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CLINICAL MANAGEMENT OF DIABETES DURING
PREGNANCYAntenatal, Intrapartum
and Postpartum Perspectives
Chukwuma I. Onyeije, M.D.Atlanta Perinatal Associates
BACKGROUND: WHAT IS DIABETES?
• A defect in body energy regulation and utilization• Causes:
– Insulin deficiency – Insulin resistance
• End result: Elevated blood sugar• Impact of elevated blood sugar:
– Pregnancy complications– Multi-organ dysfunction– Excess mortality
Epidemiology and Diagnosis
Classification of Diabetes
Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-1197.
Genetic defects in b-cell function,
Pancreatic disease,
Endocrinopathies,
Drug- or chemical- induced, and other rare forms
Other types
Insulin resistance with b-cell dysfunction
Gestational
Insulin resistance and relative insulin deficiencyType 2
b-cell destruction with lack of insulinType 1
INSULIN PHYSIOLOGY: REGULATION OF BLOOD SUGAR
TYPE 1 DIABETES: INSULIN DEFICIENCY
-cell destruction with lack of insulin
TYPE 2 DIABETES: INSULIN RESISTANCE
Insulin Resistance
GESTATIONAL DIABETES: INSULIN DEFICIENCY AND INSULIN RESISTANCE
Insulin Resistance
Insulin Deficiency
Gestational Diabetes Screening
•High risk•Marked obesity•Previous unexplained fetal demise•Personal history of GDM•Glucosuria•Strong family history of diabetes
•Low risk•Age <25 years•Normal weight before pregnancy•Ethnicity with low prevalence•No known first degree relatives with diabetes•No history of abnormal glucose tolerance•No history of poor obstetric outcome
Gestational Diabetes Screening
Universal screening is advisable
•1 hour 50 gm glucose load (GCT)•Venous plasma glucose cut-offs
•140 mg/dl•135 mg/dl•130 mg/dl
90%20-25%130
80%14-18%140
SENSITIVITYPATIENTS SCREENING
POSITIVE
THRESHOLD
SCREENING THRESHOLDS FOR GESTATIONAL DIABETES MELLITUS WITH THE 50-g ORALGLUCOSE-CHALLENGE TEST
Diagnosis of Gestational Diabetes
Three Hour 100 gm glucose tolerance test (GTT)
Not necessary if GCT is >200mg/dl on screening
Two abnormal values required for the diagnosis of gestational diabetes
Currently two diagnostic criteria acceptable
Competing Criteria
NDDG, 1979
•FBS 105•1 hour 190•2 hour 165•3 hour 145
Carpentar and Coustan, 1982
•FBS 95•1 hour 180•2 hour 155•3 hour 140
1990
2000
1997-1998
No Data Less than 4% 4% to 6% Above 6%
Diabetes Trends Among Diabetes Trends Among Adults in the U.S.Adults in the U.S.
Source: CDC, Behavioral Risk Factor Surveillance System.
Pathophysiology
PRINCIPLE DANGERS
GESTATIONAL DIABETES:Fetal hyperinsulinemia
PREGESTATIONAL DIABETES:
Fetal Anomalies
Normal Glucose Regulation in Pregnancy
•The pregnant patient has a tendency to develop HYPOGLYCEMIA between meals – Related to fetal demand
•Placental steroids cause increased tissue insulin resistance – They are “DIABETOGENIC”
• Insulin production INCREASES in normal pregnancy– By 30%
RECALL:PATHOLOGIC CHANGES IN GDM
Insulin Resistance
Insulin Deficiency
Effects of Hyperglycemia in GDM
Fetal Hyperinsulinemia
• Promotes storage of excess nutrients – Net Effect: macrosomia
• Increased catabolism of excess nutrients and increased energy usage – Net Effect: Decreased fetal oxygen storage and
episodic fetal hypoxia
• Episodic fetal hypoxia leads to increased catecholamines causing: – Fetal hypertension– Cardiac remodelling and hypertrophy– Increased erythropoietin, RBC’s, hematocrit – Poor fetal circulation and hyperbilirubinemia– Stillbirth (?)
The Impact of Fetal Macrosomnia
• Increased hyperbilirubinemia• Increased hypoglycemia• Increased acidosis• Increased birth trauma•Macrosomic children are more likely to
develop glucose intolerance in adulthood
Congenital Anomalies and Diabetic Control
Risk for Congenital Anomalies at various levels of Hemoglobin A1C
Critical periods - 3-6 weeks post conception
Importance of pre-conceptional metabolic care
2.5%
14.0%
23.0%25.0%
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
< 7.2
7.2 to 9.0
9.2 to 11.1
> 11.2
Congenital Anomalies with Pregestational Diabetes
Cardiac defects x18 8.5%
• CNS defects x16 5.3%
- Anencephaly x 13
- Spina Bifida x 20
• All Anomalies x 8 18.4%
• Background major defects 3-4%
Perinatal Risks for All Diabetic Pregnancies:
Mortality/Morbidity
MiscarriageIUGR
MacrosomiaBirth Injury
Stillbirth
Neonatal Risks for All Diabetic Pregnancies:
Morbidity and Mortality
•Polycythemia and hyperviscosity•Neonatal hypoglycemia•Neonatal hypocalcemia•Hyperbilirubinemia•Hypertrophic and congestive
cardiomyopathy•RDS•Childhood impaired glucose tolerance
Maternal Complications
•Chronic hypertension•Pre-eclampsia•Diabetic ketoacidosis•Maternal hypoglycemia•Maternal trauma•Higher C Section rate•Retinal disease/renal disease not affected
significantly by pregnancy
CARE FOR THE PATIENTWITH DIABETES
Pre-Pregnancy Management
•Preconceptional care– PRECONCEPTION CARE BEGINS AT THE END OF A
PREGNANCY WITH GDM– Tight glucose control (HbA1c)– Assessment and treatment of associated medical
problems- Hypertension, - Renal disease, - Retinal disease- Heart disease
– Folic acid– Assessment of family, financial and personal
resources to help achieve a successful pregnancy
FIRST PERINATAL VISIT or UPON HOSPITALIZATION
•Review routine prenatal lab tests•Baseline 24 hour urinalysis for protein and
creatinine clearance•Baseline retinal exam - for Type 1 Diabetics•EKG - for Type 1 Diabetics•Thyroid function tests - for Type 1 Diabetics•Hemoglobin A1C•Fetal echocardiogram for pregestational
diabetics
Antepartum Gestational Diabetes Care
•Dietary advice•Glucose monitoring (5 times per day)• Insulin therapy if necessary
– Oral Hypoglycemic agents•Frequent visits to monitor glucose control•Ultrasound monitoring of fetal growth•Mode of Delivery:
– Based on obstetric issues•Timing of Delivery:
– Based on glucose control
What is an ADA diet?
• Avoidance of large meals with high percentage of simple carbohydrates
• Three small meals with three snacks are preferred• Low glycemic index foods release calories from the
gut slowly and improve metabolic control• Caloric content:
– 35 calories/Kg Ideal body weight (or 15 calories/pound IBW)
– No less than 1800 calories and no more than 2800 calories
– “Eyeball Technique”- Small patient 1800 calories- Medium patient 2200 calories- Large patient 2400 calorie
What is a “Low” Glycemic Index•Glycemic Index (GI):
•Compares equal quantities of carbohydrate in foods
•Is a measure of the effect on blood glucose levels over a 2 hr period
•Provides a measure of carbohydrate quality.
•Expressed as a percentage
Time
GI = 30
GI = 100
BG
LB
GL
‘Traditional’ starchy foods have a lower GI
• Barley
• Legumes/beans
• Multigrain ‘Specialty’ breads
• Mueslix
• Porridge oats
33
30’s
40’s
50’s
50’s
Foster-Powell K, Holt SHA, and Brand-Miller JC. International table of glycemic index and glycemic load values:2002. Am J Clin Nutr. 2002; 76 (1): 5-56.
“Sugary” foods have a intermediate-low GI
• Soft drinks
• Flavoured milk (low fat)
• Yogurt (sweetened)
• Ice cream (low fat)
60’s
34
30-40
50’s
Foster-Powell K, Holt SHA, and Brand-Miller JC. International table of glycemic index and glycemic load values:2002. Am J Clin Nutr. 2002; 76 (1): 5-56.
Modern starchy foods have a high GI
• Potatoes
• Cornflakes
• Rice crispies
• Wholegrain bread
• Crackers
• Rice (most types)
85
77
85
70
81
83
Foster-Powell K, Holt SHA, and Brand-Miller JC. International table of glycemic index and glycemic load values:2002. Am J Clin Nutr. 2002; 76 (1): 5-56.
HOME GLUCOSE MONITORING
• Fasting and 2 hour post-prandial
• Pre-meal values only if sliding scale short acting insulin coverage is used
• Early AM value if hypoglycemia suspected
• Assure that glucose meter is calibrated
INDICATIONS FOR HOSPITALIZATION
•Persistent nausea and vomiting•Significant maternal infection•DKA•Poor control/compliance •Preterm labor
Intensive Inpatient Management:The APA Hybrid Protocol
• For poorly controlled diabetic patients admitted for rapid control.
• Empiric insulin with the patient’s current standing dose:
• Targets adequate glycemic control – Fasting values: Less than 100 mg/dl– 2 hour postparandial values: Less than
120 mg/dl – Avoidance of hypoglycemia, ketonuria,
and hyperglycemia
Intensive Inpatient Management:The APA Hybrid Protocol
•Begin 2200 to 2400 calorie ADA diet.
•Obtain fingerstick every 2 hours for 12-24 hours
•Administer HUMALOG INSULIN for sliding scale
•Retake blood sugar at 2 hours after EACH sliding dose noted below and repeat sliding scale dose of insulin based on FSG.
•Adjust Insulin after 24 hours
Intensive Inpatient Management:The APA Hybrid Protocol
2 hours14 Units220-260
2 hours16 Units>260
2 hours12 Units200-220
2 hours10 Units180-200
2 hours6 Units161-180
2 hours4 Units140-1600
4-6 hoursHold Humalog insulin
< 140
Recheck Blood sugarAdminister the following dosage of
humalog insulin
Blood sugar value
FSG
0
100
200
300
11/19/2008 11/19/2008 11/19/2008 11/19/2008 11/20/2008 11/20/2008 11/20/2008
FSG
0
100
200
300
400
11/17/08 11/17/08 11/17/08 11/17/08 11/18/08
Series1
Patient CH – Before Hybrid Approach
Patient CH – After Hybrid Approach
Intrapartum management
•ABSOLUTE REQUIREMENTS:– Dextrose containing intravenous fluids– Insulin
•Hourly glucose monitoring•Continuous fetal heart rate monitoring•Continuous tocodynametry•Manage labor as normal
THE APA INSULIN DRIP PROTOCOL
INTRAVENOUS FLUID MAINLINE: D5W @ 125 cc/hr INSULIN DRIP:
Initially Check Fingerstick every hourMIX 100 Units Regular insulin in 500 cc NS (0.2 U/cc)TITRATE INFUSION AS FOLLOWS:
2.5 U/hr12.5 cc/hr*FS> 220
2.0 U/hr10 cc/hr*FS= 181-220
1.5 U/hr7.5 cc/hrFS= 141-180
1.0 U/hr5.0 cc/hrFS=101-140
0.5 U/hr2.5 cc/hrFS= 80-100
0 U/hrTurn off dripFS= <80
Units per hourDrip RateFingerstick Value
After Fingerstick has been between 80-140 x >2 hours, decrease frequency of fingersticks to every 2 hours then every 4 hours.
HYPOGLYCEMIA DURING AN INSULIN DRIP
• For Glucose <60– Turn off Insulin drip for 30 minutes – Continue D5W (or D5LR) at 100 – 125 cc/hr– Recheck Glucose after 30 minutes– If blood glucose on recheck is still <60
- Give 25 ml of D50 IV (or 10-12 grams glucose)
– Recheck Blood Glucose every 30 minutes - Restart insulin when glucose >101 mg/dl
INSULIN DRIP FOR THE INSULIN RESISTANT PATIENT• Method for poorly controlled, morbidly obese or
noncompliant patients with gestational diabetes• 50% of total daily insulin dosage divided by 24 hours
provides initial rate for insulin drip.• EXAMPLE:
– Ms. Jones current insulin regimen - AM: 80units NPH 45 units Regular insulin- PM: 60 units NPH, 55 units Regular insulin
– Total daily dosage= 240 units per day.– ½ of 240 units = 120 units
– 120 units / 24 hours = 5 units per hour as initial dosage.
Management - Postpartum
•Use pre pregnancy insulin levels when on diet and monitor.
• If GDM monitor sugars only • Immediate postpartum goal is fingerstick <
200•GDM – Repeat GTT at 6 weeks postpartum•GDM - long term risk of NIDDM•Contraception
THANK YOU !
EXTRA SLIDES
INSULIN SECRETION
• Rising blood glucose levels. • After the uptake of glucose by the
GLUT2 transporter there is • Glycolytic phosphorylation of glucose
causing• A rise in the ATP:ADP ratio, which
then• Inactivates the potassium channel that • Depolarizes the membrane, causing • Calcium channel to open up allowing
calcium ions to flow inward. The rise in levels of calcium leads to the
• Release of insulin from their storage
granule.
1 2
34
5
6
78
INSULIN ACTION
Insulin-mediated glucose uptake begins when
• Insulin binds to the insulin receptor and
• Induces a signal transduction cascade which
• Allows the glucose transporter (GLUT4) to transport glucose into the cell.
1
23
Diagnosed and Undiagnosed Diabetes in the US:Estimated Cases Among Adults, 1997
Data from Harris, et al. Diabetes Care. 1998;21:518-524.
0
2
4
6
8
10
12
UndiagnosedDiagnosed
10.2
5.4
Mill
ion
s of
Cas
es
Glucose Tolerance Categories: NONPREGNANT Patients
Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-1197.
FPG
126 mg/dL
110 mg/dL
Impaired FastingGlucose
Normal
2-Hour PG on OGTT
200 mg/dL
140 mg/dL
Diabetes Mellitus
Impaired GlucoseTolerance
Normal
Diabetes Mellitus
FOLIC ACID
• All women of reproductive age should consume at least 0.4 mg of folic acid
• High risk women should consume 4 mg/day
• This reduces the risk of neural tube defects
• Newer evidence suggests a lower risk of facial clefting and congenital heart disease as well