Gestational Diabetes To Change or Not to Change

Lobna Farag Eltoony

Head of diabetes and Endocrinology Unit

Department Of Internal Medicine

Assuit University

Agenda

Definition

Epidemiology

The fetal and maternal consequences of GDM and pregestational diabetes.

Preconception care

The evolution of a diagnostic controversy

Screening : Who? Why? When? How?

Management

Diabetes and pregnancy

One of the most challenging aspects of diabetes practice

Seemingly easy: Practically difficult

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

Success can be achieved if we try together

Let’s begin by staying awake

for the next 20 minutes

Gestational diabetes

Definition

Carbohydate intolerance of variable severity first recognised during the present pregnancy.

This includes women with preexisting but previously unrecognised diabetes.

Gestational diabetes

Incidence

2-9%

more common in Asian and Indian women . In developed countries, increasing trend because of epidemic of obesity and T2DM.

Epidemiology

Most common medical complication of Pregnancy

affects 8% of pregnancies

Gestational DM 90% Diabetes 8%

Preexisting DM 10% 6

Nondiabetes 92%

Diabetes8% 24% Diagnosed T2DM

50%GDM

Diabetes in pregnancy

Pre-existing diabetes Gestational diabetes

Pre-existing diabetes IDDM

(Type1)

NIDDM

(Type2) True GDM

Pregestational Diabetes

In our practice , many women who are

first diagnosed with diabetes mellitus during pregnancy are classified as having gestational diabetes even though they have pre-existing, or pregestational, diabetes that had gone undiagnosed.

Pregestational vs Gestational Diabetes

This distinction is crucial because pregestational diabetes is associated with more serious consequences for the

fetus than is diabetes in the second and third trimester of pregnancy.

(A wolf in sheep’s clothing).

Pregestational Diabetes

Women with pregestational diabetes who become pregnant are at increased risk of giving birth to a baby with a serious birth defect, including cardiac, neurological, and vascular anomalies.

Reece et al 2009 lancet

Diabetes and pregnancy

Placental structure and function is affected

Early IUGR as high BG inhibits trophoblast proliferation

Hypertension, renal disease more frequent

High glycogen content in placenta

Complications of pregnancy in pre-existing DM Maternal: Increase insulin requirment’

Hypoglycemia

Infection

Ketoacidosis

Deterioration in retinopathy’

Increased proteinuria+edema

Miscarriage

Polyhydramnio

Shoulder dystocia

Preeclampsia

Increased caesarean rate

Fetal: Congenital abnormalities

Increased neonatal and perinatal mortality

Macrosomia

Late stillbirth

Neonatal hypoglycemia

Polycythemia

jaundice

Caudal regression syndrome

(abnormal development of lower spine )

Teratogen Period of

exposure Complications

Type of

Diabetes

Aberrant

fuel mixture

Hyperinsulinaemia

Foetus

delivery

G

D

M

P

G

D

M

1st trimester

2nd trimester

3rd trimester

Spontaneous abortions

Early growth delay

Congenital anomalies

Macrosomia

Selective

Organomegaly

CNS development

delay

Chronic hypoxia

Stillbirth

Birth injury

Fetal hyperinsulinemia

The Impact of Maternal Hyperglycemia

During Pregnancy

Modified Pedersen Hypothesis

Fetus

Fetal pancreas stimulated

IgG=immunoglobulin

G

Mother P

lace

nta

IgG-antibody-bound insulin

Insulin

Maternal hyperglycemia

Insulin resistance syndrome

Maternal hyperglycemia

Fetal hyperglycemia

Fetal hyperinsulinemia

Pederson

Hypothesis

(1952)

Macrosomia,organomegaly, polycythaemia,

hypoglycemia, RDS

Pathogenesis of Gestational diabetes

Neonate

Child

Adult

RDS

Hypoglycemia

Hypocalcemia

Hypomagnesemia

Thrombocytopenia

Polycythemia heel-stick blood

Renal vein

thrombosis Hyperbilirubinemia

Behavior - Intellect deficit

Obesity

Diabetes mellitus

Growth Abnormalities(1) Two Extremes Of Growth Abn:

Before conception is attempted, A1C levels Close to normal as possible (<7%) (B)

Starting at puberty Incorporate preconception counseling in routine diabetes clinic visit for all women of child-bearing potential (C)

Evaluate women contemplating pregnancy; if indicated, treat for

Diabetic retinopathy Nephropathy Neuropathy CVD (E)

Recommendations: Preconception Care (1)

ADA. VII. Diabetes Care in Specific Populations. Diabetes Care. 2011;34(suppl 1):S41.

Evaluate medications used prior to conception

Drugs commonly used to treat diabetes, complications may be contraindicated or not recommended in pregnancy, including

Statins, ACE inhibitors, ARBs, most noninsulin therapies (E)

Since many pregnancies are unplanned, consider potential risks/benefits of medications contraindicated in pregnancy in all women of childbearing potential; counsel accordingly (E)

ADA. VII. Diabetes Care in Specific Populations. Diabetes Care. 2011;34(suppl 1):S41.

Recommendations: Preconception Care (2)

Gestational Diabetes

Fetal Risks Macrosomia - shoulder dystocia and related complications Jaundice Hypoglycemia No increase in congenital anomalies

Exposure to GDM in utero

LGA children or those born to obese mother have a 7% risk of developing IGT at 7-11 yrs age Breastfeeding may lower risk

CDA CPG 2008

Pre-eclampsia: affects 10-25% of all pregnant women with

GDM

Infections: high incidence of chorioamnionitis and postpartum

endometritis

Postpartum bleeding:

Cesarian section more common due to fetal macrosmia and

cephalo-pelvic disproportion

Weight gain

Hypertension

Miscarriages

Third trimester fetal deaths

Long term risk of type-2 DM (40-60%) of within10-15 yr.

Effects of GDM on the mother

DETECTION AND DIAGNOSIS OF GESTATIONAL DIABETES

MELLITUS

Screening Tests for GDM

Best method still

controversial

NO CONSENSUS ON GDM SCREENING

Why? When? Who? How?

WHY?

•Increased risk of perinatal morbidity : Macrosomia’ Shoulder Dystocia ,Birth injuries and Hypoglycemia

Treatment reduces perinatal morbidity

Increased risk of maternal morbidity :Preeclampsia

Cesearean Section , Pregnancy-induced hypertension and Type2 diabetes mellitus

Treatment reduces maternal morbidity ,

Landon et al NEJM 2009;

Screen for undiagnosed type 2 diabetes at the

• first prenatal visit in those with risk factors, using standard diagnostic criteria (B)

In pregnant women not previously known to have diabetes, screen for GDM at 24-28 weeks gestation, using a 75-g OGTT

Recommendations: Detection and Diagnosis of GDM (1)

WHEN?

ADA. III. Detection and Diagnosis of GDM. Diabetes Care 2011;34(suppl 1):S15.

Risks for developing gestational diabetes

WHO? Aged 35 or over

Overweight BMI > 25

Positive FH of type 2 diabetes

Previous unexplained stillbirth, foetal malformation or large baby (>4.5kg)

Persistent fasting glycosuria

More than 3 previous children

polyhydramnios

Diagnosis of PCOS ADA 2011

The evolution of a diagnostic controversy

How? 1 hr 50 g OGTT.

2 hr 75 g oral OGTT

3 hr 100 g OGTT

Gestational Diabetes (GDM)

The American Congress of Obstetricians and Gynecologists (ACOG),endorses the older 1997 criteria, which involve a 2-step process:

Step 1: Screening 1 hr 50 g

OGTT. If PG >140 mg/dL,

proceed to Step 2.

Step 2: 3 hr 100 g OGTT

Fasting ≥95 mg/dL

1 hr ≥180 mg/dL

2 hr ≥155 mg/dL

3 hr ≥140 mg/dL

To Be or Not To Be , that is the question.

To Change or Not To Change .

Gestational Diabetes (GDM)

In 2011, the ADA affirmed the recommendations of the International Association of Diabetes and Pregnancy Study Groups (IADPSG),based on the results of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. Its current universal screening test is the

75 g oral OGTT, with measurement of plasma glucose (PG) over2 hr. The test is performed at 24–28 weeks of gestation, after an overnight fast of at least 8 hr. The diagnosis of GDM is made when

Any one of the following PG values is

Fasting ≥92 mg/dL

1 hr ≥180 mg/dL 2 hr ≥153 mg/dL

Diabetes Care 34:Supplement 1, 2011

Diabetes Care 2010; 33: 676–682

These new criteria will significantly increase the prevalence of

GDM, primarily because only one abnormal value, not two, is

sufficient to make the diagnosis.

The ADA recognizes the anticipated significant increase in the

incidence of GDM to be diagnosed by these criteria and is

sensitive to concerns about the “medicalization”

of pregnancies previously categorized as normal. These

diagnostic criteria changes are being made in the context of

worrisome worldwide increases in obesity and diabetes rates,

with the intent of optimizing gestational outcomes for women

and their babies.

Screening for and Diagnosis of GDM

Although the anticipated benefits include decreased rates of maternal and offspring obesity, metabolic syndrome, and diabetes, it is not yet clear how these benefits can be achieved in an environment of significantly restricted health care resources.

In addition, a dramatic increase in the rate of cesarean deliveries, the benefits of better diagnosis may be offset by increased cesarean delivery– related complications and costs.

The evolution of a diagnostic

controversy

Disclosure None ...

Where guidelines disagreed, I

picked the one I agreed with ☺

Screen women with GDM for persistent diabetes

6-12 weeks postpartum (E)

Women with a history of GDM should have lifelong screening for the development of diabetes or prediabetes at least

every three years (E)

Recommendations: Detection and Diagnosis of GDM (2)

ADA. III. Detection and Diagnosis of GDM. Diabetes Care 2011;34(suppl 1):S15.

Postpartum Care-cont:

Follow up:

Per American Diabetes Association, a 75 g two hours oral GTT should be performed 6-8 wks after delivery.

Normal glucose tolerance 5

Impaired glucose tolerance 3

Diabetes mellitus 1

1/9

5/93/9

Normal glucose tolerance Impaired glucose tolerance Diabetes mellitus

Post partum follow up at 6 weeks

Gestational diabetes

Management

Management similar as preexisting DM

Need for glucose monitoring

Start with Diet control

Commence insulin for poor control

Delivery plan individualised

Target Blood Glucose Values for GDM

Glucose level

Fasting - 90-99 mg/dL (5.0–5.5 mmol/L)

1- hr PP - < 140 mg/dL (7.8 mmol/L)

2- hr PP - < 120-127 mg/dL (6.7–7.1 mmol/L)

• HbA1c should not be used routinely for assessing glycemic control in the second and third trimesters of pregnancy.” NICE 2008

Fifth International Workshop Conference on Gestational Diabetes

Medical Nutrition Therapy

Low-carbohydrate diet , high fibre with caloric restriction

Frequent small snacks may be needed between meals

Avoid starvation

Medical Nutrition Therapy

Monitor urine ketones before breakfast to detect starvation ketonuria

3 meals and 3 snacks

50-60% complex high fiber carbohydrates

18-20% protein or at least 75 g

<30% fats ASGODIP 1996

INSULIN

MEDICATION

ORAL DRUGS

Consider insulin when ...

Diet and exercise fail to maintain glucose targets during a period of 1-2 weeks

Ultrasound suggests incipient fetal macrosomia (AC >70th percentile) NICE 2008

Insulin remains the agent of choice “In poorly resourced areas of the world,

The theoretical disadvantages of using oral glucose lowering agents ... far less than the risks of non treatment.” IDF 2011

Consider insulin when ...

Recommended insulin regimens?

Initiate a basal-bolus regimen if a patient cannot maintain glucose targets with diet alone.

NPH insulin (basal) and rapid-acting insulin at meals

Subcutaneous insulin infusion with an insulin pump AACE 2007

Which type of insulin and which regimen?. Insulin Analogues

1. rapid-acting insulin analogs

(lispro and aspart ) Cat B

concerns about teratogenesis, antibodies formation,

growth-promoting properties

majority of evidence showed that it does not cross placenta, and has no adverse maternal or fetal effects

Aspart, Lispro: category B

Regular insulin: category B

Glargine, Detemir: category C

Insulin Analogues

Insulin therapy in GDM

Initiating dose depends on the blood glucose

May start daily insulin dose

0.1-1.0 u/kg BW

ASGODIP 1996

Multidose Insulin

breakfast 25% H

lunch 15% H

supper 25% H

hs 35% NPH indicates insulin as a % of total daily dose

Gestational Diabetes

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

53

Oral Hypoglycemic agents

Implicated as teratogeneic in animal studies esp first generation sulfonyureas

In humans, scattered case reports of congenital abnormality

Risk of congenital abnormality related to maternal glycemic control rather than mode of the anti-DM agents

Option of giving metformin or glibenclamide

“Obtain and document informed consent.

... tailored to glycemic profile of, and acceptability to, the individual woman.” NICE 2008

Alternative to Insulin Therapy Metformin: Cat B drug

Commonly used in Polycystic Ovarian Disease (PCOD) to treat insulin resistance and normalize reproductive function

Not teratogeneic

Reduce first trimester miscarriage

10X reduce gestational diabetes Glueck, Fertil Steril 2002

Reece, Curr Opin Endocrinol Diabetes, 2006

Hague, BMJ, 2003

Glueck, Human Reprod, 2004

Metformin and Pregnancy

Rowan et al. New Engl J Med 2008; 358: 2003 - 15

Metformin and Gestational Diabetes

Rowan et al. New Engl J Med 2008; 358: 2003 - 15

Mother and Child are okay

Metformin for the Treatment of GDM

In women with gestational diabetes mellitus, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin

Patients prefer metformin over insulin

Rowan et al, N Engl J Med 2008; 358:19

Feig DS, Moses RG. Diabetes Care 2011; 34: 2329 - 2330

Rowan JA et al Metformin in Gestational dibetes: The Offspring Follow-Up (MiG TOFU): body composition at 2 years of age. Diabetes Care 2011; 34:2279-2284

? Healthier fat distribution in offspring

Alternative to Insulin Therapy Glyburide:

Category C

Does not cross the placenta

Some physicians are using glyburide in lieu of insulin given its ease of use.

Both the ACOG and ADA do not endorse the use of glyburide in the tx of GDM until additional RCTs support its safety and effectiveness.

Oral Hypoglycemic agents

Glyburide Insulin

Achieved N BG 82% 88%

LGA infants 12% 13%

Macrosomia 7 4

C Section 23 24

Hypoglycemia 9 6

Preeclampsia 6 6

Anomalies 2 2

63

Langer NEJM

2000

Conclusion Gestational diabetes is a growing health concern.

Although traditionally deemed not as dangerous for the developing fetus as pregestational diabetes, gestational diabetes has serious, long-term consequences for both baby and mother.

Evidence now suggests that screening, early detection, and management can greatly improve outcomes for women with this condition and their babies.

Unfortunately, screening and diagnostic standards are not uniform worldwide, which might lead to underdiagnosis and undermanagement of the disease.

Conclusion 1-step diagnostic test also will be much easier to administer and, thus, the earlier diagnosis and treatment of GDM will lead to better outcomes for mothers and their babies.

Although human insulin or human insulin analogues have been the preferred treatment for gestational diabetes for some time, oral antihyperglycaemic agents—such as glibenclamide and metformin—could be just as effective for the management of the disease.

To Be or Not To Be , that is the question.

To Change or Not To Change .

Recommendation

It is time for Outpatient Clinic care for early screening and diagnosis of GDM in our locality :

To reduce the risk of the preinatal and maternal morbidity .

To prevent or delay the development of T2DM for the mother and the fetus in their later lives .

LOBNA