current recommendations regarding gestational diabetes

Current Recommendations Current Recommendations Regarding Gestational Regarding Gestational

DiabetesDiabetes

By Brandon ErnstBy Brandon ErnstUNMC PharmD Candidate 2007UNMC PharmD Candidate 2007

Friday, January 26Friday, January 26

Objectives for TodayObjectives for Today

Define gestational diabetes mellitus (GDM)Define gestational diabetes mellitus (GDM) Indicate possible adverse effects of GDM Indicate possible adverse effects of GDM Discuss diagnosing GDM Discuss diagnosing GDM Evaluate monitoring and treatment possibilities Evaluate monitoring and treatment possibilities Reassess mother and offspring postpartumReassess mother and offspring postpartum Briefly discuss the results of the Australian Briefly discuss the results of the Australian

Carbohydrate Intolerance Study in Pregnant Carbohydrate Intolerance Study in Pregnant Women (ACHOIS)Women (ACHOIS)

What is Gestational Diabetes?What is Gestational Diabetes?11

Gestational Diabetes Mellitus (GDM) is Gestational Diabetes Mellitus (GDM) is glucose intolerance usually recognized glucose intolerance usually recognized during pregnancyduring pregnancy

GDM is thought to occur in about 7% of all GDM is thought to occur in about 7% of all pregnanciespregnancies- Hispanic, Native, African, Asian-Americans, Hispanic, Native, African, Asian-Americans,

and Pacific Islanders are at highest riskand Pacific Islanders are at highest risk

Why Why maymay GDM occur? The GDM occur? The Thought is that:Thought is that:22

1.1. The placenta supports the fetus as it grows by The placenta supports the fetus as it grows by providing hormones for developmentproviding hormones for development

2.2. These hormones block the action of the These hormones block the action of the mother’s insulin, causing insulin resistance (3x mother’s insulin, causing insulin resistance (3x more insulin)more insulin)

3.3. Mother’s body is unable to lower BGL, causing Mother’s body is unable to lower BGL, causing hyperglycemiahyperglycemia

4.4. The high BGLs remain in the blood stream, The high BGLs remain in the blood stream, cross the placenta, and cause the fetus’s cross the placenta, and cause the fetus’s pancreas to produce more insulin to regulate pancreas to produce more insulin to regulate its own hyperglycemic environmentits own hyperglycemic environment

5.5. Therefore, leading to possible adverse effectsTherefore, leading to possible adverse effects

Possible Problems in GDMPossible Problems in GDM22

As the As the babybaby continues in this high glycemic continues in this high glycemic environment:environment:- Higher glucose gives more energy than needed for Higher glucose gives more energy than needed for

growth, causing fat storage growth, causing fat storage - Macrosomia (large body size) increases the risk of Macrosomia (large body size) increases the risk of

damage to shoulders and limbs during deliverydamage to shoulders and limbs during delivery- Increased pancreas/insulin use in baby may cause Increased pancreas/insulin use in baby may cause

low BGL and breathing problems at birthlow BGL and breathing problems at birth- Cesarean deliveryCesarean delivery- Risk of children developing obesity and adults with Risk of children developing obesity and adults with

type 2 diabetestype 2 diabetes- Jaundice, polycythemia, and hypocalcemia at birthJaundice, polycythemia, and hypocalcemia at birth

Possible Problems in GDMPossible Problems in GDM22

The mother’s possible complications The mother’s possible complications include:include:- Increased chance of cesarean deliveryIncreased chance of cesarean delivery- Increased frequency of maternal hypertensive Increased frequency of maternal hypertensive

disordersdisorders- Increase risk of developing diabetes after Increase risk of developing diabetes after

pregnancy, typically type 2pregnancy, typically type 2

Diagnosing GDMDiagnosing GDM33

Risk assessment should always be done Risk assessment should always be done at first prenatal visit, especially with:at first prenatal visit, especially with:- Obese patientsObese patients- Personal history of GDMPersonal history of GDM- Glycosuria Glycosuria - Strong family historyStrong family history- High risk ethnic groupsHigh risk ethnic groups


All women, unless low risk, should be All women, unless low risk, should be tested for GDM at 24-28 weeks.tested for GDM at 24-28 weeks.- Low risk must meet Low risk must meet allall criteria: criteria:

<25 y.o.<25 y.o.Normal weight before pregnancyNormal weight before pregnancyMember of low ethnic prevalence Member of low ethnic prevalence No diabetes in first degree relativeNo diabetes in first degree relativeNo history of abnormal glucose tolerance, and No history of abnormal glucose tolerance, and

poor birth outcomepoor birth outcome

Diagnosing GDMDiagnosing GDM3,43,4

Two Different ApproachesTwo Different Approaches

One step approachOne step approach

1.1. Perform a diagnostic 75 g or 100 g Perform a diagnostic 75 g or 100 g OGTT without any prior plasma testOGTT without any prior plasma test

• This may be best for patients that can’t This may be best for patients that can’t afford more tests or in patients that are afford more tests or in patients that are already at high riskalready at high risk

Diagnosing GDMDiagnosing GDM3,43,4

Two Different ApproachesTwo Different Approaches

Two step approachTwo step approach1.1. Perform screen using 50 g oral glucose load Perform screen using 50 g oral glucose load

(OGL) and check BGL at 1 hour(OGL) and check BGL at 1 hour

2.2. If >130 mg/dL at 1 hour, retest for diagnoses If >130 mg/dL at 1 hour, retest for diagnoses using 75 g or 100 g OGTTusing 75 g or 100 g OGTT


• The OGTT diagnosis criteria

• Patient must be above the BGL at the time interval measured

• Positive result must be confirmed on a following occasion

Monitoring of GDMMonitoring of GDM3,43,4

Daily self monitoring of blood glucose (SMBG) Daily self monitoring of blood glucose (SMBG) is bestis best- Either Pre or Post -prandial testing is best for Either Pre or Post -prandial testing is best for

obtaining levels (according to ACOG and ADA)obtaining levels (according to ACOG and ADA) Screen urine for glucose, ketones, and proteinsScreen urine for glucose, ketones, and proteins Monitor blood pressure Monitor blood pressure Monitor for fetal demise when pregnancy goes Monitor for fetal demise when pregnancy goes

past termpast term Check for asymmetric fetal growth using Check for asymmetric fetal growth using

ultrasound ultrasound

Treatment Options in GDMTreatment Options in GDM33

All women should receive diet and All women should receive diet and nutrition counseling regarding pregnancynutrition counseling regarding pregnancy- If BMI > 30 kg/m2:If BMI > 30 kg/m2:

Lower caloric intake to 25 kcal/kg/dayLower caloric intake to 25 kcal/kg/day Lower carbohydrate intake to only 25-30% of total Lower carbohydrate intake to only 25-30% of total

calories calories

Moderate exercise should be done with Moderate exercise should be done with physician’s consent physician’s consent

Delivery during or before the 38Delivery during or before the 38thth week is week is encouraged, as is breast-feedingencouraged, as is breast-feeding

When to Add InsulinWhen to Add Insulin3,43,4

If medical nutritional therapy (MNT) fails then If medical nutritional therapy (MNT) fails then add insulin when BGL are:add insulin when BGL are:

ADA ACOG

Fasting ≥ 105 mg/dL ≥ 95 mg/dL

1-H postprandial ≥ 155 mg/dL ≥ 130-140 mg/dL

2-H postprandial ≥ 130 mg/dL ≥ 120 mg/dL

Treatment Options in GDMTreatment Options in GDM3,5,63,5,6

Insulin treatment is best for blood glucose Insulin treatment is best for blood glucose controlcontrol- Human insulin should be used when Human insulin should be used when

prescribed, due to lack of analogs studiesprescribed, due to lack of analogs studies NPH or RegularNPH or Regular Humalog is catagory B, and is being used under Humalog is catagory B, and is being used under

Dr. supervisionDr. supervision

Treatment Options in GDMTreatment Options in GDM3,5,63,5,6

Oral agents are still questionableOral agents are still questionable- Glyburide (category B), and insulin were compared in Glyburide (category B), and insulin were compared in

a trial and found to be similar in outcomesa trial and found to be similar in outcomes- Metformin (category B), shows some good evidence Metformin (category B), shows some good evidence

toward its use in PCOS. Its currently being studied in toward its use in PCOS. Its currently being studied in GDM and following up with offspringGDM and following up with offspring

- Glyburide and Metformin are still not FDA approved Glyburide and Metformin are still not FDA approved for GDMfor GDM

Treatment Options in GDMTreatment Options in GDM

Do not use in pregnancy:Do not use in pregnancy:- Aspirin (D)Aspirin (D)- Statins (X)Statins (X)- ACE Inhbitors (D)ACE Inhbitors (D)- ARBs (D)ARBs (D)

Delivery TimeDelivery Time22

During Labor:During Labor:- Active labor lowers insulin needs for about 24-72 Active labor lowers insulin needs for about 24-72

hours after deliveryhours after delivery After Delivery:After Delivery:

- May have better BGL control for a few weeksMay have better BGL control for a few weeks- Still could have unpredictable BGL swingsStill could have unpredictable BGL swings- Check BGLs more often during this timeCheck BGLs more often during this time- Breastfeeding is encouragedBreastfeeding is encouraged

Have snack before or during nursing, and keep something Have snack before or during nursing, and keep something close to treat low BGLsclose to treat low BGLs

Drink fluids Drink fluids

Reassessing OffspringReassessing Offspring22

Following delivery:Following delivery:- Monitor newborn for any of the possible Monitor newborn for any of the possible

abnormalities discussed earlierabnormalities discussed earlier- Monitor for development of obesity Monitor for development of obesity - Evaluate for any irregularity in glucose Evaluate for any irregularity in glucose

tolerancetolerance

Reassessing MotherReassessing Mother3,43,4

A mother having GDMA mother having GDM::- Has a 50% chance of developing type 2 diabetesHas a 50% chance of developing type 2 diabetes- Should be have BGL evaluated at least 6 weeks Should be have BGL evaluated at least 6 weeks

postpartum postpartum If normoglycemic, then testing should be done every 3 yearsIf normoglycemic, then testing should be done every 3 years If IFG or IGT, then testing should be repeated annuallyIf IFG or IGT, then testing should be repeated annually If FPG If FPG ≥≥ 126mg/dL or 2-hr 126mg/dL or 2-hr ≥ 200≥ 200, then testing should be , then testing should be

repeated on a separate occasion for DM diagnosisrepeated on a separate occasion for DM diagnosis

The Australian Carbohydrate Intolerance The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS)Study in Pregnant Women (ACHOIS)77

Randomized clinical trialRandomized clinical trialWanted to determine whether treating Wanted to determine whether treating

women with GDM reduced perinatal women with GDM reduced perinatal complicationscomplications

One thousand women randomizedOne thousand women randomized- Intervention group – 490 women, received Intervention group – 490 women, received

dietary advice, BGM, and insulin therapydietary advice, BGM, and insulin therapy- Routine group – 510 womenRoutine group – 510 women

Weeks gestation - 24-34Weeks gestation - 24-34

The Australian Carbohydrate Intolerance The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Study in Pregnant Women (ACHOIS) 77

Primary endpointPrimary endpoint- Serious perinatal complicationsSerious perinatal complications

death, shoulder dystocia, bone fracture, nerve death, shoulder dystocia, bone fracture, nerve palsy, admit. neonatal nursery, jaundice, induct. of palsy, admit. neonatal nursery, jaundice, induct. of labor, cesarean birth, anxiety, depression, healthlabor, cesarean birth, anxiety, depression, health

Secondary endpointSecondary endpoint- Birth weights, large for gestational age, Birth weights, large for gestational age,

macrosomia, small for gestational agemacrosomia, small for gestational age


Primary outcome results (Primary outcome results (only clinically only clinically

significantsignificant):):- Any serious perinatal complication was Any serious perinatal complication was

significantly lower in the treatment groupsignificantly lower in the treatment group Number needed to treat for benefit was 34 Number needed to treat for benefit was 34

- Admission to the neonatal nursery was higher Admission to the neonatal nursery was higher in the treatment group, but length of stay was in the treatment group, but length of stay was equalequal

- Induction of labor was higher in the treatment Induction of labor was higher in the treatment groupgroup


Secondary outcome results (Secondary outcome results (only clinically only clinically significant)significant)

- Birth weight was lower in the treatment Birth weight was lower in the treatment groupgroup

- There were higher rates of macrosomia There were higher rates of macrosomia and large for gestational age in the and large for gestational age in the routine grouproutine group

Questions?Questions?

ReferencesReferences1.1. Isley WL, Oki JC. Diabetes Mellitus. In: DiPiro JT, Talbert RL, Yee GC, Isley WL, Oki JC. Diabetes Mellitus. In: DiPiro JT, Talbert RL, Yee GC,

Matzke GR, Well BG, Posey LM, eds. Matzke GR, Well BG, Posey LM, eds. Pharmacotherapy: A Pathologic Pharmacotherapy: A Pathologic approachapproach. 5th ed. New York, NY: McGraw-Hill; 2002: 1335.. 5th ed. New York, NY: McGraw-Hill; 2002: 1335.

2.2. American Diabetes Association web site. Available at: American Diabetes Association web site. Available at: http://http://www.diabetes.org/home.jspwww.diabetes.org/home.jsp//. Accessed January 23, 2007.. Accessed January 23, 2007.

3.3. American Diabetes Association. Gestational Diabetes Mellitus. Diabetes American Diabetes Association. Gestational Diabetes Mellitus. Diabetes Care 2004;27:suppl 1: S88-S90.Care 2004;27:suppl 1: S88-S90.

4.4. Clinical management guidelines for obstetrician-gynecologists. ACOG Clinical management guidelines for obstetrician-gynecologists. ACOG practice bulletin no. 30. Washington, D.C.: American College of practice bulletin no. 30. Washington, D.C.: American College of Obstetricians and Gynecologists, 2001.Obstetricians and Gynecologists, 2001.

5.5. American Diabetes Association. Gestational Diabetes Mellitus. Diabetes American Diabetes Association. Gestational Diabetes Mellitus. Diabetes Care 2006;29:suppl 2: 485.Care 2006;29:suppl 2: 485.

6.6. Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes comparison of glyburide and insulin in women with gestational diabetes mellitus. New Engl J Med 2000;343:1134-1138 (Level 1)mellitus. New Engl J Med 2000;343:1134-1138 (Level 1)

7.7. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005;352:2477-86.outcomes. N Engl J Med. 2005;352:2477-86.

current recommendations regarding gestational diabetes

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