Methods, units and quality requirements for the analysis of haemoglobin A_(1c) in diabetes mellitus

The formation of glycohemoglobin, especially the hemoglobin A1c(Hb_(A1c)) fraction, occurs when glucose becomes coupled with the amino acid valine in the β-chain of Hb; this reaction is dependent on the plasma concentration of glucose. Since the early 1970 s it has been known that diabetics display higher values of Hb_(A1c) because they have elevated blood glucose concentrations. Thus Hb_(A1c) has acquired a very important role in the treatment and diagnosis of diabetes mellitus. After the introduction of the first quantitative measurement of Hb_(A1c), numerous methods for glycohemoglobin have been introduced with different assay principles: From a simple minicolumn technique to the very accurate automated highpressure chromatography and lastly to many automated immunochemical or enzymatic assays. In early days, the results of the quality control reports for Hb_(A1c) varied extensively between laboratories, therefore in United States and Canada working groups(WG) of the Diabetes Controls and Complications Trial(DCCT) were set up to standardize the Hb_(A1c) assays against the DCCT/National Glycohemoglobin Standardization Program reference method based on liquid chromatography. In the 1990 s, the International Federation of Clinical Chemistry and Laboratory Medicine(IFCC) appointed a new WG to plan a reference preparation and method for the Hb_(A1c) measurement. When the reference procedureswere established, in 2004 IFCC recommended that all manufacturers for equipment used in Hb_(A1c) assays should calibrate their methods to their proposals. This led to an improvement in the coefficient of variation(CV%) associated with the assay. In this review, we describe the glycation of Hb, methods, standardization of the Hb_(A1c) assays, analytical problems, problems with the units in which Hb_(A1c) values are expressed, reference values, quality control aspects, target requirements for Hb_(A1c), and the relationship of the plasma glucose values to Hb_(A1c) concentrations. We also note that the acceptance of the mmol/mol system for Hb_(A1c) as recommended by IFCC, i.e., the new unit and reference ranges, are becoming only slowly accepted outside of Europe where it seems that expressing Hb_(A1c) values either only in per cent units or with parallel reporting of percent and mmol/mol will continue. We believe that these issues should be resolved in the future and that it would avoid confusion if mmol/mol unit for Hb_(A1c) were to gain worldwide acceptance.

Healthy ranges of serum alanine aminotransferase levels in Iranian blood donors

AIM: The healthy ranges for serum alanine aminotransferase(ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors. METHODS: A total of 1 939 blood donors were included.ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels werecomputed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels.RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L,and for non-overweight men was 40 U/L.CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.