gestational diabetes mellitus (gdm) nabeel s. bondagji md, frcsc, facog associate professor...
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GESTATIONAL DIABETES GESTATIONAL DIABETES MELLITUS (GDM)MELLITUS (GDM)
NABEEL S. BONDAGJIMD, FRCSC, FACOGAssociate professor
Consultant PerinatologistDepartment of OB/GYN
Incidence of GDM
Approximate prevalence 3-5%IncreasingIn SA 15-20% diabeticGDM 3-7% Varies with ethnic,race,social habits
DIABETES AND PREGNANCY
0.2-0.3% of women of reproductive
age have diabetes prior to
conception.
30% of patients with gestational
diabetes
develop non-Insulin
dependent
diabetes later in life
D. M IN PREGNANCY
Type I Type IIGDM
What is Gestational Diabetes?
Carbohydrate intolerance of varying severity first manifest or diagnosed in pregnancy.
The definition applies irrespective of the need for insulin treatment and the result of any postnatal glucose tolerance test.
Effect of Pregnancy on Diabetes
Pregnancy is diabetogenicHPL, progesterone antagonize insulinPregnancy causes insulin resistance
Maternal Effects of Diabetes
Miscarriage
Polyhydramnios
Preeclampsia (more if diabetic nephropathy)
Infection (UTI, candidiasis, chorioamnionitis)
Operative delivery (CS rate 50%)
Long-term Effects
NephropathyNone if mild-moderateIf severe (creatinine > 0.25
mmol/L), may exacerbate renal failure
RetinopathySeems to make it worse
Fetal Effects of DiabetesMiscarriage
Congenital Malformations 2 - 3 times background rate minimized by good control pre
and post-conception. commonest are cardiac defects Caudal regression (sacral
agenesis)
Perinatal Death Late “unexplained” IUFD perinatal mortality rate doubled
Neonatal Effects of Maternal Diabetes
(IDM)Macrosomia (40%)Birth trauma shoulder dystociaHypoglycemiaHypocalcaemia/magnesaemiaRespiratory distress syndromeHyperbilirubinaemiaHyperviscosity/ polycythaemiaThe risk of type 1 diabetes mellitus in the child of a woman with the condition is 2%.
Risk Factors
Body mass index 25 kg/m2
Family history of type 2 diabetes Age older than 25 yearsMultiparityPrevious gestational diabetes: Macrosomic or large-for-gestational age infant
Cont. - Risk Factors
Previous impaired glucose tolerance with oral glucose tolerance test American Indian or Alaska Native; African American; Asian; Hispanic; Pacific Islander
Screening50 gram glucose challenge test
at 24-28 weeks7.8mmol or more GTT80% sensitivity 7.2, 90% sensitivity
Random blood sugarnot adequate
Fasting blood sugarinadequate data
Diagnosis
75g GTTFasting glucose, 75 g
load, 2-hour glucoseGDM = fasting 5.5
mmol/L OR 2-hour 8.0 mmol/L
O. Sullivan and Mahan
mg/dl mmol/L mg/dl mmol/L
Fasting 95 5.3 105 5.8
One hour 180 10.0 190 10.6
Two hours 155 8.6 165 9.2
Three hours 140 7.8 145 8.0
Two (2) Abnormal Reading = GDM
Treatment of Diabetes
Type 1 : diet, exercise & insulinType 2 : diet, exercise
: metformin or sulphonylurea alone
: metformin and sulphynylurea : metformin, sulphonylurea & thiazolidinedione
: insulin
GDM : diet: insulin
Drugs to treat hyperglycemia
Insulin and insulin analogues
Insulin secretagogues sulphonylurea gliclazide,
glibenclamide
glyburide. non-sulphonylurea repaglinide, nateglinide
lispro insulinaspart insulininsulin glargine
Drugs to treat hyperglycemia
Insulin sensitizers biguanide metformin
thiazolidinedione rosiglitazone, pioglitazone
Intestinal absorption inhibitorsacarboseorlistat
TEXT BOOKS TEACHINGOral hypoglycemia are contraindicated in pregnancy
Risk of fetal anomalies
Risk of neonatal hypoglycemiaIncreasing risk of PET
ACOG/ADA
Insulin and its analogues are the only agents to be used in pregnancy
SOGS !!!!!!!!!
BUILLDING EVIDANCE
No evident that it causes fetal hypoglycemia 3 cases studies.
No strong evidence it cause congenital anomalies.
Evidence
Early reports
Oral hypoglycemic Fetal congenital anomalies
Critical review of old data suggested that the
described reports associated with fetal anomalies
are most likely related to hyperglycemia
Poor control prior to pregnancy diabetic
emberyopathy
Elliot et al – (American Journal of Obstetrics & Gynecology 1991).
Elliot et al –(American Journal of Obstetrics & Gynecology 1994) proved in Lab. that Glyburide does not cross the placenta in significant amounts (in human placental modules).
Perfusion studies of glyburide transfer across thehuman placenta: Implications for fetal safety
Jennifer Kraemer, MSc, Julia Klein, MSc, Angelica Lubetsky,
Am j Ob& Gyne 2006The objective of study was to document, using
a human placenta perfusion model, whether glyburide is actively effluxed from the fetal to the maternal circulation.
Conclusion: these experiments suggest that glyburide is actively efflux by a transporter from the maternal to fetal site
Coetzee etall (South African MJ 1984)
Oral hypoglycemic in the first trimester and fetal
outcome
171 Patients retrospective review
78 used OHA
93 not
No significant difference in the outcome
Comparable results in blood sugar control
The safety of oral hypoglycemic agents in the first trimester of pregnancy :a meta-analysis
Gutzin ea alCan J Clinical Pharm 2003
OBJECTIVE: To examine the relationship between first trimester exposure to oral hypoglycemic agents and ,fetal congenital anomalies and neonatal morbidity.
METHODS: a systematic review and meta-analysis of all studies that was reported on women exposed to OHGA in the first trimester
Gulzin etalCan J. Clin. Pharmacology (2003)
Meta-analysis on the safety of OHA in
the first trimester/University of Toronto
10 studies fulfilled the criteria
Results
In all studies
No difference in major anomalies among
Exposed Vs non exposed fetuses
RESULTS: Ten studies met the inclusion criteria -There was no significant difference in the rate of congenital anomalies betweenexposed and non exposed-No difference in the neonatal deathConclusions:
First trimester exposure to OHA did not increase the rate of congenital anomalies nor the neonatal deathFurther studies needed do document the safety and the glycemic control
Safety of glyburide for gestational diabetes:a meta-analysis of pregnancy outcomes
Moretti ME, Rezvani M, Koren G.
Ann Pharmacotherapy. 2008 Apr
OBJECTIVE: To determine the safety of glyburide use in pregnancy in the treatment of gestational diabetes compared with insulin therapy by analyzing all available human studies.
METHODS: a systematic review and meta-analysis of all randomized and cohort studies that reported on the perinatal complications among women with gestational diabetes who received glyburide versus insulin
RESULTS: Nine studies met the inclusion criteria, including a total of 745 glyburide
exposed pregnancies and 637 insulin-
exposed pregnancies
CONCLUSIONS: The data do not suggest increased perinatal risks with glyburide. The effectiveness and safety of glyburide require further evaluation, as most studies to date were not randomized
Comparison of Glyburide and insulin for the management of gestational diabetes in a large managed care
organization(American j Obstet Gynecol 2005)
Jacobson GF
A retrospective study
268 insulin 1999-2000
236 glyburide 2001-2002
Conclusions:
No difference in glycemic control birth
weight NN outcome
Slight increase in PET + phototherapy
Need for glyburide group
A comparison of glyburide and insulin in women with gestational diabetes mellitus.
Department of Obstetrics and Gynecology, St. Luke’s-Roosevelt Hospital Center, New York 10019,
USA. [email protected]
Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O.
N Engl J Med. 2000 Oct. 19;343(16):1178-9
404 women randomized11 – 33 weeks
Group I Glyburide201
Group II insulin 203
Results
No difference in the glucose blood level.
No difference in congenital anomalies.
No difference in the birth weight.
Glyburide was not detected in the cord blood of any of the fetuses of the glyburide group.
There were no significant differences between the glyburide and insulin groups in lung complications (8 percent and 6 percenthypoglycemia (9 percent and 6 percentwho were admitted to a neonatal intensive care unit (6 percent and 7 percent
Conclusion
In women with GDM, Glyburide is clinically effective alternative to insulin.
Langer O. Am. J. Obst. & Gynecol ,2005 J
Insulin and glyburide therapy: dosage, severity
level of gestational diabetes , and pregnancy
outcome
Secondary analysis of the trial
Conclusion:
Glyburide and insulin are equally efficient for
Treatment of GDM at all level of severity
In PCO patients
Metformin use in the first trimester does not increase M C A
Glueck et all ( pilot study)
continues metformin through out pregnancy in women with PCO
Safe and decrease first trimester abortion(Fertility & sterility 2001)
Glueck etall (human reproduction 2004)
Follow up of 126 infants born for PCO
women on continuous metformin through
out pregnancy
Conclusion:Decrease GDM does not cause any adverse
effects on babies up to 4 year follow up
Jakubaurez et all
Effect of Metformin in early pregnancy loss in PCO
(J. Of Clinical endocrinology & Metabolism 2002)
safe
Metformin Therapy Throughout Pregnancy Reduces GDMetformin Helps Prevent Gestational DiabetesMetformin Shows Promise in Preventing Miscarriage
Wait for the MIG TRIAL 2007 ?
First Visit
Routine management PLUS Counseling Urinary protein Ophthalmoscopy each trimester Glycaemic control Organize fetal surveillance
Blood sugar control and the prevention of the complication of D.M.
Blood sugar control 100mg ml the incidence of neonatal metabolic complications and improve lung maturation.
Blood sugar 87- 100 Will the incidence of macrosomia
Blood sugar 60 – 106 Will incidence of abortion
Blood sugar 90 - 120 Will prevent still birth
Blood sugar 120 – 140Prevent congenital anomalies
Treatment
GOALS1. Achieve normoglycaemia2. Monitor fetal well-being3. Appropriate timing of delivery
Glycaemic Control
Home blood glucose monitoring qidGoals are 5.5 mmol/L fasting and 7
mmol/L 2 hours postprandial
HbA1c monthlyDietary managementAppropriate energy intake50-60% CHO, 25% fat, 15% proteinEven distribution
Exercise - 30 minutes walk a dayInsulin
DIET Blood Sugar Control
Fasting 105 5.8 mmol 1 hour 140 7.8 2 hours 120 6.7 How long on diet2 weeks
Testing <6.7mmlP.P. <7.8mml Diet
<6.7 – 7.8 <7.8 – 10
Insulin
Fetal SurveillanceUltrasound12 weeks
gross morphology, dates, plurality, nuchal translucency
18-20 weeksdetailed morphology
30 and 34 weeksgrowth
Other scans, Doppler's umbilical and UTERINE ARTERY
CTG or BPS weekly from 32 weeks
Timing and Route of Delivery
RCT suggests advantage in delivery at 38 - 39 weeksDecreased macrosomia, shoulder dystocia
40 weeks if perfect control, no complications
Cont. - Timing and Route of Delivery
?Role of elective CS for macrosomiaDiabetes is independent risk factor for shoulder dystocia
Recommend if estimated fetal weight > 4.5 kg
Consider if EFW 4 - 4.5 kg
Management in Labour1. Glycaemic control
Notify endocrinologist Omit morning insulin the day of induction.Measure blood glucose on admission and every 2 hours.
Cont. - Management in Labour
1. Glycaemic control50 U insulin in 50 mL 0.9% NaCl (1U/mL) via syringe pumpStart at 1mL/hourAdjust to keep glucose 4-7 mmol/LSimultaneous 5% dextrose at 100 mL/hour
Management at Delivery
Prepare for shoulder dystociaCease insulin if used at deliveryMonitor infant’s blood glucose after deliveryMeasure mother’s blood glucose BD for 2 days
Puerperium
Cease insulin infusion at delivery (unless Caesarean section)Often reduced needs for 24 hoursThen back to prepregnancy doseType 2 may need no treatment in puerperiumOHAs discouraged in lactation
?
Long-term management
Recall at 6 weeks postpartum for GTT2% will have diabetes10% will have IGTLong-term risk of diabetes mellitus 50% over 10 yearsLong-term follow-upLifestyle modification50% recurrence in future pregnancy
Conclusion - I
New generation of oral hypoglycemic agents glyburide does not cross the placenta and may be used to replace insulin between 11 – 33 weeks of gestation. Further studies to be done to document its safety in early pregnancy.
Conclusion - II
METFORMIN can be used in P.C.O. patients during the whole pregnancy it showed that it reduces miscarriages in the incidence of G.D.M. Nevertheless does not show good control of blood sugar.
Conclusion - III
Maintaining blood sugar at certain thresholds may reduce certain complications of GDM.
THANKYOU
Glyburide for the management of gestational diabetes: Risk factors predictive of failure and associated pregnancy outcomes. Am J ob&gyn 2006Meredith Rochon, MD,a,* Larry Rand, MD,a Lisa Roth, MD,a Sreedhar Gaddipati, M
Objective: to identify characteristics that may predict failure of glyburide therapy
101 patient 79% successfully treated
Conclusion: Predicting glyburide failure is difficult, but failure does not appear to be associated with increased adverse pregnancy outcomes.
Conclusion: Glyburide and insulin are equally efficient for treatment of GDM in all levels ofdisease severity. Achieving the established level of glycemic control, not the mode ofpharmacologic therapy, is the key to improving the outcome in GDM.