C. A. Jackson

Unexplained variability of glycated haemoglobin in non-diabetic subjects not related to glycaemia.

SummaryWe 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 bloodglucose 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 nondiabetic subjects remain to be determined.

A comparison of the relationships of the glucose tolerance test and the glycated haemoglobin assay with diabetic vascular disease in the community. The Islington Diabetes Survey.

We have compared the relationships of fasting and 2 h blood-glucose during a 75 g oral glucose tolerance test, and those of an affinity chromatography assay of glycated haemoglobin, with the presence of vascular complications of diabetes mellitus in 223 subjects without known diabetes aged over 40 years selected from a community screening study population. The subjects included 15 (6.9%) with newly diagnosed diabetes and 52 (24.1%) with impaired glucose tolerance. Employing receiver operating characteristic analysis, the tests were similar in their relationship with three cases of retinopathy, 19 of microalbuminuria and six of peripheral neuropathy. The prevalence of coronary heart disease, defined as angina, myocardial infarction, or electrocardiographic changes of ischaemia, increased linearly across all four quartiles of both 2 h blood glucose and glycated haemoglobin concentration, but using logistic regression analysis, 2 h blood glucose was a better predictor of coronary heart disease than glycated haemoglobin. Receiver operating characteristic analysis also showed that 2 h blood glucose generally performed better than any of four assays of glycated haemoglobin in classifying those subjects with coronary heart disease.

Glucose Intolerance and Hypertension in North London: The Islington Diabetes Survey

In a general practice‐based screening survey, 1040 (63.3%) of a randomly selected sample of 1644 people over the age of 40 years were examined for diabetes mellitus (DM) and hypertension (HT). Glucose intolerance was assessed by a single 2 h post‐load blood glucose estimation and HT (diastolic blood pressure ≥95mmHg by a single blood pressure reading) or being on anti‐hypertensive treatment.

The Glycohaemoglobin Assay as a Screening Test for Diabetes Mellitus: The Islington Diabetes Survey

Blood glucose 2 h after an oral glucose load (2hBG) and glycohaemoglobin (GHb) (Corning agar‐gel electrophoresis) levels were used as screening tests in a general practice diabetic screening programme. The diagnosis of diabetes (DM) was based on a separate oral glucose tolerance test (OGTT) in 223 of 1040 screened subjects, selected as a stratified sample biased towards higher levels of 2hBG and GHb. The GHb assay was also repeated at the recall examination and urine was tested for glycosuria before and after glucose administration.

The abbreviated glucose tolerance test in screening for diabetes: the Islington Diabetes Survey.

The World Health Organization has recommended a single 2‐h post‐glucose load blood glucose level as a screening test for diabetes mellitus in epidemiological surveys. We have assessed its characteristics, when compared with a full supervised glucose tolerance test (OGTT), in estimating prevalence, and in diagnosing diabetes in the individual patient. A stratified sample of 223 of 1040 subjects who had participated in a diabetic survey that utilized a single capillary 2‐h blood glucose estimation as a screening test were recalled for formal glucose tolerance testing. The numbers of subjects with diabetes at screening and at recall were similar (14/212, 6.6 %; 13/216, 6.0 %) but only 9 subjects were so classified on both occasions. Thirty‐five subjects (16.5 %) were suspected of having impaired glucose tolerance (IGT) at screening, and 52 (24.1 %) at recall. There was substantial reclassification from screening IGT, with 3/35 worsening to diabetes, and 10/35 returning to normal. Capillary 2‐h glucose levels gave an accurate assessment of the prevalence of diabetes but underestimated that of IGT. On the full OGTT, little difference in classification was found when the values of fasting and 1‐h blood glucose were used in addition to those of the 2‐h blood glucose used alone. The 2‐h glucose had a within‐subject coefficient of variation of 32.4 % which produced substantial reclassification of subjects with levels close to the diagnostic levels for diabetes, and this implies that such individuals should not be classified as having diabetes on the basis of a single glucose tolerance test. This variability is similar to that previously demonstrated in repeat OGTTs, suggesting that the unsupervised drink and the timing of the 2‐h sample do not contribute substantially to the variability.

The relationship of hospital admission and fatality from myocardial infarction to glycohaemoglobin levels

SummaryWe have performed a study to assess the relative contributions of increased hospital admission rates with acute myocardial infarction and increased hospital case fatality to the excess mortality of subjects with elevated levels of glycohaemoglobin from myocardial infarction. Glycohaemoglobin levels were estimated by isoelectric focussing in 397 subjects without known diabetes mellitus admitted with myocardial infarction and compared with a control population reconstructed from a community sample of 1084 subjects without known diabetes mellitus screened in general practice. In the case-control comparison, glycohaemoglobin levels above the 90th centile were associated with relative risks of 3.1 (95% confidence interval 1.4–6.8) for admission with myocardial infarction and 5.3 (95% confidence interval 2.1–13.4) for death in hospital. Elevated glycohaemoglobin on admission was a predictor of both death and cardiac pump failure among those admitted with myocardial infarction, as was the presence of known diabetes. In those over 40 years of age, the top 1% of the glycohaemoglobin distribution contribute 4.3% of admissions and 9.6% of hospital deaths with myocardial infarction.

Short-term effect of a 75 g oral glucose load on glycohaemoglobin levels

Two hundred and twenty-three subjects out of a total of 347 with various degrees of glucose tolerance were recalled after a screening survey for diabetes. They were a randomly selected sample of people over the age of 40 and they underwent a formal 75 g glucose tolerance test in order to assess the effect of a glucose load on glycohaemoglobin levels measured by four different assay methods. Oral glucose loading was found to affect glycohaemoglobin levels only when these were measured by an agar-gel electrophoretic method that did not remove the labile aldimine-linked Schiff base fraction. The increase in glycohaemoglobin during the glucose tolerance test as estimated by this method was proportional to the 2 h blood glucose level. Glycohaemoglobin levels measured by agar-gel electrophoresis with elimination of the Schiff base, by affinity chromatography and by iso-electric focussing, were not affected by a 75 g oral glucose load. We conclude that blood samples for glycohaemoglobin assay may be collected at any time of the day, without regard to the subjects previous food intake, provided an assay method is used that removed the aldimine-linked labile fraction.

Glucose tolerance and glycohaemoglobin: a population study of male-to-female ratios.

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 5.62±2.04 mmol/l in women and 5.33±2.14 mmol/l in men (p<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>0.2). Mean levels of glycohaemoglobin were 7.30±1.10% in women and 7.17±1.18% in men (p<0.02) but when adjusted for blood glucose and age these were 7.25% in both sexes (p>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.

Changes in Injection‐site Blood Flow and Plasma Free Insulin Concentrations in Response to Stress in Type 1 Diabetic Patients

In order to test the effect of stress on injection‐site blood flow and blood glucose control, 16 C‐peptide negative patients were studied on a stress day, when a 30‐min Stroop Colour‐Word Test was completed, and a control day, when a cartoon was shown. Unmodified insulin was injected subcutaneously into the thigh before the test, and injection‐site blood flow measured throughout the experiment with a thermal clearance probe. Blood glucose and plasma free insulin, glucagon, growth hormone, cortisol, and catecholamines were measured at intervals before, during, and after stress. Patients showed a significant overall rise in injection‐site blood flow with the Stroop test from 4.1 (SD 1.6) to 5.2 (1.8) ml 100‐g−1 min−1 (increase 38.1 (37.8) %, p < 0.001). There was no overall significant difference between stress and control days in blood glucose or plasma free insulin levels, with differences in mean blood glucose levels during stress between the 2 days varying from −4.2 mmol l−1 to +6.3 mmol l−1 in individual patients. The increase in injection‐site blood flow with stress correlated significantly with the increase in plasma free insulin concentration both during (r = 0.55) and after stress (r = 0.71). Differences in blood glucose concentration between stress and control day for each patient showed strong correlation with differences in plasma free insulin both during (r = −0.73) and after stress (r = −0.79). Differences in counter‐regulatory hormones occurred but correlated poorly with blood glucose difference. Thus, stress affects the blood flow at the injection site, and this in turn affects insulin absorption. Most of the blood glucose response to stress is explained by changes in free insulin concentration.