Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Weiss, PAM; Walcher, W; Scholz, HS.
Special aspects of insulin therapy in pregnancies complicated by gestational diabetes mellitus (GDM)
GEBURTSH FRAUENHEILK 2000 60: 366-379.
Doi: 10.1055/s-2000-7386
Web of Science
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- Co-Autor*innen der Med Uni Graz
- Scholz Heinz
- Walcher Wolfgang
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- Abstract:
- Objective: In pregnancies complicated by gestational diabetes mellitus (GDM) about 10-20% of fetuses develop hyperinsulinism. Aggressive insulin therapy is required to avoid early and late complications for fetal hyperinsulinism in these offspring. There is no universally agreed upon indication for insulin therapy. The indication for insulin can be based on maternal parameters, such as fasting blood glucose, postprandial blood glucose or mean blood glucose (MBG) values. It can also be initiated prophylactically or be based on fetal parameters, such as macrosomia or elevated amniotic fluid insulin.Methods: Suggested maternal glucose limits For the indication of insulin therapy are 95 - 105 mg/dl (5.3 - 5.8 mmol/l) for fasting blood glucose, 120 - 130 mg/dl (6.7 - 7.2 mmol/l) for postprandial blood glucose, and 90 - 108 mg/dl (5 - 6 mmol/l) for MBG. Prophylactic insulin therapy is administered independently of maternal glycemia. Macrosomia has been defined as the 75th percentile of fetal abdominal circumference; the upper limit of normal amniotic fluid insulin is 8 mu U/ml (48 pmol/l). Maternal glycemia correlates poorly with fetal hyperinsulinism because of individual variations in placental transport and the placentas barrier function. Accordingly, the materno-fetal glucose gradient can vary widely. Additionally, the fetal islet organs vary widely in sensitivity to glucose stimuli.Results: After the 31st gestational week hyperinsulinemic fetuses syphon off maternal glucose and thus reduce maternal postprandial glucose levels by 20 mg/dl (1.1 mmol/l) on average. Consequently, it cannot be distinguished whether maternal euglycemia is a result of normal glucose tolerance, adequate treatment, or the fetoplacental glucose steal phenomenon. A policy of prophylactic insulin treatment of all pregnancies complicated by GDM would overtreat the 80 - 90% of fetuses who are normoinsulinemic. A policy based on sonographic criteria of macrosomia would treat only the hyperinsulinemic fetuses who are also macrosomic, as well as large but normoinsulinemic fetuses. Also, hyperinsulinism precedes macrosomia by weeks or months so that insulin treatment is late. Insulin treatment based on measurement of insulin levels in the amniotic fluid avoids undertreatment and overtreatment. Complications of amniocentesis are negligible but patient acceptance is only 80 - 90%. We analyzed the extent of undertreatment and overtreatment with the fetus as a sensor in 542 GDM with known amniotic fluid insulin levels.Conclusions: Assuming that insulin therapy is only necessary in GDM with fetal hyperinsulinism, no undertreatment ensues from prophylactic insulin therapy or from insulin treatment based on amniotic fluid insulin levels. At a MBG of 90 - 108 mg/dl or estimating the 75th weight percentile for indication, undertreatment results in 16 - 58% or 44%, respectively. Insulin treatment based on a MBG of 90 - 108 mg/dl, the 75th weight percentile and prophylactic insulin therapy lead to overtreatment in 75 - 18%, > 25% and 100% of normoinsulinemic cases, respectively. The problem is undertreatment because preventable sequelae, such as premature births, cesarean deliveries and diabetes in the adolescent ensue from untreated fetal hyperinsulinism. Consequently a policy of insulin treatment for patients with a MBG greater than or equal to 108 mg/dl (greater than or equal to 6 mmol/l) leads to costs eight times higher than those of overtreatment with prophylactic insulin. Due to insulin resistance, insulin requirements in GDM are high. Moreover, insulin administration reduces the mother's own insulin secretion by 30 U/24 h. Consequently the insulin requirement needed to overcome insulin resistance, the reduction of maternal insulin synthesis, and fetal hyperinsulinism is 0.8 - 1.2 U/24 h. Because maternal postprandial insulin secretion is delayed in GDM, insulin administration at the main meals is essential to prevent postprandial hyperglycemia. Consequently, a basal-bolus schema is appropriate. Administration of human insulin is preferable in order to prevent development of insulin antibodies.