ueda2013 gestational diabetes-d.lobna
TRANSCRIPT
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