We have studied levels of glycated haemoglobin in a sample of 223 people aged over 40 years without known diabetes mellitus screened in a community study. Each had a glucose tolerance test and glycated haemoglobin measured by four methods - agar gel electrophoresis with and without removal of Schiff base, affinity chromatography and isoelectric focusing. The correlation coefficients between 2 h blood glucose and levels of glycated haemoglobin were between 0.43 and 0.64. This poor correlation was not explained on the basis of assay or biological variability of either 2 h blood glucose or glycated haemoglobin. Multiple regression analysis showed that other assays of glycated haemoglobin contributed to the variance of any single glycated haemoglobin value by 0.1%-52.9% (median 12.8%) compared to the variance of 18.6%-41.4% (median 30.8%) explained by 2 h blood glucose alone, suggesting that in a non-diabetic population, the degree of glucose intolerance may explain only one third of the variance of glycated haemoglobin levels, but other factors operate to produce consistent changes in levels of glycated haemoglobin. Investigation of 42 subjects with consistently high (20 subjects) or low (22 subjects) levels of glycated haemoglobin relative to their 2 h blood glucose level showed no difference in age, gender, body mass index, haemoglobin levels or smoking, although 50% of low glycators had impaired glucose tolerance. Neither ambient blood-glucose levels, as estimated on two five-point blood-glucose profiles, nor dietary intake of carbohydrate, starch, sugars, fibre or alcohol, explained the difference between high and low glycators. The determinants of the consistent interindividual differences in levels of glycated haemoglobin in non-diabetic subjects remain to be determined.
We assessed the utility of four methods of glycated hemoglobin assay (agar gel electrophoresis with Schiff base, agar gel electrophoresis with prior removal of Schiff base, boronate affinity chromatography, and isoelectric focusing) as screening tests for diabetes mellitus, studying 223 subjects undergoing an oral glucose-tolerance test after fasting and 2 h after ingestion of 75 g of glucose. Assessment of glucose tolerance status according to the 1980 World Health Organization diagnostic criteria indicated that 13 subjects (5.8%) had diabetes, 48 (21.5%) had impaired glucose tolerance, and nine (4.0%) could not be classified (six of these because of missing values). Use of receiver-operating characteristic curves to compare the assays as screening tests showed the affinity chromatography assay to be superior. Assays for glycated hemoglobin after fasting had better precision than post-glucose-load assays as screening tests, and test characteristics of glycated hemoglobin assays on fasting subjects were similar to those of the blood-glucose estimation after fasting. We conclude that measurement of glycated hemoglobin may be a useful screening test for diabetes, and that such measurement of stable glycated hemoglobin is as accurate as measurement of fasting blood-glucose in screening for diabetes. For this use, we found methods that measure stable glycated hemoglobin superior to that measuring both stable and labile Schiff-base fractions.
We have studied blood glucose concentrations 2 h after a 75g glucose load, and glycohaemoglobin as assayed by agar gel electrophoresis, in 1084 subjects over the age of 40 in a community screening survey. There were 16 newly diagnosed diabetic women (2.7%) and 11 men (2.5%). The mean level of 2h blood glucose was 5.6 +/- 2.04 mmol/l in women and 5.33 +/- 2.14 mmol/l in men (p less than 0.002) but when corrected for age and weight the mean levels were 5.55 mmol/l in women and 5.40 mmol/l in men (p greater than 0.2). Mean levels of glycohaemoglobin were 7.30 +/- 1.10% in women and 7.17 +/- 1.18% in men (p less than 0.02) but when adjusted for blood glucose and age these were 7.25% in both sexes (p greater than 0.9). Differences in glucose tolerance in this population are related to differences in age and weight. There is no evidence for differences in glycosylation in men and women.
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