Double blind clinical and laboratory study of hypoglycaemia with human and porcine insulin in diabetic patients reporting hypoglycaemia unawareness after transferring to human insulin

Abstract

Objectives-To compare awareness of hypoglycaemia and physiological responses to hypoglycaemia with human and porcine insulin in diabetic patients who reported loss of hypoglycaemia awareness after transferring to human insulin. Design-Double blind randomised crossover study of clinical experience and physiological responses during slow fall hypoglycaemic clamping with porcine and human insulin. Setting - Clinical investigation unit of teaching hospital recruiting from diabetes clinics of five teaching hospitals and one district general hospital. Subjects - 17 patients with insulin dependent diabetes mellitus of more than five years' duration who had reported altered hypoglycaemia awareness within three months of transferring to human insulin. Main outcome measures - Glycaemic control and frequency of hypoglycaemic episodes during two months' treatment with each insulin. Glucose thresholds for physiological and symptomatic responses during clamping. Results - Glycaemic control did not change with either insulin. 136 hypoglycaemic episodes (eight severe) were reported with human insulin and 149 (nine severe) with porcine insulin (95% confidence interval -4 to 2·5, p=0·63). 20 episodes of biochemical hypoglycaemia occurred with human insulin versus 18 with porcine insulin (-0·8 to 1, p=0·78). During controlled hypoglycacmia the mean adrenaline response was 138 nmol/l/240 min for both insulins; neurohormonal responses were triggered at 3·0 (SE 0·2) versus 3·1 (0·2) mmol/l of glucose for adrenaline and 2·5 (0·1) versus 2·5 (0·1) mmol/l for subjective awareness. Conclusions - These data suggest that human insulin per se does not affect the presentation of hypoglycaemia or the neurohumoral, symptomatic, and cognitive function responses to hypoglycaemia in insulin dependent diabetic patients with a history of hypoglycaemia unawareness.