Littérature scientifique sur le sujet « Carbohydrate deficient transferrin »

Alcohol abuse is an important public health problem. This condition is usually identified on the basis of clinical judgement, alcoholism related questionnaires and laboratory tests i.e. Gamma-glutamyltransferase (ggt), aspartate aminotransferase (ast ) or mean cell volume (mcv).

Abstract We describe a technique for measuring carbohydrate-deficient transferrin (CDT) in serum. Serum transferrin fractions are separated by anion-exchange chromatography on microcolumns. Sialic acid-deficient transferrin fractions are collected in the eluate, and transferrin is then quantified by a rate-nephelometric technique. Imprecision (CV) was 4-5% within-run and 7-9% between runs (n = 15). Comparison with an isoelectric focusing-immunofixation method for transferrin index (x) yielded y = 761x + 7, Sy/x = 39 mg/L. Assay of sera from 90 abstainers or moderate consumers of alcohol showed that 81 (90%) had CDT concentrations between 30 and 70 mg/L. Among 74 alcoholics admitted to an alcohol treatment center, 54 (73%) had CDT > 70 mg/L, i.e., the diagnostic sensitivity was 73% at a specificity of 90% (area under receiver-operator characteristic curve = 0.891).

Abstract In the search for more reliable blood markers for excessive alcohol consumption, considerable effort has been devoted to measurements of carbohydrate-deficient transferrin (CDT), which increases in body fluids as a result of prolonged alcohol intake. In the present work, three CDT methods, CDTect (Pharmacia & Upjohn), %CDT radioimmunoassay (%CDT RIA) by Axis (Oslo, Norway), and Axis %CDT turbidimetric immunoassay (%CDT TIA) were examined for their diagnostic performance in cases of alcohol abuse with or without liver disease. The diagnostic performance of CDT as a marker of alcohol abuse correlates positively with alcohol consumption. As compared with g-glutamyltransferase (GGT) and mean corpuscular volume of erythrocytes (MCV), which are conventionally used as laboratory markers of excessive ethanol consumption, CDT (CDTect) has the highest sensitivity (64%) at the specificity level of 100% in heavy drinkers consuming >100 g ethanol/day, but its sensitivity decreases to 34% in cases with an alcohol intake of <100 g/day, which hampers the use of CDT as a community screening method. Patients with alcoholic liver disease (ALD) have significantly higher CDT values than alcoholics with non-liver pathology. However, CDT is primarily increased in cases with an early stage of ALD, so that there is a weak negative correlation between CDT and disease severity, which may prove to be of diagnostic value. Especially in men, CDTect seems to achieve greater sensitivity than %CDT RIA or %CDT TIA for detecting recent alcohol abuse among heavy drinkers, but it does have a significant correlation with serum transferrin, especially in individuals reporting social drinking or no alcohol intake. This should be considered when interpreting the assay results in patients with increased serum transferrin. %CDT methods achieve greater specificity than CDTect when analyzing samples from patients with high serum transferrin concentrations. Acetaldehyde-protein adducts are formed in the body after excessive ethanol intake, and their formation triggers antibody production, which may contribute to some forms of tissue damage seen in alcohol abusers. To obtain more information on the association between serum antibodies against acetaldehyde adducts, ALD and alcohol consumption, assays for antibodies against albumin and haemoglobin adducts were performed. Antibodies of the immunoglobulin (Ig) isotypes A, G, and M against acetaldehyde-adducts are formed in patients with prolonged heavy alcohol consumption. IgA titres in ALD patients are significantly higher than those found in patients with non-alcoholic liver disease, non-drinking controls, or heavy drinkers with no signs of liver disease. Anti-adduct IgG titres, in turn, are increased both in ALD and in heavy drinkers with no signs of liver disease as compared with non-alcoholic liver disease patients or non-drinking controls. It appears that anti-adduct IgA, IgG and IgM titres in ALD patients correlate with the severity of the liver disease. Although this association is a limitation for the usefulness of these antibodies as markers of alcohol abuse, it may serve as a basis for the differential diagnosis of alcohol-induced liver disease.

1ABSTRACTCarbohydrate-deficient transferrin (CDT) is a biomarker for excessive and long-running intake of alcohol. It is a form of transferrin called disialotransferrin that under normal circumstances is <2 % of total transferrin in human blood. An increase is seen when alcohol consumption exceeds450 g per week. CDT is analyzed in serum usinghigh performance liquid chromatography (HPLC) and UV/VIS detection. The purpose of this study was to investigate if an “in routine” method could be improved by switching columns.With ion exchange chromatography transferrin glycoforms are separated and quantified. The carbohydrate-deficient transferrin glycoforms have an isoelectric point between 5,7-5,9 that depends on the number of sialic acids on the molecule. With the use of a salt gradient and pH above the isoelectric point the glycoforms can beseparated depending on their affinity to the stationary phase. Batches with patient and control serum was first analyzed on the routine column Source 15Q PE and then on the alternative column Reprospher 200 SAX 5μm.Student’s t-test showed that the two methods’results correlated but were significantly different. A Bland-Altman plot illustrated differences between the two columns. High and low control serum values from Reprospher were lower than the accepted interval. In this study Reprospher’s stationary phase seemed to be affected to such an extent that stabile retention time, better resolution, and stabile values could not be achieved and because the information about the column was lacking an attempt to regeneratethe columnwas not conducted.

Motivation Alcohol consumption is one of the major risk factors of cardiovascular disease (CVD). Excessive alcohol drinking is the fifth leading cause of death worldwide and the prevalence of alcohol abuse continues to increase especially in low-income areas of sub-Saharan Africa. The alarming rate of urbanisation seems to be the driving force for excessive alcohol intake in the developing world. In addition to its influence on CVD, heavy drinking also results in a number of non-cardiovascular consequences that include injury, risky sexual behaviour, violent crime and family dysfunction among black South Africans, contributing to high mortality. Moreover, the highest number of individuals with human immunodeficiency virus (HIV) infection in South Africa is partly attributable to high intake of alcohol. HIV remains a major concern in South Africa with significant funding diverted to address the pandemic. The continued increases in mortality from preventable outcomes such as stroke, myocardial infarction and renal failure are largely due to urbanisation, poverty and dysfunctional health systems working with limited budgets. These are some of the factors requiring in-depth study of the scientific aspects of alcohol intake in South Africa. Although there is enough evidence that links excessive drinking with hypertension and CVD, the markers of alcohol intake – self reporting of alcohol, gamma-glutamyltransferase (GGT) and carbohydrate deficient transferrin – are still not specific enough to isolate other confounding factors in the association of alcohol intake with CVD. The markers of alcohol that independently predict CVD and mortality need to be explored. Finally, the severe lack of longitudinal investigations on alcohol-related hypertension development and total mortality in black South Africans has compromised the early identification of risk factors associated with these outcomes. This study will therefore attempt to address the limited availability of longitudinal studies and stimulate interest for continued investigation. Aim The aim of this study was to investigate whether alcohol intake of black South Africans is related to specific measures of cardiovascular function (change in blood pressure (BP), hypertension development) and mortality over a period of 5 years. Methodology This study was based on the international Prospective Urban and Rural Epidemiology (PURE) study which includes 26 countries, investigating the cause and development of cardiovascular risk factors in low, middle and high income countries. This South African leg of the PURE study started in 2005 in which the baseline data was collected from 2021 black South Africans from rural and urban areas in Ikageng, Ganyesa and Tlakgameng in the North West Province. Eleven participants presented with missing data, leaving 2010 participants with complete datasets at baseline. However, data from these 11 participants was useful, especially for Chapter 4. All participants gave informed consent and the Ethics committee of the North-West University (Potchefstroom Campus) approved the study. The follow-up data collection was done in 2010. General health questionnaires, anthropometric measurements, lipid profiles and cardiovascular measurements were taken both at baseline and follow-up using appropriate methods. We also collected blood samples and performed biochemical analyses for lipid markers, liver enzymes, inflammatory markers and percentage carbohydrate deficient transferrin (%CDT). Finally, we obtained data on cardiovascular and non-cardiovascular mortality through verbal autopsy and death certificates. We made use of analysis of variance (ANOVA) and Chi-square tests to compare means and proportions, respectively. We used dependent t-tests and the McNemar test to compare baseline and follow-up variables. Furthermore, we employed single and partial linear regression analyses to correlate alcohol markers with each other and with the cardiovascular measures. Multiple regression analyses were used to correlate dependent variables in the study with various independent variables as required. Finally, we employed multivariable-adjusted Cox regression analyses to assess the association of the selected alcohol markers with mortality while adjusting for several independent variables. Results and Conclusions of each manuscript - With the first research article (Chapter 4), we aimed to compare self-reported alcohol intake estimates with GGT and %CDT, considering their relationship with percentage change in brachial blood pressure (BP) and central systolic blood pressure (cSBP) over 5 years. The results indicated that only self-reported alcohol intake independently predicted % change in brachial BP and cSBP. This was not found for the biochemical markers GGT and %CDT. Self-reported alcohol intake seems to be an important measure to implement by health systems in low income areas of sub-Saharan Africa, where honest reporting is expected. - Given the likely presence of high GGT levels in both alcohol consumption and non-alcoholic fatty liver disease (NAFLD), the second manuscript (Chapter 5) aimed to compare the cardiovascular and metabolic characteristics of excessive alcohol users and individuals with suspected NAFLD (confirmed with self-report, GGT and %CDT). We found that different sex and cardiometabolic profiles characterised excessive alcohol users and individuals suspected with NAFLD. Lean body mass and male sex were the dominant characteristics in excessive alcohol use while the NAFLD group had a dysmetabolic profile with obese women making up the higher proportion of this group. In excessive alcohol users systolic blood pressure and pulse pressure were independently associated with high-density lipoprotein cholesterol. Diastolic blood pressure showed a significant correlation with waist circumference. These disparate profiles may guide healthcare practitioners in primary healthcare clinics to identify individuals with elevated GGT levels who may suffer from NAFLD or alcohol overuse. These results emphasise the importance of modifiable risk factors as the main contributors to CVD and that lifestyle change should be the main focus in developing countries such as South Africa. - The third manuscript (Chapter 6) aimed to determine the measure of alcohol intake (selfreported alcohol intake, GGT and %CDT) that related best with hypertension development, cardiovascular and all-cause mortality over 5 years in the same population of black South Africans. We found that GGT was the only independent predictor of hypertension development, cardiovascular as well as all-cause mortality. Moreover, self-reporting of alcohol intake predicted incident hypertension, confirming our findings from Chapter 4. The third marker, %CDT, a highly specific marker of alcohol intake, was not related with any outcome variable, perhaps due to its low sensitivity. Although self-reported alcohol intake is useful in low-resource primary healthcare settings, measurement of GGT is encouraged due to its predictive value for hypertension and mortality. GGT represents alcohol intake, non-alcoholic steatohepatitis and obesity - all known to have severe cardiovascular consequences. Discussion and Conclusions Excessive alcohol intake remains a major concern in the development of hypertension, CVD and premature death in sub-Saharan Africa. Despite their weaknesses such as bias and nonspecificity, self-reporting of alcohol consumption and GGT emerged as reliable alcohol markers that independently predicted 5-year change in BP, hypertension development and total mortality in this population. Serum %CDT did not show any association with the mentioned cardiovascular markers. Finally, we were also able to show that black South Africans with suspected NAFLD (i.e. with high GGT levels who do not consume alcohol) are typically obese women, whereas lean men were more likely to have high alcohol consumption. Further prospective investigations are encouraged regarding (a) these mentioned associations, as well as (b) other self-reporting estimates such as quantity and frequency of drinking and (c) the use of %CDT as a highly specific marker of alcohol intake. The simultaneous presence of HIV infection in alcohol abuse in this population also warrants further investigation.
PhD (Physiology), North-West University, Potchefstroom Campus, 2015

Although erythropoiesis-stimulating agent therapy is the mainstay of renal anaemia management, maintenance of an adequate iron supply to the bone marrow is also pivotal in the process of erythropoiesis. Thus, it is important to be able to detect iron insufficiency, and to treat this appropriately. Iron deficiency may be absolute (when the total body iron stores are exhausted) or functional (when the total body iron stores are normal or increased, but there is an inability to release iron from the stores rapidly enough to provide a ready supply of iron to the bone marrow). Several markers of iron status have been tested, but those of the greatest utility are the serum ferritin, transferrin saturation, and percentage of hypochromic red cells. Measurement of serum hepcidin, which is the master regulator of iron homoeostasis, has to date proved disappointing as a means of detecting iron insufficiency, and none of the available iron markers reliably exclude the need for supplemental iron. Iron may be replaced by either the oral or the intravenous route. In the advanced stages of chronic kidney disease, however, hepcidin is upregulated, and this powerfully inhibits the absorption of iron from the gut. Thus, such patients often require intravenous iron, particularly those on dialysis. Several intravenous (IV) iron preparations are available, and they have in common a core containing an iron salt, surrounded by a carbohydrate shell. The IV iron preparations differ in their kinetics of iron release from the iron–carbohydrate complex. In recent times, several new IV iron preparations have become available, and these allow a greater amount of iron to be given more rapidly as a single administration, without the need for a test dose.