nguyen thy khue
TRANSCRIPT
Diabetes and pregnancyDiabetes and pregnancy
Nguyen Thy Khue, MD, PhD
Diabetes in pregnancyDiabetes in pregnancy
2-20% of all pregnancies
Pregestational diabetes (approximately
20%)
Gestational diabetes (GDM - approximately
80%)
What is gestational diabetesWhat is gestational diabetes
”Any degree of glucose intolerance
with onset or first recognition during
pregnancy” (1980-2010)
GDM vs ”overt diabetes” detected in
pregnancy (2010)
Metzger et al. Summary and recommendations of the Fourth International Workshop-Conference Diabetes Care 1998
International Association for Diabetes in Pregnancy Study Groups. Recommendations on the diagnosis and classification of hyperglycaemia during pregnancy Diabetes Care 2010
Pathophysiology of GDMPathophysiology of GDM
Increased Insulin resistance
Increased insulin secretion
Adequate in the first trimester
Inadequate as gestation progress
HYPERGLYCEMIA
Inadequate insulin secretion
Buchanan et al. GDM: risks and management during and after pregnancy Nat Rev Endocrinol 2012 Nov;8(11):639-49
Comparison with type 2 diabetesComparison with type 2 diabetes
Increased Insulin resistance
Stumvoll et al. Type 2 diabetes:principles of pathogenesis and therapy Lancet 2005 365(9467):1333-46
Inadequate Insulin secretion
Risk factor of GDMRisk factor of GDM
Obesity or excessive gestational weight gain
Ethnicity associated with higher type 2
diabetes risk
Current glucocorticoid use
Hypertension
Family history of diabetes
Glycosuria
Risk factor of GDMRisk factor of GDM
Previous poor obstetric outcome
Previous GDM
Polycystic Ovarian Syndrome
Age 25 or over
Previous macrosomic baby
Maternal macrosomia or low birth weight
Pedersen Hypothesis
PlacentaPlacenta
Maternal hyperglycemiaMaternal hyperglycemia
Fetal hyperglycemiaFetal hyperglycemiaFetal hyperglycemia
and hyperinsulinemiaFetal hyperglycemia
and hyperinsulinemiaFetal hyperinsulinemiaFetal hyperinsulinemia
1. Congenital anomalies (peri-conceptional)
1. Congenital anomalies (peri-conceptional)
2. Decreased early growth (0-20 weeks gestation)
2. Decreased early growth (0-20 weeks gestation)
3. Hyperinsulinemia(>20 weeks gestation)3. Hyperinsulinemia
(>20 weeks gestation)3. Immature liver
metabolism (neonatal)3. Immature liver
metabolism (neonatal)
2. Surfactant deficiency (neonatal)
2. Surfactant deficiency (neonatal)
1. Neonatal hypoglycemia (0-7 days postnatal)
1. Neonatal hypoglycemia (0-7 days postnatal)
a. Jaundicea. Jaundice
1. Fetal macrosomia(>20 weeks gestation)1. Fetal macrosomia
(>20 weeks gestation)
a. Birth asphyxiab. Cardiomyopathyc. TTN
a. Birth asphyxiab. Cardiomyopathyc. TTN
2. Fetal hypoxia(>30 weeks gestation)
2. Fetal hypoxia(>30 weeks gestation)
a. Polycythemiaa. Polycythemia
c. Iron abnormalitiesc. Iron abnormalities
b. Stroke, RVT
b. Stroke, RVT Poor neurodevelopmental
outcomePoor neurodevelopmental
outcome
Perinatal consequences of GDMPerinatal consequences of GDM
Outcome Odds ratio
Macrosomia 2.66
Large for gestational age 3.28
Caesarean section 1.88
Shoulder dystocia 4.07
Hypoglycemia 10.38
Hyperbilirubinemia 3.87
Erythrocytosis 10.88
Respiratory complications 4.40
Stillbirth 1.91
Langer et al. Gestational diabetes: the consequences of not treating Am J Obst Gynecol 2005 23(3):196-8
Type 2 diabetes Relative risk 7.7 (up to 60% at 16 years)
Metabolic syndrome 3-fold increase (38.4 vs. 13.4%)at 9.8 years
Cardiovascular disease Hazard ratio 1.66 at 12.3 years
Maternal consequences of GDMMaternal consequences of GDM
Impact of GDM on Pregnancy Outcomes
The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study
Rationale:
•Overt diabetes increases the risk of adverse pregnancy outcomes.
•What level of glucose intolerance during pregnancy, short of diabetes, is associated with the risk of adverse outcomes?
Metzger BE, et al. HAPO Study Cooperative Research Group. N Eng J Med 2008;358:1991-2002.
HAPO Protocol
75 g OGTT 24-32 weeks
Fasting, 1 & 2 hr venous plasma
N = 25,505
Unblinded at field centre ifOGTT fasting >105 &/or 2 hr >200 or random glucose ≥160 ~36 wks
Or <45 mg/dL
1,443 (5.7%) incomplete
23,316Standard care for field centre
Cord glucose & C-peptideNeonatal glucose: 1-2 hr of age
Anthropometrics by 72 hr:Length, head circ, weight, skin folds x3
746 (2.9%) unblindedfor treatment
Metzger BE, et al. HAPO Study Cooperative Research Group. N Eng J Med 2008;358:1991-2002.
• N=23,316 women
• 75g OGTT 24-32 weeks gestation– Fasting glucose ≤ 5.8 mmol/L
– 2-hour glucose ≤ 11.1 mmol/L
• Composite of 4 perinatal outcomes
Hyperglycemia and Adverse Pregnancy Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) studyOutcomes (HAPO) study
HAPO Study Group. Hyperglycemia and Adverse Pregnancy Outcomes NEJM 2008 358:1991–2002
Hyperglycemia and Adverse Pregnancy Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) studyOutcomes (HAPO) study
HAPO Study Group. Hyperglycemia and Adverse Pregnancy Outcomes NEJM 2008 358:1991–2002
OutcomeOdds Ratio
Fasting glucose
Odds Ratio 1-hour
glucose
Odds Ratio 2-
hourglucose
Birth weight > 90th centile
1.38* 1.46* 1.38*
Cord C-peptide >90th centile
1.55* 1.46* 1.37*
Primary Caesarean Section
1.11* 1.10* 1.08*
Clinical neonatal hypoglycaemia
1.08 1.13* 1.10
Hyperglycemia and Adverse Pregnancy Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) studyOutcomes (HAPO) study
*statistically significant
HAPO Study Group. Hyperglycemia and Adverse Pregnancy Outcomes NEJM 2008 358:1991–2002
GDM* Overt
diabetes
Fasting plasma glucose –
mg/dl (mmol/l)
≥92
(5.1)
≥126
(7.0)
1-hour glucose- mg/dl
(mmol/L)
≥180
(10.0)
2-hour glucose- mg/dl
(mmol/L)
≥153
(8.5)
≥200
(11.1)
IADPSG Consensus Conference 2010IADPSG Consensus Conference 2010
International Association for Diabetes in Pregnancy Study Groups. Recommendations on the diagnosis and classification of hyperglycaemia during pregnancy Diabetes Care 2010 33(3):676-82
*only one abnormal value required
GDM prevalence IADPSG criteriaGDM prevalence IADPSG criteria
Data from Sacks et al Frequency of Gestational Diabetes Mellitus at Collaborating Centers Based on IADPSG Consensus Panel–Recommended Criteria Diabetes Care 2012 35:526–528
Outcomes of GDM Pregnancies in Urban Vietnam
• Most available data on the pregnancy outcomes of GDM are from high-income countries.
• 2,772 Vietnamese women in Ho Chi Minh City were monitored through routine prenatal care.– 75 g OGTT between 24-32 weeks.– GDM diagnosis using either 2010 ADA criteria
(2 positive results from OGTT), or IADPSG criteria (1 positive result from OGTT)
No GDMBorderline GDM(IADPSG +ve; 2010 ADA -ve)
GDM (2010 ADA +ve)
Prevalence 79.6% 14.5% 5.9%
BMI 20.45 kg/m2 21.10 kg/m2 21.81 kg/m2
Hirst JE, et al. PLoS Med 2012;9(7):e1001272.
Neonatal Outcomes of GDM Pregnancies in Urban Vietnam
No GDMBorderline GDM(IADPSG +ve; 2010 ADA -ve)
GDM(2010 ADA +ve)
Gestation at birth (weeks) 1.48% 1.67% 1.70%
Preterm delivery (<37 weeks) 6.55% 9.59%* 14.02%*
>90th percentile for gestational age
11.76% 16.06% 18.90%
<10th percentile for gestational age
8.04% 6.99% 6.10%
Clinical neonatal hypoglycemia
0.70% 2.33%* 14.02%*
Jaundice requiring phototherapy
3.02% 4.15% 4.27%
Intensive neonatal care 4.0% 4.40% 5.49%
Perinatal death 0.4% 0.8% 0% Hirst JE, et al. PLoS Med 2012;9(7):e1001272.
No GDMBorderline GDM(IADPSG +ve; 2010 ADA -ve)
GDM(2010 ADA +ve)
Preeclampsia 1.63% 2.59% 0.61%
Primary caesarean section 33.46% 31.35% 40.85%
Induction of labour 2.84% 3.88% 7.64%*
Severe perineal trauma 2.81% 3.06% 2.78%
Postpartum hemorrhage(>500 mL)
4.32% 4.15% 3.66%
Maternal Outcomes of GDM Pregnancies in Urban Vietnam
Hirst JE, et al. PLoS Med 2012;9(7):e1001272.
International Recommendations on
Screening for GDM
GDM: Clinical Risk Assessment
Risk category Clinical characteristics
High risk ObesityFamily historyPersonal history IGTPrior macrosomic infantCurrent glycosuria
Average risk Neither low or high risk
Low risk <25 yrsLow-risk ethnicityNo family historyNormal pre-pregnancy weight and pregnancy weight gainNo personal history of abnormal glucose levelsNo prior poor obstetrical outcomes
ADA. Therapy for Diabetes Mellitus and Related Disorders. 5 th Edition. 2009.
When to screen for GDM?
For women at high risk:
• Screen for undiagnosed T2DM at firstprenatal visit.
• Diabetes detected during this visit constitutes a diagnosis of overt, not gestational, diabetes.
ADA. Standards of Medical Care in Diabetes. Diabetes Care 2014;37(suppl 1):S14-S80.
When to screen for GDM?
For women at average risk:
• Screen for GDM at 24-28 weeks gestation.
• Due to increasing global rates of diabetes,ADA recommends:
– 2-hr 75 g OGTT.
– Consider a single abnormal value as diagnostic.
ADA. Standards of Medical Care in Diabetes. Diabetes Care 2014;37(suppl 1):S14-S80.
Screening and Diagnosis of GDM
Criteria Diagnosis
ADA (2014) GDM defined when any of the following values are exceeded:Fasting ≥92 mg/dL (5.1 mmol/L)1-h ≥180 mg/dL (10.0 mmol/L)2-h ≥153 mg/dL (8.5 mmol/L)
IADPSG GDM defined as at least one value meeting the threshold:Fasting plasma glucose ≥5.1 mmol/L1-h plasma glucose ≥10.0 mmol/L2-h plasma glucose ≥8.5 mmol/L
WHO GDM defined as diabetes or impaired glucose tolerance. Diabetes defined as at least one value meeting the threshold: •Fasting plasma glucose ≥7.0 mmol/L•2-h plasma glucose ≥11.1 mmol/LImpaired glucose tolerance defined as:•Fasting plasma glucose <7.0 mmol/L•2-h plasma glucose ≥7.9 mmol/L
ADIPS GDM defined as at least one value meeting the threshold:Fasting plasma glucose ≥5.5 mmol/L2-h plasma glucose ≥8.0 mmol/L
Screening for GDM (ADA 2014)
• Perform a 75 g OGTT, with plasma glucose measurement fasting, and at 1 and 2 hrs, at 24-28 weeks gestation in women not previously diagnosed with overt diabetes.
• Perform OGTT in the morning after an overnight fast of at least 8 hrs.
ADA. Standards of Medical Care in Diabetes. Diabetes Care 2014;37(suppl 1):S14-S80.
GDM Diagnosis
• Plasma glucose values:– Fasting ≥92 mg/dL
– 1 hr ≥180 mg/dL
– 2 hr ≥153 mg/dL
• Women found to meet criteria at first prenatal visit should receive a diagnosis ofovert diabetes.
ADA. Standards of Medical Care in Diabetes. Diabetes Care 2014;37(suppl 1):S14-S80.
Selection of a Screening Strategy in Low-/Middle-Income Countries
• In resource-poor settings, screening must be optimized to reduce cost.1
• A 2013 study of Vietnamese patients found that:• Using a risk-threshold of 3%, the ADA 2010 criteria
had a sensitivity of 93% for GDM patients.
• Selective screening of patients results in 27% fewer glucose tolerance tests than systematic screening.2
• The study authors concluded that the ADA 2010 strategy may be a reasonable approach in conditions of limited resources.2
1.Gupta Y, Gupta A. Diabetes Care 2013;36(10):e185.2.Tran TS, et al. Diabetes Care 2013;36(3):618-24.
15-04-23 29
Outcome Routine care(n=510)
Intervention(n=490)
p value
Hypoglycaemia 15.4% 16.3% 0.75
Perinatal death 0.0% 0.0% N/A
Elevated cord C-peptide 22.8% 17.7% 0.07
Birth trauma 1.3% 0.6% 0.33
Neonatal jaundice 12.9% 9.6% 0.12
Birth weight>4kg 14.3% 5.9% <0.001*
Large for gestational age 14.5% 7.1% <0.001*
Treatment of mild GDM Landon et alTreatment of mild GDM Landon et al
*p<0.05
Landon et al. A multicentre, randomized trial of treatment for GDM NEJM 2009 361(14):1339-48
Outcome Routine care(n=510)
Intervention(n=490)
p value
Caesarean section 33.8% 26.9% 0.02*
Shoulder dystocia 4.0% 1.5% 0.02*
Preeclampsia 5.5% 2.5% 0.02*
Treatment of mild GDM Landon et alTreatment of mild GDM Landon et al
*p<0.05*p<0.05
Landon et al. A multicentre, randomized trial of treatment for GDM NEJM 2009 361(14):1339-48Landon et al. A multicentre, randomized trial of treatment for GDM NEJM 2009 361(14):1339-48
Glycemic Targets During Pregnancy: AACE & ADA Guidelines1,2
Glucose Increment
Patients with GDM Patients with
Preexisting T1DM or T2DM
Preprandial, premeal
≤95 mg/dL (5.3 mmol/L) Premeal, bedtime, and overnight glucose:60-99 mg/dL (3.4-5.5 mmol/L)
Postprandial, post-meal
1-hour post-meal: ≤140 mg/dL (7.8 mmol/L) or 2-hour post-meal: ≤120 mg/dL (6.7 mmol/L)
Peak postprandial glucose 100-129 mg/dL(5.5-7.1 mmol/L)
A1C A1C ≤6.0%
1. AACE. Endocr Pract. 2011;17(2):1-53. 2. ADA. Diabetes Care. 2013;36(suppl 1):S11-66.
Glycemic Targets During Pregnancy: Expert Recommendations
Glucose Increment
Patients With Gestational Diabetes Mellitus (GDM)1
Patients With Preexisting T1DM or
T2DM1,2
Preprandial, premeal
≤90 mg/dL (5.0 mmol/L)1,2
Postprandial, post-meal
1-hour post-meal: ≤120 mg/dL (6.7 mmol/L)1,2
A1C A1C <5.0%3 A1C <6.0%4
1. LeRoith D, et. al. Endocrinol Metab Clin N Am. 2011;40(1): xii-919. 2. Castorino K et al. Curr Diab Rep, 2012;12:53-59.
3. L. Jovanovic; personal communication.4. AACE. Endocr Pract. 2011;17(2):1-53.
Some experts recommend more stringent goals (in particular, for patients on insulin therapy) to prevent maternal and fetal complications1,2
Glucose Monitoring in GDM:Self-Monitoring of Blood Glucose
• Self-monitoring of blood glucose (SMBG) is the cornerstone of diabetes management in gestational diabetes mellitus (GDM)1
• ADA guidelines for pregnant patients requiring insulin:– SMBG ≥3 times daily– More frequent SMBG may be required, including:2
• Morning fasting • Premeal (breakfast, lunch, and dinner)• 1-hour postprandial (breakfast, lunch, and dinner)• Before bed3
1. Jovanovic L, et al. Diabetes Care. 2011;34(1):53-54. 2. ADA. Diabetes Care. 2013;36(suppl 1):S11-S66. 3. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. .
Glucose Monitoring in GDM: HbA1C
• Provides valuable supplementary information for glycemic control
• To safely achieve target glucose levels, combine A1C with frequent self-monitoring of blood glucose (SMBG)1,2
• Recent research suggests weekly HbA1C during
pregnancy:1
– SMBG alone can miss certain high glucose values
– SMBG + HbA1C = more complete data for glucose control
– Clinicians can further optimize treatment decisions with weekly HbA1C
1. Jovanovic L, et al. Diabetes Care. 2011;34(1):53-54.2. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.
Traditionally carbohydrate restriction to
approximately 40% of total intake
Limited evidence
Appropriate weight gain
Maximum 9kg if obese
Exercise plus diet lower glucose /HbA1c
High level of exercise in studies
Evidence for perinatal outcome measurements lacking
Diet/Exercise
Carbohydrate Source Exchange
1 Exchange : 175 calorie, 4 g protein, 40 g CHO
Management of GDMManagement of GDM
• Medical nutrition therapy (MNT) and lifestyle
changes can effectively manage 80% to 90%
of mild GDM cases1,2
• As pregnancy progresses, glucose intolerance
typically worsens; patients may ultimately
require insulin therapy1,3
1. Chitayat, L, et al. Diabetes Technology & Therapeutics. 2009;11:S105-111. 2. ADA. Diabetes Care. 2013;36(suppl 1):S11-66.3. ADA. Diabetes Care. 2004;27(suppl 1):S88-90. 4.
Most experience with human insulin Regular insulin, NPH
Insulin aspart and lispro appear safe and
effective
Insulin detemir appears safe and effective
Insulin glargine is likely to be safe, but less
evidence to date
Insulin
Glucose Levels for Insulin Initiation in GDM1
Fasting plasma glucose ≤105 mg/dL (5.8 mmol/L)
1-hour postprandial plasma glucose ≤155 mg/dL (8.6 mmol/L)
2-hour postprandial plasma glucose ≤130 mg/dL (7.2 mmol/L)
Gestational Diabetes Mellitus (GDM): Initiation of Insulin
1. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.
Choice of Insulin
Insulin Options Shown to Be Safe During Pregnancy1
Name Type OnsetPeak Effect
DurationRecommended Dosing Interval
AspartRapid-acting
(bolus) 15 min 60 min 2 hrs Start of each meal
Lispro Rapid-acting
(bolus) 15 min 60 min 2 hrs Start of each meal
Regular insulin
Intermediate-acting
60 min 2-4 hrs 6 hrs60-90 minutes before meal
NPH Intermediate-acting (basal)
2 hrs 4-6 hrs 8 hrs Every 8 hours
Detemir Long-acting
(basal) 2 hrs n/a 12 hrs Every 12 hours
1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.
Insulin Use During Pregnancy
1. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 2. AACE. Endocr Pract. 2011;17(2):1-53.3. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 4. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.
Women with GDM History
80-90% of women with mild GDM can be managed by lifestyle changes alone
ADA. Standards of Medical Care in Diabetes. Diabetes Care 2014;37(suppl 1):S14-S80.
Summary
• It is important to screen pregnant patients at
risk of GDM to achieve an early diagnosis.
• Diagnostic criteria (based on HAPO findings)
aim to decrease the risk of hyperglycemia in
both mothers and infants.
Summary (cont.)
• Women at high risk should be screened for TD2M at their first prenatal visit.
• Women at average risk should be screened for GDM at 24-28 weeks gestation.• 2 hr 75 g OGTT should be used with a single abnormal
value qualifying as diagnostic.
• 80-90% of mild GDM cases could be managed by lifestyle changes and medical nutrition therapy