On the decrease of glucose tolerance in pregnancy. A review

Abstract

Glucose tolerance is impaired in normal pregnancy and in approximately 1% of all pregnant women gestational diabetes develop. The present paper reviews the pathogenesis of these changes based on the modifications of glucagon and insulin secretion and action. Fasting plasma glucagon levels are increased in pregnancy in normal and gestational diabetic women. After glucose ingestion or infusion the suppression of glucagon levels is enhanced in pregnancy whereas the response to protein is unaffected. The results indicate that the changes in glucagon secretion in pregnancy are secondary to altered plasma glucose levels. In all women the fasting plasma insulin levels and the glucose--or protein--induced insulin response is increased in pregnancy. The responses are similar in normal women and normal weight gestational diabetics whereas greater responses are seen in overweight gestational diabetics. Morphological and physiological animal studies demonstrate B-cell hypertrophy and hyperplasia and increased insulin secretory responsiveness in pregnancy, which is corroborated by human studies showing an almost 4-fold increase in insulin response when the same glycemic stimulus is applied in pregnancy and postpartum. The increased insulin responsiveness seems to be caused by pregnancy-related changes in the secretion of progesterone, estradiol, human placental lactogen (hPL) and prolactin. However, the increased insulin levels are unable to maintain normal glucose tolerance and pregnancy, thus, is a state of insulin resistance. Receptor studies yield diverging results, but indicate a postreceptor defect in insulin action in pregnancy. This may be caused by the increased cortisol levels in pregnancy, as significant positive correlations between increases in cortisol levels and the decreases in glucose tolerance have been established in normal pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS)