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