Diabetes mellitus and pregnancy Małgorzata Tyloch

Diabetes mellitus is the most frequent metabolic disease in pregnancy. The discovery of insulin and insulin therapy increased chances of diabetic women to become pregnant and have offspring. At this time the rates of maternal mortality associated with pregnancy and delivery were very high. The perinatal mortality of fetuses and neonates was very high, too.

Insulin was discovered in 1922 by Frederich Bantings and Charles Best Insulin was discovered in 1922 by Frederich Bantings and Charles Best. They won the Nobel Prize in 1923 for their work.

Significant improvement of obstetric outcomes was noticed when the interdisciplinary special centers of diabetic pregnant women were established. Co-operation between specialists of diabetology, obstetrics and neonatology was necessary to decrease the mortality of pregnant women and their offspring.

In 1972, Karlsson and Kjellmer proved that there was association between a degree of glycemic control in pregnant women and the course of pregnancy as well as the condition of the fetus and neonate. In 1980, diabetes mellitus developed during pregnancy was introduced to classification of diabetes mellitus.

Carbohydrate metabolism and pregnancy The placenta produces a series of hormones with diabetogenic action : oestrogens progesterone human placental lactogen. The level of all these substances increases during pregnancy . Placental hormones influence carbohydrate metabolism. They play an important role in the increasing insulin resistence of healthy pregnant women.

Diabetic effect of pregnancy Altered endocrine function of the pancreas Changes in insulin metabolism Changes in the tissue sensitivity – tissue sensitivity to insulin decreases, insulin resistance develops Increased levels of compounds with contrainsular action- mainly hormones

With progressing pregnancy a constantly increasing quantity of insulin is necessery for maintaining physiological glucose levels. The insulin production capacity of patients affected by gestational diabetes is relatively deficient since it does not meet the increased demands of the pregnant organism.

Maternal insulin plays a central role in the immediate regulation of metabolic processes. Insulin itself does not cross the placenta but it is principal factor in maintaining maternal and fetal metabolism by regulating the blood level of glucose, amino acids, glycerol, ketone bodies and free fatty acids. Fetal blood levels of these substanses are largely dependent on maternal blood levels.

In 10 – 20% of diabetic pregnant women, diabetes mellitus was diagnosed and treated before pregnancy ( Pregestational Diabetes Mellitus- PGDM). In 80-90 % of diabetic pregnant women, diabetes mellitus is first recognized during pregnancy ( Gestational Diabetes Mellitus – GDM).

Gestational Diabetes Mellitus is each disturbance of metabolism of carbohydrates diagnosed during pregnancy ( poor fast glycemia, poor tolerance of carbohydrates or diabetes mellitus).

Risk factors of GDM 1. a family history of diabetes mellitus 2. prepregnancy body mass index > 27kg/m2 3.age > 35 years 4. a previous adverse obstetric history : macrosomia, perinatal mortality, prematurity, preeclampsia, congenital malformations in previous offspring 5. gestational diabetes mellitus in a previous gestation 6. hypertension prior to pregnancy 7. multiparity 8. polycystic ovary syndrome in history

<92 mg/dl 92-125 mg/dl >125 mg/dl perform 75 g OGTT Fasting glucose level First perinatal visit <92 mg/dl 92-125 mg/dl >125 mg/dl Measurement of glucose abnormal perform 75 g OGTT Repeat fasting glucose level test

In women with risk factors for gestational diabetes mellitus the OGTT should be done at the first prenatal visit. In this way the undiagnosed type 2 diabetes may be confirmed.

Diagnosis of GDM at 24 – 28 weeks of pregnancy Perform a 75-g OGTT, with plasma glucose measurement when the patient is fasting and at after 1h and after 2hrs, at 24-28 weeks of gestation in women not previously diagnosed with overt diabetes. The OGTT should be performed in the morning after an overnight fast of at least 8hrs.

Abnormal plasma glucose values of OGTT The diagnosis of GDM is made when any of the following plasma glucose values are met or exceeded: Fasting: 92 mg/dL (5.1 mmol/L) After 1 h: 180 mg/dL (10.0 mmol/L) After 2 hrs: 153 mg/dL ( 8.5 mmol/L)

Diabetes mellitus after GDM Women with the history of gestational diabetes are at increased risk for developing diabetes in their later life. They should be educated regarding lifestyle modifications that lessen insulin resistance. The normal body weight and physical activity are recommended. The first screening for persistent diabetes should be done at 6 - 8 weeks postpartum by a 2-hrs oral test with a 75-g glucose load. Follow- up at regular intervals should be continued. GDM may be treated as a prodrome of diabetes mellitus type 2 in the later life.

Classification of women with PGDM This classification was presented by Priscilla White in 1949 . She divided women with PGDM according to age at onest of the disease, presence or abscence of chronic diabetic complications and hypertension. In her classification the outcome of pregnancy depended on these factors. When the diabetes mellitus was very advanced she recommended preterm labor. At present, this classification is used to characterise the profile of patients.

Classification of Priscilla White A class – therapy relies on diet modification B class – diabetes mellitus before the age of 20 years or lasts ten years C class – diabetes mellitus develops in the age 10 – 19 years or duration of 10 – 19 years D class – diabetes mellitus develops before the age of 10 years or lasts 20 years, or it is DM with retinopathy or with hypertension R class – diabetes mellitus with proliferative retinopathy

F class – diabetes mellitus with nephropathy RF class – class R and F H class – diabetes mellitus with cardiovascular disease T class – patient with diabetes mellitus after kidney transplantation

The course of pregnancy and outcome pregnancy of diabetic women are influenced : by the mother’s metabolic and vascular state by the presence or absence of complications during the actual pregnancy (acidosis,hypertension,pyelonephritis) by patient’s cooperation with therapeutic team by patient’s social conditions

The complications in pregnant diabetic women Spontaneous abortions Preterm deliveries Hypertension and preeclampsia Infections Disturbance of volume of amniotic fluid Fetal and neonatal abnormalites

Preterm delivery Preterm delivery is observed more frequently ( 16 -26 %) in women with diabetes mellitus. The main risk factors are : poor glycemic control at the onset and in the course of pregnancy chronic diabetic complications – women with nephropathy, cardiovascular disease and retinopathy often deliver before the end of 37th week of pregnancy ( up to 70%)

Preterm delivery Chronic hypertension prior to pregnancy, hypertension and preeclampsia during pregnancy Infections , especially urogenital infections disturbance of volume of amniotic fluid which leads to polyhydramnions

Disorders of amniotic fluid volume Polyhydramnios which may be caused: by fetal defects of digestive tract by penetration of fluid into the amniotic cavity, due to hyperglycemia and increased osmolar amniotic pressure by increased fetal diuresis due to hyperglycemia

2. Oligohydramnios is often observed in PGDM patients with vascular complications. It may be caused by placental insufficiency and defects of urinary system due to decreased volume of amniotic fluid .

Risk for offspring of women with diabetes mellitus congenital malformations fetal macrosomia fetal hypotrophy neonatal hypoglycemia neonatal hypocalcemia neonatal polycythemia and hiperbilirubinemia respiratory distress syndrome

HbA1C and complications in early diabetic pregnancy HbA1c at 9 week of pregnancy (%) <9.0 9.0-11.0 >11.0 Number of patients 114 69 24 Spontaneous abortions 3.5% 4.8 % 26% Congenital malformations 0% 8.7 % 21% Hanson U. and all.: HbAic in early diabetic pregnancy in relation of occurrence of spontaneous abortion and congenital malformation in Sweden. IDF Congress 1985, 571.

Fetal abnormalities no fetal abnormalities characteristic of diabetes, but some birth defects occur more frequently, e.g.: caudal dysplasia syndrome – 252 times more often situs invertus of organs – 84 –II– double ureters – 23 –II– kidney defects – 5 –II– heart defects – 4 –II– defects of the central nervous system – 2 –II–

Fetal abnormalities and week of pregnancy caudal dysplasia syndrome - ocurrs at the 3rd week situs invertus of organs – at the 4th week defects of the central nervous system – at the 4th week defects of the urinary system – at the 4th week defects of the cardiovascular system – at the 5th week

Preconception Care of Women with Diabetes Mellitus All women with diabetes mellitus should plan their pregnancy they must be examined before conception, women with uncontrolled hypertension, heavy nephropathy , retinopathy and cardiovascular disease should not plan pregnancy women who were treated with oral hypoglycemic agents ( for example sulfonylurea compounds) should have intensive insulin therapy. optimum glycemic control prior to pregnancy and in the first weeks of pregnancy is necessary

Preconception Care Preconception care is successful in reducing the risk for fetal anomalies and spontaneous abortions. Intensive treatment should be administrated for 6 month before conception. Multiple insulin injections ( 4-6 daily) or use of continuous subcutaneous insulin pumps are included. Insulin therapy is initiated for patients with DM type 2 instead of oral hypoglycemic agents. When nesseccary, proliferative retinopathy should be treatmented at this time. The ACE inhibitors must be discontinued immediatiely after a missed period and a positive pregnancy test.

Glycosylated hemoglobin is the best measure of integrated metabolic control during preconception, it must be under 6.1 % Women with poor glycemic control should delay pregnancy Thyroid function should be examined

Delivery Cesarean section is often necessary . Delivery of a very large baby can be dangerous for both the infant and the mother. Cesarean section is necessary because of cardiovascular desease and preeclampsia, too.