1. 成大醫院 內科部 內分泌新陳代謝科 歐弘毅醫師
認識妊娠糖尿病
成大醫院 內科部
內分泌新陳代謝科 歐弘毅醫師

2. Standards of Medical Care in Diabetes—2011
“Standards of Medical Care in Diabetes—2011” contains all of the current and key clinical recommendations of the American Diabetes Association (ADA)
These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care
While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided
These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed
The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to affect health outcomes of patients with diabetes favorably
The slides are organized to correspond with sections within the “Standards of Medical Care in Diabetes—2011”
While not every section in the document is represented, these slides do incorporate the most salient points from the Position Statement
These standards of care are revised annually by the ADA’s multidisciplinary Professional Practice Committee, incorporating new evidence; subsequently, they are reviewed and approved by the Executive Committee of ADA’s Board of Directors
Reference
American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care 2011;34(suppl 1):S Available online at

4. Epidemiology and risk factors
A global increase in the prevalence of obesity and type 2 diabetes
The incidence of GDM is increasing
In the US: 2.2~9% of pregnancies
Taiwan: GDM=2.03%, G-IGT=6.99%
Asian
Risk factors (high risks)
Advanced maternal age
↑40y/o > 35~39y/o > ↓35y/o
Severe obesity
Inter-pregnancy BMI gain
Hypertension
Strong family history of type 2 DM
Previous history of GDM, IGT
Parity
Prepregnancy BMI
parity
Am Fam Physician Jul 1;80(1):57-62.
北市醫學雜誌2005 ; 2 (2):

5. Gestational Diabetes Mellitus
Gestational diabetes mellitus (GDM)
Carbohydrate intolerance with onset or first recognition during pregnancy
GDM occurs around weeks into pregnancy
Screening (24~28 wk)
50-g non-fasting one-hour glucose challenge
130 mg/dL (7.20 mmol/L): 90% sensitivity
140 mg/dL (7.75 mmol/L): 80% sensitivity
100-g oral glucose tolerance test
Fasting< 95 mg/dL (5.25 mmol/L)
1-hr< 180 mg/dL (10.00 mmol/L)
2-hr< 155 mg/dL (8.60 mmol/L)
3-hr< 140 mg/dL (7.75 mmol/L)
75-g oral glucose tolerance test
Fasting< 95 mg/dL (5.25 mmol/L)
1-hr< 180 mg/dL (10.00 mmol/L)
2-hr< 155 mg/dL (8.60 mmol/L)
Am Fam Physician Jul 1;80(1):57-62.
Diabetes Care Jul;30 Suppl 2:S251-60

6. Recommendations: Detection and Diagnosis of GDM (1)
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 weeks gestation, using a 75-g OGTT and the diagnostic cutpoints in Table 6 (B)
Recommendations for the detection and diagnosis of gestational diabetes mellitus (GDM) are summarized on two slides; this slide (Slide 1 of 2) includes:
As the ongoing epidemic of obesity and diabetes has led to more type 2 diabetes in women of childbearing age, the number of pregnant women with undiagnosed type 2 diabetes has increased[24]
Because of this, it is reasonable to screen women with risk factors for type 2 diabetes for diabetes at their initial prenatal visit, using standard diagnostic criteria; women with diabetes found at this visit should receive a diagnosis of overt, not gestational, diabetes
ADA. III. Detection and Diagnosis of GDM. Diabetes Care 2011;34(suppl 1):S15.
References
American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care 2011;34(suppl 1):S15.
Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care 2002;25:

7. Screening for and Diagnosis of GDM
Perform a 75-g OGTT, with plasma glucose measurement fasting and at 1 and 2 h, at weeks of gestation in women not previously diagnosed with overt diabetes
Perform OGTT in the morning after an overnight fast of at least 8 h
GDM diagnosis: when any of the following plasma glucose 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)
GDM carries risks for the mother and neonate1
The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study,2 a large-scale (25,000 pregnant women) multinational epidemiologic study, demonstrated that risk of adverse maternal, fetal, and neonatal outcomes continuously increased as a function of maternal glycemia at 24–28 weeks, even within ranges previously considered normal for pregnancy. For most complications, there was no threshold for risk. These results have led to careful reconsideration of the diagnostic criteria for GDM
After deliberations in 2008–2009, the International Association of Diabetes and Pregnancy Study Groups (IADPSG), an international consensus group with representatives from multiple obstetrical and diabetes organizations, including ADA, developed revised recommendations for diagnosing GDM. The group recommended that all women not known to have diabetes undergo a 75-g OGTT at 24–28 weeks of gestation
Additionally, the group developed diagnostic cut points for the fasting, 1-h, and 2-h plasma glucose measurements that conveyed an odds ratio for adverse outcomes of at least 1.75 compared with the mean glucose levels in the HAPO study
Current screening and diagnostic strategies, based on the IADPSG statement,3 are outlined in Table 6, which is summarized on this slide
ADA. III. Detection and Diagnosis of GDM. Diabetes Care 2011;34(suppl 1):S15. Table 6.
References
American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care 2011;34(suppl 1):S15. Table 6.
Metzger BE, Lowe LP, Dyer AR, et al, for the HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002.
Metzger BE, Gabbe SG, Persson B, et al, for the International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676–682.

8. Recommendations: Detection and Diagnosis of GDM (2)
Screen women with GDM for persistent diabetes 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 for the detection and diagnosis of gestational diabetes mellitus (GDM) are summarized on two slides; this slide (Slide 2 of 2) includes:
Women with a history of GDM have a greatly increased subsequent risk for diabetes2; therefore, they should be screened for diabetes 6-12 weeks postpartum, using nonpregnant oral glucose tolerance test (OGTT) criteria, and should be followed for the development of diabetes or prediabetes (see Section II, “Testing for Diabetes in Asymptomatic Patients”)
Information on the National Diabetes Education Program campaign to prevent type 2 diabetes in women with GDM can be found at:
ADA. III. Detection and Diagnosis of GDM. Diabetes Care 2011;34(suppl 1):S15.
References
American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care 2011;34(suppl 1):S15.
Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care 2002;25:

9. Management of gestational diabetes mellitus
GDM is associated with adverse pregnancy outcome
For maternal
For fetal
Pre-eclampsia
Large for gestational age
Cesarean delivery
Future risk of diabetes
Macrosomia
Shoulder dystocia
Clavicle fracture
Neonatal hypoglycemia
Malformation
Perinatal mortality
Shoulder dystocia 進一步造成手臂神經受損
Maternal capillary glucose goals for GDM
Preprandial ≤ 95 mg/dL (5.3 mmol/L) AND
1-hr post-meal ≤ 140 mg/dL (7.8 mmol/L) OR
2-hr post-meal ≤ 120 mg/dL (6.7 mmol/L)

10. Non-pharmacological management
Diet management
Medical nutritional therapy
Specific nutrition procedures in the treatment of an illness, injury or disease condition
Low-glycemic index diet
Objective
Investigation of the effect of a low–glycemic index (LGI) versus a conventional high-fiber diet on pregnancy outcomes, neonatal anthropometry, and maternal metabolic profile in GDM
Method
99 women (26~42y/o, BMI=24 ± 5 kg/m2) diagnosed with GDM at 20–32 weeks’ gestation
Protein (15–25%), fat (25–30%), and carbohydrate (40–45%)
LGI (target GI ≤50)
High-fiber content and moderate GI
第二型糖尿病則須改變飲食及運動習慣，控制體重以降低胰島素阻抗性，並減少飲食中的飽和脂肪、膽固醇和鈉鹽，以改善血脂及血壓。
Both diet strategies produced comparable pregnancy outcomes in women with GDM
An LGI diet appears to be a safe alternative to the traditional pregnancy diet and expands the range of dietary strategies that can be offered.
Result
Data→ No significant between LGI and HF
Diabetes Care Nov;34(11):

11. Non-pharmacological management
In type 2 diabetes
Regular physical activity enhances insulin sensitivity, facilitates weight loss, and improves glucose control
Type of exercise for pregnancy with GDM
20 minutes of supervised aerobic training 3 days a week
Lower fasting, post-pramdial glucose level and HbA1c
Lower glucose response to a glucose challenge
Delay in the requirement of insulin
Pre-pregnancy BMI> 25 can less likely to require insulin
A sensible level of light and moderate intensity physical activity until latter stages of the pregnancy
Walking for 20~30 minutes each day
Antenatal exercise classes
Vasc Health Risk Manag. 2009;5(1):153-64

12. Pharmacological management
Post-prandial monitoring
Gold standard of insulin therapy
Choice of drugs
Bad compliance
Frequency
Oral anti-hyperglycemic agents
Sulfonylurea
Metformin
Α-glucosidase inhibitors

13. Pharmacological management-insulin
The dosage of insulin increases over the third trimester of pregnancy→the end of pregnancy, insulin can drop
Significant hypoglycemia is uncommon in insulin-treated GDM
Insulin therapy in GDM
Fast-acting (regular insulin)
Intermediate-acting (isophane insulin)
Rapid-acting (insulin lisopro, aspart)
→ as effective and safe as human insulin
Long-acting (insulin glargine)
→not really clear
→as safe as NPH for fetal outcome
Concern
Human insulin does not cross the placenta
Anti-insulin antibodies pass the placenta
→influence of fetal birth-weight

14. Pharmacological management-insulin
Frequency of insulin therapy for GDM
Randomized controlled open label trial
Objective
To compare perinatal outcome and glycemic control in pregnant diabetic patients receiving two insulin regimens
Method
Twice daily regimen
GDM:138, pre-DM: 58
Morning dose: 2/3 (2/3 RI+1/3 NPH), evening dose: 1/3
Four times daily regimen
GDM:136, pre-DM: 60
Pre-meal 30min: Novopen, bedtime: NPH
Result
Adequate glycemic control (<104.5 mg/dL (5.8 mmol/L))
Four times daily regimen: 91.3%
Twice daily regimen: 74.3%
Four times daily regimen can decrease risks
Neonatal hypoglycemia
Neonatal hyperbilirubinemia
In order to improve glycemic control and the perinatal outcome
Given insulin four times daily regimen is better than twice daily regimen
BMJ Nov 6;319(7219):

15. Pharmacological management-OHA
Oral anti-hyperglycemia agents were not recommended during pregnancy
Assumption that these drugs cross the placenta
Teratogenic early in development
Neonatal hypoglycemia
Anti-hyperglycemia agent for use during lactation
Tolbutamide: approved by American Academy of Pediatrics
AAP= 美國小兒科學會
J Perinat Neonatal Nurs Sep;16(2):40-53

16. Pharmacological management-OHA
J Perinat Neonatal Nurs Sep;16(2):40-53

17. Pharmacological management-OHA
Glyburide
Randomized trial without blinding
→ as effective as insulin for GDM
Objective
To compare glyburide and insulin therapy on safety and efficacy for the pregnant women with GDM as the alternative therapy
Method
404 women with gestational diabetes
Insulin group: 0.7 unit/kg
Glyburide group: initial: 2.5mg→5 mg→ 20mg
Result
No significant differences in mean blood sugar
4% glyburide group required insulin therapy
No significant differences in fetal outcome
N Engl J Med Oct 19;343(16):

18. Pharmacological management-OHA
Metformin
Randomized trial without blinding
Objective
To assess the efficacy and safety of the use of metformin for pregnant women with GDM
Method
751 women with GDM at 20 to 33 weeks of gestation to open treatment with metformin or insulin
Metformin group: 500mg QD/BID→ Max: 2500mg/day
Insulin group: prescribed according to usual practice
Outcome
Primary outcome:
Neonatal hypoglycemia, respiratory distress, jaundice, birth trauma, 5-minute Apgar score< 7, or prematurity
Secondary outcomes
Neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance, and acceptability of treatment
N Engl J Med May 8;358(19):

19. Pharmacological management-OHA
Result
Primary outcomes→ Not significantly difference (P = 0.95)
32.0% in the metformin group
32.2% in the insulin group
Secondary outcomes→ Not significantly difference
Adverse effect
No significant differences between the treatment groups
None of the serious adverse events were considered
Metformin, alone or with supplemental insulin, is an effective and safe treatment option for women with GDM
Meet the usual criteria for starting insulin
Metformin is more acceptable to women with GDM
N Engl J Med May 8;358(19):

20. Pharmacological management-OHA
Acarbose
Not absorbed from the gut, unlikely to affect the fetus
An open, randomized clinical trial
Objective
To compare neonatal results from patients with GDM who were treated with insulin, glyburide and acarbose
Method
70 pregnant women diagnosed with GDM
Insulin group (n=27): RI+NPH 0.7→0.8→0.9 IU/kg
Glyburide group (n=24): 5 mg→ Max 20 mg
Acarbose group (n=19): 50mg→ Max 300mg
Result
Not achieve glucose level
Glyburide: 5 (20.8%)
Acarbose: 8 (42.1%)
Hypoglycemia in neonates
Insulin: 1 (3.7%)
Glyburide: 8 (33.3%)
Acarbose: 1 (5.2%)
Reducing post-prandial glucose almost the same as insulin in GDM
High frequency of abdominal cramping
Absorbed systemically, safety, potential trans-placenta need more evaluation
J Perinat Med. 2005;33:519–523

21. Pharmacological management-OHA
Recommendation
The evidence of acarbose used in GDM must be evaluated in larger and more studies
Metformin
Glyburide
J Perinat Neonatal Nurs Sep;16(2):40-53

22. Pharmacological management-OHA
Comparison between glyburide and metformin
Randomized trial without blinding
Objective
To compare the efficacy of metformin with glyburide for glycemic control in gestational diabetes.
Method
149 pregnant women at 11~33 weeks gestation with GDM
Metformin group (n=75): 500mg/day→2000mg/day
Glyburide group (n=74): 2.5mg,BID→ 10mg, BID
Result
Blood Glucose Levels
Not achieve:
metformin= 34.2%
glyburide= 16.2%
Neonatal outcome
No significant difference
Metformin
Glyburide
Not achieve
26 (34.7%)
12 (16.2%)
Hypoglycemia
2 (2.7%)
1 (1.4%)
Pre-eclampsia
3 (4%)
The use of glyburide and metformin as single-agent therapies
The failure rate of metformin was 2.1 times higher than the failure rate of glyburide in GDM
The failure of oral anti-hyperglycemia agents should required insulin therapy
Obstet Gynecol Jan;115(1):55-9.

24. Follow-up of gestational diabetes mellitus
Postpartum management
Most cases resolve with delivery
Linear increase in cumulative incidence during first 10 years after pregnancy
Increased risk of developing diabetes after GDM
Impaired glucose tolerance
Increased HbA1c at GDM
Low high-density lipoprotein cholesterol
Age> 35 y/o
Postpartum hyperglycemia
Continue medical nutrition therapy
If necessary, pharmacologic treatment
(insulin, glyburide, glipizide are safe)
No diabetes after postpartum
Glucose tolerance testing 6~12 weeks
Repeat at 1 year and then every 3 years
CMAJ Jul 29;179(3):

25. Take home message
GDM occurs around weeks into pregnancy, which may significantly affect both maternal and fetal outcomes.
The goals of management of GDM
Preprandial ≤ 95 mg/dL (5.3 mmol/L) AND
1-hr post-meal ≤ 140 mg/dL (7.8 mmol/L) OR
2-hr post-meal ≤ 120 mg/dL (6.7 mmol/L)
When GDM happened, diet and activity management are the first ways to control the glucose level.
The gold standard of pharmacologic management of GDM is insulin therapy, but recently found that metformin and glyburide can also be used to control the glucose level.

29. Thanks for Your Attention