creation date: 2025-07-28 20:36
tags: Pathologies
Gestational Diabetes Mellitus
Background
Definitions
Gestational diabetes mellitus (GDM) refers to a carbohydrate/glucose intolerance that develop during pregnancy.
The American Diabetes Association defines GDM more specifically as diabetes diagnosed after 15 weeks of gestation and that is not present prior to conception. In this framework, diabetes diagnosed early in pregnancy is sometimes named “overt diabetes” which refers to undiagnosed preexisting type 2 diabetes.
Risk factors and Pathogenesis
The pathogenesis of GDM is thought to develop in pregnant patients whose pancreatic beta-cell function is insufficient to overcome the insulin resistance associated with pregnancy.
Placental hormone releases, specifically and primarily placental lactogen, results in marked insulin resistance. However, the hormones also increases insulin secretion and beta-cell proliferation in normal physiology.
In cases of GDM, conditions or factors result in beta-cell dysfunction that causes decreased insulin secretion leading to hyperglycemia. Factors that result in even greater insulin resistance may also contribute to development of GDM.
These factors include:
- Increased body weight (BMI >25)
- Decreased physical activity
- First-degree relative with diabetes mellitus
- High risk ethnicity
- Past history of GDM, newborn birth weight ≥4 kg, and/or cardiovascular disease
- Hypertension
- Low HDL or high triglyceride level
- PCOS
- HbA1C >5.7
- Abnormal oral glucose tolerance test
- Any markers of insulin resistance
Clinical Presentation
Signs & Symptoms
Gestational diabetes is generally asymptomatic and identified through screening.
In some cases, clinical features may be present:
- Disproportionate weight gain
- Obesity
- Elevated BMI
History & Physical
During preconception or early prenatal visits, ask about:
- Past medical history of GDM
- Family history of DM
- Associated findings such as obesity of high rate of gestational weight gain
- Diet and exercise habits
Diagnosis
Screening
As an increasing proportion of patients have unrecognized type 2 diabetes, screening for overt diabetes is recommended to reduce the risk of miscarriage and congenital anomalies. During the initial prenatal visit, an A1C can be used for overt diabetes and risk assessment:
- HbA1C < 6.0%: continue to usual screening at 24-28 weeks
- HbA1C 6.0-6.4%: consider referral to diabetes education for diet and exercise guidance, continue to usual screening at 24-28 weeks
- HbA1C ≥6.5%: refer to diabetes care, usual screening unnecessary (diagnosis of overt diabetes)
Screening for gestational diabetes occurs at 24-28 week gestational age but may occur sooner in patients with risk factors (within first trimester).
Criteria
For the diagnosis of GDM, the SOGC/CDA recommends the following. Use of HbA1C is not recommended for diagnosis.
A 2-step approach is preferred:
- 50g non-fasting OGCT
- Normal: 1h PG <7.8 mmol/L
- Inconclusive (needs step 2): 1h PG 7.8-11 mmol/L
- GDM: 1h PG ≥11.1 mmol/L
- 75g fasting OGTT - GDM is diagnosed if at least one of the following met:
- FPG ≥ 5.3 mmol/L
- 1h PG ≥ 10.6 mmol/L
- 2h PG ≥ 9.0 mmol/L
Alternatively, a 1-step 75g OGTT can be used, requiring one of the following for a GDM diagnosis:
- FPG ≥5.1 mmol/L
- 1h PG ≥10.0 mmol/L
- 2h PG ≥8.5 mmol/L
Differential
The differential for GDM consist of overt diabetes and other causes of hyperglycemia:
- Medications (eg. corticosteroids)
- Endocrine disorders
- Pancreatic insufficiency (eg. due to cystic fibrosis, pancreatitis)
Red Flags / Complications
Maternal complications
Obstetrics:
- Hypertensive disorders of pregnancy (insulin resistance implicated in hypertension etiology)
- Polyhydramnios (due to fetal hyperglycemia and polyuria)
- Spontaneous abortion
- Preterm labour
Diabetes related: - Diabetic emergencies
- End-organ involvement/vascular complications
- Increased risk of developing T2DM post-partum
Other: - UTI (from glucosuria)
- Increased risk of spontaneous abortion
Fetal complications
Diabetic fetopathy
Growth abnormalities:
- Macrosomnia (hyperinsulinism results in accelerated anabolism)
- IUGR (due to placental vascular insufficiency)
Delayed organ maturity: - Lung immaturity (hyperglycemia interferes with surfactant synthesis) can result in ARDS/transient tachypnea
Labour and delivery: - Preterm/prematurity
- Increased incidence of stillbirth
- Birth trauma (due to macrosomnia and/or shoulder dystocia)
Neonatal: - Hypoglycemia (excess insulin secretion from chronic hyperglycemia results in hypoglycemia following loss of maternal glucose supply)
- Hyperbilirubinemia and jaunice (maternal and fetal hyperglycemia increases metabolic effects and oxygen demand resulting in increased erythropoietin and thus RBC count)
- Hypocalcemia and hypomagnesemia (maternal hyperglcemia results in maternal hypomagnesemia and hypocalcemia)
- Polycythemia (hyperglycemia stimulates fetal erythropoietin production)
- ARDS (surfactant production impairment)
Note, a number of congenital anomalies are associated with overt diabetes but not GDM as GDM develops after critical period of organogenesis in trimester 1
Diabetic embryopathy
Hyperglycemia results in an inhibition of myo-inositol update. This causes abnormalities in arachidonic acid-prostaglandin pathway which results in early pregnancy loss and congenital anomalies.
In should be noted that in true gestational diabetes (of which onset is following the critical period of organogenesis in trimester 1), diabetic embryopathies are uncommon.
Congenital heart disease:
- Transposition of the great vessels
- Ventricular septal defect
- Truncus arteriosus
- Coarctation of the aorta
- Patent ductus arteriosis
CNS defects: - Anencephaly
- Spina bifida
- Myelomeningocele
Genitourinary defects: - Renal agenesis
- Ureteral duplication
- Hydronephrosis
Skeletal defects: - Caudal regression syndrome (complete or partial absence of sacrum)
- Vertebral anomalies
Gastrointestinal defects: - Small left colon syndrome (transient intestinal obstruction)
- Duodenal atresia
- Anorectal malformation
Others: - Cleft palate
Management
Prevention
For patients with increased risk of developing GDM, lifestyle interventions may reduce risk. This includes:
- Weight loss for overweight or obese individuals prior to conception
- Diet modification and increased exercise
- Management of gestational weight gain
- Smoking cessation
Post-diagnosis management
Blood glucose targets are:
- Fasting/preprandial <5.3 mmol/L
- 1h postprandial <7.8 mmol/L
- 2h postprandial <6.7 mmol/L
Blood glucose should be kept >3.7 mmol/L for patients on insulin therapy.
Non-pharmacological
For patients highly motivated and borderline diabetic, a trial of lifestyle management may be attempted. This consist of:
- Diet (replacing high-glycemic index food with low-GI foods) - possibly involve dietitian
- Physical activity (30-60 minutes of moderate-intensity exercise at least 5 days a week)
Pharmacological
Insulin therapy is initiated if targets are not achieved within 1-2 weeks of lifestyle modifications. Options in order of preference are:
- Basal-bolus insulin injection (human regular insulin has lowest immunogenicity)
- Rapid-acting insulin analogue (eg. aspart, lispro, glulisine) - comparable to regular insulin but less evidence
- Metformin (note, crosses the placenta but studies are inconclusive) - insulin may still be necessary for adequate control
- Glyburide (if other options declined)
Insulin is discontinued post-partum.
Monitoring
At home blood glucose monitoring should be done:
- Before breakfast for fasting glucose level
- One or two hours after each meal
It is recommended to monitor blood glucose at least 4 times daily initially but once glucose levels are in target range after a week of frequent monitoring can consider monitoring every other day.
Glucose target vary but the ACOG recommends:
- Fasting BG: <5.3 mmol/L
- 1hr PP: <7.8 mmol/L
- 2hr PP: <6.7 mmol/L
Fetal surveillance
Monitoring of fetal growth, BPP, NST in late 2nd trimester and 3rd trimester:
- Weekly testing at 34-36 weeks (may start earlier if overt))
- Consider fetal echocardiogram in 2nd trimester, especially if overt diabetes
Delivery
Consider induction of labour at week 39-40 if glycemic control is poor or there is risk of complication (eg. macrosomnia). This may vary slightly depending on the severity/level of control on hyperglycemia.
The newborn must be monitored for hypoglycemia following birth. It should be noted that presentation may vary so a high level of suspicion should be maintained.