Читать книгу Gestational Diabetes - Группа авторов - Страница 20

During the first trimester, there is evidence that insulin sensitivity increases transiently, but throughout the rest of pregnancy, insulin resistance supervenes [1, 2]. During early pregnancy, energy is stored as body fat, anticipating later fetal anabolic needs. Both fasting and postprandial insulin levels are somewhat lower in early pregnancy than prior to pregnancy, but markedly increase as pregnancy progresses [3]. Insulin sensitivity decreases by one half to two-thirds by the end of the third trimester [1, 4]. Numerous studies have demonstrated an increase in the insulin response to glucose and other secretogogues as pregnancy progresses [1, 4], resulting in increasing circulating insulin levels, increasing insulin:glucose ratios, increasing hepatic glucose production [3], and decreasing insulin action [5].

Studies in animal models, as well as human observations, demonstrate that pancreatic β-cell mass is increased during pregnancy. Most information on β-cell proliferation in pregnancy comes from murine models, and it is not always appropriate to extrapolate to humans. For example, β-cell hyperplasia in pregnant mice arises primarily from existing β-cells [6], while in human pregnancy, new β-cells appear to develop from progenitor cells rather than from mature β-cells [7]. A hypothesis to explain the need for β-cell expansion is that as pregnancy progresses, the fetus diverts glucose from the mother to the extent that maternal glucose levels would be lowered, threatening the concentration gradient that allows glucose transfer across the placenta. The placenta then secretes hormones to increase maternal insulin resistance, raising glucose levels and maintaining the concentration gradient [6]. This in turn leads to the need for increased insulin secretion to prevent maternal hyperglycemia. One possible explanation of the phenomenon of fetal macrosomia despite good maternal glucose control in diabetic pregnancy is the “fetal glucose steal.” The normal fetal pancreas secretes insulin rather sluggishly, but exposure to hyperglycemia can upregulate fetal insulin secretion. The early onset of fetal hyperinsulinemia may lower fetal glycemia so as to increase the glucose concentration gradient across the placenta, enhancing glucose transfer to the fetus and favoring fetal fat accretion and overgrowth [8].

An intriguing finding is that gravidas carrying a male fetus have, on average, poorer β-cell function and higher fasting [9] and postchallenge [10] glucose levels, and a greater risk of gestational diabetes. This phenomenon could be at least a partial explanation for the observation that male newborns tend to weigh more than female newborns. The reasons for this fetal sex difference in maternal metabolism are a subject of ongoing investigation, but one possibility is the differential secretion and release of placental hormones and cytokines, since the placenta is genetically fetal rather than maternal.