diabetes mellitus and reproductive system of woman. a. tiselko, n. borovik, o. volgina reproductive...
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Diabetes mellitus and reproductive system of woman.
A. Tiselko, N. Borovik, O. VolginaReproductive endocrinology departmentOtt’s Research Institute of Obstetrics and GynecologySaint-Petersburg, 2011
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 Diabetes mellitus register, Russia, 2006
Гипергликемия
Hyperglycemia
Оvary insufficiency
Abnormalities of gonadotropin’s
secretion
Autoimmune oophoritis
Compensation of diabetes metabolic disturbances
Restoration of ovulatory cycle
Before insulin discovery
• Maternal mortality
• Perinatal mortality
44%
60%
44%
60%
Hare JW, White P: Pregnancy in diabetes complicated by vascular disease. Diabetes 26: 953-55, 1977
Hare JW, White P: Pregnancy in diabetes complicated by vascular disease. Diabetes 26: 953-55, 1977
Diabetes mellitus – the disease that still leads to complicated course of pregnancy and delivery and forms some problems in foetus and newborn
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%
Frequency of congenital malformations development in
case of maternal type 1 diabetes mellitus.
00
1010
2020
3030
4040
(%) 50(%) 50
<6.9<6.9 7.0 – 8.57.0 – 8.5 >8.6>8.6 >10.0>10.0 >14.4>14.4
0 – 1%0 – 1%4 – 5%4 – 5%
10 – 15%10 – 15%
20%20%
40%40%
HbA1c (%)
Decompensated diabetes mellitus and it’s influence on foetus’ and newborn’s
development
• Foetus abnormalities20-40% of cases
- anencephalia, - ventricular septal
defect, atrial septal defect,
- Fallot’s tetrad, - atresia of anus and
rectum
• Diabetic fetopathy 75-85% of cases
- macrosomia, - neonatal hypoglycemia, - hypocalcemia,
hypomagnesemia, -
polycythemia,hyperbilirubinemia,
- cardiomyopathy, - immaturity of lung and
central nervous system - hepatomegaly
Components that define the risk of diabetes complications development:
fasting glucose (a), postprandial hyperglycemia (b),
glucose variability (c)
Monnier L. et al. Horm Metab Res 2007; 39: 683 – 686
b
c
b
а
с
Fasting glucose
Oxidative stress activationGlucose variability
Risk of complications
PPG
6% HbA1c
Glucose monitoring: new possibilities and standarts ?
Glucose monitoring and
glucometr usage
Glucose monitoring
trough subcutaneous
sensor
Glucose monitoring with alarming sensir
signals
Only adequate monitoring of glucose level predetermine the optimal insulin therapy
Glycemic profile during normal pregnancy
Glycemic control in woman with type 1 diabetes,НbA1c 6, 7% Insulin therapy:
Detemir TID (7+6+8 IU), Aspart QID (6-8 IU)
Hypoglycemia: hemodinamic effects
hypoglycemia
↑ cardiac output
↑ periferal systolic BP
↓ central BP
↑ coagulability
B.M. Frier, 2010
CatecholamineAcetylcholone
CortisoleHypercalcemia
Hypomagnesemia
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
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
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)
Continuous glucose monitoring systems( CGMS, CGM Paradigm Real-time Medtronic)
and insulin pumps from Medtronic and Accu-Chek companies
Glucose level in patients on MDI and CSII
7,4 **
6.3
7,8 **
6.77.5
6.47.1 6.6
0
1
2
3
4
5
6
7
8
МИИ
ППИИ
MDI
CSII
Avg. glucose Glucose after breakfast
Glucose afterlunch
Glucose after dinner
HbA1c during I, II and III trimester of pregnancy on MDI and CSII
7,8 ***
6.97,7 ***
6.76,6 **
6.06,5 ***
5.7
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
МИИ
ППИИ
With high degree of correlation between HbA1c and boluses frequency (r 0,57)
MDI
CSII
before I trimester II trimester III trimester
Glucose variability measuremrnts: SD (а), MOOD (б), CONGA (в) on CSII and MDI
Features of pregnancy course on MDI and CSII
MDI CSII p
n=90 n=90
Time of gestosis manifestation 34,3±0,4 31±0,6 <0,0001
Frquency of severe gestosis. % 17,9 9,6
Sys BP 134±2,6 117±2,3 <0,001
Dias BP 84±1,5 72,1±1,34 <0,001
GFR, III trimester of pregnancy 96,9±3,6 107,7±2,3 <0,05
Daily protein loss, III trimester of pregnancy
0,5±0,1 0,09±0,1 <0,0001
Delivery time 36,7±0,3 37,9±0,3 <0,01
Frequency of cesarean section % 87,9 77,6
Frequency of urgent cesarean section%
13,5 12,8
Hemostasis system features on MDI and CSII
MDI CSII p
n=65 n=65
Degree of erythrocytes aggregation 76,9±2,69 74,6±3,4
Rate of aggregation 76,4±4,01 72,2±4,2
D-dimer level 616±60 416±53,9 <0,01
Fibrinogen level 3,82±0,14 3,68±0,13
Antitрrombin III level 105,8±4,6 95±4,3
Von Willebrand factor level 2,34±0,2 1,51±0,16 <0,01
With high degree of correlation between glucose variability and fibrinogen level(r 0,6)
Insulin demand during delivery decreases in 70-80%
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
Neonatal hypoglycemiaIncreasing of maternal glucose level during pregnancy more 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*
PEDIATRICS Vol. 103 No. 4 April 1999, pp. 724-729
*Nationwide prospective study in the NetherlandsBMJ 2004;328:915
Real-time glucose monitoring Planned cesarean section (10.30 am)
Patient with type 1 diabetes
Real-time glucose monitoring during delivery in woman with type 1 diabetes (extraction of
newborn at 6 pm)
Pregnancy and delivery outcomes in women with type 1 dibetes mellitus on
MDI and CSII
MDI CSII p
n=90 n=90
Newborn’s glycemia during delivery (mmol/l) 3,70±0,19 3,3±0,18
Newborn’s glycemia after 2 hours after delivery (mmol/l) 2,30±0,10 2,9±0,11 <0,01
Newborn’s weght (gr)
3428±109,4
delivery time 36,7±0,3
3425±94,7
delivery time 37,9±0,3
Diabetic fetopathy frequency % 77,4% 46,2%
Frequency of congenital malformations %
3,4% 1,6%
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