Maternal and fetal predictors of therapymanagement in gestational diabetes

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1 Maternal and fetal predictors of therapymanagement in gestational diabetes Dr. Tanja Groten Kompetenzzentrum Diabetes und Schwangerschaft Universitätsfrauenklinik Abteilung Geburtshilfe Direktor: Univ. Prof. Dr. med. E. Schleußner Klinik und Poliklinik für Innere Medizin III Direktor: Univ. Prof. Dr. med. G. Wolf Note: for non-commercial purposes only Dr. Tanja Groten

2 Background Cascade of pathophysiologic events in gestational diabetes Glucose intolerance of the mother Hyperglycaemia Normoglycaemia of the of mother mother Hyperglycaemia of the fetus Hyperinsulinaemia of the fetus Macrosomia Inhibition of surfactant production Hypoxia leading to polycythaemia Fetal programming postnatal hypoglyceamia postnatal respiratory distress postnatal icterus elevated risk for diabetes and obesity

3 Background Treatment of GDM: The preliminary goal of intervention in GDM is the prevention of fetal hyperinsulinaemia by monitoring and controlling maternal blood glucose levels. The preliminary therapeutic strategies are medical nutrition therapy (MNT) and physical activity. Patients who fail to maintain glycaemic control should receive additional pharmacological treatment. In Germany this means: insulin

4 When to start insulin therapy goals for glucose control Previous German guidelines New German guidelines ADA ACOG fasting < 95 mg/dl < 5.3 mmol/l ( 5.0 mmol/l) 1 h pp < 140 mg/dl < 7.8 mmol/l 2 h pp < 120 mg/dl < 6.7 mmol/l Start insulin if more than three elevated measurements at two different days within one week < 95 mg/dl < 5.3 mmol/l < 140 mg/dl < 7.8 mmol/l < 120 mg/dl < 6.7 mmol/l Start insulin if 50% of the values in one week are elevated < 95 mg/dl < 5.3 mmol/l < 120 mg/dl < 6.7 mmol/l < 95 mg/dl < 5.3 mmol/l < 140 mg/dl < 7.8 mmol/l < 120 mg/dl < 6.7 mmol/l If euglycaemia isn`t achieved by nutrition therapy and exercise within 10 days, insulin therapy is started or/and in the case of accelerating or macrosomic growth of the fetus

5 German guidelines: incorporating fetal growth parameters Individual definition of blood sugar goals depending on fetal growth (abdominal circumference, asymetric growth favouring the abdomen) However, here therapeutic intervention starts when fetal hyperinsulinaemia already caused growth acceleration in the fetus and prevention of fetal hyperinsulinaemia failed?

6 Study population perinatal outcome 267 pregnant women presenting for 75 g ogtt Exclusion: 5 x Twins. 7 x decline study participation 255 pregnant women to analyse GDM was diagnosed in 135 women 120 healthy pregnant women Insulin therapy medical nutrition therapy (MNT) Lost of follow up: 5 Analysis of 115 perinatal outcomes Control group 1 case of IUFT Analysis of 59 perinatal outcomes Insulin group Analysis of 75 perinatal outcomes MNT group

7 Perinatale Outcome Healthy controls (n = 115) GDM (n=134) GDM MNT (n=75) GDM Insulin-therapy (n=59) Mode of delivery (%): Vaginal planned caesarean Secondary caesarean Birth weight (g) 3452 ± 485 [ ] 3330 ± 701 [ ] 3242 ± 769 [ ] 3470 ± 571 [ ] Birth weight > 95 percentile (%) SGA (%) Neonatal hypoglycaemia (%) ** ** Neonatal hyperbilirubinaemia (%) Respiratory distress (%) ** p<

8 Further questioning Why is the outcome of GDM patients receiving insulin therapy less sufficient? Is therapy started to late? In 14% (n=8) of the insulin cases insulin therapy was started due to fetal growth parameters. In these cases treatment was started after fetal hyperinsulinaemia occured and effected abnormal fetal growth. How can we identify patients who need insulin earlier? Are there parameters at the time of GDM diagnosis predicting the necessity of insulin therapy?

9 Results: Maternal predictors of insulin therapy at the time of diagnosis of GDM MNT (n=79) Insulin group (n=60) p BMI before pregnancy (kg/m²) 25.0 ± ± 6.2 <0.001 BMI before pregnancy 25 kg/m² (%) <0.01 BMI before pregnancy 30 kg/m² (%) <0.01 History of GDM (%) <0.01 HbA1c at diagnosis (%) 5.2 ± ± 0.6 <0.001 Maternal age (years) 30.8 ± ± 6.7 n.s. Wait gain during pregnancy (kg) 14.6 ± ± 6.3 n.s

10 Percetage of GDM patients without insulin therapy Anteil ohne Insulintherapie Percetage of GDM patients without insulin therapy Anteil ohne Insulintherapie Universitätsfrauenklinik Jena Results: Kaplan-Meier Analysis HbA1c at diagnosis and BMI prior to pregnancy Discriminated for HbA1c > 5.2% at the time of diagnosis Discriminated for BMI > 25 prior to pregnancy 1,0 1,0 0,8 0,6 0,4 HbA1c-Wert bei Diagnosestellung (%) <= 5,2 > 5,2 <= 5,2-zensiert > 5,2-zensiert 0,8 0,6 0,4 BMI vor der Gravidität (kg/m²) < 25 >= 25 < 25-zensiert >= 25-zensiert 0,2 0,0 p<0, Zeitraum von Diagnosestellung bis Beginn einer Insulintherapie (Wochen) Time from diagnosis of GDM to start of insulin therapy (weeks) 0,2 0,0 p<0, Time from diagnosis of GDM to start of insulin therapy (weeks) Zeitraum von Diagnosestellung bis Beginn einer Insulintherapie (Wochen)

11 Results: Fetal predictors of insulin therapy at the time of diagnosis of GDM Estimated fetal weight >75. percentile (%) >90. percentile (%) Abdominal circumference >75. percentile (%) >90. percentile (%) MNT (n=78) Insulin therapy (n=57) p <0.05 n.s. Fetal fat layer (mm) 3.1 ± ± 0.9 <0.05 n.s. n.s. Fetal fat layer = 63% variability of abdominal circumference

12 Results: Predictive value Logistic regression analysis revealed the combination of Maternal age >30 years BMI > 25 prior to pregnancy History of GDM. HbA1c > 5.2% at diagnosis and estimated fetal weight >75. percentile at diagnosis as predictors for the need of insulin therapy. The positive predictive value is 77.6%

13 Conclusion and Discussion The presented data show, that maternal and fetal parameters at the time of diagnosis could predict the need of insulin therapy. These predictors may help to identifying women in whom therapy should be started earlier

14 Discussion and open Questions? Is it possible to completely prevent fetal alteration in cases of impaired Glucose tolerance of the mother by initiating insulin therapy earlier?? Do we need to more extensively rule out the possibilities of medical nutritional therapy (MNT) and exercise or start insulin earlier? Do we need more strict indications for insulin therapy?? Will the general screening of all pregnant women lead to prevention of delay in diagnosis and therapy initiation?

15 Thank you for your attention! and the team of the Kompetenzzentrum für Diabetes und Schwangerschaft Jena for their contribution. PD Dr. W. Battefel Dr. F. Weschenfelder C. Helbich (diabetes advisor) B. Milke (diabetes advisor) C. Spreda (midwife) A. Fiedler-Pape (midwife) S. Nestler (midwife) C. Mantschew (diabetes advisor assistence)