Alan G Rumley

Free Radical Activity and Hemostatic Factors in NIDDM Patients With and Without Microalbuminuria

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA′] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (Bβ15–42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA′ was elevated in the microalbuminuric patients compared with control subjects (P < 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P < 0.05) and control subjects (P < 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P < 0.01). Except for Bβ15–42, all the hemostatic variables were increased (P < 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P < 0.03) and t-PA (P < 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria. These changes may contribute to vascular disease, which is particularly prevalent in NIDDM patients with microalbuminuria.

Glycated haemoglobin values: problems in assessing blood glucose control in diabetes mellitus

Abstract Objective: To see whether two measures of glycated haemoglobin concentration - the haemoglobin A1 (HbA1) value and the haemoglobin A1c (HbA1c) value - assess blood glucose control differently in diabetes. Design: Diabetic patients had glycaemic control assessed on the basis of HbA1 and HbA1c values measured by the same high performance liquid chromatography instrument and on the basis of HbA1 measured by electrophoresis. Setting: A diabetic outpatient clinic. Subjects: 208 diabetic patients and 106 non-diabetic controls. Main outcome measures: Glycated haemoglobin concentrations classified according to European guidelines as representing good, borderline, or poor glycaemic control by using standard deviations from a reference mean. Results: Fewer patients were in good control (25;12%) and more poorly controlled (157;75%) as assessed by the HbA1c value compared with both HbA1 assays (39 (19%) and 130 (63%) respectively when using high performance liquid chromatography; 63 (30%) and 74 (36%) when using electrophoresis). The median patient value was 8.0 SD from the reference mean when using HbA1c, 5.9 when using HbA1 measured by the same high performance liquid chromatography method, and 4.1 when using HbA1 measured by electrophoresis. Conclusions: Large differences exist between HbA1 and HbA1c in the classification of glycaemic control in diabetic patients. The HbA1c value may suggest a patient is at a high risk of long term diabetic complications when the HbA1 value may not. Better standardisation of glycated haemoglobin measurements is advisable.

Urine dipstick testing: comparison of results obtained by visual reading and with the Bayer CLINITEK 50

Bayer Multistix urine test strips have been in widespread use for many years for point-of-care testing. They rely on the visual comparison of colour development with a chart for semiquantitative results. These tests are essentially for screening; positives should be followed up by conventional laboratory tests. The accuracy of these tests has been assessed and their widespread use demonstrates their clinical value. The Bayer Diagnostics CLINITEK 50 Urine Chemistry Analyser (Bayer PLC, Newbury, UK) is a portable re ectance meter for reading Bayer reagent strips for urinalysis. The timing of the test is automatic and the results are printed when analysis is complete. We use the Bayer Multistix SG at the diabetic clinic and record protein, blood, glucose and ketones (bilirubin, speci®c gravity, pH and urobilinogen are also measured but not recorded). If a urinalysis produces a negative or trace result for protein or a negative result for blood, the sample is also analysed for microalbumin by turbidimetry, but if the results are positive microalbumin is not measured. The results are given to the clinical staff in time for the consultation. This study was carried out to compare the performance of visual reading compared with re ectance meter measurement.

The Effect of Haemolysis on Blood Glucose Meter Measurement

A study was performed to assess the effect of varying degrees of sample haemolysis on the measurement of blood glucose by the Accutrend, Companion 2, ExacTech, Glucometer II, Glucometer 4, One Touch II, and Reflolux II blood glucose meters. Fresh venous blood was sonicated to induce complete haemolysis and then added in increasing proportions to homologous untreated blood to obtain nine samples with free haemoglobin concentrations up to 50 g I−1. The Accutrend meter showed the only significant (p<0.05) linear relationship to degree of haemolysis (r = 0.988, p<0.0001). For every 7 % of red cells lysed, the Accutrend value increased by 15 %. All other meters gave results which were within 15 % of the non‐haemolysed value. However, extreme (100 %) haemolysis not only affected the Accutrend (glucose value 108 % greater than reference) but also the ExacTech (+98 %), the Glucometer II (‐32 %), and the Companion 2 (‐41 %). Thus, unwitting use of a haemolysed sample to measure whole blood glucose may, with the Accutrend in particular, lead to erroneous results.

Improving the quality of near-patient blood glucose measurement.

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Evaluation of Glycaemic Control Limits Using the Ames DCA 2000 HbA1c Analyser

The Ames DCA 2000 is a benchtop analyser that measures HbA1c by an agglutination inhibition immunoassay using a monoclonal antibody. Laboratory and nursing staff measured HbA1c on‐site in 78 patients with Type 1 diabetes at the outpatient clinic. Significant correlations were noted with both the Corning Glytrac total HbA1 assay (r = 0.89) and the Novoclone assay for HbA1c (r = 0.95). Mean within‐assay CV was 1.6% and 3.0% at HbA1c of 5.4% and 13.0%, respectively, while between‐assay CVs were 4.2% and 3.8%. These results are as good as our routine laboratory method based on the Corning HbA1 assay. Locally derived reference population data for HbA1c were produced and patients were assigned to categories of good, acceptable, and poor glycaemic control using conventional recommendations for Type 2 diabetes. There was poor agreement between the methods, with only 22% of patients achieving good/acceptable control using the DCA 2000, while 46% of patients had an HbA1 in this range. It appears that the convention for derivation of control limits for HbA1 does not hold for this HbA1c assay.

Reply from E.S. Kilpatrick and A.C. Rumley

The situations which could conceivably lead to the physiological sequelae which are being duplicated occur in states of extreme physiological perturbations. The ExacTech system i s a reliable and accurate blood glucose monitoring system aimed primarily at the ambulatory patient who needs to maintain glucose homeostasis. Our label copy clearly has many instances cautioning against potential errors if iised in situations of extremes of haematocrit, patients with circulatory failure, or undergoing oxygen therapy. This paper clearly aims to draw conclusions about the use of ExacTech in similar extreme situations. We are grateful for the opportunity of clarifying the situation with regard to inappropriate use of ExacTech outside label copy claims. Regards,

Effect of Favourable Treatment of Samples on Indices of Performance in External Quality Assessment Schemes

This study was carried out to examine the effect on performance, as assessed by external quality assessment schemes, of (a) replicate analysis of external quality assessment samples, and positioning of external quality assessment samples immediately after the calibrants, and (b) alteration of results on the basis of previous performance in order to bring them closer to the method mean values obtained from all laboratories participating in the external quality assessment scheme. Indices of performance were then compared with those obtained from our normal practice where external quality assessment samples were treated as patient samples. Using these methods we were unable to improve significantly our precision or league ranking based on precision over the six-month period of study. We were able to reduce our bias from method means but at the expense of making precision and league ranking worse.