ALCOHOL DEPENDENCE: IS CARBOHYDRATE-DEFICIENT TRANSFERRIN A MARKER FOR ALCOHOL INTAKE?

Alcohol & Alcoholism Vol. 31, No. 3, pp. 257-264, 1996 ALCOHOL DEPENDENCE: IS CARBOHYDRATE-DEFICIENT TRANSFERRIN A MARKER FOR ALCOHOL INTAKE? OTTO M. LESCH*, HENRIETTE WALTER, JOZSEF ANTAL 2 , ROLF D. KANITZ3, ATTILA KOVACZ 2 , ADELHEID LEITNER, BRIGITTE MARX1, ALEXANDER NEUMEISTER, MONIKA SALETU 1 , BRIGITTE SEMLER, IMRE STUMPF 2 and RUDOLF MADER 1 Universitatsklinik fur Psychiatrie, Wahringer Gurtel 18-20, 1090 Vienna, 'Anton Proksch Institut, Kalksburg, Mackgasse 7-9, 1237 Vienna, Austria, 2Alkoholzentrum Pomaz-Dolina, Pomaz, Hungary and 3Universitatsklinik fur Psychiatrie, Ratzeburgerallee 160, 2400 Lubeck, Germany {Received 21 October 1994; in revised form 25 April 1995; accepted 30 May 1995) Abstract — We investigated %CDT (carbohydrate-deficient transferrin) in 92 ethanol-intoxicated alcohol-dependent patients after consecutive admission to hospital and followed them for 28 days under controlled conditions. At admission, 63% (58 patients) showed elevated CDT (>2.5%) and 34 patients (37%) had normal CDT levels (<2.5%). No correlation of the %CDT values to alcohol-related disabilities, severity of the withdrawal syndrome, alcohol-drinking pattern before admission, or several other factors was found. The sensitivity of GGT (y-glutamyl transferase) was 58% for the same group of patients. Levels of %CDT decreased during the 28 days following abstinence, whereby we could separate four statistically different groups of 'CDT decrease'. In two of these groups, comprising most of the cases studied, normal %CDT levels were reached after 14 days of abstinence. Those patients with %CDT levels exceeding the upper normal level after 14 days of sobriety, showed a decrease during the following 14 days to levels of 2.55-2.61%. INTRODUCTION The iron-transporting protein transferrin consists of a polypeptide backbone to which several polysaccharide chains are linked. These polysaccharide chains are desialylated by alcohol consumption. This desialylated transferrin, carbohydrate-deficient transferrin (CDT), was introduced as a biochemical 'state marker' of heavy alcohol consumption by Stibler et al. (1979). Since then, many investigations of its usefulness as a marker of heavy alcohol consumption have been reported (see, e.g., Stibler and Borg, 1986; 1988; Stibler et al, 1986; Behrens et al, 1988; KwohGain et al, 1990; Nystrom et al, 1992; Rosman and Lieber, 1992; Borg, 1993; Bell et al, 1993; Allen et al, 1994; Lof et al, 1994). Although these studies showed clearly that CDT generally reflects high alcohol intake, a number of questions 'Author to whom correspondence should be addressed. remain unanswered; in particular, the precise relationships between levels of CDT and extent of alcohol intake, pattern and duration of consumption, and decline in CDT following abstinence. These aspects are of particular importance in assessing the suitability of CDT as a 'relapse', as well as 'state' marker of alcohol consumption (Schmidt and Rommelspacher, 1990; Rosman and Lieber, 1992). In the preceding paper (Lesch et al, 1996a) we have demonstrated the usefulness of CDT as a marker of high alcohol consumption irrespective of changes in total transferrin levels or the presence of liver disease, and its superiority to yglutamyl transferase (GGT) in a general hospital population. In the present paper, we report the results of experiments in which we investigated the value of CDT in alcohol-dependent patients in relation to: (1) GGT and blood ethanol concentration at admission; (2) extent and pattern of alcohol consumption before admission; (3) level and pattern of decline in CDT with duration of 257 1996 Medical Council on Alcoholism O. M. LESCH et al. 258 abstinence; (4) severity of withdrawal and other alcohol-related disabilities. PATIENTS AND METHODS Patients and design Ninety-two male alcohol-dependent patients were investigated at the time of admission for detoxification and during a 4-week follow-up period. We only included patients who were diagnosed according to DSM-III-R as having 'Alcohol dependence, severe' (at least seven symptoms present) with no remission. Additionally, we applied a semi-structured questionnaire related to the typology of Lesch (1985), in order to classify the drinking pattern as well as the severity of somatic, psychic and social deterioration. The drinking pattern of the patients before admission was established with respect to amount, frequency and drinking rhythm. Sobriety control was checked daily by a breathalyser test. Correlations We attempted possible correlations between different patient-related factors and the %CDT values. For this purpose, the latter values were divided into the following categories: <2.5%, 2.5-3.5%, 3.6-4.5%, 4.6-5.5%, 5.6-10.5% and > 10.5%, to enable more precise correlations to be made. For statistical evaluation, we applied the Pearson x2-test. The patient-related factors considered in these correlations were the following: (1) Diseases: liver diseases, severe chronic diseases (including psychiatric diseases) in the first and second degree relatives, disorders of the perinatal period, polyneuropathy, cardiac, pancreatic or gastrointestinal disease, epilepsy, cerebral dysfunctions, withdrawal syndromes, tolerance reduction, loss of control and loss of memory. (2) Drinking pattern: history, type of beverage preferred (beer, wine, strong drinks, mixtures), alcohol consumption before the age of 14 (two patients had regular alcohol consumption before the age of 8, and both had %CDT values of ~ 10.6%) and accidents under the influence of alcohol. (3) Psychological factors and life events: behavioural disorders during childhood, brain trauma (e.g. due to accidents), self-destructive or other aggressive behaviour, sleep disorders, sexual dysfunction, depression and suicide attempts. (4) Typology: according to Jellinek (1946) and Lesch (1985). (5) General factors: age, social status, profession, age of mother/father at the patient's birth, alcoholism in first or second degree relatives, order of nascence among siblings and tobacco consumption. Laboratory tests Upon admission, in addition to the severity of alcohol intoxication, levels of the laboratory markers GGT, ALAT, ASAT, MCV, CDT, total transferrin and blood counts were determined. Both relative (%) and absolute (U/l) values of CDT were measured. For measurement of %CDT, U/l CDT and total transferrin, serum was frozen to - 3 0 °C before analysis at the laboratories of Axis Biochemicals in Norway, in accordance with the procedure outlined in the preceding paper (Lesch et al, 1996a). The normal range was set at values of 0-2.4% in accordance with Behrens et al. (1988), Kwoh-Gain et al. (1990) and Axis's own experience. The %CDT was measured at admission (day 0) and on days 3, 7, 14, 21 and 28 after the start of abstinence (detoxification), and the numbers of patients tested on these days were 92, 91, 89, 90, 66 and 67 respectively. The smaller RESULTS numbers at the later (...truncated)