Association of carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) with serum lipid profile in the Finnish population

BACKGROUND: Moderate consumption of alcohol may reduce mortality from vascular diseases. The beneficial effects of alcohol may partly be mediated by its effects on lipoprotein metabolism. We studied the connection between alcohol consumption and the serum lipid profile from a well-documented national health program study. METHODS AND RESULTS: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) were used as biochemical markers for alcohol consumption. The laboratory analyses were carried out on 5675 subjects (3097 males and 2578 females). The subjects were divided into quartiles on the basis of CDT or GGT value. The highest CDT quartile and the lowest GGT quartile seemed to be associated with a favorable lipid profile and the lowest CDT quartile and the highest GGT quartile were associated with an unfavorable lipid profile. Serum high density lipoprotein (HDL) cholesterol values were significantly higher and triglycerides lower with increasing serum CDT concentrations for both men and women. Increasing serum GGT was associated with higher serum total cholesterol and higher triglycerides in both men and women and lower HDL cholesterol in men. CONCLUSIONS: CDT and GGT seem to detect different populations of subjects in regard to lipid metabolism. These observations may lead to a better understanding of the effects of alcohol consumption on lipids as well as mechanisms behind favorable and detrimental effects of alcohol on vascular diseases. Condensed abstract: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) were used as biochemical markers for alcohol consumption. A total of 3097 males and 2578 females were divided into quartiles on the basis of their CDT or GGT values. The highest CDT quartiles had higher HDL and lower triglycerides, whereas the highest GGT quartiles appeared to be associated with higher total cholesterol and triglycerides in both genders and lower HDL in men. CDT and GGT seem to detect different populations of subjects in regard to lipid metabolism. These observations may have important clinical and public health implications.     

The Alcohol Use Disorders Identification Test (AUDIT) and carbohydrate-deficient transferrin (CDT) in a routine workplace health examination

BACKGROUND: Only a few studies on workplaces have examined the Alcohol Use Disorders Identification Test (AUDIT) or carbohydrate-deficient transferrin (CDT) as screening instruments for the early identification of elevated and risky levels of alcohol consumption. The purpose of this study was to compare the performances of AUDIT, CDT, and gamma-glutamyltransferase (GGT) in a routine health examination (alcohol screening) in the workplace. METHODS: The study, carried out over 16 months in a large workplace in the transport sector, was part of an on-going controlled study. Employees who came to the company health service for a routine health examination were offered the opportunity to undergo an alcohol screening and check their alcohol habits. RESULTS: Of the 570 subjects who participated, 105 (18.4%) screened positive according to AUDIT, CDT, or both. Only 7.6% of the persons who screened positive did so according to both instruments. If GGT had been included as a screening instrument, the proportion of positive results would have increased to 22.0%. If we had only used AUDIT in the screening process, the proportion of positives would have fallen by nearly half. CONCLUSIONS: The present findings suggest that AUDIT and CDT are complementary instruments for alcohol screening in a routine workplace health examination, and each has value for identifying a different segment of the risky drinking population.     

Operating characteristics of carbohydrate-deficient transferrin (CDT) for identifying unhealthy alcohol use in adults with HIV infection

Unhealthy alcohol use (the spectrum of risky use through dependence) is common in HIV-infected persons, yet it can interfere with HIV medication adherence, may lower CD4 cell count, and can cause hepatic injury. Carbohydrate-deficient transferrin (CDT), often measured as %CDT, can detect heavy drinking but whether it does in people with HIV is not well established. We evaluated the operating characteristics of %CDT in HIV-infected adults using cross-sectional data from 300 HIV-infected adults with current or past alcohol problems. Past 30-day alcohol consumption was determined using the Timeline Followback (TLFB), a validated structured recall questionnaire, as the reference standard. Sensitivity and specificity of %CDT (at manufacturer's cut-off point of 2.6%) for detecting both "at-risk" (≥4 drinks in a day or >7 drinks per week for women, ≥5 drinks in a day or >14 per week for men) and "heavy" drinking (≥4 drinks in a day for women, ≥5 drinks in a day for men on at least seven days) were calculated. Receiver operating characteristic (ROC) curves were estimated to summarize the diagnostic ability of %CDT for distinguishing "at risk" and "heavy" levels of drinking. Exploratory analyses that stratified by gender and viral hepatitis infection were performed. Of 300 subjects, 103 reported current consumption at "at-risk" amounts, and 47 reported "heavy" amounts. For "at-risk" drinking, sensitivity of %CDT was 28% (95% confidence interval (CI) 19%, 37%), specificity 90% (95% CI 86%, 94%); area under the ROC curve (AUC) was 0.59. For "heavy" drinking, sensitivity was 36% (95% CI 22%, 50%), specificity 88% (95% CI 84%, 92%); AUC was 0.60. Sensitivity appeared lower among women and those with viral hepatitis; specificity was similar across subgroups. Among HIV-infected adults, %CDT testing yielded good specificity, but poor sensitivity for detecting "at-risk" and "heavy" alcohol consumption, limiting its clinical utility for detecting unhealthy alcohol use in this population.     

Objective diagnosis of alcohol abuse: compared values of carbohydrate-deficient transferrin (CDT), gamma-glutamyl transferase (GGT), and mean corpuscular volume (MCV)

BACKGROUND: Alcohol abuse is roughly twice as common as alcohol dependence. Subjects with alcohol problems are usually diagnosed only when medical complications are present. Therefore, both doctors and patients need a method for early diagnosis of alcohol abuse. METHODS: The mean corpuscular volume, gamma-glutamyl transferase, and carbohydrate-deficient transferrin in alcohol abusers, alcohol-dependent patients, and "nonalcohol hospital" individuals were compared. RESULTS: For objective diagnosis of alcohol abuse, we found a sensitivity of 24%, a specificity of 96%, and a global predictive value of 63% for mean corpuscular volume; a sensitivity of 42%, a specificity of 76%, and a global predictive value of 61% for gamma-glutamyl transferase; and a sensitivity of 67%, a specificity of 97%, and a global predictive value of 84% for carbohydrate-deficient transferrin. CONCLUSIONS: Carbohydrate-deficient transferrin proves to be the best marker of alcohol abuse. It allows objective detection so that therapeutic action can be started early, which is easier and more effective than in alcohol dependence.     

Secondary alteration of the transferrin isoelectric focusing pattern in a case of bacterial meningitis

Summary Congenital disorders of glycosylation (CDG) are a group of inherited defects in the synthesis and processing of the linked glycans of glycoproteins and other glycoconjugates. The phenotypic spectrum presents wide variability, and clinical diagnosis is not reliable in most cases. Isoelectric focusing (IEF) of serum transferrin is widely used as a tool to detect CDG. We describe a paediatric patient presenting an altered serum transferrin pattern due to a secondary disorder of glycosylation caused by pneumococcal meningitis (Streptococcus pneumoniae, serotype 19A). During admission, brain CT scan and MRI showed acute ischaemic lesions in brain frontotemporal parenchyma, and enlarged subarachnoidal spaces in the frontal area resembling a chronic injury. This led us to screen for inborn errors of metabolism potentially associated with these findings (homocystinuria, glutaric aciduria, CDG syndromes). Biochemical studies for the screening of these inborn errors of metabolism were normal except for sialotransferrin isoelectric focusing, which showed a type 2 pattern. However, 16 days later, together with the remission of the meningitis process, the sialotransferrin pattern had normalized. The apolipoprotein C-III (an O-glycoprotein) profile was normal in all samples analysed. In conclusion, infectious events should be ruled out in the differential diagnosis of CDG syndromes. Furthermore, our findings highlight the possibility that the type 2 IEF pattern of serum sialotransferrin detected in some patients with neonatal death due to organ failure and septic events might be secondary to the infectious process. Electronic Supplementary Material Supplementary material is available for this article at Communicating editor: Jaak Jaeken     

The level of Hb F-Sardinia (alpha 2A gamma 2(75)Ile----Thr) in the fetal hemoglobin of Sardinian beta-thalassemic homozygotes determined by isoelectric focusing

A simple thin-layer isoelectric focusing technique was used to separate Hb F-Sardinia, containing the A gamma T-globin chain, from the Hb F containing the G gamma- and the A gamma I-globin chains. The identity of the slow-moving Hb F fraction as Hb F-Sardinia was verified by PAGE. A negative correlation (R2 = 0.747, p less than 0.001) was found between the percent Hb F-Sardinia and percent G gamma-chain in homozygotes for beta-thalassemia. Of 31 Sardinian beta-thalassemic patients studied, 21 were homozygous and eight heterozygous for the A gamma T polymorphism with a gene frequency of 0.823. The mean values of Hb F-Sardinia were 39.1 +/- 5.9% for the homozygotes and 17.1 +/- 3.6% for the heterozygotes. The percentage of Hb F-Sardinia found in beta o-thalassemic newborns was similar to that of corresponding normal newborns who also had the A gamma T polymorphism. No measurable differences in the percent Hb F-Sardinia level were observed among beta o-thal patients who were polytransfused, beta o-thal patients studied before transfusion, and beta o-thal patients exhibiting the intermediate form of the disease who had never been transfused.     

Carbohydrate-deficient transferrin (CDT) and HDL cholesterol (HDL) are highly correlated in male alcohol dependent patients

BACKGROUND: Serum levels of total HDL cholesterol (HDL) are reportedly influenced by recent alcohol intake. We examined the correlation between HDL cholesterol and widely used markers of excessive alcohol intake, such as carbohydrate-deficient transferrin (CDT), gamma-glutamyl-transferase (GGT), or mean corpuscular volume of erythrocytes (MCV), of which CDT is thought to be the most specific. METHODS: Several serological markers [i.e., CDT, GGT, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), MCV, and HDL] were determined in 100 actively drinking male patients with alcohol dependence (DSM-IV) and in 27 non-alcohol-dependent controls, according to routine procedures. Spearman's rank correlation coefficients were calculated. RESULTS: We found a highly significant positive correlation between HDL and CDT (r(s) = 0.55; p < 0.0005) in patients, but not in controls (r(s) = 0.13;p = 0.51). HDL was also positively correlated with GGT, ALAT, ASAT, and MCV only in patients. CONCLUSIONS: HDL cholesterol, as a widely determined parameter, may represent a useful routine marker for recent excessive alcohol intake. High HDL cholesterol levels should alert clinicians to investigate a patient's recent pattern of alcohol consumption.     

Neonatal screening of beta-thalassemias by thin layer isoelectric focusing

As an alternative to the recently proposed screening for beta-thalassemias by isoelectric focusing (IEF) of denatured globin chains in urea-detergent gels [6], IEF of intact hemoglobins, obtained from umbilical cord blood in neonatal units, is reported here. For maximum separation, IEF should be performed in nonlinear pH gradients, in gels containing 0.2 M beta-alanine and 0.2 M 6-amino caproic acid, which flatten the pH gradient around pH 7, thus increasing the resolution between HbA and HbFac. The method can unambiguously detect homozygous and heterozygous beta-thalassemic conditions. A bimodal distribution of HbA at birth has been found: In heterozygous patients, HbA values of 9.02% (range 6.8-9.98%) have been found while in normal newborns HbA levels of 20.34% (range 11.02-30.6%) have been demonstrated.     

The effect of iron overload and iron reductive treatment on the serum concentration of carbohydrate-deficient transferrin

Summary. The concentration of carbohydrate-deficient transferrin in serum (CDT) has been used as a reliable indicator of recent alcohol consumption. We have investigated the utility of this laboratory test in 20 patients with hereditary haemochromatosis (HH) by simultaneous evaluation of serum concentrations of liver transaminases, γ-glutamyl transpeptidase, iron, transferrin and asessment of the liver iron concentration by magnetic resonance imaging. 11 patients were re-examined during iron depletion with phelebotomies. In all 11 patients intensive but not maintenance iron removal was associated with an increase in serum CDT, in three patients even to levels above the reference range. The mean serum CDT increased from 8.5 (SD 2.2) U/1 to 16.6 (SD 7.2) U/1 (P < 0.001). Iron mobilization from the liver was found particularly responsible for the increase in serum CDT. Independent of this finding we found a significant semi-logarithmic correlation (r =−0.77. P = 0.009) between the MRI determined liver iron depletion. Our findings indicate that the utility of serum CDT as a measure of alcohol consumption in patients with HH may be compromised, especially during intensive iron depletion.     

Identification of cystic fibrosis homozygotes and heterozygotes by isoelectric focussing of serum proteins

Screening of 44 cystic fibrosis homozygotes, 17 heterozygotes and 36 normal controls, by identification of cystic fibrosis protein (CFP), was performed on sera using an improved isoelectric focussing technique. CFP was observed in 91% of homozygotes, 88% of heterozygotes and 8% of normal controls tested. Partial purification of CFP by chromatofocussing indicates that CFP has a molecular weight of about 52000u. It is speculated that CFP is a normal serum protein that exhibits a quantitative difference in concentration between CF homozygotes, heterozygotes and normals.     

Defective uptake of alpha-fetoprotein (AFP) and transferrin (Tf) by PHA-activated peripheral blood lymphocytes from patients with AIDS and related syndromes.

Serum alpha-fetoprotein (AFP) and transferrin (Tf) are actively endocytosed by many growing cells during ontogenic and neoplastic growth, but also by peripheral T lymphocytes upon mitogen activation. AFP and Tf uptake occurs through receptor-mediated endocytosis. The purpose of the present work was to assess whether the expression and functional activity of AFP and Tf receptors are impaired in mitogen-activated T cells from several groups of HIV-1 seropositive (HIV+) individuals. Forty HIV+ cases were studied, including 12 patients with AIDS, 12 with lymphoadenopathy syndrome (LAS), as well as 16 asymptomatic homosexuals (As). Quantification of AFP and Tf uptake was carried out by fluorescence-activated cell sorting (FACS) using fluoresceinated derivatives of these proteins. Compared with healthy blood donors, the three HIV-1 seropositive groups exhibited clear impairment in the ability of their peripheral blood mononuclear cells (PBMC) to internalize AFP and Tf. The decrease in mean values of AFP uptake correlates roughly with the severity of the clinical status. Although these observations need to be confirmed after a much wider study groups, the AFP-Tf-endocytosis assay presented here clearly reveals early defective functions of mitogen-responsive T cells in disease-free subjects and may provide the basis for a prognostic test. The pathophysiological implications of these facts are discussed in relation to the structural and/or metabolic activities of fatty acids and iron, the ligands carried by AFP and Tf, respectively.     

Characterization of Trypanozoon stocks by isoelectric focusing and isoenzyme analysis

Isoelectric focusing on ultrathin polyacrylamide foils, coupled with isoenzymatic analysis using five different enzymes, was used to characterize blood-forms of T.b. brucei, T.b. rhodesiense and T.b. gambiense and procyclic forms of T.b. brucei and T.b. rhodesiense. The protein concentrations in the lysates were quantified. Qualitative as well as quantitative differences were found.     

Determination of glycosylated hemoglobins in neonatal blood by isoelectric focusing

Isoelectric focusing (IEF) with suitable "spacers" can be used to distinguish glycosylated hemoglobins from HbA and HbF in adults and infants, respectively. Using this technique we have shown that there is a good correlation between glycosylated hemoglobins measured by IEF and column chromatography (r = 0.778, P less than 0.001). There was no significant difference in the rate of glycosylation between adult and cord blood hemolysates following incubation with glucose in vitro: In both instances there was an increase from the normal levels of about 5% to 26% through 31% after 18 hours of incubation. The levels of glycosylated hemoglobins in infants of varying gestation, neonates, and normal adults was remarkably constant, varying from 4.7 +/- 1.1% to 6.1 +/- 1.6%. These results show that IEF can be useful in the quantitation of glycosylated hemoglobins, particularly in the presence of hemoglobins (eg, HbF) where standard chromatographic techniques cannot be used. IEF has the added advantage of using small quantities of blood, and allows a number of samples to be tested at the same time, thus facilitating the identification of abnormal hemoglobins.