Elevated Carbohydrate-deficient Transferrin Levels Research Articles

It Is Not Always Alcohol Abuse--A Transferrin Variant Impairing the CDT Test.

Elevated Carbohydrate-deficient transferrin (CDT) levels are used as a biomarker in order to screen for chronic alcohol abuse. Transferrin (Tf) variants can impair methods to measure elevated CDT levels such as high-performance liquid chromatography (HPLC). We present a Tf variant affecting the second glycosylation site of Tf and the complications it causes in diagnosing alcoholism. A blood sample from a patient with suspected alcohol abuse was analyzed with HPLC, isoelectric focusing, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), immunoprecipitation and SDS-Page. Sanger sequencing of Tf was performed to detect Tf mutations. HPLC, SDS-Page and IEF showed a distinctly increased disialo-Tf fraction while the tetrasialo-Tf fraction was decreased, ESI-TOF-MS confirmed these results. Sanger sequencing revealed the Tf mutation c.1889 A>C, deleting a Tf glycosylations site and thereby causing elevated disialo-Tf levels. Transferrin mutations can severely impair the diagnostics of chronic alcohol abuse by causing false positive results. This has to be considered when CDT screening is used to detect alcoholism.

Reflex Testing for Carbohydrate-Deficient Transferrin (CDT) in Insurance Applicants with Elevated High Density Lipoprotein Cholesterol (HDL)

Objectives .- Ascertain the utility of testing carbohydrate deficient transferrin (CDT) levels in insurance applicants with elevated high density lipoprotein cholesterol (HDL) levels. Background .- Chronic alcoholism is not uncommon and is a risk factor for health and longevity and thus of interest to providers of insurance. A number of tests serve as markers of alcohol use, eg, blood alcohol level, elevated liver enzymes, ethyl glucuronide in urine, whole blood associated aldehyde (WBAA), macrocytosis, elevated HDL, elevated CDT and others. WBAA and CDT are usually only done, if some other screening test suggests alcohol use. HDL testing is routinely done for assessing cardiac risk, however, chronic alcohol intake tends to raise HDL and some insurance providers reflex to CDT testing when HDL is elevated. Methods .- A number of the clients of Heritage Labs Inc. have rules in place to test for CDT levels in specimens showing elevated HDL levels. The commonest HDL level that serves as the trigger for reflex testing for CDT is 80mg/dL. The results of this practice were analyzed to assess the utility of reflex testing for CDT to identify chronic alcohol abusers among the applicants. Results .- In examining the results of CDT levels done as a reflex test due to elevated HDL levels, about 2% of the applicants, 0.7% of women and 3% of men, tested positive for elevated CDT levels. Conclusions .- The incidence of elevated CDT levels is high enough to warrant routinely testing for this analyte in applicants, especially men, with high HDL levels.

Transferrin immunoextraction for determination of carbohydrate-deficient transferrin in human serum by capillary zone electrophoresis

CZE-based assays for carbohydrate-deficient transferrin (CDT) in which serum is mixed with an Fe(III) ion-containing solution prior to analysis are effective approaches for the determination of CDT in patient samples. Sera of patients with progressed diseases, however, are prone to interferences comigrating with transferrin (Tf) that prevent the proper determination of CDT by CZE in these samples. The need of a simple and economic approach to immunoextract Tf from human serum prompted us to investigate the use of a laboratory-made anti-Tf spin column containing polyclonal rabbit anti-human Tf antibodies linked to Sepharose 4 Fast Flow beads. This article reports extraction column manufacturing and column characterization with sera having normal and elevated CDT levels. The developed procedure was applied to a number of relevant hepatology and dialysis patient samples and could thereby be shown to represent an effective method for extraction and concentration of all Tf isoforms. Furthermore, lipemic sera were delipidated using a mixture of diisopropyl ether and butanol prior to immunoextraction. CDT could unambiguously be determined in all pretreated samples.

Carbohydrate-deficient transferrin (CDT): A reliable indicator of the risk of driving under the influence of alcohol when determined by capillary electrophoresis

Carbohydrate-deficient transferrin (CDT) is a marker of chronic alcohol abuse, which has recently been introduced to evaluate the physical fitness for obtaining a driving license. The aim of the present study was to evaluate the prevalence of elevated CDT levels in subjects stopped while driving under the influence of alcohol by using a validated method based on capillary electrophoresis. The study was carried out on a group of 40 drunken drivers (group A) and on a control group ( n = 51) of subjects chosen from the general population (group B). CDT was directly determined by capillary electrophoresis in free solution and UV detection at 200 nm. CDT results from both groups were classified as “negative” or “positive” on the basis of the cut-off set at 2.00% (CDT index). The subjects classified as “positive” in group A were 24 (60%), whereas in group B were 2. The subjects classified as “negative” in group A were 16 (40%), whereas in group B was 49 (96.1%). The comparison of the observed percentages, evaluated with the χ 2-test, was highly significant ( p < 0.001). The present study confirms the high prevalence of chronic alcohol abusers among drunken drivers and the usefulness of CDT as a predictor of the risk of drunk driving.

Elevated Carbohydrate-Deficient Transferrin (CDT) and Its Normalization on Dietary Treatment as a Useful Biochemical Test for Hereditary Fructose Intolerance and Galactosemia

Abnormalities in protein glycosylation are reported in fructosemia (HFI) and galactosemia, although, particularly in HFI, the published data are limited to single cases. The purpose was to investigate the usefulness of the carbohydrate-deficient transferrin (CDT) profile for identification and monitoring of these disorders. First we analyzed CDT values before and shortly after the diagnosis in 10 cases of HFI and 17 cases of galactosemia. In all patients, elevated CDT levels were found that significantly (p < 0.0001) decreased with the therapeutic diet (27.3 +/- 11.5% versus 9.3 +/- 5.1% for HFI and 43.8 +/- 14.1% versus 11.2 +/- 4.0% for galactosemia). To evaluate the use of CDT test in monitoring compliance, the test was performed in 25 HFI patients on fructose-restricted diet. We found an elevated CDT level on 104 from 134 tests (mean 11.3 +/- 5.5%, control 1.5%-6.2%). The fructose intake was found to be 90 +/- 70 mg/kg/d, and the diet was unbalanced. A number of patients presented lower height, elevated urinary uric acid excretion, and hypercalciuria. In conclusion, abnormal percentage of CDT (%CDT) values may allow prompt detection of HFI (or galactosemia). Persistence of some abnormalities in HFI on treatment may be caused by trace amounts of fructose ingestion and/or a deficient diet. Regular %CDT measurements are suggested for HFI treatment monitoring.

Detection of serum concentration of carbohydrate-deficient transferrin (CDT) in patients with head-neck carcinomas

It is now well known that chronic alcohol abuse is an important factor for developing head and neck squamous cell carcinoma (HNSCC). While hospitalized, these patients are at great risk for developing an unexpected alcohol-withdrawal syndrome. Compared to common markers of alcohol abuse, carbohydrate-deficient transferrin (CDT) has been found to be more sensitive and specific. It is therefore very useful for detecting alcoholism and controlling compliance of alcohol withdrawal. We analyzed the serum concentrations of CDT, liver enzymes and mean corpuscular volume in 49 male patients with HNSCC. Elevated CDT levels were found in more than 25% of patients who earlier denied a history of chronic alcohol abuse. Over one-third of these patients developed an alcohol-withdrawal syndrome. These findings demonstrated that analysis of elevated CDT serum levels was a valuable method for detecting chronic alcohol abuse and recognizing patients at risk for developing an alcohol-withdrawal syndrome post-operatively.

Increased gamma-glutamyltransferase in hypertriglyceridaemia: the value of carbohydrate-deficient transferrin measurement.

Excess alcohol consumption is a common cause of hypertriglyceridaemia.'.2 It has, therefore, been recommended that hypertriglyceridaemic patients be screened for elevated serum y glutamyltransferase activity (yGT), a marker of ethanol intake.2,3 It has also been suggested that hypertriglyceridaemia itself may be associated with increased yGT.435 This, nevertheless, is controversial, first, because subjects often under-report their alcohol intakeh and, secondly, because of the limited sensitivity and specificity of routine laboratory markers of alcohol intake, including Y C T . ~ Measurement of carbohydrate-deficient transferrin (CDT) has provided a sensitive and specific marker of chronic elevated alcohol ingestion.h Daily intake in excess of 60g of alcohol for longer than 2 weeks results in elevated CDT levels. To assess whether elevated yGT activity in hypertriglyceridaemic patients was due to undisclosed excess ethanol ingestion, we measured CDT in hypertriglyceridaemic patients with and without raised yCT activity who reported an alcohol intake of less than 4 units (40g) per day.

Is Carbohydrate‐Deficient Transferrin a Specific Marker for Alcohol Abuse? A Study in Patients with Chronic Viral Hepatitis

Carbohydrate-deficient transferrin, a transferrin isoform, is hailed as a new marker of chronic alcohol abuse, but its specificity is, however, not unequivocally accepted. The aim of the present study was therefore to determine carbohydrate-deficient transferrin levels in patients with chronic hepatitis B and C with or without documented chronic alcohol intake. Carbohydrate-deficient transferrin was measured using a double-antibody radioimmunoassay (CDTect, Pharmacia) in serum samples from 66 patients (45 males and 21 females; mean age: 39 years) with chronic viral hepatitis B (n = 20) or C (n = 46). Diagnosis of the underlying liver disease was established by liver biopsy. Carbohydrate-deficient transferrin levels were raised in 15 patients [23%; hepatitis B (n = 2) and hepatitis C (n = 13)]. In patients with chronic hepatitis B, the carbohydrate-deficient transferrin level was raised in two abstainers. In the 46 patients with chronic hepatitis C, 10 (22%) patients with an alcohol consumption of < 60 g/day for the men and 30 g/day for the women had raised carbohydrate-deficient transferrin levels. The overall specificity of carbohydrate-deficient transferrin for chronic alcohol abuse was thus 78%, suggesting an association between elevated carbohydrate-deficient transferrin levels and the presence of chronic viral hepatitis. Carbohydrate-deficient transferrin levels were not correlated with the histological grading or staging of chronic hepatitis B and C, or with biological markers of hepatic synthesis and cellular damage. Thus, an increased carbohydrate-deficient transferrin level may occur in patients with chronic viral hepatitis in the absence of chronic alcohol abuse. This fact should be kept in mind by physicians when using this marker to detect alcohol abuse.

Detection of Relapses in Alcohol‐Dependent Patients Using Carbohydrate‐Deficient Transferrin: Improvement with Individualized Reference Levels during Long‐Term Monitoring

The present study examined whether the sensitivity of carbohydrate-deficient transferrin (CDT) in serum, a biochemical marker of recent excessive alcohol consumption, could be improved during long-term monitoring by introducing individualized cut-offs between normal and elevated CDT levels. Alcohol-dependent male outpatients (n = 22), trying to abstain from alcohol for 6 months, were monitored by comparing weekly measurements of CDT with self-reports of alcohol consumption three times/week and daily urinary levels of 5-hydroxytryptophol (5-HTOL), a new marker of recent alcohol intake. The method used to calculate cut-offs was based on the intraindividual variation in CDT not dependent on excessive alcohol consumption or analytical variations. An increase in CDT exceeding the minimum level for each patient by 3 and 4 times the mean coefficient of variation for healthy social drinkers (i.e., by 30% and 40%) was compared as an indication of alcohol consumption, even if the value did not exceed the conventional cut-off. By using individualized CDT cut-off points, 68 and 41 episodes of drinking were detected in the patients with the cut-offs of > 30% and > 40%, respectively, as compared with 25 with the conventional limit. Most episodes could be verified clinically and/or by elevated urinary 5-HTOL levels during the 2-week period preceding each serum sampling. The results suggest that the possibility to detect relapses by CDT can be improved during long-term monitoring of alcohol-dependent outpatients by introducing individualized cut-off points between normal and elevated CDT levels.

CARBOHYDRATE DEFICIENT TRANSFERRIN LEVELS IN HAZARDOUS ALCOHOL CONSUMPTION

Little information is available on the value of carbohydrate deficient transferrin (CDT) in detecting persons with hazardous alcohol consumption. In the present study isoelectric focusing (IEF) and immunofixation were used to examine the sensitivity of CDT in hazardous drinkers compared with control subjects and alcohol dependent persons. Elevated CDT levels (> 100 mg/l) were found in 62% of hazardous drinkers and 67% of alcohol dependent persons compared with only 5% of controls. CDT was more sensitive than serum gamma glutamyltransferase (GGT) activity in detecting hazardous alcohol consumption (sensitivity of GGT 19%; P < 0.001), but was of comparable sensitivity to GGT for alcohol dependence. Neither the transferrin index nor transferrin ratio offered any advantage over CDT in detecting hazardous consumption. We conclude that serum CDT, as measured by IEF and immunofixation, is a sensitive and specific test for hazardous drinking.

MEASUREMENT OF CARBOHYDRATE-DEFICIENT TRANSFERRIN BY ISOELECTRIC FOCUSING/WESTERN

At present, the most reliable marker of recent and heavy alcohol intake is carbohydrate-deficient transferrin (CDT). While most CDT quantitation methods (including immunofixation and micro anion-exchange chromatography [MAEC] combined with radioimmunoassay [RIA]) either lack the precision required for diagnostic usage or are not commercially available, we recently described an isoelectric focusing/Western blotting (IEF/WB) procedure that provides sensitive and specific assessment of serum CDT content. However, a modified MAEC/RIA kit, supposedly more reliable than the original, is also being advanced as suitable for widespread clinical application. Therefore, we compared this modified MAEC/RIA procedure to the IEF/WB method of CDT quantitation in the following 108 subjects; 53 alcoholics undergoing detoxification without clinical or histological evidence of liver disease, 24 recently drinking alcoholics with biopsy-proven liver disease, eight alcoholics abstinent for more than 30 days with biopsy-proven liver disease, seven non-drinking patients with non-alcoholic liver disease, and 16 healthy controls. Although CDT measurements by the two methods were correlated (r = 0.60, P < 0.01), serum CDT values obtained with IEF/WB were nearly five-fold higher than those obtained with MAEC/RIA (e.g. 140.0 +/- 58 versus 28.5 +/- 16 mg/l among the active drinkers). Of the two methods, IEF/WB exhibited significantly greater sensitivity than MAEC/RIA for detecting recent, heavy drinking (75% versus 61%, P < 0.05) and generated no false positives whereas MAEC/RIA gave falsely elevated CDT levels in 37% of the abstinent alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)