CIRCADIAN VARIATION OF INSULIN REQUIREMENT IN INSULIN-DEPENDENT DIABETES-MELLITUS - THE RELATIONSHIP BETWEEN CIRCADIAN CHANGE IN INSULIN DEMAND AND DIURNAL PATTERNS OF GROWTH-HORMONE, CORTISOL AND GLUCAGON DURING EUGLYCEMIA

In 13 subjects with type 1 (insulin dependent) diabetes mellitus the 2 4 hour insulin requirements to maintain euglycemia were assessed by me ans of feed back controlled insulin infusion. For the study steady sta te conditions, i.e. bed rest and fasting were required. Venous blood s amples were collected, at 2 hour intervals, for the measurement of glu cagon, growth hormone and cortisol. During the day, the insulin demand showed small changes. However, the early morning requirement for insu lin was twice as much as the daytime demand (dawn phenomenon). There w as a significant difference (p < 0.05) in the insulin requirement betw een 6.00 to 8.00 hours in the morning and 12.00 to 16.00 hours in the afternoon. The plasma glucagon levels showed no significant changes du ring the euglycemic period (median range from 28.7 to 30.1 ng/ml) (p < 0.05). The median of the growth hormone level decreased throughout th e night from a peak of 4.41 ng/ml at midnight to a nadir of 1.05 ng/ml at 4.00 hours. There was a significant difference (p < 0.05) between the growth hormone concentration between midnight and the early mornin g. The cortisol concentration indicated a circadian variation. The med ian was significantly higher from 4.00 to 8.00 hours in comparison wit h the median at 20.00 to 24.00 hours (p < 0.05). The results of the st udy showed that the early morning rise in the insulin demand is relate d to the increased early morning cortisol secretion and to the nocturn al peaks of growth hormone concentration (p < 0.05).