GESTATIONAL DIABETES MELLITUS UPDATES AND OVERVIEW - DISCLOSURES 2/21/2018
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
2/21/2018
GESTATIONAL DIABETES MELLITUS
UPDATES AND OVERVIEW
Kacy Herron MD R3
Idaho Perinatal Project Winter Conference 2018
DISCLOSURES
NONE
1
2/21/2018
LEARNING OBJECTIVES
• Gestational Diabetes Mellitus Pathophysiology
• Gestational Diabetes Mellitus Updates & Rationale for Screening /Diagnosis
• Appreciate Fetal and Maternal Morbidity/Mortality Correlated with GDM
• Management Guidelines Updates: Identifying Appropriate 1 st and 2nd Line Therapies
• Future Research Considerations in Regards to Screening and Management
PATHOPHYSIOLOGY IN
GESTATIONAL DIABETES MELLITUS
Condition in Which Carbohydrate Intolerance Develops During Pregnancy
2
2/21/2018
MATERNAL INSULIN
RESISTANCE IN
NORMAL PREGNANCY
Maternal Insulin Resistance:
Provides fetus with Glucose and AA’s in 3rd Trimester
Maternal Fuel:
Fatty acids, Ketones & Glycerol
Mediated by Hormones:
Prolactin + Chorionic Somatotropin (HPL),
Progesterone, Cortisol
GDM PATHOPHYSIOLOGY
E T I O L O G Y: “ U N K N OW N ”
H Y P OT H E S I S : O B E S I T Y, AU TO I M M U N E ,
S I N G L E G E N E M U TAT I O N
Figure 1: Insulin bind to its receptor on cell membrane (1). Starts
many protein activation cascades (2). Includes translocation of Glut-
4 transporter to the plasma membrane and influx of glucose (3), Glycogen synthesis Glycolysis
glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).
Fatty Acid
Synthesis
3
2/21/2018
PERINATAL MORBIDITY AND MORTALITY
MATERNAL FETAL
• Pre-Eclampsia Association • Macrosomia
• Cesarean Section • Hypoglycemia
• Increased Risk of Type 2 Diabetes • Hyperbilirubinemia
Mellitus
• Shoulder Dystocia
• Gestational Hypertension
• Birth Trauma
LONG TERM FETAL EFFECTS
VIA
FETAL PROGRAMMING
• “Fetuses exposure to maternal diabetes have a
higher risk of abnormal glucose homeostasis in later
life beyond that attributable to genetic factors
leading to increased rates of future cardiovascular
disease, hypertension and T2DM”
4
2/21/2018
EPIGENETIC MODIFICATION
DIAGNOSTIC CRITERIA
FIRST TRIMESTER SCREENING
&
UNIVERSAL SCREENING 24-28 WEEKS GESTATION
5
2/21/2018
ACOG FIRST TRIMESTER SCREENING INDIC ATIONS
OBESE OR OVERWEIGHT WOMEN WITH ONE OF THE
FOLLOWING RISK FACTORS
• Physical inactivity • High-density lipoprotein cholesterol level less than
35 mg/dL (0.90 mmol/L), a triglyceride level greater
than 250 mg/dL (2.82 mmol/L)
• First-degree relative with diabetes
• Women with polycystic ovarian syndrome
• High-risk race or ethnicity (eg, African American,
Latino, Native American,Asian American, Pacific • A1C greater than or equal to 5.7%, impaired
Islander) glucose
tolerance, or impaired fasting glucose on previous
• Have previously given birth to an infant weighing testing
4,000g (approximately 9 lb) or more
• Other clinical conditions associated with insulin
• Previous gestational diabetes mellitus resistance (eg, pre-pregnancy body mass index
greater
• Hypertension (140/90 mm Hg or on therapy for than 40 kg/m2, acanthosis nigricans)
hypertension)
• History of cardiovascular Disease
AMERICAN DIABETES ASSOCIATION
EARLY SCREENING RECOMMENDATION
6
2/21/2018
ACOG EARLY SCREENING RECOMMENDATION
2 STEP SCREENING PROCESS
Step 1 50 g Glucose Challenge Test
Step 2 3 hour OGTT
HEMOGLOBIN A1C DURING
PREGNANCY
BENEFITS: PITFALLS:
• Cost effective • Values vary with age, race,
• Convenient hemoglobinopathies and
• Less Daily Variability ethnicity
• Greater Pre-Analytical • A1C levels fall 2nd and 3rd
Stability Trimester
• Less sensitive than OGTT
7
2/21/2018
Objective: Examine prevalence of previously diagnosed
diabetes and undiagnosed diabetes using Undiagnosed diabetes in the U.S. population aged ≥20 years by
suggested A1C criteria in US and compared
three diagnostic criteria—NHANES 2005–2006.
to other glucose criteria
Methods: Survey sample of 14,611 individuals from
National Health and Nutrition Examination
Survey
Participants were classified on glycemic
status by interview for diagnosed diabetes
and by A1C, fasting, and 2-h glucose
challenge values measured in subsamples.
Results:
Using A1C criteria, prevalence of ©2010 by American Diabetes Association
undiagnosed diabetes and high risk of
diabetes were one-third that and one-tenth
that, respectively, using glucose criteria.
UNIVERSAL SCREENING
24-28 WEEKS
8
2/21/2018
STUDY DESIGN: Multinational Cohort Study
POWER: 23,000 in 3rd trimester
OBJECTIVE: Obtain data on associations between
Maternal Glycemia and Risk of Adverse
Outcomes
PURPOSE: Derive International Acceptable Criteria
for Diagnosis and Classification of GDM
HAPO PRIMARY OUTCOMES
RESULTS:
Adverse Outcomes Increase as Function of Maternal Hyperglycemia
9
2/21/2018
OVERVIEW OF SCREENING
RECOMMENDATIONS
ONE STEP SCREENING PROCESS
FOR
I N T E R N AT I O N A L A S S O C I AT I O N O F D I A B E T E S A N D P R E G N A N C Y
102/21/2018
TWO STEP STRATEGY
FOR
ACOG
PRACTICAL APPROACH
112/21/2018
COMPARI S ON
AN D
FUTURE CONSIDE RATI O NS
MANAGEMENT OF GESTATIONAL
DIABETES MELLITUS
122/21/2018
BENEFITS OF TREATMENT
Shoulder dystocia
USPTF SYSTEMATIC REVIEW
Neonatal
Objective Summarize maternal and Hypoglycemia
neonatal benefits and
harms of treating GDM
Data Source 15 electronic databases
from 1995-2012
Study Types RCT’s and Retrospective
Cohort Studies Macrosomia
Summary: Support for treating mild
GDM
LIFESTYLE MANAGEMENT
132/21/2018
MEDICAL NUTRITION THERAPY
GOALS: CLINICAL RECOMMENDATIONS:
Caloric Allotment 1st Trimester: 30 kcal/kg
2nd Trimester: 36 kcal/kg
3rd Trimester: 38 kcal/kg
Total daily approximation: 2000 kcal
Carbohydrate Intake Starch Portions: 1cup, 2 pieces of bread
Dairy: 1cup of Milk
Fruit: 1-3 Portions Fruit Daily
Caloric Distribution 40% Carbohydrates
Conventional Approach 20%. Protein
40%. Fat
CARBOHYDRATES
CALORIC ALLOTMENT 15 GRAMS OF CARB SERVINGS
Women: 12-13 servings of Carbohydrates per Day
1 serving=15 grams Carbs
Total daily carbs= 15x12= 180 Grams Carbs
Recommend Splitting between :
3 small meals: 40 g per meal
2 snacks: 30 g per snack
142/21/2018
WHICH DIET DO I
CHOOSE?
“The conventional diet approach to
gestational diabetes mellitus (GDM)
advocates carbohydrate restriction,
resulting in higher fat (HF), also a substrate
for fetal fat accretion and associated with
maternal insulin resistance. Consequently,
there is no consensus about the ideal
GDM diet.”
SURVEILLANCE + DIET +EXERCISE
TRIAL TIME MONITOR FASTING AND POSTPRANDIAL BG’s:
Fasting < 95
1 hour < 140
2 hour < 120
TRANSITION TO MEDICAL THERAPY if >2/7 Abnormal in 2
WEEKS or if >50 % are BELOW goal.
152/21/2018
ACOG
PHARMACOLOGIC THERAPY
-INSULIN FIRST LINE
-METFORMIN SECOND LINE
-GLYBURIDE NO LONGER RECOMMENDED
FIRST LINE: INSULIN
Basal Insulin 1)NPH
2)Glargine or Detemir
Short Acting 1) Lispro
2) Aspart
More rapid onset that
Regular Insulin.
Starting Dose 1) 0.7-1.0 Unit/kg
2) Divided into long
acting and short*
162/21/2018
METFORMIN
SECOND LINE TREATMENT
• Mechanism of Action: Inhibits hepatic gluconeogenesis and glucose absorption. Stimulates glucose uptake into
tissues.
• Dosing: 500 mg BID. Up to 3000 mg BID in 2 divided doses
• Fetal Concerns: Crosses the placenta with unknown long term fetal outcomes
SUMMARY for PATIENT COUNSELING
• Reasonable Second Line Therapy
• Benefits: Lower risk of neonatal hypoglycemia, gestation
hypertension, less visceral fetal fat mass and less maternal weight
gain
• Risks: Long term outcomes unknown, Risk of prematurity with RR
of 1.5, ½ treat with Metformin eventually need insulin
172/21/2018
QUE STIONABLE OUTCOME S Neurodevelopmental outcome at 2 years in
WITH ME TFORMIN offspring of women randomized to metformin or
insulin treatment for gestational diabetes
Study design Prospective Study.
Mothers assigned to
insulin vs metformin at
Further studies need to be done 20-33 weeks gestation
to query whether there is: Power 211
Methods Neurodevelopment
1) Long term change in assessment with Bayles
neurodevelopmental Scales of Infant
Development to 2
outcomes years of age
Results No significant
2) Effects on long term insulin- developmental
sensitive pattern of growth differences appreciated
GLYBURIDE
NO LONGER
RECOMMENDED
MECHANISM: Binds
pancreatic beta cell ATP
calcium channel receptors
to increase secretion and
insulin sensitivity
DOSAGE: 2.5-20 mg Daily
CONCERNS:
1) Concentration in umbilical cord
approximately 70% higher than maternal
levels.
2) Meta Analyses demonstrated worse
neonatal outcomes
182/21/2018
SOCIETY FOR MATERNAL FETAL
MEDICINE RECOMMENDATIONS
-INSULIN or METFORMIN FIRST LINE
-GLYBURIDE: DATA INSUFFICIENT for RECOMMENDATION
TRIALS COMPARING METFORMIN TO
INSULIN
OUTCOMES
192/21/2018
HEALTHCARE DISPARITIES IN GDM
FOOD INSECURITY • Affects 1/7 Find out community
• Higher rate among resources for your patients
minorities
LANGUAGE BARRIER • GDM/Diabetes more Develop education
common among non- materials in multiple
English speaking languages
individuals
HOMELESSNESS • Associated with literacy Temporary housing. Secure
and numeracy place to keep supplies
deficiencies, cog
dysfunction and mental
health issues
Community Support can Include: Promotoras, Clinical Pharmacists, Community
Health Workers and Dieticians
INTRAPARTUM MANAGEMENT
• Goal is to reduce the risk of transient neonatal hypoglycemia
• NO consensus about optimal glycemic controls during pregnancy
• Endocrine Society Recommends 72-126
• Monitoring: Every 1-2 hours while in active labor
• Consider start IV insulin infusion if Blood Glucoses >120 mg/dl
202/21/2018
MATERNAL PROGNOSIS
INCREASED PREVALENCE
Recurrent GDM Obesity
Type 2 DM Hypertension
Hyperlipidemia Stoke
CHF Myocardial Infarction
Renal Disease Retinopathy
POSTPARTUM
MANAGEMENT
Timing: Changed to 4-12 weeks postpartum
75 g OGTT recommended over A1C
Rescreen every 1-3 years based on risk factors
Can use A1C, fasting plasma glucose or 75 g OGTT for screen
*Up to 80% of women affected by GDM will develop T2DM
212/21/2018
PRE VE NTIO N OF TYPE 2
DIABE TE S ME LLITUS AFTE R
GDM
Study: Prospective Nurse’ Health
Study
Observation: GDM and Postpartum
weight gain
Adverse Pregnancy
Outcome
Early Progression to
T2Dm
Intervention of Lifestyle Delayed progression of Type
Modification and Metformin 2 DM
NNT: 5-6 to prevent 1 case over 3 years
CLOSING THE GAP
222/21/2018
SUMMARY
• Test for undiagnosed diabetes at the first prenatal visit in those with risk factors, using
standard diagnostic criteria
• Test for gestational diabetes mellitus at 24–28 weeks of gestation in pregnant women not
previously known to have diabetes.
• Lifestyle Management with Medical Nutrition Therapy and Exercise is Primary Therapeutic
Intervention for GDM
• Insulin is the ONLY Appropriate first line therapy. Metformin ONLY 2 nd line therapy.
• Screen women with gestational diabetes mellitus for persistent diabetes at 4–12 weeks'
postpartum, using the oral glucose tolerance test and clinically appropriate nonpregnancy
diagnostic criteria
• Women with history of gestation diabetes should have lifelong screening every 1-3 years
• Women with history of gestational diabetes mellitus found to have prediabetes should
receive intensive lifestyle intervention or metformin to prevent diabetes. Need to ensure
follow up with PCP.
REFERENCES
American Diabetes Association. Management of diabetes in pregnancy. Sec. 13. In Standards of Medical Care in Diabetes 2017. Diabetes Care 2017; 40(Suppl. 1):S114–S119
Balsells M, Garcia-Patterson A, Sola I, Roque M, Gich I, Corcoy R. Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis. BMJ
2015;350:h102. (Meta-analysis)^
Bernstein JA, Quinn E, Ameli O, et al. Follow-up after gestational diabetes: a fixable gap in women’s preventive healthcare. BMJ Open Diabetes Research and Care 2017;5:e000445. doi: 10.1136/bmjdrc-
2017-000445
Camelo Castillo W, Boggess K, Stu ̈rmer T, Brookhart MA, Benjamin DK Jr, Jonsson Funk M. Association of adverse pregnancy outcomes with glyburide vs insulin in women with gestational diabetes.
JAMA Pediatr 2015;169: 452–458
Catherine C. Cowie, Keith F. Rust, Danita D. Byrd-Holt, Edward W. Gregg, Earl S.Ford, Linda S. Geiss, Kathleen E. Bainbridge, Judith E. Fradkin. “Prevalence of Diabetes and High Risk for Diabetes Using
A1C Criteria in the U.S. Population in 1988–2006.” Diabetes Care Mar 2010, 33 (3) 562-568; DOI: 10.2337/dc09-1524
Farrar D, Simmonds M, Bryant M, et al. Treatments for gestational diabetes: a 160 systematic review and meta-analysis. BMJ Open. 2017 2017 Jun 24;7(6):e015557.
Gupta Y, Kalra B, Baruah MP, Singla R, Kalra S. Updated guidelines on screening for gestational diabetes. International Journal of Women’s Health. 2015;7:539-550. doi:10.2147/IJWH.S82046.
Hernandez, Teri L. et al "A Higher-Complex Carbohydrate Diet in Gestational Diabetes Mellitus Achieves Glucose Targets and Lowers Postprandial Lipids: A Randomized CrossoverStudy." Diabetes
Care 37.5 (2014): 1254-1262. Web. 14 Jan. 2018.
Moon JH, Kwak SH, Jang HC. Prevention of type 2 diabetes mellitus in women with previous gestational diabetes mellitus. The Korean Journal of Internal Medicine. 2017;32(1):26-41.
doi:10.3904/kjim.2016.203.
The HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcomes. N Engl J Med 2008; 358: 1991-2002. May 8, 2008DOI: 10.1056/NEJMoa0707943
Practice Bulletin No. 180: Gestational Diabetes Mellitus. Obstetrics & Gynecology: July 2017 - Volume 130 - Issue 1 - p e17–e37. doi: 10.1097/AOG.0000000000002159
Wouldes TA, Battin M, Coat S, et al. Neurodevelopmental outcome at 2 years in offspring of women randomised to metformin or insulin treatment for gestational diabetes. Archives of Disease in
Childhood - Fetal and Neonatal Edition 2016;101:F488-F493.
232/21/2018
QUESTIONS?
24You can also read
