Carbohydrate-deficient transferrin: a new biochemical marker for chronic excessive alcohol consumption

OBJECTIVE: To assess the usefulness of the biochemical marker 'carbohydrate deficient transferrin' (CDT) in relation to conventional markers for chronic excessive alcohol use. DESIGN: Prospective. SETTING: Addiction clinic Paschalis, Wanssum, the Netherlands. METHOD: Addicts for weaning (n = 125) were questioned at admission about their drinking habits in the last two weeks. Based on the criterion more or less than 60 g alcohol per day, the group was divided into excessive and nonexcessive alcohol users (men: 52 abusers, 51 non-abusers; women: 12 abusers, 10 non-abusers). Mean cell volume (MCV), gamma-glutamyl transpeptidase (gamma GT) and total transferrin were measured in blood collected 2 days after admission, as well as CDT by two methods (CDTect and % CDTriTIA). RESULTS: In men the CDTect test was the most sensitive: sensitivity 82% with specificity 88%. The sensitivity and specificity were 62% and 86% for gamma GT, 50% and 95% for % CDTriTIA, and 34% and 98% for MCV. The combination of a positive CDTect result and a positive gamma GT result gave a predictive value of use of alcohol > 60 g/day of 100%. The results of CDT and gamma GT were also used for a logistic regression model, giving a statistical prediction for excessive alcohol use. The subgroups of women were too small to detect statistical significant differences between tests. CONCLUSION: The CDTect test was more sensitive for the detection of chronic excessive alcohol use than the conventional markers. The combination of gamma GT and CDTect results increased the positive predictive value.     

Carbohydrate-deficient transferrin: diagnostic efficiency among patients with end-stage liver disease before and after liver transplantation

We tested the diagnostic validity of carbohydrate-deficient transferrin (CDT) as an indicator for relapse into elevated alcohol consumption among patients who were examined under follow-up treatment before (n = 147) and after (n = 102) orthotopic liver transplantation (OLT) in the outpatient-department of the University Hospital Department of Surgery in Hamburg-Eppendorf. CDT measurements were performed with two commercial kits in parallel (CDTect-RIA and CDT%-RIA). Short-term parameters of alcohol consumption (ethanol, methanol) indicated relapses into elevated alcohol consumption in 11.4% of the evaluated patients with alcoholic liver disease (ALD) before transplantation. Before OLT, median CDT values were determined to be elevated among patients with alcoholic as well as nonalcoholic end-stage liver diseases (NALD). Among patients with ALD, we found elevated CDT medians even in those who were successfully scheduled for OLT after long-term evidence of abstinence proved by biochemical short-term parameters and psychological tests. Both CDTect and CDT% assays had comparable low specificities in selected patient groups before transplantation. CDT% and CDTect were negatively correlated with the albumin level. Before the study ended, CDT was no longer implemented in the evaluation of whether an OLT should be administered. This was due to inconsistent results of CDT in ALD as well as NALD. After OLT, patients with ALD, as well as NALD, had statistically significant lower CDT medians than before OLT, which ranged within reference levels. We determined, according to CDT, elevated alcohol consumption subsequent to OLT in 4 of 13 patients with ALD who underwent transplantation during the study (median observation period: 10 months). CDT does not appear to be useful in evaluating patients before OLT. With regained specificity and high sensitivity in patients after OLT, CDT could be recommended as a standard instrument for quality control in patients with ALD after liver transplantation.     

Prognostic value of some biochemical and immunologic factors in the management of multiple myeloma

The aim of this study was to measure serum carbohydrate-deficient transferrin (CDT) in consecutive patients attending a general medical clinic with a range of alcohol intakes to determine its value in assessing such intake. Eighty-one consecutive patients (42 male, 39 female) aged 20-85 years (median = 49.5 years) attending an out-patient clinic were selected for the study. Each patient completed an alcohol diary detailing the units of alcohol consumed in the previous week, a CAGE questionnaire and an alcohol history, and underwent conventional blood tests including mean corpuscular volume (MCV), liver function tests, and gamma-glutamyl transferase (GGT). CDT was estimated using an enzyme immunoassay (CDTect, Pharmacia). The group comprised of 17 teetotallers, 28 light (<100 g/week), 23 moderate (100-400 g/week), and 13 heavy (>400 g/week) drinkers. Median serum CDT for heavy drinkers (25.5 U/l) was significantly higher than for the rest (median = 17 U/l, Kruskal-Wallis test, P = 0.01). Serum CDT correlated significantly with the CAGE score (Mann-Whitney test, P = 0.01), but poorly with alcohol diary records (r = 0.1, P = 0.4). However the correlations between GGT and diary records (r = 0.43, P = 0.001) and MCV with diary records (r = 0.5, P < 0.001) were significant. Sensitivity, specificity, and positive predictive value for elevated serum CDT were 69, 81 and 41% respectively in detecting heavy drinking. The positive predictive values for the various parameters were 43% for elevated serum GGT, 41% for raised erythrocyte MCV, and 75% for a positive score on the CAGE questionnaire. When a combination of the markers CDT, GGT, and MCV was used, elevation in two of the three markers detected heavy drinking with sensitivity of 85%, specificity of 88%, and positive predictive value of 61%. We conclude that, in out-patients with a wide range of alcohol intakes conventional markers such as serum GGT and erythrocyte MCV were more suitable than serum CDT for assessing alcohol intake. Serum CDT when used in combination with serum GGT and erythrocyte MCV was useful in detecting heavy drinking. The importance of careful history-taking including a standardized questionnaire is emphasized.     

Comparison of serum beta-hexosaminidase isoenzyme B activity with serum carbohydrate-deficient transferrin and other markers of alcohol abuse

We have compared beta-hexosaminidase (beta-Hex) activity, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values in serum from male alcoholic patients with the corresponding values in moderate and non-drinking subjects. The total beta-Hex activity was 2.5 times higher in the alcoholics than in the moderate drinkers and this increase was mainly due to a 5-fold increase in the activity of the B-isoform of the enzyme. This was expressed as a percentage of the total beta-Hex activity and called 'beta-Hex B%'. Strong correlations were found between alcohol consumption (g/ day) and beta-Hex B% (r = 0.757, P < 0.001, n = 42), alcohol consumption and CDT (r = 0.671, P < 0.001, n = 42), and beta-Hex B% and CDT (r = 0.628, P < 0.001, n = 57). Serum beta-Hex B% had a sensitivity of 94% and a specificity of 91% in detecting alcoholic drinking of > 60 g/day. As a single marker of alcoholic drinking, it was markedly more sensitive than MCV and the liver enzymes GGT, AST and ALT, and slightly more sensitive than serum CDT (94 vs 83%). At the CDT cut-off level of 20 U/l, 17% of the moderate and non-drinkers would have been classified as alcoholic drinkers and 17% of the alcoholics would have been classified as moderate drinkers. Some of these misclassifications were eliminated if the beta-Hex B% results were taken into account. We suggest that serum beta-Hex B% can be a useful and inexpensive laboratory test for alcohol abuse.     

The effect of drinking intensity and frequency on serum carbohydrate-deficient transferrin and gamma-glutamyl transferase levels in outpatient alcoholics

Whereas heavy alcohol consumption is known to elevate serum carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT) levels, the contribution of drinking pattern to these effects is not completely understood. We present data on 423 men and 146 women evaluated 1 year after treatment in a large-scale alcoholism treatment study (Project MATCH). Relationships between drinking frequency (number of days drinking), intensity (drinks per drinking day), and blood levels of CDT and GGT were analyzed by using response surface regression models and thin-plate spline-smoothing techniques. Both models indicated differences between CDT- and GGT-drinking pattern relationships in men and, also, a difference between men and women in CDT drinking-pattern relationships. For men, CDT levels appeared to respond primarily to frequency of drinking, whereas GGT was influenced primarily by drinking intensity. For women, both CDT and GGT were influenced more by drinks per drinking day (intensity) than by number of days drinking (frequency). The data confirm both the independent nature of these biological markers of alcohol consumption and gender differences in alcohol-induced CDT response reported previously.     

Screening trauma patients for alcoholism according to NIAAA guidelines with alcohol use disorders identification test questions

Drinking pattern criteria (drinking frequency and number of drinks per occasion) issued by the National Institute on Alcohol and Abuse and Alcoholism (NIAAA) to screen primary practice patients for alcohol problems were evaluated in 1216 injured patients treated in a regional trauma center. Vehicular crash victims predominated (50.2%, of whom 64.5% were drivers), followed by victims of violence (31.2%) and nonviolent-injury victims (18.5%). Alcohol Use Disorders Identification Test (AUDIT) questions #1 (drinking frequency) and #2 (drinks/day) were used to assess the patients for current alcohol dependence (CAD). AUDIT responses roughly approximating NIAAA guidelines (high threshold: drinks > or = 4 times/week, > or = 5 drinks/day) and those indicating less drinking (low threshold: drinks > or = 2-3 times/ week, > or = 3 drinks/day) were chosen. Comparisons were made relative to sensitivity and specificity of responses in detecting CAD. When low threshold responses were used for either question, sensitivity to detect CAD increased overall (#1 from 0.53 to 0.80, #2 from 0.62 to 0.88) as well as among the subgroups of patients, whereas specificity remained high or at acceptable levels overall (#1 from 0.95 to 0.82, #2 from 0.92 to 0.71) and among the subgroups of patients. Study findings suggest that, among injured drivers and other groups of trauma center patients, lesser amounts of drinking should be used as screening criteria for CAD than are used for the general population.     

Relations between dietary restraint and patterns of alcohol use in young adult women.

The present study examined relations between dietary restraint and self-reported patterns of alcohol use, including separate assessment of quantity and frequency of alcohol consumption. One hundred seventy-six female university undergraduates completed the Restraint Scale (RS) and measures of their usual quantity and frequency of alcohol consumption over the past year. Quantity and frequency self-reports were scored separately and were also used to calculate 3 additional drinking variables: a composite weekly alcohol consumption score (drinks per week), a binge drinking categorical variable (where participants were classified as either binge drinkers or non-binge drinkers), and a yearly excessive drinking score (number of times in the past year that each participant consumed at least 4 alcoholic beverages per drinking occasion). RS scores were significantly positively correlated with scores on 4 of the 5 drinking behavior measures (i.e., quantity, drinks per week, binge drinking, and yearly excessive drinking, but not frequency). Thus, chronic dieting appears to be related to a relatively heavy drinking pattern that can be characterized as potentially risky, due to its established associations with adverse health and social consequences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transferrin isoform distribution: gender and alcohol consumption

Transferrin (Tf) has different isoforms based on the degree of sialylation of its two N-linked oligosaccharide chains. The least sialylated isoforms of Tf; with 0 (asialo Tf), 1 (monosialo Tf), and 2 (disialo Tf) sialic acids are referred to as carbohydrate-deficient transferrin (CDT). CDT has been reported to be a specific and sensitive marker for the detection and monitoring of alcohol abuse. However, the possible differences between the three CDT isoforms in males and females relative to alcohol consumption has not been known. The present study included 82 males (M) and 43 females (F) with well documented drinking habits. The Tf isoforms were separated by FPLC and measured by RIA in the collected fractions, as well as by a commercially available method (CDTect RIA). The results were expressed as relative values and absolute values. Female low consumers compared to male low consumers had higher levels of asialo Tf (p < 0.01) and monosialo Tf (p < 0.01), but not of disialo Tf or sum of asialo, monosialo, and disialo Tf. Male high consumers and chronic consumers compared to male low consumers had 53% and 219% higher levels of asialo Tf, 4% and 28% higher monosialo Tf, 57% and 148% higher disialo Tf, and 48% and 134% higher sum of CDT isoforms, respectively. The corresponding increases in females were for asialo Tf 68% and 249%, for monosialo Tf 36% and 58%, for disialo Tf 54% and 225%, and for sum of CDT isoforms 52% and 192%, respectively. For both genders, total Tf, trisialo Tf, and the levels of more sialylated transferrin isoforms were constant when comparing the consumption groups. Results expressed as relative values and absolute values were in good agreement. In conclusion, the present study indicates that alcohol consumption strongly increases the levels of asialo Tf and disialo Tf and slightly increases the level of monosialo Tf. However, women had higher asialo Tf and monosialo Tf levels than men. Alcohol consumption does not increase trisialo or more sialyated Tf subfractions. Expressing the CDT results as absolute or relative values made no obvious difference in diagnostic efficiency.     

Usefulness of carbohydrate-deficient transferrin in alcohol-elated problems

BACKGROUND: Carbohydrate-Deficient Transferrin (CDT) is a new marker for excessive alcohol drinking. It appears to be useful to detect alcoholism, harmful consumption and relapse. It have been introduced in our country recently. METHOD: Recent studies about utility of CDT have been reviewed. RESULTS: Sensitivity and specificity of CDT level as a marker of alcoholism were 72-97% and 31-81% respectively. As a marker of harmful consumption its sensitivity was 15-69% and its sensitivity was higher than 82%. CDT was demonstrated to be a effective maker for evaluating alcoholic abstinence in alcoholic patients. CONCLUSIONS: CDT determinations have a high specificity for screening heavy drinking in different settings. Problems related to its sensitivity are discussed.     

Does carbohydrate-deficient transferrin predict the severity of alcohol withdrawal syndrome?

Alcohol withdrawal often causes severe complications. However, many addicts deny any abuse. Thus, the diagnosis of alcohol abuse frequently becomes difficult. Laboratory parameters are often used to support the diagnosis of alcohol abuse. Furthermore, laboratory parameters should facilitate the prediction of the severity of alcohol withdrawal syndrome (AWS). The most promising laboratory parameter indicating a recent elevated alcohol consumption is carbohydrate-deficient transferrin (CDT). The aim of this study was to examine whether the measurement of CDT at admission can indicate a higher risk for the development of a complicated AWS. The severity of AWS was assessed by the AWS scale, consisting of two subscales for somatic and mental symptoms. CDT was measured by different methods (radioimmunoassay and HPLC). The radioimmunoassay for CDT (CDTect) yielded the best prediction. Our results showed a weak correlation between CDTect and the severity of AWS. However, there were great gender differences. In men, CDTect had the highest positive predictive value for a severe AWS (86.7%), whereas in women mean corpuscular volume was the best predictor (77.8%). However, the sensitivity of CDTect in men (25.5%), as well as mean corpuscular volume in females (29.2%), was too low for a screening test in a general hospital.     

Screening for problem drinking: comparison of CAGE and AUDIT. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test

OBJECTIVE: To compare self-administered versions of three questionnaires for detecting heavy and problem drinking: the CAGE, the Alcohol Use Disorders Identification Test (AUDIT), and an augmented version of the CAGE. DESIGN: Cross-sectional surveys. SETTING: Three Department of Veterans Affairs general medical clinics. PATIENTS: Random sample of consenting male outpatients who consumed at least 5 drinks over the past year ("drinkers"). Heavy drinkers were oversampled. MEASUREMENTS: An augmented version of the CAGE was included in a questionnaire mailed to all patients. The AUDIT was subsequently mailed to "drinkers." Comparison standards, based on the tri-level World Health Organization alcohol consumption interview and the Diagnostic Interview Schedule, included heavy drinking (> 14 drinks per week typically or > or = 5 drinks per day at least monthly) and active DSM-IIIR alcohol abuse or dependence (positive diagnosis and at least one alcohol-related symptom in the past year). Areas under receiver operating characteristic curves (AUROCs) were used to compare screening questionnaires. MAIN RESULTS: Of 393 eligible patients, 261 (66%) returned the AUDIT and completed interviews. For detection of active alcohol abuse or dependence, the CAGE augmented with three more questions (AUROC 0.871) performed better than either the CAGE alone or AUDIT (AUROCs 0.820 and 0.777, respectively). For identification of heavy-drinking patients, however, the AUDIT performed best (AUROC 0.870). To identify both heavy drinking and active alcohol abuse or dependence, the augmented CAGE and AUDIT both performed well, but the AUDIT was superior (AUROC 0.861). CONCLUSIONS: For identification of patients with heavy drinking or active alcohol abuse or dependence, the self-administered AUDIT was superior to the CAGE in this population.     

Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy

Although studies generally support a positive association between alcohol consumption and lung-cancer risk, the relationship between specific alcoholic beverages and lung-cancer risk has been inconsistent. We examined recent and past alcoholic beverage intake among 261 incident cases and 615 population controls enrolled in a lung-cancer case-control study of African Americans and Caucasians in Los Angeles County between 1991 and 1994. An in-person interview elicited information about past alcohol intake from ages 30 to 40 y, smoking, other lung-cancer risk factors, as well as recent intake of alcohol, and recent dietary intake. An association was observed between recent hard-liquor consumption and lung-cancer risk. The odds ratio (OR) for 1 or more drinks (1.5 oz or 0.051 mL) per day of hard liquor compared with infrequent liquor drinking (0-3 drinks per month), adjusted for smoking, the matching factors, saturated fat and other alcoholic beverages was 1.87 [95% confidence interval (CI) = 1.02-3.42]. No appreciable association was observed for total alcohol, whereas small inverse associations were observed for beer and wine, although confidence intervals were wide. An elevated lung-cancer risk was also observed for past liquor consumption (between ages 30 and 40 y). The adjusted OR for 1 or more drinks per day of liquor compared with infrequent drinkers was 1.83 (95% CI = 1. 06-3.15). Confounding of the association between alcohol and lung cancer by smoking was apparent. Although we devoted considerable efforts to adjusting for smoking in our analyses, residual confounding is still possible because smoking and alcohol are closely associated. In addition, case-control studies including this study should be viewed with caution because of possible selection bias. An increased risk of lung cancer might occur with moderate drinking of hard liquor but confirmation is required in larger studies.     

Alcohol and breast cancer in the Swiss Canton of Vaud

The relationship between alcoholic beverage drinking and the risk of breast cancer was considered using data from a case-control study of breast cancer conducted between 1990 and 1995 in the Swiss Canton of Vaud on 230 incident cases of breast cancer below age 75 years, linked with the Vaud Cancer Registry, and 507 controls admitted to the same network of hospitals for a wide spectrum of acute, non-neoplastic, non-hormone-related conditions. Overall, 70.4% of cases versus 57.4% of controls consumed alcohol, corresponding to a multivariate odds ratio (OR) of 1.5 (95% confidence interval (CI): 1.1-2.2). The ORs were 1.3 for < 1 drink per day, 1.8 for 1 to 2, 1.5 for 2 to 4, and 2.7 for > 4 drinks per day, and the trend in risk with dose was significant. The association was consistent for wine (OR = 2.0), beer (OR = 2.6) and spirits (OR = 2.0) and was apparently stronger in premenopausal women, whereas no noticeable interaction was observed with any of the hormonal or reproductive risk factors for breast cancer. The alcohol-related risk was unrelated to duration; the OR was 1.8 for women who started drinking below the age of 30 years and 1.4 for those starting at the age of > or = 30 years. Thus, the present study confirms that alcohol is a correlate of breast cancer risk in this European population, where alcohol drinking among women is common and relatively high. Assuming that this association reflects causality, in terms of attributable risk, alcohol could explain 25% (8-42%) of breast cancer cases.     

Evaluation of acetaldehyde-modified hemoglobin and other markers of chronic heavy alcohol use: effects of gender and hemoglobin concentration

The present study examined whether measurement of hemoglobin-acetaldehyde (HbA1-AcH) using an improved methodology may be useful as a biological marker of alcohol abuse. Red blood cell hemolysates of 182 patients consecutively admitted to the drug and alcohol treatment unit of our institution were analyzed for HbA1-AcH concentration using cation exchange HPLC. Mean HbA1-AcH of those who claimed to drink > or = 6 drinks/day [mean = 0.055 (% total hemoglobin), SD = 0.051] was significantly higher than the mean of those who drank < 6 drinks/day (mean = 0.026, SD = 0.0174). The greatest sum of sensitivity (67%) and specificity (77%) came with a cut-score of 0.030 area% of total hemoglobin. A cut-score of 0.080 produced a 100% specificity, but lowered the sensitivity to 20%. The Pearson product moment correlation (r) between HbA1-AcH and reported drinks per day was r = 0.30 (p < 0.001). There was no significant difference in the association of HbA1-AcH and reported drinking between males and females, and the small difference observed was shown to be entirely associated with differences in hemoglobin levels between the sexes. Cocaine use did not significantly alter the correlation between reported drinking and HbA1-AcH levels. Hemoglobin levels were shown to have a significant correlation with HbA1-AcH independent of drinking. HbA1-AcH was shown to have a better sensitivity and specificity than gamma-glutamyltransferase, ALT, AST, or mean corpuscular volume in this population. The results suggest that HbA1-AcH may be a useful marker to help detect alcohol abuse, especially in populations where other markers have been shown to fail.     

Association of biochemical and subjective indicators of drinking habits with performance on different neurobehavioral tasks

The present paper outlines the association of biochemical and subjective indicators of alcohol consumption. Due to its relevance as a potential confounding variable in occupational neurotoxicology, both sources of information about drinking habits were related to neurobehavioral test performance. A sample of 308 rotogravure printers and control subjects from a cross-sectional longitudinal study in various German printing plants was studied. Duration of employment was 4 months to 44 years (mean = 14.9, sd = 9.67). Mean age was 38.4 years (range 21 - 60). From venous blood samples three parameters considered to be sensitive for increased consumption of alcohol were used. They were carbohydrate-deficient transferrin (CDT), gamma glutamyl transferase (GGT), and mean cell volume (MCV). During the medical interview subjects with any chronic liver disease were identified and excluded from data analysis. Additionally, information about weekly consumption of alcohol was assessed and transformed to grams per day (g/d) values. Neurobehavioral testing included simple reaction time (SPES version), switching attention, symbol digit substitution, and digit span (EURONEST version). Additionally, a questionnaire of neurotoxic complaints was administrated. Other covariates, i.e. verbal ability, history of solvent exposure, and age were controlled. GGT and CDT were elevated in 10.5% and 6.6% of the population. 3.5% of the subjects reported daily consumption higher than 60 gram. There were positive correlations of CDT and GGT with the subjective indicator of drinking habits. The magnitude of these relationships were low, but the associations were significant. MCV was not correlated with subjective reports of drinking habits, but it showed convergent correlations with CDT and GGT. Comparison of these two parameters with performance on neurobehavioral tasks yielded only one negative association, i.e. between the memory-loaded tasks factor and GGT. CDT and subjective estimation of alcohol consumption were not related to any cognitive function tested in this study. Especially, the digits-backward task was negatively correlated with increased GGT.     

Utility of biological markers during outpatient treatment of alcohol-dependent subjects: carbohydrate-deficient transferrin responds to moderate changes in alcohol consumption

A group of 25 alcohol-dependent subjects in outpatient treatment were monitored for a period of 4 weeks. They were weekly interviewed for their alcohol consumption and their serum levels of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) were analyzed. The majority of the patients reported an excessive and fairly constant alcohol intake during the observation period. When selecting those patients that reported periods of 1 or 2 weeks with moderate changes in alcohol consumption, corresponding changes in CDT were demonstrated. Thus, of 14 patients reporting an increased alcohol consumption for 2 weeks (mean values increased from 57 to 101 g/day), 11 showed an increase in CDT at the end of the period. The mean CDT value of all 14 increased from 5.5 to 6.7% (p < 0.05). Slight, but not significant, increases were noted in GT, indicating that CDT is more sensitive than GT in detecting increased alcohol consumption. Furthermore, of 17 patients that reported decreased alcohol consumption for one or several weeks, 14 showed decreased CDT and GT values. The mean values of all 17 were reduced from 5.1% to 4.5% (CDT) and from 126 units/liter to 97 units/liter (GT) (p < 0.05 for both parameters). The results indicate that CDT responds to moderate changes in alcohol consumption in alcohol-dependent patients and may thus be useful as a corrective tool to self-reports of alcohol consumption during outpatient treatments.     

Evaluation of the efficacy of naltrexone in alcoholism by the determination of serum carbohydrate-deficient transferrin

Naltrexone (NTX) has been shown to be a useful drug for the treatment of alcohol dependence (AD). Carbohydrate-deficient transferrin (CDT) in serum is a new biologic marker of alcohol abuse. To evaluate the efficacy of NTX (50 mg/d) in AD, a group of 20 alcoholics with CDT > 20 U/l was studied using monthly laboratory tests (CDT, ESR, AST, ALT, GGT) and specific psychological testing (CAGE). After the second month statistically significant differences in CDT levels were found. By the end of the study, 13 patients (responders) had normalized their CDT levels. There was no correlation between CDT values and the other laboratory markers. The difference in routine laboratory markers between responders and non responders was not significant. NTX was well tolerated by all the patients and significant alcohol abstinence was achieved. CDT was demonstrated to be a effective marker for the evaluation of alcoholic abstinence during treatment with NTX. Superior results were obtained in comparison with the routine customary markers for AD.     

Long-acting injectable bromocriptine does not reduce relapse in alcoholics

Dopamine is one of several neurotransmitters that may mediate alcohol intake and dependence. A randomized, double-blind, placebo-controlled international, multicentre study was conducted to assess the effects of a long-acting injectable preparation of bromocriptine, a dopamine agonist, (Parlodel-LAR) in reducing relapse in 366 moderately/severely dependent alcoholics (DSM-III-R), drinking approximately 200 g alcohol (14.5 standard drinks) per day. After detoxification they were randomized to receive six monthly injections of bromocriptine 25 mg (n = 120), bromocriptine 50 mg (n = 124), placebo (n = 122). Brief psychosocial treatment was allowed. At 6 months there were no significant differences between treatment groups in rates of relapse to any drinking or to drinking > or = 5 days per month and > or = 3 drinks per day. Pre-treatment alcohol intake did not determine response. Efficacy ratings by subjects and investigators and adverse events, reported by 51% of subjects, did not differ between treatments. The results of this large study, in which compliance was enhanced by Parlodel-LAR, do not indicate that bromocriptine is efficacious in the maintenance of abstinence or reduced drinking. Possible reasons for the discrepancy between these conclusions and those of some previous clinical trials, in which bromocriptine was reported to reduce symptoms of alcohol withdrawal and dependence, are discussed.     

Smoking, obesity, and hypertension alter the dose-response curve and test sensitivity of carbohydrate-deficient transferrin as a marker of alcohol intake

Serum carbohydrate-deficient transferrin (CDT) is a specific and comparatively sensitive marker of excessive alcohol use; however, reports of its sensitivity vary according to the population or patient groups studied and their average alcohol intake. We have characterized the dose-response curve between alcohol intake and CDT concentrations in a study of 1400 men and women from a community-based twin registry. Our results show that mean CDT increases with increasing reported alcohol consumption even within the range of alcohol use considered to be nonhazardous. We found significant effects of sex, age, smoking, previous alcohol dependence, body mass index, and diastolic hypertension on the alcohol-CDT dose-response curve. These variables either affect test sensitivity or require adjustment of reference intervals. The results also provide insight into the physiological and biochemical factors that affect CDT concentration.     

Carbohydrate-deficient transferrin is associated with insulin sensitivity in hypertensive men

An elevated concentration of carbohydrate-deficient transferrin in serum (CDT) has been reported to indicate excessive ethanol consumption. However, in hypertensive men, we found low values for diagnostic sensitivity and specificity. Furthermore, in the individuals with high CDT values, the concentrations of serum triglycerides and blood glucose were low rather than high, indicating that factors related to insulin/glucose metabolism may be operative. The current study addresses this issue by examining 48 patients with treated hypertension and at least 1 of following: hypercholesterolemia, history of smoking, and diabetes mellitus. We determined serum CDT, fasting plasma insulin, and glucose disposal rate during hyperinsulinemic euglycemic clamp. Seven patients had elevated CDT concentrations. This group of patients had higher glucose disposal rates than the others (mean difference, 19 mumol/min.kg lean body mass; 95% confidence interval, 5-33 mumol/min.kg lean body mass; P = 0.0096), but did not differ in body mass index or alcohol intake. Serum CDT correlated positively with glucose disposal rate (r = 0.55; P = 0.0004) and negatively with fasting plasma insulin (r = -0.43; P = 0.0039). These relationships remained after exclusion of 8 patients with diabetes mellitus and adjustment for potentially confounding factors. We conclude that the serum CDT concentrations in our patients were associated with insulin sensitivity.