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The mechanism whereby hyperglycaemia inhibits neutrophil function is unclear. We have examined neutrophil killing of Candida albicans in the presence of increased concentrations of glucose and galactose. Killing was abolished in 50 mmol/l glucose and 10 and 50 mmol/l galactose. The oxidative phase of killing was examined using lucigenin-enhanced chemiluminescence. An increase in glucose concentration from 5 to 50 mmol/l produced a fall in chemiluminescence output from 128.5 +/- 16.8 (mean +/- SE) to 82.2 +/- 9.8 mV min (a reduction of 36%). These data suggest the existence of aldose reductase activity in neutrophils and using gas chromatography we have demonstrated the presence of sorbitol in extracts of diabetic neutrophils. As oxidative killing and sorbitol production are both NADPH-dependent the inhibition of killing is likely to be due to competition for this electron donor. This abnormality of neutrophil function may aggravate various infections in the patient with diabetes.

Summary.In a single blind randomised cross-over study, 40 patients were changed from ordinary bovine to highly purified porcine insulins for a period of 6 months. Half were later rechallenged with bovine insulin. Sequential determinations of IgG insulin binding capacity for bovine insulin were correlated with insulin dose and diabetic control. After changing to highly purified insulins the following correlations were observed between percentage change in insulin dose and change in insulin binding capacity: at 2 months r = 0.35 (p < 0.05), at 4 months r = 0.38 (p < 0.02) and at 6 months r = 0.37 (p < 0.02). When the patients who showed substantial changes in HbA~ were removed from the analysis, the remaining 29 demonstrated a clearer relationship between these two variables (r = 0.56,p < 0.01). Removal of patients with a low initial insulin binding capacity left 18 patients with stable diabetes, and changes in insulin binding capacity and insulin dose showed an even closer correlation for this group (r = 0.77, p < 0.001). A similar degree of positive correlation was observed after rechallenge with bovine insulin. We conclude that the level of circulating insulin antibody affects the dose of insulin required to maintain stable diabetic control.Key words: Insulin, insulin antibody, diabetic control.Most patients treated with ordinary bovine insulins develop circulating insulin antibodies [1]. Higt/ly purified porcine insulins are much less immunogenic and patients changing to these insulins often experience a reduction in insulin requirement [2,3], a fall in circulating insulin binding capacity [4] and an increase in circulating levels of free insulin [5]. Although antibody mediated insulin resistance is unusual [6], injection site lipoatrophy is a common complication of the use of ordinary bovine insulins [7]. Other possible effects of insulin antibodies are less clear. Andersen [8] showed that the presence of antibodies was associated with a reduction in the honeymoon period independent of the level of diabetic control and the hypothesis that insulin antibody might 'buffer' the effect of circulating insulin [9] has not been substantiated. We report a study of the relationship between changes in insulin antibody, insulin dose and diabetic control in established diabetics changing from ordinary bovine soluble and isophane to highly purified porcine equivalents and the effects of rechallenge with the original insulins. Patients and MethodsThe practice of one hospital diabetologist was surveyed to identify all the patients aged between 16 and 65 years who had had diabetes for at least 3 years and had been treated regularly with ordinary bovine soluble and isophane insulins for at least that time. Those who were blind or pregnant or who had other serious medical or psychological illness were excluded. Fifty-nine of the 71 eligible patients consented to be studied and 40 completed the 18 month protocol. These 14 women and 26 men were aged between 16 and 64 years (mean 40 years). The age at diagnosis ranged from 2 to 5...

Summary Three cases are described showing a seasonal exacerbation of their nephrotic syndrome in association with an atopic trait and grass pollen allergy. The first patient has a history of four consecutive seasonal relapses each requiring steroid therapy. Following a course of desensitization injections he has now been free of relapse for 3 consecutive years. The second patient has also had a recurrent steroid‐sensitive nephrotic syndrome often associated with the pollen season and allergic rhinitis. In this patient a course of cyclophosphamide has reduced his tendency to relapse. The third patient who has been on continuous prednisone therapy shows a seasonal increase in proteinuria. Serum changes in the first two patients include: a seasonal rise in total and grass pollen specific IgE; the continued presence of grass pollen specific IgG throughout the year but with a reduction during the pollen season in association with a more pronounced fall in the total IgG level; a depression in the C3 level in association with each major relapse; a mild rise in the I‐K titre and a positive result in the C1q test for circulating complexes. A renal biopsy performed on the first patient when in relapse showed minor histological changes only and IgG. IgM, IgA, IgD, IgE, C3 and fibrinogen were undetectable by immunofluorescent examination. The probable mechanism for the development of proteinuria in these patients is discussed.

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