DM in Pregnancy DM in Pregnancy

Dr.Sushma Sharma

Prof.,Dept. of ObGyn,

MIMER Medical college,

Talegaon

Dr.Sushma Sharma

Prof.,Dept. of ObGyn,

MIMER Medical college,

Talegaon

Increasing Prevalence of GDM Increasing Prevalence of GDM Abnormal maternal glucose

regulation occurs in 3-10% of pregnancies

GDM accounts for 90% of cases of DM in pregnancy

Overt - 35% type 1 DM, and 65% type 2 DM

Abnormal maternal glucose regulation

occurs in 3-10% of pregnancies

GDM accounts for 90% of cases of DM in pregnancy

Overt - 35% type 1 DM, and 65% type 2 DM

Not limited to western countries

Increase is noted in India and China

3.8-20% in different part of India, more in urban – DIPSI

Compared with white women the RR of GDM in Indian women is 11.3

Increase is attributable to: Sedentary lifestyles

Changes in diet

Immigration from high-risk populations

Childhood and adolescent obesity

CLASSIFICATION GESTATIONAL DIABETES: 1 abnormal value

on GTT or hgbA1c - 5.7 to 6.4%. A1 - Euglycemia achieved with diet and

exercise. A2 - Require medication

PREEXISTING DIABETES

Type I. No endogenous insulin, ketosis prone

Type II. Late onset,insulin resistant

Gestational Diabetes Mellitus Gestational Diabetes Mellitus

Glucose intolerance with onset or first recognition during pregnancy.

Many are denovo pregnancy induced

Some are type 2 ( 35-40%)

Whether insulin or only diet modification is needed

Persists or not after Delivery.

Glucose intolerance with onset or first recognition during pregnancy.

Many are denovo pregnancy induced

Some are type 2 ( 35-40%)

Whether insulin or only diet modification is needed

Persists or not after Delivery.

D M D M

conceptionconception

Preexisting type 2Preexisting type 2

Incipient type 2Incipient type 2

type 1type 1

10 20 30 40

True GDMTrue GDMdeliverydelivery

Follow upFollow up

Maternal-fetal Metabolism in Normal Pregnancy

Metabolism in Pregnancy Goal is uninterrupted nutrient

supply to fetus Metabolic goals of pregnancy are

In early pregnancy to develop anabolic stores to meet metabolic demands in late pregnancy

In late pregnancy to provide substrate for fetal growth and energy needs.

Metabolic Changes

Meal sets in motion a complex series of hormonal actions,

Increase in blood glucose

Sec. secretion of pancreatic insulin, glucagon, somatomedins, & adrenal

catecholamines.

These adjustments ensure that an ample, but not excessive, supply of

glucose is available to mother & fetus.

Placental steroid & peptide hormones (eg, E, P, chorionic

somatomammotropin) ↑se linearly throughout 2nd & 3rd trimesters.

↑se insulin resistance

↑sed insulin secretion.

24 hr mean insulin levels are 50% higher in 3rd trimester compared with nonpregnant state

Glucose Metabolism in Pregnancy

Fetus

Fat

Glucose Aminoacids

Insulin resistance

Hyperinsulinemia

FASTINGaccelerated starvation

(maternal hypoglycemia,

hypoinsulinemia,

hyperlipidemia,

hyperketonemia)

FEDhyperglycemia, hyperinsulinemia,

hyperlipidemia,

reduced sensitivity to insulin

GDM Precise mechanisms unknown Hallmark is ↑sed insulin resistance Inability to secrete sufficient insulin to

compensate for the increased nutritional needs of gestation due to: ↑sed adiposity of pregnancy, ↑sed anti-insulin hormones, such as HPL,

HPGH, prolactin, cortisol (potent), P & E (weak)

enzymes with insulinase activity Oxytocinase, histaminase, alkaline phosphatase

Precise mechanisms unknown Hallmark is ↑sed insulin resistance Inability to secrete sufficient insulin to

compensate for the increased nutritional needs of gestation due to: ↑sed adiposity of pregnancy, ↑sed anti-insulin hormones, such as HPL,

HPGH, prolactin, cortisol (potent), P & E (weak)

enzymes with insulinase activity Oxytocinase, histaminase, alkaline phosphatase

Compartment Metabolic Effect

MotherMother

PlacentalHormones

HPLHPGH

CortisolOestrogen

Progesterone

PlacentaPlacenta

FoetusFoetus

Insulin resistance

Impaired insulin action

Aberrant Fuel Mixture

Mode oftransport

Glucose Amino acids Cholesterol TG Ketones

FacilitatedFacilitatedDiffusionDiffusion

By GLUT3 carriers

ActiveActive Diffusion

Lipase

DiffusionDiffusionFFAFFA GlycerolGlycerol

DiffusionDiffusion

Aberrant fuel mixture

HyperinsulinemiaHyperinsulinemia

Fuel Mediated TeratogenesisFuel Mediated TeratogenesisFuel Mediated TeratogenesisFuel Mediated Teratogenesis

Perinatal Mortality, Morbidity & Birth Injury

Maternal Hyperglycemia

Fetal Hyperglycemia

Fetal Hyperinsulinemia

↑Fetal substrate uptake ↑Oxygen uptake Lung Surfactant↓

Respiratory Distress Syndorme

Lipids / Amino acid ↑ Hypoxemia

Polycythemia Marosomia

↑Erythropoietin

? SB

↑BMR

Hypotrophy Pancreaticislet & B cells

PATHOGENIC EVENTS

PEDERSEN THEORY

Maternal Diabetes

Glucose crosses placenta

Carbohydrate surplus of fetus

Increased secretion of insulin

Stimulation of protein, lipid & glycogen synthesis Free amino acid

Stimulatory effect on development of B cells

Release Insulin like growth factor

MACROSOMIA

MACROSOMIA

SHOULDER DYSTOCIA

Perinatal Mortality to Maternal Blood Glucose During Last Weeks of Pregnancy

Mean glucose level Perinatal mortality

>150 mg%100–150 mg% <100 mg%

24%15%4%

Fetal Consequences

First Trimester Second Trimester Third Trimester

-Malformations-Growth Restriction-Fetal Wastage

-Hypertrophic cardiomyopathy-Polyhydramnios-Erythraemia-Placental Insufficiency-Preeclampsia-Fetal loss-Low IQ

-Hypoglycemia-Hypocalcemia-Hyperbilirubinemia-Respiratory distress syndrome-Macrosomia-Hypomangnesmia-Intrauterine Death

Malformations in infants of Diabetic Mothers, No Risk in GDMMalformations in infants of Diabetic Mothers, No Risk in GDM

Anomaly Onset

Caudal regressionSpina bifida

3 wks6 wks

AnencephalyMyeloceleHydrocephalus

4 wks4 wks5 wks

DextrocardiaConus arteriosus defectsVSD

4 wks5 wks6 wks

Renal agenesis/hypoplasia

6 wks

Neonate

ChildAdult

RDSHypoglycemiaHypocalcemia

HypomagnesemiaThrombocytopenia

RDSHypoglycemiaHypocalcemia

HypomagnesemiaThrombocytopenia

Polycythemiaheel-stick blood

Renal vein thrombosis

HyperbilirubinemiaHyperbilirubinemia

Behavior - Intellect deficitObesity

Diabetes mellitusDiabetes mellitusDiabetes mellitusDiabetes mellitus

Maternal Complications

Worsening retinopathy – 10% new DR, 20% mild NPDR and 55% mod-severe NPDR progresses

Worsening proteinuria.

Hypertension and Cardiovascular disease

Neuropathy – No worsening

Infection

Hypoglycemia Diabetic Ketoacidosis Preeclampsia: 18 % Preterm delivery: 42 % Cesarean delivery: 56 %

50% lifetime risk in developing Type II DM in GDM

Recurrence risk of GDM is 30-50%

MANAGEMENT

Patient education

Medical Nutrition therapy

Glycemic monitoring: SMBG and targets

Pharmacological therapy

Fetal monitoring: ultrasound

Planning on delivery

Interdisciplinary team effort

PRENATAL MANAGEMENT

Screening Tests for GDM

Best method still controversial

Criteria of Diagnosis

ADA recommendations

WHO criteria

Urine Glucose

Spot Test

HbA1C, Serum fructosamine

Whom and When to Screen? Indian Scenario - The DIPSI Guidelines

75 gm GCT with single PG at 2 hrs ≥ 140 mg/dL is GDM ≥ 120 mg/dL is DGGT

Universal screening

First trimester, if negative at 24 – 28 wks and then at 32 – 34 weeks

First visit

Hb A1C

Collect 24 hr urine (protein, creatinine clearance, creatinine)

CVS status - ECG and echocardiogram

Eye exam Bl urea nitrogen, serum creatinine,

TSH, and free thyroxine levels

2nd Trimester Laboratory Testing Spot urine protein-to-creatinine

study in women with elevated value in first trimester

MSAFP HbA1C Capillary blood sugar 4-7 times

daily

Ultrasound

Dating scan at 8 – 12 wks Nuchal translucency 11-14 wks Targeted scan including fetal echo at

18-20 wks Growth scan at 26 wks and every 4

wks thereafter NST + AFI twice wkly starting at 32

wks; 28 -wks if poorly controlled or class D- T.

Fetal Evaluation

Procedure Low risk High risk

Fetal kick counts 28 28

USG for fetal growth

28 & 37 weeks Monthly

NST In GDM 36weeks Semiweekly

28-34 weeks, Semiweekly

FHS/BPP/Doppler 36 weeks, weekly

27 weeks-1-3/week

AmniocentesisFor lung maturity

- 35 - 38 wks

Tx Targets - Controversial

ACOG F venous plasma ≤ 95 mg/dl 1 hr PP ≤ 140 mg/dl 2 hr PP ≤ 120 mg/dl Pre-meal ≤ 100 mg/dl A1C ≤ 6%

ADA Premeal 80-110 2 hr PP not >155

These are venous plasma targets, not glucometer targets

Medical Nutrition Therapy

Goals Achieve normoglycemia Prevent ketosis Provide adequate weight gain Contribute to fetal well-being

Nutritional plan Calorie allotment Calorie distribution CH2O intake

Dietary Therapy Avoid single large meals with large %

of simple CHOs

6 feedings/day, with 3 major & 3 snacks

Artificial Sweeteners and Caffeine:

Avoid saccharin as it crosses the placenta.

Aspartame , acesulfame-K and sucralose allowed in limited amounts. Artificial sweeteners containing CHO counted as part of total CHO

Caffeine is allowed in moderation. <300 mg/day is allowed to limit potential harm to the fetus

Exercise

ACOG recommends – 30 min/day of moderate exercise .

Begin with 5 – 10 min of warm up period involving stretching exercises.

In sedentary women, exercise HR should not exceed 140 bpm.

Exercising lowers maternal glucose conc in GDM .

Exercise

Absolute Contraindication Preterm Labor PROM Incompetent Cervix Persistent 2nd or 3rd trimester bleeding IUGR Placenta Previa beyond 26 week PIH

INSULIN

MEDICATION ORAL DRUGS

When to Start Insulin Therapy in GDM

Fastinga Postprandial Reference

105b None Metzger

>95 2 h> 120 Langer et al.

>100 1 h > 130 Ramus and Kitzmiller

>90 1 h> 120 Jovanovic–Peterson

a – Glucose concentrations (mg/dl) measured in finger–stick wholeblood samples unless designated otherwise. b – Venous plasma sample.

Gold standard because of its- safety and efficacy

it can not cross placenta because large mol wt (6000Da)

NPH insulin is the only basal insulin that has been adequately studied in pregnancy

Why Insulin?

Insulin regimen should: Result in a smooth glucose profile

throughout the day, with no hypoglycemic reactions bet meals or at night.

HbA1C is (< 6.5%) at least 3 months before conception

1.0 mg/day of folic acid for at least 3 months before conception to minimize the risk of neural tube defects in the fetus.

Regimen and timing of insulin injections different from non-pregnant state because as pregnancy progress:

↑sing fetal demand for glucose

Progressive lowering of maternal F & PPBG

↑ses the risk of symptomatic hypoglycemia

.

Monitoring BG

At least 4 times (SMBG) Fasting and 3 one hr postprandial

Pre vs. postprandial monitoring Better glycemic control (HbA1c value

6.5 vs. 8.1 %) ↓ incidence of LGA infants (12 vs. 42

%) ↓rate of CS delivery for CPD (12 vs. 36

%)

Monitoring BG Home monitoring

Maintain log book Use a memory meter Calibrate the glucometer frequently

HbA1C Ancillary test for feedback to the pt Lower values when compared to non-

pregnant state – lower BG – measured every 2-4 weeks

Target < 5.1%

Cross placenta.

Fetal hperinsulinemia.

Prolonged fetal hypoglycemia

OHA in Pregnancy

WHEN TO DELIVER

Class A1 Labor spontaneously or induce 40-42

weeks, Cochrane review-”little evidence to support elective induction at 38wks

Class A2 -C ( good control with nl antepartum testing) Induce at 39 – 40 weeks

Class D - T or class A2 - C with poor control Deliver at 37-38 weeks

Mode of Delivery

Vaginal route – preferred

Indications of C.S.

-EFW->4.5 Kg [ACOG ]

-H/O shoulder Dystocia,

previous stillbirth

-other obstetric indications

EFW - 4 - 4.5Kg - Role of CS controversial

Scheduled C-Section

Usual medication (insulin or glyburide) at bedtime

Eat nothing after midnight Do not take morning medication Check blood glucose Perform CS within 2 hrs If unable to perform surgery

immediately or pt in poor control, start insulin drip, Perform CS after 4-6 hrs euglycemia.

Vaginal delivery : Management

• Strict asepsis • Restrict number of PV examinations • Electronic fetal heart rate

monitoring• Partogram • Obstetrician to be well versed with

the Mx of SHOULDER DYSTOCIA• Call Paediatrician

Tight control of maternal glycaemia is essential throughout labor.

In labor no extra insulin is required because labor is a form of exercise

Monitor BS- 1 hourly Target BS-70-100 mg/dl Monitor urine sugar & ketone 2-4

hourly

Insulin During Labor

Postpartum Care

Prevent infection

Insulin infusion is discontinued

GDM on diet-no monitoring

GDM on insulin /Pre-gestational DM-

-Monitor BS

Postpartum Care Continued

Type 1 DM-restart insulin [0.5-0.6U/Kg] on day 2-5 post delivery.

Breast feeding: helps in weight loss.

Insulin, tolbutamide compatible.

Chlropropamide secreted small amounts

Glyburide and glipizide not secreted

Metformin secreted - no adverse effects

Check BG before discharge

Lifestyle modification: exercise, weight

reduction & healthy diet

75 OGTT at 6-12 wks postpartum: classify

patients into normal/impaired glucose

tolerance and diabetes

Contraception

Low dose EP can be used

Progestin only pills shown to ↑se risk of T2DM in GDM

IUCD – ↑sed PID

Women and Diabetes

Diabetes no longer means› Abstinence› Amenorrhea › Inability to

conceive› Inability to

deliver healthy children

› Death during pregnancy

Teachable Moments

Women with a history of GDM present an ideal group for diabetes prevention, not only in preventing diabetes in themselves, but for their family, for whom they are often the gatekeepers for nutrition and exercise.

Pregnancy is a teachable moment when women are usually very focused on their own health and the health of their baby.