The Characterization of Pregnancy Induced Changes in Glucose Metabolism
Abstract
Many reports indicate that pregnancy is a diabetogenic state in which there is both insulin resistance and an exaggerated maternal glucose and insulin response to food ingestion. However, the magnitude of these aberrations and their temporal relationship have not been adequately characterized. This study utilizes the hyperglycemic clamp technique to investigate the insulin secretory response and tissue sensitivity to insulin under hyperglycemic conditions in normal and gestational diabetic pregnancies. Our results indicate that third trimester normal pregnancy is characterized by an increased first phase ( 108 . 81+/-13 . 03 uU/ml) and second phase (228 . 57+/-43 . 40 microunits/ml) insulin secretory response as compared to non-pregnant controls (72 . 93+/-15. 76, 103 . 02+8/-12 . 43)(p<0.05). However, C-peptide values did not mirror those of insulin in that normal pregnant women during the third trimester of pregnancy demonstrated a significantly lower C-peptide to insulin ratio than either non-pregnant controls or gestational diabetic women in their third trimester (p<0.05). In contrast to normal pregnant women, gestational diabetic women in their third trimester of pregnancy showed Glucose uptake under hyperglycemic conditions tended to decrease progressively through pregnancy and was significantly lower than non-pregnant controls (10 . 60+/-1. 19 mg/kg/min) in the third trimester of normal pregnancy (7. 20+/-0. 79 mg/kg/min) and gestational diabetic pregnancy (5. 87+/-0. 27 mg/kg/min) (p<0.05). Furthermore, there was a significantly lower tissue sensitivity to insulin (defined by the ratio of the glucose uptake to the circulating insulin level during the final sixty minutes of the study) in normal third trimester pregnancies (0. 03+/-0. 01 mg/kg/min per uU/ml) and gestational diabetic pregnancies (0. 04+/-0. 01 mg/kg/min per uU/ml) as compared to non-pregnant controls (0. 11+/-0. 02 mg/kg/min per uU/ml) (p<0.05). Neither glucagon nor growth hormone were found to be significantly different between the normal pregnant or gestational diabetic groups. These studies suggest that normal pregnancy is indeed characterized by a tissue insensitivity to insulin and that glucose tolerance (defined in this study as the rate of glucose uptake) in normal pregnancy is primarily related to the degree of compensatory hyper insulinism. However, this increased compensatory insulin secretion appears to be absent in gestational diabetic women, thereby contributing to the deterioration of glucose tolerance observed in these women.