Objective: The measurement of plasma glycated albumin is particularly useful in the short-middle term monitoring of glycometabolic control in diabetics. The aim of this work is to evaluate a new enzymatic method for the measurement of glycated albumin in plasma, with particular attention to some selected cases and comparison with other relevant tests (fasting plasma glucose, after glucose load, fructosamine, glycated hemoglobin).Design and methods: We have performed a multicenter study by which sample collection was performed in three different centers (Milano, Padova and Cagliari) and serum samples, frozen at −80°C, were then delivered under dry ice to the centralized laboratory in Milano. Glycated plasma albumin was measured with reagents from Asahi Kasei Pharma (Lucica GA-L enzymatic assay; AKP, Tokyo, Japan) on a Modular P Roche system. Fructosamine was assessed by a Roche method and HbA 1c (measured separately in the three centers on fresh EDTA blood) by DCCT-aligned HPLC systems. We have investigated 50 type 2 diabetics, 26 subjects with gestational diabetes, 35 subjects with thalassemia major, 10 subjects with cirrhosis, 23 patients with end-stage renal disease subjected to dialysis treatment and 32 healthy adult control subjects.Results: The main analytical performance characteristics of the new GA test were the following: (a) the within-assay reproducibility was between 3.0 and 3.9% (in terms of GA% CV, measured on 2 serum pools and 2 control materials at normal and pathological glycated albumin levels); (b) the between-assays reproducibility was from 2.8 to 4.1%; (c) the linearity was tested in the interval between 13 and 36% and found acceptable (r 2 = 0.9932). Concerning the clinical utility of the new test, we have evaluated the relationships between GA, HbA 1c , fructosamine and fasting and post-prandial glucose in several patients, as well as the changes in the abovementioned parameters in a sub-group of type 2 diabetic patients for 18 weeks as they progressed from severe hyperglycemia (HbA 1c ≥10.0%) toward a better glycemic control. The correlations between glycated albumin and HbA 1c were as follows: (a) type 2 diabetics: r 2 = 0.483 (good glycemic control), r 2 = 0.577 (poor control); (b) diabetic patients under dialysis: r 2 = 0.480; (c) liver disease: r 2 = 0.186; (d) transfused non-diabetics with thalassemia: r 2 = 0.004. Glycated albumin, as well as HbA 1c and fructosamine, was of little value in the study of women with gestational diabetes, mainly because of the very limited glucose fluctuations in this particular category of subjects. In 11 type 2 diabetic patients under poor metabolic control, GA was better correlated with fasting plasma glucose then HbA 1c (r 2 = 0.555 vs. 0.291, respectively), and decreased more rapidly than HbA 1c during intensive insulin therapy. Conclusions: The experience we have acquired with the new enzymatic test demonstrates its reproducibility and robustness. We confirm that plasma glycated albumin is better related to fasting plasma glucose with resp...

Summary. Cholelithiasis has been reported with a variable incidence in homozygous b-thalassaemia, the reasons for which have only partially been defined. Disease-associated factors or specific modifier genes may be implicated. We assessed the prevalence of cholelithiasis and the effect of coinherited Gilbert's syndrome genotype on its development in 261 thalassaemia major (TM) and 35 thalassaemia intermedia (TI) patients. Cholelithiasis was found in 20´3% of TM and in 57´1% of TI patients. Its incidence was higher (P , 0´05) in patients homozygous for the (TA 7 ) motif in the promoter of the UGT1-A1 gene, the genotype associated with Gilbert's syndrome, which seems to be a risk factor for the development of gallstones in TM and TI patients.Keywords: cholelithiasis, Gilbert's syndrome, b-thalassaemia, UGT1-A1, hyperbilirubinaemia.Cholelithiasis occurs with variable (2´3±52%) incidence in homozygous b-thalassaemia (Dewey et al, 1970; BorgnaPignatti et al, 1981;Scutellari et al, 1981;Goldfarb et al, 1990). The reported variation is partly related to the age of the patients, as its incidence increases with age, and partly to its clinical severity, as it is more common in thalassaemia intermedia (TI) than thalassaemia major (TM). However, the reasons for this variation are not completely understood. We evaluated the effect of co-inherited Gilbert's syndrome genotype on the development of cholelithiasis in homozygous b-thalassaemia. This genotype consists of a promoter variation of the uridine-diphosphoglucuronyl transferase (UGT1-A1) gene, which may interfere with bilirubin solubility by decreasing the production of bilirubin diglycuronide (Bosma et al, 1995). PATIENTS AND METHODSWe studied 261 unrelated TM patients (130 females) (mean age 22 years, range 6±30 years) and 35 TI patients (13 females) (mean age 27 years, range 10±50 years). The patients were all b8-thalassaemia homozygotes for the b39 C3T nonsense mutation, except for six with TI, who were genetic compounds for b8/b 1 -thalassaemia. We evaluated the presence of gallstones by ultrasonography and determined serum bilirubin (mean of the last three determinations), alanine-aminotransferase (ALT), ferritin level (mean of five or six determinations) in all patients and blood consumption (ml/kg/year) in TM patients.The promoter region of the UGT1-A1 gene was analysed by automated sequencing (ABI-PRISM 377; Applied Biosystems, USA) on genomic DNA obtained from leucocytes. Chisquare test was used to analyse the prevalence of cholelithiasis in relation to UGT1-A1 genotypes. RESULTSWe characterized by DNA sequencing the arrangement of the TATA motif of the UGT1-A1 gene, of which the (TA) 6 is the wild-type motif, whereas (TA) 7 is the variant motif associated with Gilbert's syndrome. The (TA) 7 variant was found in the homozygous form in 10% of TM and in 14´3% of TI patients and was heterozygous in 39´1% of the TM and in 54´3% of the TI patients. The genotype distribution in both groups of patients was similar to that found in the normal population (Galanello et a...

SummaryThis study aimed to verify the impact of heart magnetic resonance imaging on chelation choices and patient compliance in a single-institution cohort as well as its predictive value for heart failure and arrhythmias. Abnormal cardiac T2* values determined changes in treatment in most subjects. Heart T2* was confirmed to be highly predictive over 1 year for heart failure and arrhythmias. The choice of chelation regimens known to remove heart iron efficiently was not sufficient by itself to influence the risk. Compliance with treatment had a more remarkable role.Keywords: beta thalassaemia major, heart magnetic resonance imaging, compliance, heart failure, arrhythmia.The introduction of magnetic resonance imaging (MRI) technology to measure iron overload and the availability of the oral chelators have had a profound impact on the care and prognosis of patients with beta thalassaemia major (Modell et al, 2008;Chouliaras et al, 2011). Identifying those patients at risk of a fall in left ventricular ejection fraction, cardiac T2* also identifies those whose chelation treatment should be intensified. Kirk et al (2009) determined the predictive value of cardiac T2* magnetic resonance for heart failure and arrhythmia in thalassaemia major. The present study aimed to verify the impact of heart MRI on chelation choices and patient compliance as well as its predictive value for heart failure and arrhythmias in patients attending our Centre. MethodsA total of 313 patients (900 consecutive scans) with beta thalassaemia major followed at DH talassemia Et a EvolutivaOspedale Regionale per le Microcitemie-Cagliari, Italy were included in this study. MRI scans were performed with a 1Á5 T General Electric CVi scanner or with a 1Á5 T Magneton Siemens Avanto, using previously reported techniques (Westwood et al, 2003), between 2002 and 2012. Of these patients, 157 were male and 156 female, with a mean age at time of their first scan of 26Á7 AE 6Á2 years. Twenty-two had experienced one or more episodes of heart failure and 13 a history of arrhythmia. At the time of the first scan, 168 patients were receiving deferoxamine (20-50 mg/kg 5-6 d per week), 24 were on deferiprone (75-100 mg/kg per d), 76 were taking deferoxamine (20-50 mg/kg 2-7 d per week) combined with deferiprone (75 mg/kg per d) because of high serum ferritin values and 45 were receiving deferasirox at a dose of 20-35 mg/kg per d. Adherence to and acceptance of chelation therapy (compliance) was evaluated according to pharmacy records of the dispensed drug. It was classified as good, if the mean number of the doses taken was ≥80% of those prescribed, average if it was >50 < 80% and poor if it was <50%. The predictive value of T2* for cardiac events in the year after scan was evaluated including the MRI before heart failure and/or arrhythmias for patients with cardiac events, and a random MRI otherwise. To obtain the most similar control group we randomly sampled one MRI within 'time to first MRI' stratas, to respect case group distribution.Accuracy of T2* predict...

Adult subjects with Thalassemia who live in Western countries have a good quality of life in accordance with the advances in the management of the disease.