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DOI: 10.1055/s-2000-7386
Georg Thieme Verlag Stuttgart · New York
Besonderheiten der Insulintherapie bei Gestationsdiabetes (GDM)
Special Aspects of Insulin Therapy in Pregnancies Complicated by Gestational Diabetes Mellitus (GDM)Publication History
Publication Date:
31 December 2000 (online)
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Zusammenfassung
Fragestellung
Fragestellung: Bei Gestationsdiabetes (GDM) entwickeln rund 10 - 20 % der Feten einen Hyperinsulinismus. Da dieser alle frühen und späten kindlichen Komplikationen verursacht, ist eine aggressive Insulintherapie nur bei fetalem Hyperinsulinismus erforderlich. Für die Indikation zur Insulinbehandlung bestehen keine einheitlichen Richtlinien. Sie erfolgt nach internistischen Gesichtspunkten anhand der mütterlichen Glykämie und/oder nach geburtshilflichen Gesichtspunkten als prophylaktische Insulintherapie, oder nach fetalen Parametern wie Makrosomie oder dem Fruchtwasserinsulinspiegel.
Methode
Methode: Als Grenzwerte zur Indikation einer Insulintherapie werden für den Nüchternblutzucker ≥ 95 - ≥ 105 mg/dl (≥ 5,3 - ≥ 5,8 mmol/l), für die postprandiale Glukose ≥ 120 - ≥ 130 mg/dl (≥ 6,7 - ≥ 7,2 mmol/l) und für die mittlere Blutglukose (MBG) ≥ 90 - ≥ 108 mg/dl (≥ 5 - ≥ 6 mmol/l) vorgeschlagen, während die prophylaktische Insulintherapie unabhängig von der mütterlichen Glykämie erfolgt. Der Grenzwert für die Makrosomie ist die 75. Perzentile des fetalen Bauchumfanges und für den Fruchtwasserinsulinspiegel ein Wert von ≥ 8 µE/ml (≥ 48 pmol/l). Die mütterliche Glykämie hat eine schlechte Korrelation mit dem fetalen Hyperinsulinismus wegen der unterschiedlichen plazentaren Transportfunktion für Glukose und einer unterschiedlichen Sensitivität des fetalen Inselorganes gegenüber Glukosereizen.
Ergebnisse
Ergebnisse: Nach der 31. Woche können hyperinsulinämische Feten postprandiale mütterliche Glukosewerte um durchschnittlich 23 mg/dl (1,3 mmol/l) senken. Es kann dann nicht mehr unterschieden werden, ob eine mütterliche Euglykämie durch eine adäquate Behandlung oder einen exzessiven fetalen Glukosediebstahl bedingt ist. Bei prophylaktischer Insulintherapie werden alle GDM mit normoinsulinämischem Fetus überbehandelt. Bei der Indikation anhand einer 75. sonographischen Perzentile werden nur makrosome hyperinsulinämische Feten erfasst. 25 % normoinsulinämischer Feten müssen per definitionem die 75. Perzentile überschreiten und werden überbehandelt. Die Behandlung erfolgt auch zu spät, da eine Makrosomie erst nach dem Hyperinsulinismus auftritt. Bei der Indikation nach dem Fruchtwasserinsulinspiegel findet keine Unter- oder Überbehandlung statt. Die Amniozentese hat keine nennenswerten Komplikationen. Die Akzeptanz beträgt jedoch nur 80 - 90 %. Das Ausmaß der Unter- oder Überbehandlung wurde anhand von 542 GDM mit bekanntem FWI überprüft.
Schlussfolgerung
Schlussfolgerung: Geht man davon aus, dass nur GDM mit fetalem Hyperinsulinismus eine Insulintherapie benötigen, führt eine prophylaktische Insulintherapie und die Indikation nach Fruchtwasserinsulinwerten zu keiner Unterbehandlung. Bei der Indikation nach einer MBG von ≥ 90 - ≥ 108 mg/dl werden 16 - 58 % und bei Schätzung der 75. Gewichtsperzentile 44 % unterbehandelt. Bei einer Insulinbehandlung nach Fruchtwasserinsulinwerten findet keine Überbehandlung statt. Bei einer MBG von ≥ 90 - ≥ 108 mg/dl werden 75 - 18 %, bei der 75. Gewichtsperzentile > 25 % und bei prophylaktischer Insulintherapie 100 % der normoinsulinämischen Fälle überbehandelt. Das Problem ist die Unterbehandlung, da daraus alle vermeidbaren medizinischen Probleme wie Frühgeburten, Kaiserschnitte und Diabetes der Nachkommen entstehen. Die Folgekosten sind daher bei der Indikation nach einer MBG von ≥ 108 mg/dl (≥ 6 mmol/l) > 8fach höher als die Kosten der Überbehandlung bei prophylaktischer Insulintherapie. Der Insulinbedarf ist bei GDM wegen der Insulinresistenz besonders hoch. Auch wird die Eigenproduktion an Insulin durch die Insulinzufuhr um rund 30 E/24 h gedrosselt. Um die Insulinresistenz, die Drosselung der mütterlichen Insulinproduktion und die fetale Überproduktion zu kompensieren, wird eine Insulinmenge von 0,8 - 1,2 E/kg/24 h benötigt. Eine Basis-Bolustherapie hat sich als vorteilhaft erwiesen.
Abstract
Objective
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
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 µU/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
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
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 ≥ 108 mg/dl (≥ 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.
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Diabetes in pregnancy: Lessons from the fetus. Dornhorst A, Hadden DR Diabetes and Pregnancy: An International Approach to Diagnosis and Management. Chichester, New York, Brisbane, Toronto, Singapore; John Wiley & Sons Ltd 1996: 221-240 - 114 Weiss P AM. Klinische Bedeutung des Geburtsgewichts bei Diabetes mellitus. Gynäkologe. 1998; 31 58-67
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Gestational diabetes: A survey and the Graz approach to diagnosis and therapy . Weiss PAM, Coustan DR Gestational Diabetes. Wien, New York; Springer 1988: 1-55 - 123 Widness J A, Cowett R M, Coustan D R, Carpenter M W, Oh W. Neonatal morbidities in infants of mothers with glucose intolerance in pregnancy. Diabetes. 1985; 34 (Suppl 2) 61-65
- 124 Zoupas C, Mastrantonakis E, Diakakis I. et al . The importance of insulin administration in gestational diabetes. Acta Endocrinol. 1984; 265 26-28
Prof. Dr. Peter AM Weiss
Universitäts-Frauenklinik
Auenbruggerplatz 14
8036 Graz
URL: http://Departmentleiter Perinatologie