Title: DIABETES IN PREGNANCY
1DIABETES IN PREGNANCY
- Josephine Carlos-Raboca, MD
- Chief, Section of Endocrinology,Diabetes and
Metabolism - Makati Medical Center
2M.E 39 year old female
- She is a G3P1 (1011) who was referred to
Endocrinology service on her 28th week of
gestation due to findings of elevated blood
sugar values in her 75g OGTT. (fasting 107 mg/dL,
1hr 191 mg/dL 2-h 158 mg/dL)
3Past Medical History
- Non diabetic, non hypertensive, non asthmatic
- FMHx
- () Diabetes and Hypertension Mother
- PSHx
- Non smoker, non alcoholic beverage drinker
- No regular form of exercise
4Physical Examination
- BP 120/70 mmHg, HR 76 bpm, RR 16
- Wt 85 kg, Ht 53 BMI 33.2
- Anicteric, pink palpebral conjunctivae, (-)
cervical adenopathy, (-) carotid bruits, Thyroid
not enlarged, no pharyngeal congestion - Equal chest expansion with clear breath sounds
both lungs, (-) crackles - Adynamic precordium, Normal rate, regular rhythm
with distinct S1, S2, (-) murmur
5Physical Examination
- Gravid abdomen, normal bowel sounds, () fetal
heart tones - Full and equal pulses, pink nail beds with good
turgor, (-) edema, (-) cyanosis, (-)
hyperpigmentation
6- She was initially started on a diet plan and
4x/day blood sugar monitoring for 1 week
Fasting 1-h post BF 1-h post Lunch 1-h post dinner
mg/dL 96 148 129 157
7- She was started on 2x/day insulin with a dose of
aspartame insulin 6 units (novorapid) pre
breakfast and pre dinner
Fasting 1-h post BF 1-h post lunch 1-h post diner
mg/dL 88 117 112 124
8- repeat LSCS 2, breech presentation cord coil
- Live baby boy BW 2,863 gm AS 8/9
9Outline
- Gestational Diabetes
- Definition/Prevalence
- Pathogenesis
- Complications
- Screening and Diagnosis
- Management
- Pregestational Diabetes
10Gestational Diabetes Mellitus (GDM)
- Any degree of glucose in tolerance with onset or
first recognition during pregnancy. - 4th International Workshop-Conference on GDM,
1998.
11Prevalence of GDM
- 1 14
- USA--- 3-5
- MMC (Asian Population) Raboca et al 13.4
12Pathogenesis
13Pregnancy is a diabetogenic state characterized
by insulin resistance and hyperinsulinemia
14Metabolic Adaptations during Pregnancy
- placental hormones affect both glucose and
lipid metabolism to ensure ample fetal fuel
supply and nutrients always. - There is a switch from carbohydrate to fat
utilization that is facilitated by both insulin
resistance and increased plasma concentration of
lipolytic hormones - Butte, NF. Carbohydrate and lipid metabolism in
pregnancy normal compared with gestational
diabetes mellitus. Am J Clin Nutr 2000 711256S.
15Maternal metabolic adaptation
- Accelerated starvation during fasting to provide
fuel and nutrients to fetus at all times - Fasting plasma glucose 63-75 mg/dl
- Fasting capillary blood glucose 55-65 mg/dl
- rise in ketones and fatty acids
16Metabolic Adaptations during Pregnancy
- The fasted state is one of accelerated
starvation. Alternative fuels are made available
for the mother and glucose is reserved for the
fetus - Maternal Fuels Free fatty acids, ketones,
glycerol - There is hyperplasia of Beta cells, increased
insulin secretion and early increase in insulin
sensitivity followed by progressive insulin
resistance. - Butte, NF. Carbohydrate and lipid metabolism in
pregnancy normal compared with gestational
diabetes mellitus. Am J Clin Nutr 2000 711256S.
17- Maternal insulin resistance results from
increased release of diabetogenic hormones such
as - Corticotropin Releasing Hormone
- Chorionic Somatomammotropin
- Progesterone
- Tumor necrosis factor-a
- A post receptor defect in the skeletal muscle
B-subunit and at Insulin receptor substrate-1 may
also contribute to the decline in insulin action. - Yamashita, H, Shao, J, Friedman, JE. Physiologic
and molecular alterations in carbohydrate
metabolism during pregnancy and gestational
diabetes mellitus. Clin Obstet Gynecol 2000
4387.
18diabetogenic hormones during pregnancy
- Growth hormone
- Corticotropin releasing hormone
- Placental lactogen
- Progesterone
19Pathogenesis
- Autoimmune beta cell destruction
- Highly penetrant genetic abnormality that leads
to impaired insulin secretion - Beta cell dysfunction with chronic insulin
resistance
20Metabolic Adaptations during Pregnancy
- Insulin levels are higher in both the fasting and
the postprandial states during pregnancy - The fasting glucose is 10-20 lower in pregnancy
due to - Increased storage of tissue glycogen
- Increased peripheral glucose utilization
- Decreased hepatic glucose production
- Glucose consumption by the fetus
21Metabolic Adaptations during Pregnancy
- The placenta readily transfers glucose, amino
acids, and ketone bodies to the fetus but is
impermeable to large lipids. - Serum triglyceride and cholesterol levels
increase during pregnancy by approximately 300
and 50 respectively. - The large rise in TG is largely due to
- Increased hepatic lipase activity
- Reduced lipoprotein lipase activity
- Herrera, E. Metabolic adaptations in pregnancy
and their implications for the availability of
substrates to the fetus. Eur J Clin Nutr 2000
54 Suppl 1S47.
22Why Screen for GDM?
23Pregnancy outcome GDM
Outcome Relative risk 95 percent confidence level
Macrosomia Macrosomia Macrosomia
ADA 1.3 0.7 to 2.2
WHO 1.4 1.1 to 2.0
Preeclampsia Preeclampsia Preeclampsia
ADA 2.3 1.2 to 4.2
WHO 1.9 1.2 to 3.0
Perinatal death Perinatal death Perinatal death
ADA 3.1 1.4 to 6.5
WHO 1.6 0.9 to 2.9
Adapted from data in Schmidt, MI, Duncan, BB,
Reichelt, AJ, et al. Diabetes Care 2001 241151
24Perinatal Complications
- Macrosomia
- Hypoglycemia
- Respiratory Distress Syndrome (RDS)
- Hypocalcemia
- Hyperbilirubinemia
- Polycythemia
25Congenital Malformations
- Skeletal
- Cardiac (septal and outflow tract lesions)
- CNS and neural tube defects
- Gastrointestinal Defects
- Genitourinary Tract lesions
26Other complications
- Pre-ecclampsia
- Operative delivery
- Obesity and diabetes later in life
27Who do we screen?
- Pregnant women with any of the following
- A family history of diabetes, especially in first
degree relatives - Prepregnancy weight 110 percent of ideal body
weight or significant weight gain in early
adulthood - Age greater than 25 years
- Previous delivery of a baby greater than 9 pounds
4.1 kg - Personal history of abnormal glucose tolerance
- Member of an ethnic group with higher than the
background rate of type 2 diabetes (in most
populations, the background rate is approximately
2 percent)
28Who do we screen?
- Previous unexplained perinatal loss or birth of a
malformed child - Maternal birth weight greater than 9 pounds 4.1
kg or less than 6 pounds 2.7 kg - Glycosuria at the first prenatal visit
- Polycystic ovary syndrome
- Current use of glucocorticoids
- Essential hypertension or pregnancy-related
hypertension - Solomon, CG, Willett, WC, Carey, VJ, et al. A
prospective study of pregravid determinants of
gestational diabetes mellitus. JAMA 1997
2781078.
29When to screen?
- Screening is optimally performed at 24-28 weeks
of gestation. - Jovanovic, L, Peterson, CM. Screening for
gestational diabetes. Optimum timing and criteria
for retesting. Diabetes 1985 34 Suppl 221. - It should be done during the first prenatal visit
if there is high degree of suspicion that the
patient has undiagnosed type 2 diabetes - Gestational diabetes mellitus. Diabetes Care
2004 27 Suppl 1S88. - Women with a history of GDM have a 33-50 risk of
recurrence, and some of these recurrences may
represent type 2 DM - ACOG Practice Bulletin. Clinical management
guidelines for obstetrician-gynecologists.
Number 30, September 2001 (replaces Technical
Bulletin Number 200, December 1994). Gestational
diabetes. Obstet Gynecol 2001 98525.
30How to screen for GDM
- A fasting plasma glucose level of gt126 mg/dL (7.0
mmol/l) or a casual plasma glucose gt200mg/dL
(11.1 mmol/l) meets the threshold for the
diagnosis of diabetes, if confirmed on a
subsequent day - Precludes the need for any glucose challenge
- Diabetes care vol 26, jan 2003
31Screening and Recommendations5th International
Workshop Conference on GDM
- Diabetes Care Vol 30 Sup 2 July 2007
- GDM should be ascertained at first prenatal visit
32Low Risk screening is not routine if all
conditions are met
- Belongs to an ethnic group with low prevalence of
GDM - Negative history of diabetes mellitus type 2 in
first degree relative - Less than 25 years old
- Normal weight before pregnancy
- Normal weight at birth
- No history of abnormal glucose metabolism
- No history of poor obstetric outcome
33Average risk screen at 24-28 weeks of gestation
- Two step method
- 50gm GCT if positive go to diagnostic test
- One step method
- proceed to diagnostic test
-
34High Risk
- Severe obesity
- Strong family history of diabetes mellitus type 2
- Previous history of GDM, impaired glucose
metabolism or glucosuria. - If initially negative for GDM, repeat at 24-28
weeks of gestation or anytime with signs and
symptoms suggestive of hyperglycemia
35Screening
- Glucose Challenge Test
- Give 50 g oral glucose load without regard to
time of day. - Measure plasma or serum glucose after 1 hour.
- A glucose level gt130 mg/dL (7.8 mmol/l) is
abnormal. - Proceed with Oral Glucose Tolerance Test (OGTT)
36Screening test
- Glucose Challenge Test
- 50 gm oral glucose load
- Plasma glucose 1 hour after
- gt 130 mg/dl (90 sensitive)
- gt 140 mg/dl (80 sensitive)
37Diagnosis
Plasma or serum glucose level Carpenter/Coustan Plasma or serum glucose level Carpenter/Coustan Plasma level National Diabetes Data Group Plasma level National Diabetes Data Group
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
100 gram oral glucose load is given to patient
who is fasting. Data from Expert Committee on
the Diagnosis and Classification of Diabetes
Mellitus. Report of the Expert Committee on the
Diagnosis and Classification of Diabetes
Mellitus. Diab Care 2000 23(suppl 1)S4.
38Diagnosis of GDM
- 100 gm OGTT 75 gm OGTT
- mg/dl mml/L mg/dl
mml/L - F 95 5.3 95
5.3 - 1H 180 10.0 180
10.0 - 2H 155 8.6 155
8.6 - 3H 140 7.8
- gt 2 values met GDM
- ASGODIP, WHO
- European Diabetes
- Policy Group 1992-1998 75 gm OGTT, 2H gt140
39Diagnosis
American Diabetes Association American Diabetes Association
At least two values that meet or exceed the following glucose concentrations At least two values that meet or exceed the following glucose concentrations
Fasting gt95 mg/dL (5.3 mmol/L)
One hour gt180 mg/dL (10.0 mmol/L)
Two hour gt155 mg/dL (8.6 mmol/L)
World Health Organization World Health Organization
Fasting gt125 mg/dL (7.0 mmol/L)
OR OR
Two hour gt140 mg/dL (7.8 mmol/L)
Criteria for a positive 2 hour 75 g OGTT for the
diagnosis of GDM
40Management of GDM
- Diet/Medical Nutrition therapy
- Blood Glucose Monitoring
- Exercise
- Medication
41GOALS
- Normal outcome of index pregnancy.
- Decrease risk for abnormal glucose and
insulin homeostasis. - Mother (before, during, after pregnancy).
- Infant subsequent generations.
42Medical Nutrition Therapy
- Goals
- Achieve normoglycemia
- Prevent ketosis
- Provide adequate weight gain
- Contribute to fetal well-being
43Medical Nutrition Therapy
- Caloric allotment
- Nutritional management of obese gestational
diabetic woman. J Am Coll Nutr 199211246
BMI kcal/kg
lt22 40 kcal
22 25 30 kcal
26 - 29 24 kcal
30 12 15 cal
44Medical Nutrition Therapy
Carbohydrate 33 40
Proteins 20
Fats 40
Timing Total Calories
Breakfast 10
Lunch 30
Dinner 30
Snacks 30
- Gestational Diabetes mellitus 2004
45ADA 2004
- Medical Nutrition Therapy
- provide adequate calories to sustain
maternal and fetal requirements and - to achieve glycemic control
- adequate weight gain
- Avoid starvation ketosis
- Protein 0 .75 g/kg/d 10 g
- Carbohydrate portion 35-40
- Folic acid 400 ug/day
46Weight Gain in Pregnancy
- BMI weight gain 1st trim 2nd-3rd trim
- lt20 28-40 lbs 5lb 1.07lb/wk
- 21-26 25-35 3.5 .97
- 26-29 15-25 2.0 .67
- gt29 15
- Krause Food Nutrition and Diet 11th ed L.
Kathleen, Mahan and Strump 2004
47Diet for GDM patient
- For normal weight 30 kcal/kg of Present BW
- For overweight 24 kcal/kg of Present BW
- For morbidly obese 12 kcal/kg Present BW
- 3 meals, 3 snacks, 40 of total calories CHO
- Medical Management of Pregnancy Complicated
by Diabetes
48Self Blood Glucose Monitoring
- Monitor Blood Glucose concentration at least 4
times daily. - Timing Fasting and 1 hour after the first bite
of each meal - Gestational Diabetes Mellitus. Diabetes care
2004
49Blood glucose monitoring
- Frequency has not been established
- 4-6x a day depending on severity
- PPPG more correlated with macrosomia
- (RCT PPPG vs Preprandial
- lower A1c -3 vs -.6 plt.001
- lower BW 7lbs10oz vs 8lbs7oz plt0.01
- Less CS 12 vs 42 p,0.04
50Self Blood Glucose Monitoring
- One hour postprandial monitoring was associated
with the following benefits as compared to
preprandial monitoring - Better glycemic control (HbA1c 6.5 vs 8.1
percent) - Lower incidence of large for gestational age
infants (12 vs 42 percent) - A lower rate of cesarian delivery for
cephalopelvic disproportion (12 vs 36 percent). - Postprandial vs preprandial blood glucose
monitoring in women with GDM requiring insulin
therapy. N Engl J med 1995 3331237
51Insulin
- When to use?
- maternal blood glucose levels
- fetal abdominal circumference at 29-33 weeks
- amniotic fluid insulin at 28 weeks
52Abdominal circumference
- Study by Buchanan 1994
- gt75th percentile abdominal circumference
used to initiate insulin - lesser LGA 13 vs 45 in diet treated
53ADA 2001
- Insulin Required if diet fails to maintain
glucose - at following levels.
- Fasting whole blood glucose lt 95 mg/dl (5.3
mml/L) - Fasting Plasma Glucose lt 105 mg/dl (5.8 mml/L)
- OR
- 1H Postprandial whole blood glucose lt 140 mg/dl
(7.8 mml/L) - 1H Postprandial Plasma Glucose lt 155 mg/dl (8.6
mml/L) - OR
- 2H Postprandial whole blood glucose lt 120 mg/dl
(6.7 mml/L) - 2H Postprandial Plasma Glucose lt 130mg/dl (7.2
mml/L)
54Blood glucose levels
- FPG gt 95mg/dl (90)
- 1 hour PPBG gt 140 mg/dl (120)
- 2 hppg gt 120 mg/dl
- ( ) Jovanovic
55Insulin in pregnancy
- Human insulin should be used if prescribed
- SBMG should guide the doses and timing of insulin
regimen - The rapid Insulin analogs lispro and aspart have
been found to be clinically effective with
minimal transfer across placenta and no evidence
of teratogenesis. Level B - Long acting analogs no study in pregnancy
56Insulin Therapy
- 15 of women with GDM are placed on insulin
therapy - The dose of insulin varies in different
populations because of varied rates of obesity,
ethnic characteristics, and other demographic
criteria - Generally 0.5 to 1.4 U/kg (present weight) is
required to maintain target glucose levels. - A mixed/split insulin regimen is generally used
57Insulin Therapy
- 50 as NPH Insulin given in three equal doses
before breakfast, before dinner and before
bedtime - 50 as three preprandial rapid-acting insulin
injections - Four times a day insulin regimen is more superior
to twice a day regimen in improving glycemic
control and perinatal outcome. - Nachum, Z. twice daily vs four times daily
insulin dose injection for diabetes in
pregnancy. RCT BMJ 1999
58Insulin Regimen
- If High FBS HS intermediate insulin at 0.15
u/kg - High PPBS regular insulin premeals
- High preprandial and postprandial
- multiple injections
- 0.7 u/kg 6-18weeks
- 0.8 u/kg 9-26 weeks
- 0.9 u/kg 27-36 weeks
- 1.0 u/kg 37 weeks to term
59Oral Anti-hyperglycemic Agents
- Currenlty the ADA and ACOG do not endorse the use
of oral hyperglygemic agents during pregnancy - Gestational diabetes mellitus care 2004
- Tolbutamide or chlorpropamide
- Cross the placenta and can cause fetal
hyperinsulinemia which can lead to macrosomnia
and prolonged neonatal hypoglycemia. - Maternal-fetal transport of hyperglycemic
drugs. Clin pharmacokinet 2003
60Oral diabetic drugs
- Langer NEJM 343(16)1134-38,2000
- use of glyburide after 8 weeks of
gestation in 201 women on glyburide vs 203
insulin - Conclusion No difference in neonatal outcomes
such as LGA, hypoglycemia anomaly or stillbirth
61Glyburide vs Insulin
- A study of 404 women with singleton pregnancy and
GDM that required treatment. (San Antonio,Texas) - FBS of at least 95mg/dl and less than 140mg/dl
- Between 11th and 33rd week of pregnancy
- 201 patients assigned to receive glyburide
- 83 Hispanics, mostly Mexican-American, 12 non
Hispanic white, 5 Black - 8 women in the glyburide group switched to
insulin - Glyburide not detected in cord serum of any
infant.
62Metformin in PregnancyGlueck,Fertility and
Sterility Vol 77 Issue 3 March 2002 520-25
- Metformin 1.5 - 2.55 g/d throughout pregnancy
in women with PCOS - Number 19 with live births
- Outcome reduction of GDM
- no bad maternal effects and
no birth defects -
63Metformin
- Crosses placenta
- Should be discontinued in first trimester
- Higher perinatal mortality and preecclampsia
- Off label use PCOS pregnancy with recurrent
fetal loss
64Treatment with metformin compared with insulin
(the Metformin in Gestational Diabetes MiG
Trial)
65Metformin in Gestational Diabetes (MIG) Trial
- Prospective Randomized controlled trial in women
with GDM 20-33 weeks gestation - Randomized to insulin or metformin
- Primary outcome composite of neonatal morbidity
- Key trial in assessing potential role of
metformin during pregnancy
66Metformin versus Insulin for the treatment of
Gestational Diabetes
- 751 women with GDM enrolled at 20-33 weeks
gestation - 373 (metformin) 378(insulin)
- Primary Outcomes
- neonatal hypoglyvemia(2.6mmol/l)
- Respiratory distress
- need for phototherapy
- birth trauma
- 5 min APGAR lt7
- prematurity lt37 weeks)
67- Secondary outcomes
- Maternal hypertensive complications
- Neonatal anthropometric measurements
- Maternal glycemic control
- Postpartum glucose tolerance
- Acceptability of treatment
68Results
- rate of primary outcome
- 32 (Met) vs 32.2 (insulin)
- Acceptability
- 76.6 vs 27.2
- No difference in secondary outcomes
69Conclusions
- Metformin is an effective and safe treatment
option in gestational diabetes requiring insulin - Metformin is more acceptable to women than
insulin - Long term study needed to establish long term
safety
70Acarbose
- Eficacia de la acarbose para controlar el
deterioro de la tolerancia a la glucose durante
la gestacion. Zarate A, Ochoa R, Hernandez M,
Basurto L Ginecol Obstet Mex 68 4245, 2000 - A case series of six GDM patients treated with
50mg acarbose TID with meals. - Glucose levels were normalized in all 6 patients
- All six babies born were apparently normal
- Side effect GI discomfort
71Acarbose
- A comparison of oral acarbose and insulin in
women with gestational diabetes mellitus.
deVeciana M, Trail PA, Lau TK, Dulaney KObstet
Gynecol 99 (Suppl.)5S, 2002 - Randomized trial in 91 GDM patients failing diet
therapy - Glucose control and glycohemoglobin were similar
- 6 of acarbose treated patientd required insulin
72Other Agents
- The use of thiazolidinediones, glitinides, and
GLP-1 is considered experimental - No controlled data available in pregnancy
- Chan, LY, Yeung, JH, Lau, TK. Placental transfer
of rosiglitazone in the first trimester of human
pregnancy. Fertil Steril 2005 83955.
73Exercise
- Safe exercise
- 1. does not cause fetal distress, decrease in
birth weight, uterine contractions or - maternal hypertension
- 2. Not supine
- 3. Upper body exercise arm ergometry
- 4. walking
74Exercise contraindicated
- Hypertension
- Preterm rupture of membranes
- Preterm labor
- Incompetent cervix
- Persistent 2nd and 3rd trimester bleeding
- IUGR
75Peripartum Management
- Maternal hyperglycemia should be avoided during
labor to prevent fetal hyper-insulinemia and
subsequent neonatal hypoglycemia. - Maternal blood glucose concentration should be
maintained between 70 and 90 mg/dL - Blood glucose should be monitored on the day
after delivery to ensure that the mother no
longer has hyperglycemia.
76Post partum care/concerns
- 50-60 risk for DM 2 in 10-15 years
- DM 1 in GAD
- 75 gm OGTT 6 weeks after for prognostication
(earlier DM2 in 5 years in IGT )
77- 75 gm OGTT gt 6-12 wks postpartum
- if normal, repeat after one year and every
3 years - if IFG, test every year and lifestyle
- modification
- Follow up offspring for development of
obesity and glucose intolerance
7850 in 20 years timePredictors of DM
- maternal obesity
- fasting hyperglycemia
- duration of time from index pregnancy
79Follow-Up
- At least six weeks after delivery, or shortly
after cessation of breast feeding, all women with
previous GDM should undergo an oral glucose
tolerance test using a two-hour 75 gram oral
glucose tolerance test. - In women who did not undergo screening for GDM,
but diabetes is suspected postpartum because of
infant outcome, postpartum screening for diabetes
may be considered.
80Pregestational Diabetes
81- Counseling about risk of malformation with
poor control - Use of low dose estrogen progestogen
- contraceptive till good metabolic control is
- achieved.
- Goals
- HBA is 1 above normal
- Preprandial CBG 70-110 mg/dl (3.9-5.6mml/L)
CPG 80-110 mg/dl (4.4-6.1
mml/L) - 2H Postprandial CBG lt 140 mg/dl (7.8mml/L)
CPG lt 155 mg/dl
(8.6mml/L)
82 What medical problems should you
consider in a diabetic pregnant?
83- Acceleration of retinopathy
- Pregnancy induced hypertension
- Progression of Nephropathy
84retinopathy
- Stabilize prior to pregnancy
- Photocoagulation if necessary
- Monitor for progression
- high risk for biggest drop in a1c
- due to hypercoagulable state
85Coronary artery disease
- Pregnancy increases oxygen consumption
- Avoid pregnancy if possible
- Statins not used
- If necessary, fibrates and niacin may be used
86BP meds in pregnancy
- Methyldopa
- Hydralazine
- Calcium antagonist
- Clonidine
- labetalol
87DM Nephropathy
- Renal function may deteriorate in more sever
disease - Prone to pre-eclampsia
- BP target lt130/80
- Stop ACE inhibitors and ARBs
- may cause fetal anuria, pulmonary
hypoplasia, oligohydramnios
88- Preparing for delivery
- Target glucose 120 mg/dl
- D5 0.45 NSS at 100-125 ml/hour
- CBG every 1-4 hours
- Insulin infusion to start at 1unit/hour of
regular insulin if CBG gt 120 mg/dl
89Conclusions
- Pregnancy is a diabetogenic state
- Hyperglycemia causes adverse effects in pregnancy
for mother and fetus. - Detection, diagnosis and proper treatment are
necessary for good pregnancy outcome. - Diabetic patients must be prepared and assessed
for complications prior to pregnancy. - Special problems for pregnant diabetics need to
be addressed.
90THANK YOU.