The metabolic response to insulin deprivation in idiopathic brittle diabetes

To test the hypothesis that frequent episodes of ketoacidosis and severe hyperglycaemia in brittle diabetes result from an exaggerated response to insulin withdrawal, the metabolic response to insulin deprivation in 16 severely brittle female diabetics has been compared with that in 6 C-peptide negative stable female diabetic patients of similar age and body weight. 4 hr after stopping insulin infusion, blood glucose was significantly higher in the brittle diabetics (22.8 vs 17.0 mmol/l, p less than 0.001) but blood 3-hydroxybutyrate was not different (1.8 vs 1.6 mmol/l). Concentrations of free insulin and counter-regulatory hormones were similar, basally and during the deprivation. Insulin antibody levels were significantly elevated in the brittle patients (11.2 vs 5.2 mmol/l, p less than 0.05) and there was no relationship between glucose or ketone body response and antibody level. Blood lactate, pyruvate, alanine and glycerol were significantly elevated basally in the brittle diabetic patients, but did not respond differently to insulin deprivation. Basal lactate and pyruvate concentrations were significantly correlated with overnight insulin requirements (lactate, rs 0.62, p less than 0.05; pyruvate, rs 0.70, p less than 0.05) suggesting that the elevated basal concentrations resulted from the higher peripheral insulin delivery rates required to maintain overnight normoglycaemia in the brittle patients. We conclude that although there are demonstrable abnormalities of intermediary metabolism in brittle diabetics, neither elevated levels of counter-regulatory hormones, nor an exaggerated response to insulin withdrawal explains the frequent episodes of ketoacidosis in these patients.