CARBOHYDRATE-DEFICIENT TRANSFERRIN AS A MARKER OF ALCOHOL INTAKE: A STUDY WITH HEALTHY SUBJECTS

Alcohol & Alcoholism Vol. 31, No. 3, pp. 265-271, 1996 CARBOHYDRATE-DEFICIENT TRANSFERRIN AS A MARKER OF ALCOHOL INTAKE: A STUDY WITH HEALTHY SUBJECTS OTTO M. LESCH*, HENRIETTE WALTER, JOZSEF ANTAL 1 , DAG-ERIK HEGGLI2, ATTILA KOVACZ 1 , ADELHEID LEITNER, ALEXANDER NEUMEISTER, IMRE STUMPF 1 , ERLING SUNDREHAGEN 2 and SIEGFRIED KASPER Universitatsklinik fur Psychiatrie, Wahringer Giirtel 18-20, Wien, Austria, 'Alkoholzentrum Pomaz-Dolina, Pomaz, Hungary and 2Axis Biochemicals AS, Helgesensgate 30, P.O. Box 2123 Grunerlokka, 0505 Oslo, Norway (Received 21 October 1994; in revised form 25 April 1995; accepted 30 May 1995) Abstract — This paper reports the results of a 3-week drinking experiment in 51 healthy male subjects, examining the value of %CDT (carbohydrate-deficient transferrin) in the context of different levels of alcohol intake. All healthy persons were urine-tested drug-free and underwent daily breath alcohol tests for the 7 days preceding, and during the whole 3 weeks of, the experiment. Subjects were divided into five groups, consuming different amounts of alcohol daily over a 3-h period in the presence of the investigators. The five groups consisted of 10, 9,10, 16 and 6 subjects respectively and consumed a daily dose of ethanol of 20, 40, 60, 80 and 80 g respectively for 3 weeks. No significant changes in %CDT were detected in most subjects, even in the 80 g alcohol-consuming groups. The results suggest that CDT is not sensitive for the detection of short-term heavy drinking by healthy subjects. INTRODUCTION Normal serum transferrin has several polysaccharide side-chains, a deficiency in which appears to be induced by alcohol consumption (Stibler et al, 1979, 1986). The resulting carbohydrate-deficient transferrin (CDT) was introduced as a 'state marker' for chronic alcohol abuse by Stibler and Borg (1988) and this was followed by many investigations of this marker in different clinical situations (for references, see the preceding two papers by Lesch et al., 1996a,b). In these two papers, we investigated the value of CDT as a marker of alcohol consumption in a general hospital population and in alcohol-dependent subjects respectively. In their discussion of state markers, Rosman and Lieber (1992) suggested that these could be further subdivided into two groups of markers, 'screening markers' for chronic alcohol consumption and 'relapse markers' for acute alcohol consumption. At present, it is not certain if CDT can serve both as a screening and a relapse marker (see also Allen et al, 1994). Borg et al. (1992) and Borg (1993) stated that daily consumption of at least 60 g of 'Author to whom correspondence should be addressed. alcohol for 10 days or more increases CDT values (measured in absolute units), implying that CDT could serve as a relapse marker. In the preceding paper (Lesch et al., 1996£>), we found, however, that %CDT does not correlate with blood ethanol concentration at the time of admission nor with pattern and duration of alcohol consumption during the 2 months preceding detoxification. In the present paper, we have investigated the possible suitability of CDT as a relapse marker, by measuring its level following a controlled drinking experiment in healthy volunteers. SUBJECTS AND METHODS Subjects and design Fifty-one male volunteers participated in the study. Initially, we had planned to investigate 45 subjects divided into four groups. For reasons given below, we included a fifth group of six subjects. The participants and their first degree relatives, as well as their other family members, had no history of alcoholism, other addictions or psychiatric disease. All participants were only occasional social drinkers and had normal gammaglutamyl transferase (GGT) values. Table 1 lists the subjects' details of numbers per group, mean age and range, mean body weight and range and 265 © 1996 Medical Council on Alcoholism 0. M. LESCH et al. 266 Table 1. Details of subjects groups Group 1 Parameter Number Age (years) Mean Range Body wt (kg) Mean Range Daily alcohol dose (g) 2 10 9 23.8 21-26 72.0 70-115 20 4 3 5 10 16 6 28.5 20-50 31.8 26-41 32.5 20-43 32.5 22-48 70.3 70-90 40 76.3 60-113 60 82.7 71-133 80 87.3 65-112 80 daily alcohol dose consumed over 3 h for the 3 week experimental period. Because we could not demonstrate changes in %CDT values, even in subjects of group 4, who consumed the largest dose of ethanol (80 g daily for 3 weeks), a fifth group was added to the study, consisting of six subjects all of whom were given the above dose of ethanol as in group 4, and whose alcohol intake during the experiment was followed hourly with a breathalyser. Determination of CDT CDT was measured in most experiments as a percentage. However, because the observation by Borg et al. (1992) and Borg (1993) that CDT is CDT Fig. 1. Correlation between the %CDT axis and the Pharmacia absolute CDT assay procedures (n = 42). CDT(%) and CDT (U/l) correlation. The result of a Pearson-Product-Momentum-Correlation = 0.7922. elevated after 10 days of daily consumption of at least 60 g of ethanol was made in absolute (mg/1), rather than relative (%) units of CDT, a comparison of our Axis procedure (see below) with that used by the group of Borg (Pharmacia, 1990) was made in the present work, and has demonstrated a very good correlation (Fig. 1). For measurement of %CDT, serum was frozen at -30 °C and was sent to Axis Biochemicals Laboratories in Norway. The period between venesection and analysis of samples did not exceed 3 months. The principle of the Axis %CDT test is briefly as follows: labelled 125 Iantibody fragments are allowed to react with an excess of transferrin in the serum sample. After a 10 min incubation, the mixture is passed through a single use ion-exchange column, followed by two elution steps. During the first elution step, nonspecific bound labelled antibody is separated, whereas in the second elution step low sialic acid transferrin is collected in the eluate. The radioactivity of the second-step eluate is interpolated on a calibration curve, yielding the %CDT value of the serum sample. The cut-off point for a pathological result was fixed at >2.4% CDT. The %CDT was determined in blood samples taken before and on days 3, 7,14 and 21 after the start of experimental alcohol consumption period. Other measurements Sera of the subjects were also analysed for gamma-glutamyl transferase, aspartate aminotransferase and alanine aminotransferase activities using standard clinical laboratory techniques. CDT AS A MARKER OF ALCOHOL CONSUMPTION 267 Table 2. %CDT in subjects drinking 20 g of alcohol daily (group 1) %CDT Subject Day 0 Day 3 Day 7 Day 14 Day 21 1 2 3 4 5 6 7 8 9 10 0.3 0.7 0.9 0.5 0.6 0.0 0.9 0.6 0.6 0.0 0.3 0.9 1.1 0.3 0.5 0.2 0.3 0.5 0.7 0.0 0.1 0.9 1.1 0.4 0.7 0.2 0.5 0.5 0.7 0.0 0.3 0.8 0.9 0.5 0.4 0.5 0.7 0.5 1.0 0.0 0.2 0.7 0.9 0.4 0.8 0.8 0.6 0.6 0.7 0.1 Day 0 = before drinking. Table 3 (...truncated)