DIABETES MELLITUS

Chapter 57, Williams’ Obstetrics 25th edition

Interesting Information:
Early imprinting is believed to have effects later in life (Saudek, 2002). For example, in utero
exposure to maternal hyperglycemia leads to fetal hyperinsulinemia, causing an increase in fetal
fat cells. This leads to obesity and insulin resistance in childhood (Feig, 2002). These factors in
turn lead to impaired glucose tolerance and diabetes in adulthood.

I. Types of Diabetes Mellitus

A. Non-Pregnant
- based on its presumed etiopathogenesis and its pathophysiological manifestations

Type I Type II
Pathology • Absolute insulin deficiency § Insulin resistance,
• Generally autoimmune § Relative insulin deficiency, or
• Pancreatic β-cell destruction § Elevated glucose production
Prediabetes Present Present
Age at Often before age of 30 Advancing age
presentation *There is increasing incidence
among young obese adolescents
§ The terms insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes
mellitus (NIDDM) are now OBSOLETE
B. Pregnant
Pre-Gestational diabetes mellitus Gestational diabetes mellitus
Known/diagnosed with diabetes mellitus Diagnosis was made DURING pregnancy
BEFORE pregnancy
*NOTE: In Williams’, the terms Pre-Gestational diabetes mellitus and OVERT diabetes mellitus
are used interchangeably. However, in practice…we use Pre-Gestational diabetes mellitus if
diagnosis is made before pregnancy, while we use Overt diabetes mellitus if the diagnosis is
made during pregnancy but the values of the 75-gram OGTT / FBS/ RBS/ HbA1c reach the cut-
off
II. PRE-GESTATIONAL DIABETES MELLITUS
A. Diagnosis
o Made when ANY of the following values are met:

FBS > 126 mg/dL (> 7 mmol/L)

RBS > 200 mg/dL (> 11.1 mmol/L)
HbA1c > 6.5%
nd
2 hr value (75gm OGTT) > 200 mg/dL (> 11.1 mmol/L)
*NOTE: In Williams’, the terms Pre-Gestational diabetes mellitus and OVERT diabetes
mellitus are used interchangeably. However, in practice…we use Pre-Gestational diabetes
mellitus if diagnosis is made before pregnancy, while we use Overt diabetes mellitus if the
diagnosis is made during pregnancy but the values of the 75-gram OGTT / FBS/ RBS/ HbA1c
reach the cut-off. Pre-Gestational diabetes mellitus is confirmed when 75gram OGTT
results showed elevated values at 6-12 weeks postpartum.

B. Fetal and Neonatal Effects

1. Spontaneous abortion
o early miscarriage is associated with poor glycemic control
o Up to 25 percent of diabetic gravidas have an early pregnancy loss (Galindo, 2006;
Rosenn, 1994)
o HbA1c concentrations were >12%

2. Preterm delivery
o More than 26% were delivered preterm VS 6.8% in the general obstetrical population
o 60% were indicated preterm births, that is, due to obstetrical or medical complications

3. Malformation
o at least doubled and approximates 11%
o Account for almost half of the perinatal deaths in diabetic pregnancies
o Most common: cardiovascular malformations

o Pathogenesis:
§ alterations in cellular lipid metabolism
§ excess production of toxic superoxide radicals
§ activation of programmed cell death
4. Altered fetal growth
o Diminished growth
à result from congenital malformations
à from substrate deprivation due to advanced maternal vascular disease
o Fetal overgrowth
à more typical of pregestational diabetes
à Maternal hyperglycemia à fetal hyperinsulinemia à stimulates excessive somatic
growth
§ Except for the brain, most fetal organs are affected by the macrosomia
§ excessive fat deposition on the shoulders and trunk à predisposes to shoulder
dystocia or cesarean delivery

o The incidence of macrosomia rises significantly when mean maternal blood glucose
concentrations chronically exceed 130 mg/dL (Hay, 2012)

5. Unexplained fetal deaths

o risk of fetal death is 3 to 4x higher in women with pregestational diabetes
o associated with poor glycemic control
o common factors such as obvious placental insufficiency, placental abruption, fetal-
growth restriction, or oligohydramnios are not identified
o fetuses are typically large for gestational age and die before labor, usually late in the
third trimester
o Possible causes:
§ Hyperglycemia-mediated chronic aberrations in oxygen and fetal metabolite
transport (Pedersen, 1977)
§ Maternal ketoacidosis
§ Placental insufficiency may also occur (usually in association with severe
preeclampsia) à 7x higher risk if diabetes mellitus + preeclampsia

6. Hydramnios / Polyhydramnios
o amnionic fluid index (AFI) >24 cm in the third trimester
o Women with elevated HbA1c values in the third trimester were more likely to have
hydramnios
o Possible cause: fetal hyperglycemia causes polyuria à increased amniotic fluid

7. Neonatal Effects
o Respiratory distress syndrome
§ Gestational age rather than overt diabetes is likely the most significant factor
associated with respiratory distress syndrome

o Hypoglycemia
§ Low glucose concentration (defined as <45 mg/dL) are particularly common in
newborns of women with unstable glucose concentrations during labor (Persson,
2009)
§ Chronic maternal hyperglycemia à hyperplasia of the fetal β-islet cells à
hyperinsulinemia à low plasma glucose (rapid decrease after delivery)

o Hypocalcemia
§ Defined as total serum calcium concentration <8 mg/dL in term newborns
 § Early onset hypocalcemia is one of the potential metabolic derangements in
neonates of diabetic mothers.
§ Possible causes: aberrations in magnesium–calcium economy, asphyxia, and
preterm birth

o Polycythemia
§ Thought to be a fetal response to relative hypoxia
- According to Hay (2012), the sources of this fetal hypoxia are:
Ø hyperglycemia-mediated elevations in maternal affinity for oxygen, and
Ø fetal oxygen consumption
- Together with insulin-like growth factors, this hypoxia leads to elevated fetal
erythropoietin levels and red cell production

o Hyperbilirubinemia
§ Secondary to polycythemia, which increases bilirubin load

o Cardiomyopathy
§ Hypertrophic cardiomyopathy that primarily affects the interventricular septum
§ Most neonates asymptomatic
§ Possible cause: insulin excess
§ Hypertrophy usually resolves spontaneously months after delivery
§ In severe cases, it may lead to obstructive cardiac failure

o Long-term neurocognitive consequence

§ Impaired memory, autism spectrum, or developmental delay
§ Link between glycemic control and neurodevelopment is not yet established

8. Maternal Effects
o Long term course of diabetes is NOT affected by pregnancy, EXCEPT for higher risk of
development of diabetic retinopathy

o Preeclampsia
§ The incidence of chronic and gestational hypertension—and especially
preeclampsia—is remarkably increased à relative risk of 3.7 for preeclampsia in
women with Pre-GDM
§ Chronic hypertension + diabetes mellitus type II = 12x increased risk for
preeclampsia

o Diabetic nephropathy
§ Approximately 5% of pregnant women with diabetes already have renal
involvement. Approximately 40% of these will develop preeclampsia
§ In general, pregnancy does not appear to worsen mild diabetic nephropathy
§ Pregnancy in women with moderate-to-severe renal impairment may have
accelerated progression of their disease
§ In women with glomerulopathies, hypertension or substantial proteinuria before
or during pregnancy is a major predictive factor for ultimate progression to renal
failure
o Diabetic retinopathy
§ Microaneurysms – the first and most common visible lesions
§ Blot hemorrhages
- follow the development of aneurysm
- form when erythrocytes escape from the aneurysms.
§ Non-proliferative retinopathy – areas of blot hemorrhages leak serous fluid that
creates hard exudates
§ Preproliferative retinopathy
- production of cotton wool exudates
- result from retinal ischemia and infarctions that are caused by occlusion of the
abnormal vessels of background eye disease due to increasingly severe
retinopathy
§ In response to ischemia, neovascularization begins on the retinal surface and out
into the vitreous cavity. Vision is obscured when these vessels bleed

o Diabetic neuropathy
§ Peripheral symmetrical sensorimotor diabetic neuropathy is uncommon in
pregnant women.
§ Diabetic gastropathy
- causes nausea and vomiting, nutritional problems, and difficulty with glucose
control
- this complication is associated with a high risk of morbidity and poor perinatal
outcome (Kitzmiller, 2008)
- Treatment with metoclopramide and D2-receptor antagonists is sometimes
successful.
- Gastric neurostimulators have also been successfully used during pregnancy

o Diabetic ketoacidosis
§ develops in approximately 1% of diabetic pregnancies and is most often
encountered in women with type 1 diabetes (Hawthorne, 2011)
§ DKA may develop with hyperemesis gravidarum, infection, insulin noncompliance,
β-mimetic drugs given for tocolysis, and corticosteroids given to induce fetal lung
maturation
§ DKA results from an insulin deficiency combined with an excess in counter-
regulatory hormones such as glucagon à leads to gluconeogenesis and ketone
body formation
 o Infection
§ Common infections:
- candidal vulvovaginitis,
- urinary tract infections, (2x increased risk for ASB)
- respiratory tract infections, and
- puerperal pelvic sepsis
§ 16.5% of women with pregestational diabetes had postoperative wound
complications following cesarean delivery

9. Management
o Preconception counseling à achieve adequate glucose control to minimize early
pregnancy loss and congenital malformations

Optimal glucose values pre-conception:

Target measurement
Preprandial glucose 70 – 100 mg/dL
2-hour postprandial 100 – 120 mg/dL
Mean daily glucose concentrations < 110 mg/dL
HbA1c < 6.5%
 Optimal glucose values during pregnancy:

o Start folate 400µg daily preconception

o Insulin
o Diet / Medical nutrition therapy
§ Weight loss is NOT recommended
§ Modest caloric restriction for overweight or obese women.
§ Ideal dietary composition:
- 55% carbohydrate
- 20% protein
- 25% fat (of which < 10% is saturated fat)

o CBG monitoring
o Fetal well-being studies:
§ Maternal serum AFP to check for neural tube defects
§ Congenital anomaly scan
§ Fetal 2D echocardiogram
§ Monitoring of fetal growth (biometry) and well-being (biophysical profile +/- NST)

o Labor and delivery à ensure normal glucose levels, stable maternal status and
reassuring fetal status

o Puerperium:
§ Glucose control
§ Family planning method
III. GESTATIONAL DIABETES MELLITUS
A. Screening and Diagnosis
1. One-step approach à IADPSG: 75 grams OGTT
2. Two-step approach à screening: 50-gram OGCT; diagnostic: 100-gram OGTT
o begins with either universal or risk-based selective screening using a 50-g, 1-hour oral
glucose challenge test
B. Fetal and Neonatal Effects
o Congenital anomalies à not as high as in overt diabetes mellitus
o Fetal macrosomia
§ Risk of birth injury and shoulder dystocia

o Neonatal hypoglycemia

C. Maternal Effects
o Maternal obesity
o Risk of recurring gestational diabetes mellitus and long-term diabetes mellitus type II
o Risk of metabolic syndrome

D. Management
1. Diet:
- carbohydrate-controlled diet sufficient to maintain normoglycemia and avoid ketosis
- Daily caloric intake of 30 to 35 kcal/kg

2. Exercise
3. CBG monitoring
4. Insulin
- First line therapy
- starting dose: 0.7 to 1.0 units/kg/d and is given in divided doses
(American College of Obstetricians and Gynecologists, 2017a)
- Insulin therapy is typically added if fasting levels persistently exceed 95 mg/dL in
women with gestational diabetes
- The American College of Obstetricians and Gynecologists (2017a) also recommends
that insulin be considered in women with 1-hour postprandial levels that persistently
exceed 140 mg/dL or those with 2-hour levels >120 mg/dL

5. Oral hypoglycemics
- Metformin
- Glyburide

6. Labor and delivery

- Women with gestational diabetes and adequate glycemic control are managed
expectantly
- Elective CS: ACOG acknowledges that cesarean delivery in women with gestational
diabetes whose fetuses have a sonographically estimated weight ≥4500 g may be
considered to avoid risk of birth trauma

7. Postpartum