Quantifying early diabetic retinopathy.

A precise and accurate method of numerically quantifying diabetic retinopathy, on standardised retinal colour photographs, has been developed which allows small changes and trends to be monitored. Colour slides are projected onto a screen and features noted on an acetate sheet which provides a permanent record. Sector analysis showed microaneurysms and haemorrhages to occur most often at the temporal-to-macula area, exudates at the macula and cotton wool spots on the nasal side of the retina. Seventy percent of microaneurysms appeared in the previous year, irrespective of the severity of the retinopathy. In proportion to their usual relative prevalences, after normalisation of distribution, the various features can be combined to provide a single value, the Retinopathy Index. This provides an overall assessment of retinopathy which is suitable for comparing the progress of mild retinopathy in prospective studies.

NADPH-oxidising activity in lens and erythrocytes in diabetic and nondiabetic patients with cataract.

Levels of lens aldose reductase, aldehyde dehydrogenase activity, and erythrocyte NADPH-oxidising (or glyceraldehyde reductase) activity were determined in 17 diabetic and 16 nondiabetic patients undergoing cataract extraction. Lens aldose reductase and aldehyde dehydrogenase activities were significantly lower in diabetics than in nondiabetics. Both enzymes showed significant inverse correlations with grouped HbA1c and fasting blood glucose levels. By contrast, erythrocyte NADPH-oxidising activity showed a significant positive correlation with grouped HbA1C. It is suggested that a direct effect of the glycaemic status on the lens enzymes is masked by a loss of enzymes secondary to the development of cataract. It is not yet possible to say whether erythrocyte NADPH-oxidising activity can be used to monitor aldose reductase activity in the lens or other tissues in clinical trials of aldose reductase inhibitors.

The relationship between diabetic control and retinopathy in a group of diabetic teenagers.

Twenty insulin-dependent diabetic teenagers from the Oxford pediatric diabetic clinic were recruited to study the relationship between diabetic control and retinal microvascular disease. Two patients (10%) had evidence of minimal background diabetic retinopathy on careful ophthalmoscopy. Retinal color photography and fluorescein angiography each revealed retinopathy in 5 patients (25%) and together revealed retinopathy in 7 patients (35%). Color photography demonstrated retinopathy which had not been discovered on ophthalmoscopy. The presence of retinopathy was related to the duration of diabetes (p less than 0.02) and the glycosylated hemoglobin level (p less than 0.01). It is concluded that multiple field color photography is a useful method of assessing patients with minimal or no ophthalmoscopic retinopathy.

Genetic susceptibility to the development of retinopathy in insulin-dependent diabetics.

HLA types and blood glucose control were investigated in 127 insulin-dependent diabetics with different grades of severity of retinopathy. The means of all afternoon clinic blood glucose levels from the diagnosis of diabetes were 9.9 +/- 2.1 mmol/L for patients with no retinopathy, 11.8 +/- 2.1 mmol/L for patients with background retinopathy, and 12.4 +/- 2.1 mmol/L for patients with proliferative retinopathy (P less than 0.0001). HLA-DR4 was present in 61 of 87 patients (70%) with background or proliferative retinopathy and 21 of 39 (54%) with no retinopathy. The frequency of HLA-DR4 was lowest in patients with no retinopathy despite "poor control" (mean blood glucose greater than or equal to 11.5 mmol/L) and highest in those who had developed retinopathy despite "good control;" the frequencies of HLA-DR2 showed the reverse pattern. Mantel-Haenszel tests were used to calculate the odds ratios for the presence of retinopathy associated with "poor control" and with HLA-DR4, since each modified the effect of the other. The odds ratio for retinopathy associated with "poor control" was 6.7 (P less than 0.0001). The odds ratio with HLA-DR4 was 3.7 (P less than 0.005). When both risk factors were present, the odds ratio increased to 33.3 (P less than 0.0001). Genetically determined factors appear to influence susceptibility to retinopathy in insulin-dependent diabetics.

Unsuspected hypoglycaemia, haemoglobin A1 and diabetic control.

Control of diabetes in a group of 82 insulin-treated diabetics was assessed by in-patient 24-hour plasma glucose profiles and haemoglobin A1 (HbA1) estimation. Thirty-two of these patients (39 per cent) had hypoglycaemia (plasma glucose less than or equal to 2 mmol/l) which was rarely associated with symptoms. Twenty-seven (61 per cent) of 44 patients who took a series of out-patient pre-prandial capillary blood samples over a three-day period had hypoglycaemia. Conventional measurements of diabetic control including fasting plasma glucose and HbA1, were lower in patients with hypoglycaemia than in those without. Rebound hyperglycaemia following hypoglycaemia was not seen and its absence was not due to diabetic autonomic neuropathy. Cortisol/creatinine ratios in early morning urine samples were similar in patients with and without nocturnal hypoglycaemia, consistent with the absence or rebound hyperglycaemia. Diabetic retinopathy was less prevalent in patients with hypoglycaemia, possibly reflecting better long-term diabetic control in this group. HbA1 concentration reflects overall blood glucose control in diabetes but near-normal levels must be interpreted with caution since they may be associated with recurrent hypoglycaemia.

Erythrocyte glyceraldehyde-reductase levels in diabetics with retinopathy and cataract.

The activity levels of glyceraldehyde reductase, an aldose-reductase-like enzyme present in the erythrocyte, were determined in 104 subjects, who were divided into five groups--diabetics with retinopathy and cataract, diabetics with retinopathy and no cataract, diabetics with no retinopathy and no cataract, non-diabetics with senile cataract, and non-diabetic normal controls. Diabetics with retinopathy and cataract had significantly higher mean enzyme activity levels than normal control subjects (2.5 fold increase, p < 0.001); so had diabetics with retinopathy but no cataract (2 fold, p < 0.01) and patients with senile cataract (1.5 fold, p < 0.05). Juvenile diabetics had a significantly higher enzyme level than maturity onset diabetics. There was no significant difference in glyceraldehyde reductase between normal controls and diabetics without retinopathy or cataract, and no significant difference in polyol-dehydrogenase activity levels between any group studied. Enzyme activity did not correlate with age or glycosylated haemoglobin (HbA1c) levels. The increase in levels of erythrocyte glyceraldehyde reductase were due to increased amounts of active enzyme, rather than to elaboration of new kinetic pathways.