Diabetes mellitus and reproductive system of woman.

1. Diabetes mellitus and reproductive system of woman. A. Tiselko, N. Borovik, O. Volgina Reproductive endocrinology department Ott’s Research Institute of Obstetrics and Gynecology Saint-Petersburg, 2011

2. Women in reproductive age (18-44 yo)with diabetes mellitus in Russia 186 964 women Morbidity 261,8 per 100000 Diabetes mellitus register, Russia, 2006

3. ГипергликемияHyperglycemiaОvary insufficiency Abnormalities of gonadotropin’s secretion Autoimmune oophoritis

4. Compensation of diabetes metabolic disturbances Restoration of ovulatory cycle

5. Before insulindiscovery Maternal mortality Perinatal mortality 44% 60% Hare JW, White P: Pregnancy in diabetes complicated by vascular disease. Diabetes 26: 953-55, 1977

6. Diabetes mellitus – the disease that still leads to complicated course of pregnancy and delivery andforms some problems in foetus and newborn

7. Decompensated diabetes mellitus and it’s influence on pregnancy coursе Noncarring of pregnancy – 20-30% Gestosis – 40-79% (O. Arzhanova, 2006; Ecbom P., 2001) Polyhydramnios - 20-60% Urogenital infections - 30-60% Placental insufficiency, preterm delivery - 25-60% Caesarian section - 55-85%

8. Frequency of congenital malformations development in case of maternal type 1 diabetes mellitus. (%) 50 40% 40 30 20% 20 10 – 15% 10 4 – 5% 0 – 1% 0 <6.9 7.0 – 8.5 >8.6 >10.0 >14.4 HbA1c (%)

9. Foetus abnormalities 20-40% of cases - anencephalia, - ventricular septal defect,atrial septal defect, - Fallot’s tetrad, - atresia of anus and rectum Diabeticfetopathy 75-85% of cases - macrosomia, - neonatal hypoglycemia, - hypocalcemia, hypomagnesemia, - polycythemia,hyperbilirubinemia, - cardiomyopathy, - immaturity of lung and central nervous system - hepatomegaly Decompensated diabetes mellitus and it’s influence on foetus’ and newborn’s development

10. Components that define the risk of diabetes complications development:fasting glucose (a),postprandial hyperglycemia(b),glucose variability(c) Glucose variability Oxidative stress activation c с Risk of complications PPG b b 6% HbA1c а Fasting glucose Monnier L. et al. Horm Metab Res 2007; 39: 683 – 686

11. Glucose monitoring and glucometr usage Glucose monitoring trough subcutaneous sensor Glucose monitoring with alarming sensir signals Glucose monitoring: new possibilities and standarts ? Only adequate monitoring of glucose level predetermine the optimal insulin therapy

12. Glycemic profile during normal pregnancy

13. Glycemic control in woman with type 1 diabetes,НbA1c 6, 7%Insulin therapy: Detemir TID (7+6+8 IU), Aspart QID (6-8 IU)

14. Hypoglycemia: hemodinamic effects hypoglycemia ↑ cardiac output ↑ periferal systolic BP ↓ central BP ↑ coagulability Catecholamine Acetylcholone Cortisole Hypercalcemia Hypomagnesemia B.M. Frier, 2010

15. imperfection of multiple daily injections regimen: Non-physiological method (subcutaneous insulin depot) Inadequate speed of insulin action during carbohydrates, proteins consumtion Absence of physiologically acting basal insulin Absence of possibility to inject insulin before every meal

16. Advantages of insulin pump Maximal imitation of physyiological insulin injection – continuous preset infusion of insulin (basal) and bolus injection before every meal Only insulin of shot/ultrashot usage Small doses of insulin with possibility to inject 0,1 – 0,025 IU Absence of insulin depot in subcutaneous tissue Predictable insulin pharmacodynamic Possibility to stop infusion in case of hypoglycemia Different types of boluses

17. Analysis of diabetes compensation degree, features of pregnancy and delivery course in women with type 1 diabetes mellitus was performed on insulin pump therapy (CSII) - n=90 on multip;e daily injection regimen (MDI) - n=90 For all women continuous glucose monitoring was performed (during I,II, III trimesters)

18. Continuous glucose monitoring systems(CGMS, CGM Paradigm Real-time Medtronic)and insulin pumps fromMedtronic and Accu-Chek companies

19. Glucose level in patients on MDI and CSII MDI CSII Glucose after dinner Glucose after breakfast Glucose after lunch Avg. glucose

20. HbA1c duringI, IIandIII trimester of pregnancy on MDI and CSII MDI CSII before I trimester II trimester III trimester With high degree of correlation between HbA1c and boluses frequency (r 0,57)

21. Glucose variability measuremrnts: SD (а), MOOD (б), CONGA (в) on CSII and MDI

22. Features of pregnancy course on MDI and CSII

23. Hemostasis system features on MDI and CSII With high degree of correlation between glucose variability and fibrinogen level(r 0,6)

24. Insulin demand during delivery decreases in70-80%risk of maternal and newborn hypoglycemia is very high Visual control of glucose level during delivery helps to program doses of insulin with maximal precision

25. Neonatal hypoglycemia Increasing of maternal glucose level during pregnancymore than 6,7 mmol/l stimulates foetus’insulin production, that can lead to hypoglycemia after the delivery Frequency of neonatal hypoglycemia – 64% and it is not depend on macrosomia presence* *Nationwide prospective study in the Netherlands BMJ  2004;328:915 PEDIATRICS Vol. 103 No. 4 April 1999, pp. 724-729

26. Real-time glucose monitoring Planned cesarean section (10.30 am) Patient with type 1 diabetes

27. Real-time glucose monitoring during delivery in woman with type 1 diabetes (extraction of newborn at 6 pm)

28. Pregnancy and delivery outcomes in women with type 1 dibetes mellitus on MDI and CSII

29. Real-time glucose monitoring, continuous subcutaneous insulin infusion optimise glucose control in patients with type 1 diabetes during pregnancy, decrease the risk of maternal and newborn’ morbidity, New technologies usage in diabetes patients during pregnancy must be the standard of care