Diabetes In Pregnancy

The bad news is: time flies. The good

news is: you are the pilot.

Ben Trolled

Detrimental….. But Manageable!

• Diabetes is the most common Medical complication of

pregnancy worldwide.

• Gestational Diabetes Mellitus occurs with a particularly increasing frequency in Asians, African Americans, people of indigenous Australian ancestry and Hispanics. This makes it very important from our regional perspective.

• Seemingly easy: Practically very difficult to deal with.

• Needs a lot of commitment on the part of doctor, patient and her family

• Success can be achieved if all the three cooperate together.

Let’s begin by staying

awake for the next 30

minutes

NORMAL GLUCOSE-INSULIN DYNAMICS

• The cells in the body rely primarily on glucoseas their chief energy supply

This glucose is mostly a product of the food we consume and some is the consequence of the breakdown from body stores

• After digestion, glucose is absorbed into the bloodstream for transport to the various cells of the body.

• Glucose is not able to enter most cells directly – insulin, a hormone secreted by the beta cells of the islets of Langerhan is required for the cells to uptake glucose.

WHAT HAPPENS TO CARBOHYDRATE

METABOLISM DURING PREGNANCY?

• During pregnancy, there is increased tissue resistance to the effects of insulin, thereby resulting in increased levels of insulin and glucose in the bloodstream.

• The increased tissue resistance is due to increased production of certain hormones during pregnancy which include Human Placental Lactogen and Cortisol.

• Growth Hormone, Progestogens, Prolactin and Glucagon have also been implicated in some studies.

• Normally, the glucose concentration stays between 4-4.5 mmol/L throughout the pregnancy, except after meals.

• Transient maternal hyperglycemia occurs after meals because of increased insulin resistance.

• There is hypoglycemia between meals and at night because of continuous fetal draw.

• With increasing degree of insulin resistance, the requirement for insulin progressively increases and in third trimester, the requirement is almost double of that before pregnancy.

• Thus a woman whose pancreas were producing adequate amounts of insulin to meet her daily requirement before pregnancy, may fail to increase the production of insulin sufficiently to meet the increased demand of pregnancy, culminating in the development of gestational diabetes.

WAYS IN WHICH CARBOHYDRATE

DERANGEMENT CAN MENIFEST

DURING PREGNANCY

1. A known diabetic becomes pregnant

2. Gestational diabetes

3.Pre-diabetes

1. A KNOWN-DIABETIC GETS PREGNANT

• Type-I diabetes mellitus or IDDM is seen more commonly in pregnancy as compared to Type-II diabetes mellitus since most of the pregnant women are relatively young.

• A diabetic woman who had been achieving normoglycemia with diet only, may need medication to achieve a similar control.

• Those taking medication may require a progressive increase in dosage as the pregnancy heads towards term.

• Pre-existing diabetes at conception can lead to congenital anomalies

2.GESTATIONAL DIABETES

Definition:It is defined as glucose

intolerance of varying severity with onset or first recognition during pregnancy.

This subset constitutes 90% of women with pregnancies complicated by diabetes. The most important perinatal concern in this group is macrosomia with resulting birth trauma. More than 50% women ultimately develop diabetes in the ensuing 20 years and this is linked with obesity

Prevalence: 1-14% of all pregnancies, the variations being largely geographic and ethnic.

Indicates predisposition to a later development of Type 2 Diabetes

Chance of recurrence in future pregnancies: 30-84%

RISK FACTORS: For the development of GDM

Overweight before pregnancy (BMI > 25)

1st degree relative with diabetes

Previous glucose intolerance/ GDM

Previous macrosomia or large for gestational age baby

Polycystic Ovary Syndrome

• Age > 25 yrs

• Members of certain ethnic groups

• Multiparous women

3. PRE-DIABETES

Higher than normal blood glucose or glycosylated Hemoglobin A1C levels, but not high enough to be classified as diabetes.

American Diabetes Association values placing person at risk for DM when there is:

Fasting blood sugar: 100 – 125 mg/dl. 2 hours after 75 gram glucose load:140-190 Hemoglobin A1C value: 5.7 – 6.4 % (or <6%) In patients with pre-diabetes, there is an increased risk

of:• Developing type 2 diabetes

• Heart disease

• Stroke

• Gestational diabetes

ADA Criteria for Diagnosis of Diabetes

Diagnosis FBG (mg/dl) 2 Hour

Postglucose

Load (75 gm

OGTT)

Hemoglobin

A1C (%)*

Normal < 100 < 140 <5.7

Pre-Diabetes 100-125 140-199 5.7-6.4

Diabetes

Mellitus**

≥ 126 ≥ 200*** ≥6.5

***Or a random glucose 200 mg/dl with symptoms

ADA. Diabetes Care 2011;34 (suppl 1):S13-S61.

**Must be repeated on a separate day

*Measured according to DCCT methodology

WHY IS PRE-PREGNANCY

COUNSELING FOR DIABETICS

IMPORTANT?

Hyperglycemia exerts its teratogenic effects during the period of organogenesis-the first 42 days of pregnancy-often before the pregnancy is medically confirmed. Pre-pregnancy care could significantly reduce the rates of congenital malformations.

The aim of pre-pregnancy counseling is to achieve the best possible control before pregnancy and to educate diabetic women about the implications of pregnancy and the associated risks.

Diabetic women should be advised to take high dose (5mg) folic acid pre-conception and for the first 12 weeks.

first 12 weeks.

The level of HbA1c in early pregnancy correlates well with the risk of early fetal loss and congenital anomalies. If HbA1c is >10 percent, the risk of fetal loss and congenital malformations is around 40% Targets for pre-pregnancy therapy should be to maintain HbA1c at 6.5% and fasting glucose levels of 4-7mmol/L.

Relationship between miscarriage and HbA1c

levels

0

5

10

15

20

25

30

35

40

<6.05 6.05-7.2 7.2-8.3 8.3-9.5 >9.5

HbA1c

Perc

en

t o

f w

om

en

White Classification of Diabetes in

Pregnancy

TYPE AGE AT

ONSET (YRS)

DURATION

OF DM (YRS)

COMPLICATIONS

A1 ANY AGE ANY LENGTH None; diet controlled

A2 ANY AGE ANY LENGTH None; requires RX

B <20 OR <10 No vascular disease

C 10-19 OR 10-19 No vascular disease

D1-5 <10 OR >20 Retinopathy or HTN

E(NOW

CLASS D3)

Arterial calcification

F Proteinuria; nephropathy

G Pregnancy failures

H Arterisclerotic heart disease

R Proliferative retinopathy

T After renal transplant

Maternal and Fetal

Complications of Diabetes

Complications Of Diabetes in Pregnancy

Maternal complications Fetal complications

• Preeclampsia

• Increased caesarean delivery

• Subsequent development of T2DM

• 30% maternal mortality rate

• Progression of chronic complications of

diabetes

• Gestational hypertension

• Hypoglycemia

• Infections (eg, pyelonephritis)

• Ketoacidosis

• Polyhydramnios

• Preterm labor

• Seizures

• Doubled spontaneous abortion risk

• Maternal birth weight <4 lbs 7 oz

Unexplained fetal death

Childhood obesity

Hyperbilirubinemia

Hypoglycemia

Macrosomia and birth injuries

Shoulder dystocia

Respiratory distress syndrome

Premature birth

Increased cord-blood serum C-peptide

levels

Abnormal birth weight (low or high)

Increased risk of T2DM and/or GDM

later in life

Increased congenital malformations

1.

FETAL COMPLICATIONS

1. Diabetes and embryogenesis

Early fetal loss due to apoptosis of blastocyst, modulated by the regulatory gene Bax, which is stimulated by high blood glucose.

High BG reduces total cell mass and number of blastocysts, esp. in inner cell layer

Cardiac congenital anomalies 4 times higher.

Anencephaly 5x

Spina bifida 3x

Caudal regression

syndrome 212x

Arthrogryposis 28x

Ureteric duplication 23x

Renal agenesis 5x

Pseudohermaphroditism

11x

Anorectal atresia 4x

Caudal Regression Syndrome(abnormal development of lower spine)

2. FETAL MACROSOMIA

Macrosomia (large for gestational age or big baby syndrome)

(birth weight >90% percentile for gestational age)

Macrosomia is a result of persistent maternal hyperglycemia leading to fetal hyperglycemia and prolonged fetal hyperinsulinism. This stimulates excessive somatic growth mediated by insulin-like growth factors (IGFs). IGFS stimulate insulin release and inhibit the release of glucagonTheexcess glucose is converted by excess insulin into fat and stored in the body, resulting in macrosomia. Macrosomia affects all organs except the brain.

There is :

• Increased adipose tissue deposition in the body.

• Accelerated skeletal maturation

• Increased hepatic glycogen content

• Organomegaly: liver, spleen, heart

• Risks of macrosomia include shoulder dystocia, Erb’s palsy, 5 min APGAR score, admission to NICU and obesity in later

In mothers with macrosomic babies, the fundal height is more than duration of gestation.

Predisposition to prolonged obstructed labor and increased risk of shoulder dystocia.

Macrosomia In a Nutshell…..

17 pound baby born to Brazilian diabetic mother

INTRAUTERINE GROWTH RETARDATION

Rarely, placental function may be compromised in the presence of hypertension or vascular complications, in which case fetal growth restriction may occur.

Associated with poor prognosis.

4.RESPIRATORY DISTRESS SYNDROME

Fetal hyperinsulinemia reduces pulmonary phospholipids production particularly phosphatidyl-glycerol, leading to surfactant deficiency.

The incidence is 8 times higher as compared to non-diabetics.

MATERNAL COMPLICATIONS

1. Pre-eclampsia: Affects 10-25% of all pregnant women with GDM.

In diabetic mothers with pre-eclampsia, the perinatal mortality is

doubled due to increased need for elective preterm labor.

2. Infections: High incidence of chorioamnionitis and postpartum

endometritis

3. Postpartum bleeding: High incidence caused by exaggerated

uterine distension

4. Cesarean section more common due to fetal macrosomia and

cephalo-pelvic disproportion

5. Weight gain

6. Polyhydramnios: Occurs due to fetal polyuria which is secondary

to osmotic diuresis when a high glucose content in the urine carries

a large amount of water with it. There is increased predisposition to

premature labor and malpresentation.

7. Hypertension

8. Spontaneous miscarriages: Congenital malformations are

responsible.

9. Third trimester fetal deaths

10. Long term risk of type-2 diabetes mellitus

MANAGEMENTAIM: To achieve maternal near-normoglycemic levels to

prevent adverse perinatal outcomes

MANAGEMENT IN A KNOWN DIABETIC BECOMING PREGNANT

11. PRE-CONCEPTIONAL COUNSELING AND CARE MAY MAKE

THE DIFFERENCE:

All women with pre-existing type-1 or type-2 diabetes, when planning on

pregnancy, should receive pre-conception counseling so that they

understand the importance of achieving near-normal blood glucose before

conception to reduce the risk of congenital malformations and spontaneous

abortions. Assess maternal and fetal risk Mother should learn self-administration of insulin and regular

monitoring of blood glucose. Target: HbA1c < 6% Emphasize diet and exercise

.

Folic acid supplementation: 5 mg/day Ensure no transmissible diseases: HBsAg, HIV, rubella Try and achieve normal body weight: diet/exercise

Stop drugs: oral hypoglycemic drugs, ACE inhibitors, beta blockers and potentially teratogenic drugs

2. BOOKING VISIT SHOULD BE AS EARLY AS POSSIBLE

The known diabetic woman should be advised to attend the hospital the moment she discovers she is pregnant. Early booking offers the advantage of achieving the tight control of blood glucose during the period of organogenesis.

Clinical perimeters checked at each visit:

Medications

Pre-pregnancy weight

Weight gain

Edema

Pallor

Thyroid enlargement

Blood pressure

Fundal height

Laboratory parameters to be monitored at each visit

Hemoglobin

Blood Sugar

HbA1C (first trimester only)

Urine microscopy and albumin

MANAGEMENT IN GDM

Medical and Nutritional Therapy

Insulin

Exercise

Obstetrical Management

Antenatal care

Delivery

Care of the Newborn

Post-partum care

Blood Sugar Goals

Fasting:

< 90 mg/dl

Pre-meal:

60-90 mg/dl

One-hour post-prandial <120 mg/dl

Two-hour post-prandial: <120 mg/dl

2AM-6AM:60-90 mg/dl

Why these tight glycemic targets?

(Prospective study in type-1 patients with pregnancy)

Fasting blood sugar Macrosomia

>105 mg/dl 28.6 %

95-105 10%

<95 mg/dl 3%

NUTRITIONAL THERAPY:

6 meal pattern (3 meals, 3-4 snacks). Bed time snack to prevent ketosis

Calorie intake= 30 cal/kg/day = 1500 cal for a 50 kg lady

Encourage taking complex carbohydrates and fruits. > 40-45% of the foot should be carbohydrates

Avoid starvation/ketosis

Choose food sources which are lower in saturated and trans-fats

Substantial night snack; light breakfast

NUTRITIONAL THERAPY:

Slight increase in calorie intake in 3rd trimester

Weight reduction before pregnancy if BMI > 27

No > 10 hours overnight fast. Tight glycemic control can reduce fetal risk but, stringent glycemic control puts the mother at increased risk of hypoglycemic events and the fetus at risk of being small-for-gestational age.

Nutritional issues in pregnancy

Caloric demands are increased in

pregnancy

Carbohydrate type and amount should

be decreased in diabetics in pregnancy

Weight gain recommendation in

pregnancy has changed

Institute of Medicine Guidelines for weight gain in

pregnancy (2009)

PRE-

PREGNANCY

BMI (KG/M2 )

BMI TOTAL WT

GAIN (LBS)

RATE OF WT

GAIN 2nd-3rd

TRIMESTER

S

(PER WK)

UNDERWEIGH

T

<18.5 28-40 1-1.3

NORMAL WT 18.5-24.9 25-35 0.8-1

OVERWEIGHT 25-29.9 15-25 0.5-0.7

OBESE >30 11-20 0.4-0.6

INSULIN

INSULIN

A dynamic approach is imperative.

Choose regime according to Blood Glucose profile

Insulin, rather than oral drugs, is preferred for use in pregnancy because:

fewer antibodies

limited transplacental crossing

no teratogenicity

Most clinical experience with:

Lispro (Humulin)

Aspart (Novolog), Regular and NPH insulin

Type 1 diabetics should remain on insulin in pregnancy

Estimated insulin needs

Postpartum <0.6 U/kg

Weeks 36-40 1.0 U/kg

Weeks 26-36 0.9 U/kg

Weeks 16-26 0.8 U/kg

Weeks 2-16 0.7 U/kg

Pre-pregnancy 0.6 U/kg

Exercise

Programs of moderate physical exercise have been shown to lower maternal glucose concentrations in women with GDM.

The beneficial glucose-lowering effects warrant a recommendation that women without medical or obstetrical contraindications be encouraged to start or continue a program of moderate exercise as a part of treatment for GDM.

Upper limb exercises

Avoid resistance exercises

Walking + swimming+

Breathing exercises +

Avoid jogging

Pelvic floor exercises

ANTE-NATAL CARE

1st trimester

• Time of organogenesis.

• Tight control of glycemic levels + Avoid exposure to other possible teratogenic agents.

2nd trimester

• Best period for detection of congenital malformations.

• Ultrasound examination should be carried out at 18-20 weeks for fetal anatomic survey, major malformations

• Fetal echocardiography should be performed at 20-22 weeks to detect cardiac anomalies.

• US at 26weeks onwards to : evaluate fetal growth and amniotic fluid volume.

3rd trimester

• Complications like PIH, Polyhydramnios, Fetal Macrosomia, Preterm labor and Intrauterine death are more likely to surface in this period.

• In the absence of complications, the pregnancy can be safely continued till term. Continuation beyond term not recommended because the incidence of peri-natal deaths increases thereafter.

Vaginal delivery: preferred Cesarian section only for routine obstetric indication

GDM alone is not an indication! > 4.5 Kg fetus: Cesarean delivery may reduce the likelihood

of brachial plexus injury in the infant, preferred in this case/ Maintain euglycemia during labor Maternal hyperglycemia in labor: fetal hyperinsulinemia and

worsen fetal acidosis Maintain sugars: 80-120 mg/dl (capillary: 70-110mg/dl ) Maintain basal glucose requirement Insulin requirements are low in labour Insulin requirements falls further after delivery Monitor sugars 1-4 hrly intervals during labour Give insulin only if blood sugar >120 mg/dl

Labor and Delivery

Management of Neonate Hypoglycemia <40 mg/dl Encourage early breast feeding If symptomatic give a bolus of 2- 4 ml/kg, IV, 10% dextrose Check after 30 minutes, start feeding IV dextrose : 6-8 mg/kg/min infusion Check for calcium, if seizure/irritability/RDS Examine infant for other congenital abnormalitiesHypoglycemia: 50 % of macrosomic infants 5–15 % in optimally controlled GDMStarts when the cord is clamped Exaggerated insulin release secondary to pancreatic ß-cell hyperplasia

o Check blood sugars before discharge

o Breast feeding: helps in weight loss. Breast feeding women should take 50g extra of carbohydrates.

o Lifestyle modification: exercise, weight reduction

o Oral glucose tolerance test at 6-12 weeks postpartum: classify patients into normal/impaired glucose tolerance and diabetes

o The patient should be properly advised regarding family planning

o Diabetics after delivery should revert to the insulin regimen they were using before pregnancy. Women with GDM and impaired glucose tolerance who were being treated with insulin during pregnancy do not require any form of treatment after delivery but blood glucose levels should preferably be monitored thereafter too.

o Preconception counseling for next pregnancy

Post-partum Follow up

Our greatest glory is not in never falling, but in

rising every time we fall.

Confucius.

Umair Nasir08-201