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
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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
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Гипергликемия
Hyperglycemia
Оvary insufficiency
Abnormalities of gonadotropin’s
secretion
Autoimmune oophoritis
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Compensation of diabetes metabolic disturbances
Restoration of ovulatory cycle
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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
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Diabetes mellitus – the disease that still leads to complicated course of pregnancy and delivery and forms some problems in foetus and newborn
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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%
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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 (%)
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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
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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
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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
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Glycemic profile during normal pregnancy
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Glycemic control in woman with type 1 diabetes,НbA1c 6, 7% Insulin therapy:
Detemir TID (7+6+8 IU), Aspart QID (6-8 IU)
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Hypoglycemia: hemodinamic effects
hypoglycemia
↑ cardiac output
↑ periferal systolic BP
↓ central BP
↑ coagulability
B.M. Frier, 2010
CatecholamineAcetylcholone
CortisoleHypercalcemia
Hypomagnesemia
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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
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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
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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)
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Continuous glucose monitoring systems( CGMS, CGM Paradigm Real-time Medtronic)
and insulin pumps from Medtronic and Accu-Chek companies
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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
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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
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Glucose variability measuremrnts: SD (а), MOOD (б), CONGA (в) on CSII and MDI
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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
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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)
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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
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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
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Real-time glucose monitoring Planned cesarean section (10.30 am)
Patient with type 1 diabetes
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Real-time glucose monitoring during delivery in woman with type 1 diabetes (extraction of
newborn at 6 pm)
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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%
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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