DIABETES IN PREGNANCY

Dr. Nidhi Singh

INTRODUCTION

• Abnormalities of carbohydrate metabolism occur frequently

during pregnancy

• 3-5% of all pregnant patient show glucose intolerance

• 90% of these have gestational diabetes

• Approximately 50% of women with GDM will develop type II

diabetes later in life.

Diabetogenic effects of pregnancy

1. Insulin resistance

• Production of human placental lactogen

• Production of cortisol, estriol and progesterone

• Destruction by kidney and placenta

2. Increased lipolysis

3. Changes in gluconeogenesis

Effects of diabetes on mother

• Preeclampsia

Affects 10-25% of all pregnant diabetics

• Infections

Chorioamnionitis and postpartum endometritis

• Postpartum bleeding

• Cesarean section

Effects of diabetes on fetus

• Congenital abnormalities

• Hypoglycemia

• Hyperviscosity syndrome

• Hyaline membrane disease

• Macrosomia

• Hypocalcemia

• Apnea and bradycardia

• Traumatic delivery

Effects of pregnancy on diabetes

• More insulin required to achieve homoeostasis

• Progression of diabetic retinopathy

• Worsening of diabetic retinopathy

• Increased risk of death in diabetic cardiomyopathy

Etiological classification of diabetes• Type I: β cell destruction

– Immune mediated– Idiopathic

• Type II DM• Others

– Genetic defects of beta-cell function– Genetic defects in insulin action– Genetic syndrome– Endocrinopathies– Drugs– Infections

• Gestational DM

White’s classification during pregnancy

Gestational diabetes Discovered during pregnancy, glycemia may or may not be maintained by diet alone; insulin may be required

Class A Discovered before preg, controlled with diet alone, any duration or age of onset

Class B Onset age 20 yr or older, duration less than 10yrs

Class C Onset age 10-19yrs, duration 10-19yrs

Class D Onset age under 10yrs, duration >20yrs, background retinopathy

Class R Proliferative retinopathy, or vitreous hemorrhage

Class F Nephropathy with proteinuria over 500mg/day

Class RF Criteria for both classes R and F coexist

Class H Arteriosclerotic heart disease clinically evident

Class T Prior renal transplantation

Classification scheme used from 1986 through 1994 for Diabetes complicating pregnancy

Class Onset Fasting 2 hour PP Therapy

A1 Gestational <105 mg/dl <120 mg/dl Diet

A2 Gestational >105 mg/dl >120 mg/dl Insulin

Class Age of onset (yr) Duration (yr) Vascular disease Therapy

B >20 <10 yr None Insulin

C 10-19 yr 10 to 19 None Insulin

D <10 yr >20 Benign retinopathy

Insulin

E Any Any Nephropathy Insulin

R Any Any Proliferativeretinopathy

Insulin

H Any Any Heart Insulin

Gestational diabetes

• Onset in pregnancy

• Affects 1-2% of all pregnancies

• More than half of Gestational diabetes

develop overt diabetes in 20yrs

• Obesity and diabetes in offspring

High risk for GDM

• History of still birth

• History of neonatal death

• History of fetal macrosomia

• Concomitant obesity and hypertension

• Development of oligohydramnios, polyhydramnios, preeclampsia and fetal macrosomia

• Inadequate metabolic control with diet alone

Screening strategy for detecting GDM

• Low risk: * Blood glucose testing not routinely required in:

– Member of an ethnic group with low prevalence

– No known diabetes in 1st degree relatives

– Age < 25yrs

– Weight normal before pregnancy

– Weight normal at birth

– No history of abnormal glucose metabolism

– No history of poor obstetrical outcome

Screening strategy for detecting GDM

• Average risk

* Blood glucose testing at 24-28 wks (1 step/2step)

– Member of an ethnic group with high prevalence

– Diabetes in a first degree relative

– Age ≥ 25yrs

– Overweight before pregnancy

– Weight high at birth

Screening strategy for detecting GDM

• High risk

* Blood glucose testing as soon as feasible

– Severe obesity

– Strong family history of type 2 diabetes

– Previous history of GDM

– Impaired glucose metabolism

– Glucosuria

Screening (OGTT)

• Plasma glucose level measured 1 hr after 50g glucose load

• Without regarding to time of day/ time of last meal

• Plasma glucose level > 130mg/dl; sensitivity 90%

• Plasma glucose level > 140mg/dl; sensitivity is 80%

Diagnosis of GDM by OGTTTime 100 g Glucose

(American diabetes association criteria)

75 g glucose(WHO criteria)

Fasting 95 mg/dl 5.3 mmol/L 95 mg/dl 5.3mmol/L

1-h 180mg/dl 10mmol/L 180mg/dl 10mmol/L

2-h 155mg/dl 8.6mmol/L 155mg/dl 8.6mmol/L

3-h 140mg/dl 7.8mmol/L - -

Maternal risks

• Birth trauma

• Operative delivery

• Polyhydraminos

• 50% lifetime risk in developing Type II DM

• Recurrence risk of GDM is 30-50%

Fetal risks

• No increase in congenital anomalies

• Increased risk of stillbirth if fasting+ PP hyperglycemia

• Macrosomia, BW >4000gm occurs in 17-29% of

pregnancies

• Birth trauma-shoulder dystocia and related complications

• Neonatal hypoglycemia

Fetal macrosomia

• Defined as fetal weight > 4000gm

• Brain not effected, shoulder dystocia 3%

Maternal hyperglycemia

Fetal hyperinsulinemia

Excessive somatic growth

• Diagnosis and management is important

• USG should begin at 20wks; to be done at every 4 wks

• Also due to IGF-1 and IGF-2

• Maternal obesity is important confounding factor

Management of GDM

Class Onset Fasting 2 hour PP Therapy

A1 Gestational <105 mg/dl <120 mg/dl Diet

A2 Gestational >105 mg/dl >120 mg/dl Insulin

Nutritional therapy-total calorie intake:

average 2000-2500 kcal/day.

BMI >40 -- 12 kcal/kg/ideal body weight/d

BMI>27 -- 25 kcal/kg/ideal body weight/d

BMI 20-26 -- 30 “

BMI<20 -- 38 “

Management of GDM

• Diet : general principles

• 55% CHO 25% Protein 20% fat

• Normal weight gain 10-12 kg

• Avoid ketosis

• Liberal exercise program to optimize BG control

• Daily self BG monitoring

• Breakfast should provide 25%, Lunch 30% and dinner 30%. Obese women may be managed with lower caloric intake.

Management of GDM

• If persistent hyperglycemia after one week of diet control proceed to insulin

• 6-14 weeks 0.5u/kg/day

• 14-26 weeks 0.7u/kg/day

• 26-36 weeks 0.9u/kg/day

• 36-40weeks 1 u /kg/day

Oral hypoglycaemic agents

• Traditionally not recommended in pregnancy because of teratogenic effects

• Glyburide and Metformin

Glyburide

• Sulfonylureas

• MOA- release of insulin

• Hypoglycemia and weight gain are the main

side effects

• Non-teratogenic, classified as category B drug

Glyburide treatment regimen who fail Diet therapy

1. Glucometer BG measurment fasting and 1 or 2 hrs following breakfast, lunch and dinner

2. Glucose level goals (mg/dl): fasting < 100, 1-h < 155 and 2hrs < 130

3. Glyburide starting dose 2.5mg orally with morning meals

4. Increased daily glyburide dose by 2.5mg/wk, increment until 10mg/day, then switch to twice daily dosing until max of 20mg/day, then switch to insulin if 20mg/day does not achieve glucose goal.

Obstetrical management

• Cesarean delivery should be considered in women with sonographical estimated weight > 4500gm

• Elective cesarean delivery has no significant effect on incidence of brachial plexus injury

• Fetal monitoring

Postpartum evaluation• Women diagnosed with GDM to be evaluated with 75gm

OGTT at 6-12wks postpartum

• Metabolic assessment recommended after preg with GDM

• Contraception: low dose hormonal contraceptives

Time Test purpose

Postdelivery (1-3 d) Fasting or random plasma glucose

Detect persistent, overtdiabetes

Early postpartum (6-12wk) 75g 2h OGTT PP classification of Glu met

1yr Postpartum 75g 2h OGTT Assess Glu metabolism

Annually Fasting plasma glucose Assess Glu metabolism

Tri- annually 75g 2h OGTT Assess Glu metabolism

Prepregnancy 75g 2h OGTT Classify glu metabolism

Pregestational diabetes/ overt diabetes

• Patients with symptoms of DM and plasma Glucose concentration 200mg/dl or more

• The condition may be preexisting or detected during present pregnancy

Criteria for diagnosis of impaired Glucose tolerance and diabetes with 75g oral

glucose

Time Normal tolerance

Impaired glucose tolerance

diabetes

Fasting < 110 mg/dl ≥ 110 and <126 ≥ 126 mg/dl

2 hr Post glucose <140 mg/dl ≥ 140 and <200 ≥ 200 mg/dl

Maternal effects

• During pregnancy– Abortions

– Preterm labor 20%

– Infections (UTI)

– Preeclampsia 25%

– Polyhydraminos 25-50%

– Maternal distress

– Diabetic retinopathy

– Diabetic nephropathy

– Ketoacidosis

Maternal effects

• During labor:– Prolongation of labour due to big baby

– Shoulder dystocia

– Perineal injury

– Postpartum hemorrhage

– Operative interventions

• During Puerperium:– Puerperal sepsis

– Lactation failure

Fetal hazards• Congenital anomalies 3 times increased risk

– Caudal regression- 1.3/1000

– Situs invertus

– Spina bifida, hydrocephaly, other CNS defects

– Anencephaly

– Cardiac anomalies: VSD, TGA, ASD, COA

– Anorectal atresia

– Renal anomalies: agenesis, cystic kidney, duplex ureter

Fetal hazards

• Unexplained stillbirth

• Hypoglycemia, hypocalcemia, hyperbilirubinemia, polycythemia

• Cardiomyopathies

• Inheritance of diabetes

• Shoulder dystocia

• Macrosomia

• IUGR

• RDS

Preconceptional counselling

• Preconception Counselling

• Risk of NTD ~1-2%

• Folic Acid 400µg/day

• Preconceptional glucose control using insulin.

• Fasting < 70-100 mg/dl, and PP <140mg/dl at the

end of 1 hr and <120mg/dl at the end of 2hr.

Preconceptional counselling

• Normoglycemia prior to conception

• Ideally HBA1C 6% or less

• Team approach

• Glucose monitoring qid

• ACE inhibitors contraindicated

• Baseline HbA1C, 24h urine for protein Cr Cl , ophthalmology review

• Switch from OHA to insulin

Pregestational /Overt Diabetes

• Assess for end organ disease

– assess for nephropathy - inc risk of PIH

– Assess and treat retinopathy - may progress

– assess for neuropathy

• generally remains stable during pregnancy

– assess and treat vasculopathy

• CAD is a relative C/I for pregnancy

Maternal Surveillance

- Blood pressure monitoring

– renal function every trimester

– urine culture monthly

– thyroid function

– BG control HB A1C every trimester

Fetal Surveillance

– USG for dating/viability ~ 8 weeks– Transvaginal USG examination at 10-14 weeks– Fetal anomaly detection

• nuchal translucency 11-14weeks• maternal serum screen- free β HCG and PAPA-A• MSAFP at 16w to screen for open Neural tube

defect• anatomy survey 18-20 weeks• Fetal echo 22weeks

– Weekly biophysical profile, NST

Trimestric approach• 1st Trimester:

– Careful monitoring of glucose control is essential

– OHA to Insulin therapy

• 2nd trimester:– Maternal serum alpha fetoprotein at 16-20wks

– Targeted sonographic examination at 18-20wks

– Euglycemia with self monitoring is the goal

– Increased insulin requirement after 24wks

• 3rd Trimester:– Cesarean delivery to avoid traumatic birth

Admissions

– At 34-36 weeks in uncomplicated cases

– It facilitates

i. Stabilisation of diabetes

ii. Less incidence of Preeclampsia, Polyhydramnios

and Preterm labour

iii. Selecting time and mode of termination

Insulin therapy

• OHA not currently recommended for overt diabetes

• Maternal glycemic control with multiple daily insulin

inj and adjustment of dietary intake

• S/C insulin infusion by calibrated pumps

• Self monitoring using glucometer recommended

Self monitored capillary BG goals

Specimen Level (mg/dl)

Fasting ≤ 95

Premeal ≤ 100

1 hr- postprandial ≤140

2 hr- postprandial ≤ 120

2-6hr ≥ 60

Mean (average) 100

Hb A1c ≤ 6

Management of diabetes in pregnancyinsulin therapy

• Insulin Pump– Allows insulin release close to physiologic levels

– Use short acting insulin

– 50-60% of total dose is basal rate

– 40-50% given as boluses

– Potential complications• Pump failure

• Infection

• Increased risk of DKA

Management of diabetes in pregnancyinsulin therapy

Short acting Onset Peak Duration

Regular

Lispro

Aspart

0.5 – 1 hr

20 mints

25 mints

2 – 4 hrs

0.5 – 1½ hr

30 – 1½ hr

4-6 hrs

3 – 4 hrs

3 – 4 hrs

Intermediate acting

NPH/ Isophane

lente

(Insulin zinc suspension

1 – 3

1 - 3

5 - 7

4 - 8

13 - 18

13 – 20

Long Acting

Ultra lente / Protamine

Glargine

4 – 6

1 – 4

14 – 18

Minimal peak

activity

24 – 36 g

24hrs

Insulin therapy

• Regular and NPH are the most commonly used preparations

• Regular insulin/NPH combination-

– Slow absorption, administered 30min before meals

– Midmorning & midafternoon snacks necessary

– Rapidly acting insulin like Lispro prevent hypoglycemia

Insulin therapy

• Lispro and aspartate–

– should be taken immediately before meals

– Lispro and aspartate used for prandial insulin and

insulin pump therapy

Insulin therapy

• Glargine-

– Longest acting

– Less episodes of nocturnal hypoglycemia

– Given in morning hours

• Detemir

Timing of Delivery

• Diet controlled– Same as non diabetic

– Offer induction at 41 weeks if undelivered

• On Insulin/Type II/Type I– If suboptimal control deliver following confirmation of lung

maturity if <39 weeks

– Otherwise deliver by 40 weeks

– Generally do not allow to go post term

• DOC for initial tocolysis: Nifedipine

Mode of Delivery

• Macrosomic infants of diabetic mothers have

higher rates of shoulder dystocia

• Cord is to be clamped immediately

• Reasonable to recommend C/S delivery if EFW

is >4500g

Insulin requirement in labor

Insulin requirements

During induction of labor During elective caesarean section•Usual insulin dose and meal on evening before surgery•Overnight fast from 12 midnight

Day before IOL•Normal diet•Normal insulin dose evening before IOL•No overnight fast

Day of IOL•give half the morning dose of insulin before light breakfast•Insert prostaglandin gel as early as possible•Continuous CTG•Start IV insulin infusion once labor establishes

Insulin therapy intrapartum

CG Level Management• 60-90 mg/dl 5%-10% DNS at 100 ml/hr• 90-120mg/dl 0.9% NS or RL at 100ml/hr• 120-140 mg/dl 5Uin 500ml 5% dex at 100ml/hr• If >140 mg% then plain insulin sc by sliding scale:• 140-180 mg/dl 4U • 180 -250 mg/dl 8U • 250-400 mg/dl 12U • >400 mg% 16U• CG and urinary ketone level should be measured every

2 hourly.

Contraception in DM

• Barrier methods are safe, inexpensive with fewer side effects

• OCPs cause insulin resistance due to progesterone component

and there is high risk of thromboembolism, MI and CVA.

• IUCDs cause infection, glucose precipitates with Copper and

thus reduction of efficacy.

• Permanent method are used in couples with complete family

Diabetic Ketoacidosis

• 5-10% of pregnant Type 1 patients

• Serious medical emergency

• Risk factors

– New onset DM

– Infection

– Insulin pump failure

– Steroids

• Fetal mortality 10%

Diabetic Ketoacidosis

• Diagnosis:

– BG conc > 250mg/dl

– Ketone bodies in urine and plasma

– Arterial pH <7.3

– Serum bicarbonate < 15meq/L

Diabetic Ketoacidosis• Management

– ABC’s and ABG• Assess BG, ketones electrolytes

– Insulin • 0.2-0.4U/Kg loading and 2-10U/h maintenance

– Begin 5% dextrose when BG is 250 mg%– When potassium is N range begin 20mEq/h– Rehydration isotonic NaCl

• 1L in 1st hour • 0.5-1L/h over 2-4h• 6-8 L over 1st 24 hours.• 250cc/h until 80% replaced• Replace Bicarb and phosphate as needed

Metabolic syndrome

• Definition (WHO)

– Diabetes, impaired glucose tolerance, impaired fasting glucose, insulin resistance+ atleast 2 of foll:

• Abdominal obesity

• Trigycerides > 150 mg/dl

• HDL < 40 mg/dl

• BP≥ 140/90 mm Hg

• Microalbuminuria > 20µg/min

Metabolic syndrome

• Definition (NCEPATP III)

– At least 3 of the following:

• Fasting plasma glucose > 110mg/dl

• Abdominal obesity (waist circumference> 35 in.)

• Triglycerides >150 mg/dl; HDL < 50mg/dl

• BP ≥ 130/85 mmHg

Indian experience

• Incidence of GDM is 3-5%• Numbers are increasing • 90% diagnosed cases are of GDM• Fetal macrosomia 32%• PIH 48%• Hydramnios 4%• IUD 12%• Fetal malpresentation 16%• Cesarean section 44%• Maternal mortality 10 times

Medicolegal Pitfalls

• Congenital anomalies in infant-

– Explained to the mother

– Preventability by good glycemic control should be

mentioned and recorded

• Birth injuries and Perinatal asphyxia

– USG should be done 2-3wks prior to delivery

– Offer cesarean section if EFW >4500gm

Take Home Message

• Preventing congenital anomalies is a challenge

• Maintaining euglycemia is the key

• Educating community is the cornerstone