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 24 hour insulin requirements to maintain euglycemia were assessed by means of feed back controlled insulin infusion. For the study steady state conditions, i.e. bed rest and fasting were required. Venous blood samples were collected, at 2 hour intervals, for the measurement of glucagon, growth hormone and cortisol. During the day, the insulin demand showed small changes. However, the early morning requirement for insulin was twice as much as the daytime demand (dawn phenomenon). There was a significant difference (p < 0.05) in the insulin requirement between 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 during 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 the 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 morning. The cortisol concentration indicated a circadian variation. The median was significantly higher from 4.00 to 8.00 hours in comparison with the median at 20.00 to 24.00 hours (p < 0.05). The results of the study showed that the early morning rise in the insulin demand is related to the increased early morning cortisol secretion and to the nocturnal peaks of growth hormone concentration (p < 0.05).