Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft Maternal and fetal predictors of therapy- management 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
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft Background Cascade of pathophysiologic events in gestational diabetes Glucose intolerance of the mother Normoglycaemia of the mother Hyperglycaemia of the mother Hyperglycaemia of the fetus Hyperinsulinaemia of the fetus Macrosomia postnatal hypoglyceamia Inhibition of surfactant production postnatal respiratory distress Hypoxia leading to polycythaemia postnatal icterus Fetal programming elevated risk for diabetes and obesity 02.04.2014 2
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft 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. 02.04.2014 3
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft When to start insulin therapy – goals for glucose control Previous German New German ADA ACOG guidelines guidelines fasting < 95 mg/dl < 95 mg/dl < 95 mg/dl < 95 mg/dl < 5.3 mmol/l < 5.3 mmol/l < 5.3 mmol/l < 5.3 mmol/l (≤ 5.0 mmol/l) 1 h pp < 140 mg/dl < 140 mg/dl < 140 mg/dl < 7.8 mmol/l < 7.8 mmol/l < 7.8 mmol/l 2 h pp < 120 mg/dl < 120 mg/dl < 120 mg/dl < 120 mg/dl < 6.7 mmol/l < 6.7 mmol/l < 6.7 mmol/l < 6.7 mmol/l Start insulin if more than Start insulin if 50% If euglycaemia isn`t achieved by three elevated of the values in one nutrition therapy and exercise measurements at two week are elevated within 10 days, different days within one insulin therapy is started week … or/and in the case of accelerating or macrosomic growth of the fetus 02.04.2014 4
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft 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? 02.04.2014 5
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft Study population – perinatal outcome 267 pregnant women presenting for 75 g oGTT 255 pregnant women to analyse Exclusion : 5 x Twins. 7 x decline study participation 120 healthy pregnant women GDM was diagnosed in 135 women Lost of follow Analysis of 115 75 medical nutrition Insulin therapy 60 up: 5 perinatal outcomes therapy (MNT) Control group Analysis of 59 perinatal Analysis of 75 perinatal 1 case of IUFT outcomes outcomes Insulin group MNT group 02.04.2014 6
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft Perinatale Outcome Healthy GDM GDM GDM controls Insulin-therapy (n=134) MNT (n=75) (n = 115) (n=59) Mode of delivery (%): Vaginal 74.1 64.9 67.5 61.4 planned caesarean 11.2 20.9 20.8 21.1 Secondary caesarean 14.7 14.2 11.7 17.5 3452 ± 485 3330 ± 701 3242 ± 769 3470 ± 571 Birth weight (g) [695-4680] [2260-4620] [695-4430] [1380-4680] Birth weight > 95 percentile (%) 11.3 10.4 7.7 14.3 SGA (%) 6.1 6.0 6.0 0 Neonatal hypoglycaemia (%) 3.5 14.9** 5.3 27.1** Neonatal hyperbilirubinaemia (%) 21.9 26.3 23.4 30.4 Respiratory distress (%) 6.1 9.0 9.1 8.9 ** p<0.01 02.04.2014 7
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft 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? 02.04.2014 8
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft Results: Maternal predictors of insulin therapy at the time of diagnosis of GDM Insulin group MNT (n=79) p (n=60) 25.0 ± 5.2 29.0 ± 6.2 BMI before pregnancy (kg/m²) <0.001 BMI before pregnancy ≥ 25 kg/m² (%) 41.0 66.7 <0.01 BMI before pregnancy ≥ 30 kg/m² (%) 16.7 40.0 <0.01 History of GDM (%) 5.1 22.8 <0.01 5.2 ± 0.4 5.6 ± 0.6 HbA1c at diagnosis (%) <0.001 30.8 ± 5.7 31.2 ± 6.7 Maternal age (years) n.s. 14.6 ± 6.6 15.3 ± 6.3 Wait gain during pregnancy (kg) n.s. 02.04.2014 9
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft Results: Kaplan-Meier Analysis HbA1c at diagnosis and BMI prior to pregnancy Discriminated for Discriminated for BMI > 25 prior to HbA1c > 5.2% at the time of diagnosis pregnancy 1,0 1,0 Percetage of GDM patients Percetage of GDM patients HbA1c-Wert bei Diagnosestellung (%) BMI vor der 0,8 0,8 Anteil ohne Insulintherapie Anteil ohne Insulintherapie without insulin therapy Gravidität (kg/m²) without insulin therapy <= 5,2 > 5,2 < 25 0,6 0,6 <= 5,2-zensiert >= 25 > 5,2-zensiert < 25-zensiert 0,4 0,4 >= 25-zensiert 0,2 0,2 p<0,01 0,0 0,0 p<0,01 0 5 10 15 20 0 5 10 15 20 Time from diagnosis of GDM Time from diagnosis of GDM to start of insulin therapy (weeks) to start of insulin therapy (weeks) 10 10 02.04.2014
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft Results: Fetal predictors of insulin therapy at the time of diagnosis of GDM MNT (n=78) Insulin therapy (n=57) p Estimated fetal weight >75. percentile (%) 26.7 44.0 <0.05 >90. percentile (%) 13.3 26.0 n.s. Abdominal circumference >75. percentile (%) 14.9 24.1 n.s. >90. percentile (%) 5.4 11.1 n.s. 3.1 ± 0.6 3.5 ± 0.9 Fetal fat layer (mm) <0.05 Fetal fat layer = 63% variability of abdominal circumference 02.04.2014 11
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft 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%. 02.04.2014 12
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft 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. 02.04.2014 13
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft 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? 02.04.2014 14
Universitätsfrauenklinik Jena Kompetenzzentrum für Diabetes und Schwangerschaft 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) 02.04.2014 02.04.2014 15
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