average BAC was found to parallel each class of CDT. ConclusionsThe reported data strongly support the use of CDT as a biomarker of increased risk of alcohol-related traffic accidents in the procedures of re-granting of the driving license upon confiscation for “drink driving”.

ВКЛАД МЕДИЦИНЫ ТРУДА В ПРОФИЛАКТИКУ ПАГУБНОГО УПОТРЕБЛЕНИЯ АЛКОГОЛЯ

Abstract. Introduction. The European Mental Health Action Plan, approved by the World Health Organization in 2013, outlines the objectives of the strategy for reducing harmful alcohol use, including reducing harmful effects and reducing alcohol-associated mortality. The implementation of the set goals will make it possible to improve the health, quality of life and increase the working capacity of population. Аim. Тo assess the involvement of occupational medicine in the prevention of harmful alcohol use. Material and methods. Аnalytical review of the current scientific databases for the period from 2004 to 2022 was carried out. Results and discussion. Тhe analysis of 32 data’s, including reviews and current legislative acts, which reflect the provisions on the state of mental health in connection with the occupational environment, the job-place conditions and the influence of harmful working factors on the health of workers, including data related to the harmful use of alcohol. Conclusion. Тo identify such a behavioral risk factor as «harmful alcohol consumption» (or consumption with harmful consequences), encoded by F10.1 in the International Classification of Diseases of the 10th revision, it is necessary to include in the list of mandatory, if a psychiatrist detects suspicion of alcohol abuse during a periodic medical examination, studies on the concentration of carbohydrate deficient transferrin - a marker of alcohol abuse.

Transferrin analysis in wistar rats plasma: Towards an electrochemical point-of-care approach for the screening of alcohol abuse

Simple and low-cost point-of-care testing (POCT) approaches are necessary not only for the diagnosis of alcohol abuse but also for the follow-up of patients during the treatment of alcohol dependence.To advance the development towards these approaches, a disposable screen printed-based electrochemical sensor is proposed for the diagnosis of chronic alcohol abuse. The selected biomarker to be screened (and followed up) was the carbohydrate deficient transferrin (CDT), which was assessed using the parameter “Electrochemical index of glycosylation” (EIG). EIG is defined as the ratio between the signal generated by carbohydrates present in transferrin (Tf) (selectively labeled with an Os(VI) tag) and the signal generated by the electroactive amino acids present in Tf, measured by adsorptive transfer square wave voltammetry (AdTSWV). The electrochemical sensor exhibited a good limit of detection (LOD ≤ 0.7 g L−1) well below the normal range of transferrin in serum (ranging from 2 to 3.6 g L−1). In addition, the diagnostic capabilities of the sensor were evaluated in plasma rats from 31 individuals (16 chronically exposed to alcohol and 15 saline control), yielding a very good clinical sensitivity and specificity (81% and 87%, respectively).These results draw the potential of this approach to be used for POCT of alcohol abuse, making it a useful tool to help therapists/clinicians even patient’s family in the follow-up of alcohol rehabilitation.

Biomarkers and Clinical Laboratory Detection of Acute and Chronic Ethanol Use.

Ethanol use can lead to many health and socio-economic problems. Early identification of risky drinking behaviors helps provide timely clinical and social interventions. Laboratory testing of biomarkers of ethanol use supports the timely identification of individuals with risky drinking behaviors. This review provides an overview of the utility and limitations of ethanol biomarkers in the clinical laboratory. Direct assessment of ethanol in tissues and body fluids has limited utility due to the pharmacokinetics of ethanol. Therefore, the evaluation of ethanol use relies on nonvolatile metabolites of ethanol (direct biomarkers) and measurement of the physiological response to the toxic metabolites of ethanol (indirect biomarkers). Ethanol biomarkers help monitor both chronic and acute ethanol use. The points discussed here include the clinical utility of ethanol biomarkers, testing modalities used for laboratory assessment, the specimens of choice, limitations, and clinical interpretation of results. Finally, we discuss the ethical principles that should guide physicians and laboratorians when using these tests to evaluate alcohol use. Indirect biomarkers such as carbohydrate-deficient transferrin, mean corpuscular volume, and liver enzymes activities may suggest heavy ethanol use. They lack sensitivity and specificity for timely detection of risky drinking behavior and have limited utility for acute ethanol use. Direct biomarkers such as ethyl glucuronide, ethyl sulfate, and phosphatidylethanol are considered sensitive and specific for detecting acute and chronic ethanol use. However, laboratory assessment and result interpretation lack standardization, limiting clinical utility. Ethical principles including respect for persons, beneficence, and justice should guide testing.

Alcohol Consumption and Its Influence on the Clinical Picture of Puumala Hantavirus Infection.

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. Characteristic clinical findings include acute kidney injury (AKI), thrombocytopenia, and capillary leakage. Smoking increases the risk of severe AKI, but it is not known whether alcohol consumption predisposes patients to a more severe infection. Liver and pancreatic enzymes, as well as biomarkers of alcohol consumption (gamma-glutamyl transferase, GGT; carbohydrate-deficient transferrin, CDT; GGT-CDT combination; and ethyl glucuronide, EtG), were measured from 66 patients with acute PUUV infection during hospitalization and at the convalescence phase. Alcohol consumption was present in 41% of the study population, 15% showing signs of heavy drinking. Alcohol use did not affect the severity of PUUV induced AKI nor the overall clinical picture of the infection. Liver enzyme levels (GGT or alanine aminotransferase, ALT) were elevated in 64% of the patients, but the levels did not associate with the markers reflecting the severity of the disease. Serum amylase activities at the convalescent stage were higher than those at the acute phase (p < 0.001). No cases with acute pancreatitis were found. In conclusion, our findings indicate that alcohol consumption does not seem to affect the clinical course of an acute PUUV infection.

Monitoring the use of alcohol—A critical overview of the state‐of‐the‐art biomarkers

AbstractThe use of alcohol, despite it being a psychoactive substance, is widely accepted. This acceptance and the ease of access may lead to alcohol abuse and dependence. Misuse of alcohol is one of the leading causes of preventable illness, injury or death, has social consequences, and can be linked to various types of criminal activities. Upon monitoring alcohol consumption, the question is not necessarily solely whether or not someone is or was abstinent, but may also imply what kind of drinking behavior or patterns are displayed. To reveal the answer, a portfolio of different biomarkers for alcohol (ab)use has been established. A distinction is made between indirect and direct markers. Indirect biomarkers are proteins, enzymes, or cells of which the level or activity undergoes typical changes as a result of (excessive) alcohol intake [e.g., carbohydrate‐deficient transferrin (CDT)], while direct biomarkers are ethanol itself and molecules which are directly related to the metabolism of alcohol [e.g., ethyl glucuronide (EtG), ethyl sulphate (EtS), fatty acid ethyl esters (FAEE), and phosphatidylethanol (PEth)]. These direct biomarkers have the potential to differentiate between drinking behaviors because they allow a higher sensitivity and specificity, in particular for the detection of abstinence or any drinking, and because they can be measured in different matrices, with different detection windows. These assets open the possibilities for testing strategies based on a combination of different markers that can be used both in retrospective and prospective assessments of alcohol intake.This article is categorized under: Toxicology &gt; Alcohol

Increased Transferrin Sialylation Predicts Phenoconversion in Isolated REM Sleep Behavior Disorder.

BackgroundSialic acid–protein interactions are involved in regulating central nervous system immunity; therefore, derangements in sialylation could be involved in neurodegeneration.ObjectivesWe evaluate the differences in serum transferrin sialylation in prodromal and early‐stage Parkinson's disease (PD), its relation to substantia nigra degeneration, and the risk of phenoconversion to manifest disease.MethodsSixty treatment‐naive PD patients; 72 polysomnography‐confirmed isolated rapid eye movement sleep behavior disorder (iRBD) patients, that is, patients with prodromal synucleinopathy; and 46 healthy volunteers aged ≥45 years and drinking ≤60 standard drinks per month were included. The proportion of serum low‐sialylated, carbohydrate‐deficient transferrin (CDT) isoforms was assessed using high‐performance liquid chromatography, and the values were adjusted for alcohol intake (CDTadj). Dopamine transporter single‐photon emission computed tomography (DaT‐SPECT) imaging was performed. In iRBD, phenoconversion risk of DaT‐SPECT and CDTadj was evaluated using Cox regression adjusted for age and sex.ResultsMedian CDTadj was lower in PD (1.1 [interquartile range: 1.0–1.3]%) compared to controls (1.2 [1.1–1.6]%) (P = 0.001). In iRBD, median CDTadj was lower in subjects with abnormal (1.1 [0.9–1.3]%) than normal (1.3 [1.2–1.6]%) DaT‐SPECT (P = 0.005). After a median 44‐month follow‐up, 20% of iRBD patients progressed to a manifest disease. Although iRBD converters and nonconverters did not significantly differ in CDTadj levels (P = 0.189), low CDTadj increased the risk of phenoconversion with hazard ratio 3.2 (P = 0.045) but did not refine the phenoconversion risk associated with abnormal DaT‐SPECT yielding hazard ratio 15.8 (P < 0.001).ConclusionsDecreased serum CDTadj is associated with substantia nigra degeneration in synucleinopathies. iRBD patients with low CDTadj are more likely to phenoconvert to manifest disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Changes in Serum N-Glycome for Risk Drinkers: A Comparison with Standard Markers for Alcohol Abuse in Men and Women.

Background and aim: Glycomic alterations serve as biomarker tools for different diseases. The present study aims to evaluate the diagnostic capability of serum N-glycosylation to identify alcohol risk drinking in comparison with standard markers. Methods: We included 1516 adult individuals (age range 18–91 years; 55.3% women), randomly selected from a general population. A total of 143 (21.0%) men and 50 (5.9%) women were classified as risk drinkers after quantification of daily alcohol consumption and the Alcohol Use Disorders Identification Test (AUDIT). Hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) was used for the quantification of 46 serum N-glycan peaks. Serum gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and red blood cell mean corpuscular volume (MCV) were measured by standard clinical laboratory methods. Results: Variations in serum N-glycome associated risk drinking were more prominent in men compared to women. A unique combination of N-glycan peaks selected by the selbal algorithm shows good discrimination between risk-drinkers and non-risk drinkers for men and women. Receiver operating characteristics (ROC) curves show accuracy for the diagnosis of risk drinking, which is comparable to that of the golden standards, GGT, MCV and CDT markers for men and women. Additionally, the inclusion of N-glycan peaks improves the diagnostic accuracy of the standard markers, although it remains relatively low, due to low sensitivity. For men, the area under the ROC curve using N-glycome data is 0.75, 0.76, and 0.77 when combined with GGT, MCV, and CDT, respectively. In women, the areas were 0.76, 0.73, and 0.73, respectively. Conclusion: Risk drinking is associated with significant variations in the serum N-glycome, which highlights its potential diagnostic utility.

Carbohydrate-deficient transferrin is a sensitive marker of alcohol consumption in fatty liver disease.

The prevalence of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated/related liver disease (ALD) with metabolic syndrome is increasing globally. Metabolic syndrome and excessive alcohol consumption synergically exacerbate liver pathologies; therefore, drinking-specific serum markers unaffected by liver injury or metabolic syndrome are essential for assessing alcohol consumption. We evaluated the ratio of carbohydrate-deficient transferrin to total transferrin (%CDT) in patients with fatty liver disease, particularly focusing on its correlation with metabolic factors (UMIN000033550). A total of 120 patients with fatty liver disease, including ALD and NAFLD, were screened for alcohol misuse using the Alcohol Use Disorders Identification Test. Associations of metabolic syndrome-related factors and hepatic steatosis/liver stiffness with drinking markers, such as %CDT, gamma-glutamyl transferase (GGT), and mean corpuscular volume (MCV), were assessed using multiple linear regression analyses. %CDT significantly increased with 3-4 drinks/day. The optimal cutoff value for identifying non- to light drinkers was 1.78% (sensitivity, 71.8%; specificity, 83.7%; and area under the receiver operating characteristic curve [AUROC], 0.851), which was significantly higher than that for GGT. The cutoff value for identifying heavy drinkers was 2.08% (sensitivity, 65.5%; specificity, 86.8%; and AUROC, 0.815). Multiple regression analysis revealed that this proportion was negatively correlated with body mass index, whereas GGT and MCV were influenced by multiple factors involved in liver injury and dyslipidemia. %CDT showed a strong correlation with alcohol consumption, independent of liver damage, steatosis/stiffness, or metabolic syndrome-related factors, indicating that it is a useful drinking marker for the accurate diagnosis of NAFLD and ALD.

Investigating the use of PEth, CDT and MCV to evaluate alcohol consumption in a cohort of homeless individuals– A comparison of different alcohol biomarkers

In a cohort including individuals with suspected high alcohol consumption, the concentrations of the indirect alcohol biomarkers carbohydrate-deficient transferrin (CDT) and mean corpuscular volume (MCV) and the direct alcohol biomarker phosphatidylethanol (PEth) were investigated. Blood alcohol concentration (BAC) was analysed as a marker for acute alcohol ingestion.In addition to questions about subjective alcohol consumption behaviour, 147 homeless persons underwent a physical examination with blood sampling. BAC, PEth, CDT and MCV were determined in the blood samples. Special focus was on the comparison of PEth and CDT for indicating excessive alcohol consumption.BAC was measured above 0.1‰ in 39 blood samples (0.1–2.5‰, median 0.75‰). PEth was detected in all of them. Overall, PEth was positive (≥10 ng/ml) in 104 samples (71%) (11–5687 ng/ml, median 650 ng/ml) with 68 (46%) being above the cut-off for excessive alcohol consumption (210 ng/ml). In 26 subjects PEth was the only positive alcohol biomarker. CDT was ≥ 1.7% in 66 cases (47%) (1.8–22.2%, median 4.4%) and ≥ 2.5% in 52 (35%) cases. MCV was elevated (≥95 fl) in 58 subjects (39%). CDT and PEth concentrations showed a significant positive correlation (spearman's correlation coefficient ρ = 0.77, p < 0.001). PEth concentrations were significantly higher in samples that were also CDT positive than solely PEth positive (p = 0.004). PEth did not indicate excessive alcohol consumption (< 210 ng/ml) in eight and two cases in which CDT was ≥ 1.7% and ≥ 2.5%, respectively. On the other hand, CDT was< 1.7% and< 2.5% in ten and 18 cases, respectively, in which PEth was above cut-off for excessive alcohol consumption. Taking the self-reports of the participants into consideration, PEth’s sensitivity for detecting excessive alcohol consumption was 100% (10 ng/ml) and 94% (210 ng/ml) and CDT’s was 88% (1.7%) and 75% (2.5%).In individuals of the investigated cohort unusually high concentrations of the alcohol consumption markers PEth and CDT were quantified, which proves the assumption of chronic excessive alcohol consumption in parts of the cohort. PEth was the marker that was positive most often and was more sensitive for excessive alcohol consumption than CDT.