The 24-hour excursion and diurnal rhythm of glucose, insulin, and C-peptide in normal pregnancy

Abstract

A longitudinal study to quantitate the progressive effects of the second and third trimesters of normal pregnancy on the levels of plasma glucose, immunoreactive insulin (IRI), and C-peptide (C-P) at hourly intervals throughout the 24-hour “metabolic clock” was made. Identical studies were conducted in each subject at 6 to 11 weeks post partum and these data were used as nonpregnant control values. Data analyses were made to determine the role of meal-activity-sleep cycles as physiologic modifiers. A diurnal rhythm of plasma glucose, IRI, and C-P was demonstrated in all study periods. During meals anabolic values of plasma glucose (increments above the 24-hour mean) in response to meal intake were remarkably small, ranging between 30 and 35 mg/100 ml in the postpartum state, and were not significantly modified by pregnancy. The corresponding IRI levels were similarly small with a mean increase on only 31% in pregnancy. However, during the third but not the second trimester of pregnancy, the peak anabolic values for both plasma glucose and IRI were significantly (p < 0.05) increased and consequently the 2-hour postprandial glucose and IRI levels were significantly elevated after meal ingestion. When values were compared with those of the postpartum state, there was a progressive increase in the degree of catabolic excursion (decrease from 24-hour mean) of plasma glucose during sleeping hours from the second to third trimester of pregnancy. This resulted in a state of relative hypoglycemia, with significantly reduced fasting (8 a.m.) plasma glucose and 24-hour integrated glucose levels. This relative nocturnal hypoglycemia was associated with synchronous IRI values but without concomitant reduction of absolute IRI levels. Consequently, the fasting, premeal, and 24-hour IRI/glucose ratios were increased. Thus, basal insulin secretion is significantly augmented relative to levels of plasma glucose, but a quantitative increase in insulin secretion following food intake is relatively small during pregnancy. These observations together with the finding of a marked diurnal rhythm of plasma glucose and relative nocturnal hypoglycemia provide important insights for the formulation of guidelines for the timing, amount, and mode of delivery of exogenous insulin necessary for the management of diabetic patients during pregnancy.