Observations on the metabolic basis for altered insulin dose distribution in diabetic pregnancy

Insulin requirements are known to increase during pregnancy, but it has not been reported whether this relates to prandial or basal requirements, or to a change in insulin pharmacokinetics. In nine unselected pregnant patients the pattern of this increase was that of a large increase in the total morning dose and a reduction in the evening dose of intermediate acting insulin, in order to maintain good control while avoiding nocturnal hypoglycaemia. 24 h metabolic profiles were carried out in these patients in the third trimester of pregnancy. Plasma free insulin profiles reflected the dosage patterns and there was no change in insulin metabolic clearance rate in pregnancy. Pregnant diabetic patients had a broad peak of free insulin concentration around lunchtime followed by a steady fall until next morning. Blood lactate and alanine were higher than normal and 3-hydroxybutyrate lower than is usually seen in non-pregnant diabetic patients. The observations suggest that there may be differential changes in insulin sensitivity in diabetic pregnancy between the fed and fasting states, and that the therapeutic response to this causes a measurable metabolic change.