Diabetes Mellitus in Pregnancy

March

Hyperglycemia during pregnancy includes pregestational diabetes, prediabetes, and gestational diabetes mellitus (GDM).

Pregestational Diabetes Mellitus (PGDM) Complicating Pregnancy

Pregestational diabetes refers to diabetes diagnosed prior to pregnancy and is classified into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) based on the type of diabetes.

Prediabetes Complicating Pregnancy

Prediabetes complicating pregnancy includes impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) present before pregnancy.

Gestational Diabetes Mellitus (GDM)

GDM refers to abnormal glucose metabolism first diagnosed during pregnancy in individuals with previously normal blood glucose levels. Although glucose metabolism abnormalities in individuals with GDM often resolve postpartum, the risk of developing type 2 diabetes in the future increases.

Among pregnant individuals with hyperglycemia, over 85% are diagnosed with GDM, while less than 15% have PGDM. Hyperglycemia during pregnancy poses significant risks to both the mother and the fetus, necessitating careful attention. This section focuses on the discussion of GDM and PGDM.

Gestational Diabetes Mellitus (GDM)

Characteristics of Glucose Metabolism During Pregnancy

Glucose transferred from the mother via the placenta serves as the primary energy source for the fetus. During early and mid-pregnancy, maternal plasma glucose levels decrease as pregnancy progresses, with fasting blood glucose levels decreasing by approximately 10%. This physiological change is due to several factors:

Increased glucose transfer from the mother to the fetus with advancing gestation.
Increased renal blood flow and glomerular filtration rate during pregnancy, coupled with a limited increase in tubular reabsorption, leading to increased glucose excretion in the urine.
Estrogens and progesterone enhance maternal glucose utilization, increasing the fasting glucose clearance capacity compared to the non-pregnant state.

In late pregnancy, maternal levels of insulin-antagonistic substances, such as human placental lactogen, estrogens, progesterone, cortisol, and placental insulinases, increase. As a result, insulin sensitivity decreases with advancing gestation, leading to increased insulin demand to maintain normal glucose metabolism. When insulin secretion is insufficient to meet the increased demands of pregnancy, maternal blood glucose levels rise, resulting in the development of GDM, particularly in individuals with high-risk factors.

High-risk factors for GDM include advanced maternal age, pre-pregnancy overweight or obesity, polycystic ovary syndrome, a history of GDM in prior pregnancies, a history of macrosomia, chronic hypertension, or a family history of diabetes.

Impact of GDM on the Mother and Fetus

The impact of GDM on maternal and fetal health depends on the level of glycemic control during mid-to-late pregnancy. Poor glycemic control increases the risk of short- and long-term complications for both the mother and fetus.

Maternal Impact

These impacts include:

Increased risk of hypertensive disorders of pregnancy compared to non-GDM individuals.
Poor glycemic control leads to a higher incidence of infections, such as genitourinary infections.
Increased incidence of polyhydramnios compared to non-GDM individuals, potentially due to fetal hyperglycemia and osmotic diuresis.
Increased risk of macrosomia, which elevates the likelihood of birth complications, including labor dystocia, birth canal injuries, surgical deliveries, and postpartum hemorrhage.
Increased risk of developing type 2 diabetes and cardiovascular diseases postpartum compared to non-GDM individuals. The recurrence rate of GDM in subsequent pregnancies approaches 50%.

Fetal Impact

Macrosomia

Poor glycemic control leads to a state of fetal hyperinsulinemia caused by maternal hyperglycemia, enhancing fetal protein and fat synthesis while suppressing lipolysis. This results in excessive fetal growth and an increased incidence of macrosomia.

Preterm Birth

GDM increases the risk of preterm birth, with preterm delivery rates ranging from 8.0% to 12.1%. Premature rupture of membranes due to polyhydramnios or early delivery related to complications such as hypertensive disorders of pregnancy and fetal distress are contributing factors.

Fetal Distress

Fetal hyperinsulinemia, caused by chronic exposure to maternal hyperglycemia, can lead to excessive fetal oxygen consumption, increasing the risk of intrauterine hypoxia.

Fetal Growth Restriction (FGR)

Excessive limitation of maternal energy intake during pregnancy may place the fetus at risk of growth restriction.

Fetal Malformations

Poor glycemic control in pregnancies complicated by hyperglycemia significantly increases the risk of fetal malformations.

Neonatal Impact

Neonatal Respiratory Distress Syndrome (NRDS)

Fetal hyperinsulinemia, resulting from high maternal glucose levels, antagonizes the corticosteroid-mediated promotion of type II alveolar cell surfactant production and release. This delays fetal lung maturation and increases the risk of NRDS.

Neonatal Hypoglycemia

Following delivery, the neonate is removed from the maternal hyperglycemic environment, but hyperinsulinemia persists. Without timely glucose supplementation, neonatal hypoglycemia may occur, posing a serious risk to the neonate's life in severe cases.

Clinical Presentation and Diagnosis

Clinical Presentation

Gestational diabetes mellitus (GDM) is diagnosed through the oral glucose tolerance test (OGTT), usually with no significant clinical symptoms observed.

Diagnosis

A 75g OGTT is performed at 24–28 weeks of gestation for individuals not previously diagnosed with PGDM. For those undergoing their first prenatal checkup after 28 weeks with normal fasting blood glucose (FBG) levels, an OGTT is also required. The diagnostic criteria for a 75g OGTT are fasting blood glucose ≥5.1 mmol/L, 1-hour post-glucose ≥10.0 mmol/L, or 2-hour post-glucose ≥8.5 mmol/L. A diagnosis of GDM is made if any one of these thresholds is met or exceeded.

In regions with limited medical resources, FBG measurement is performed first at 24–28 weeks of gestation. If FBG is ≥5.1 mmol/L, a diagnosis of GDM can be made without conducting a 75g OGTT.

GDM Classification

Individuals who achieve target blood glucose levels through medical nutrition therapy (MNT) and exercise guidance are classified as GDM-A1. Those requiring additional hypoglycemic medications to meet blood glucose targets are classified as GDM-A2.

Management

Blood Glucose Management During Pregnancy

The majority of individuals with GDM achieve optimal blood glucose control through MNT and exercise guidance, with only a small proportion requiring hypoglycemic medications.

Medical Nutrition Therapy (MNT)

MNT is the primary method for managing blood glucose in GDM. It aims to maintain blood glucose levels within the target range, ensure adequate nutritional intake for both the mother and fetus, and reduce maternal and fetal complications. Total daily caloric intake is guided by pre-pregnancy BMI and the rate of gestational weight gain, usually ranging from 1,800 to 2,200 kcal/day during mid-to-late pregnancy. An individualized dietary plan is established, distributing total calories across three main meals and 2–3 snacks per day, with a focus on consuming low glycemic index foods. Excessive restriction of caloric intake is avoided to prevent starvation ketosis, which could negatively impact maternal and fetal health.

Exercise Guidance

Exercise helps reduce baseline insulin resistance during pregnancy, increases the rate of blood glucose control, and improves maternal and fetal outcomes. For those without contraindications to exercise, moderate-intensity physical activity for at least 30 minutes on five or more days per week is recommended.

Blood Glucose Targets During Pregnancy

Blood glucose targets for individuals with GDM during pregnancy are: fasting/pre-meal blood glucose <5.3 mmol/L, 1-hour post-meal <7.8 mmol/L, 2-hour post-meal <6.7 mmol/L, and nighttime blood glucose ≥3.3 mmol/L. For those without a risk of hypoglycemia, HbA1c should be ≤6.0%; for those with a tendency toward hypoglycemia, the HbA1c target may be relaxed to ≤7.0%.

Blood Glucose Monitoring

Upon diagnosis of GDM, blood glucose is monitored with a glucometer to track fasting and post-meal glucose levels until control is achieved. GDM-A1 individuals then monitor fasting and post-meal blood glucose levels one day per week, while GDM-A2 individuals monitor these levels every 2–3 days.

Medical Treatment

Individuals who fail to achieve blood glucose targets through MNT and exercise, or who develop starvation ketosis after dietary adjustments or hyperglycemia after increased caloric intake, require hypoglycemic medications. Approximately 10% of individuals with GDM need medications, with insulin and metformin being commonly used; insulin is the preferred treatment. Insulin dosage is tailored based on the condition, gestational progress, and blood glucose levels, typically starting with low doses and adjusted incrementally to achieve target glucose levels. A common approach involves injecting ultra-short-acting or short-acting insulin before main meals to control post-meal glucose and long-acting insulin at bedtime to manage fasting glucose.

Maternal and Fetal Monitoring During Pregnancy

In addition to blood glucose monitoring, regular prenatal checkups assess blood pressure, edema, urinary protein, and fetal status. More frequent checkups may be necessary when complications occur or when blood glucose control is inadequate. Renal function and HbA1c levels are assessed periodically if complications arise or blood glucose remains uncontrolled. Ultrasound is performed approximately every four weeks to monitor fetal growth, development, and amniotic fluid levels. Fetal heart rate monitoring begins at 34 weeks for GDM-A1 individuals and at 32 weeks for GDM-A2 individuals. If additional risk factors are present, monitoring can be initiated earlier based on clinical judgment.

Time to Delivery

GDM-A1 individuals without maternal-fetal complications may continue the pregnancy under close monitoring until the due date, with delivery recommended by 40 weeks.

GDM-A2 individuals with well-controlled blood glucose and no maternal-fetal complications may deliver at 39 weeks. Those with poor glucose control or complications should be hospitalized for observation, and the timing of delivery is determined based on the clinical condition.

Mode of Delivery

GDM alone is not an indication for cesarean delivery. Vaginal delivery is pursued when appropriate, with a delivery plan developed to closely monitor maternal blood glucose, uterine contractions, and fetal heart rate during labor. For suspected macrosomia, fetal distress, abnormal fetal position, history of stillbirth, or other obstetric indications, cesarean delivery may be considered more liberally.

Intrapartum and Postpartum Management

General Management

Adequate dietary intake is provided with close monitoring of vital signs and enhanced fetal surveillance.

Vaginal Delivery Management

Maternal stress and pain during labor may cause blood glucose fluctuations. Blood glucose is closely monitored during labor, with target levels set at 5.0–8.0 mmol/L. Individuals previously receiving subcutaneous insulin discontinue its use during labor, transitioning to intravenous insulin drip therapy with doses adjusted based on glucose monitoring.

Perioperative Management During Cesarean Delivery

On the day of surgery, subcutaneous insulin is discontinued, and blood glucose is monitored preoperatively and intraoperatively to maintain levels between 5.0 and 8.0 mmol/L. Postoperatively, blood glucose is checked every 2–4 hours until regular dietary intake resumes.

Postpartum Management

Blood glucose continues to be monitored postpartum. Insulin therapy initiated during pregnancy is typically discontinued after delivery. Breastfeeding is encouraged as it reduces the risk of future type 2 diabetes. OGTT is conducted 4–12 weeks postpartum, and those with normal results are advised to repeat testing every 1–3 years. Abnormal results warrant lifestyle interventions and follow-up in endocrinology clinics.

Neonatal Care

All neonates born to GDM individuals are considered high-risk and require monitoring of respiratory status, early feeding initiation, and blood glucose testing within 30 minutes of birth. Blood glucose is subsequently checked every 3–6 hours in the first 24 hours. Neonates with hypoglycemia are treated promptly with glucose solution, blood glucose reassessment, and pediatric consultation or transfer for specialized care if needed.

Pregestational Diabetes Mellitus Complicating Pregnancy

Effects of Pregnancy on Diabetes

Hyperglycemia in the non-pregnant state includes type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). Physiological changes during pregnancy may exacerbate preexisting diabetes, particularly in individuals requiring medication for diabetes management prior to pregnancy.

During early pregnancy, fasting blood glucose may decrease due to physiological changes, early pregnancy symptoms, and reduced food intake. For individuals using insulin therapy, adjustments in insulin dosage are necessary to avoid hypoglycemia. In mid-to-late pregnancy, physiological insulin resistance progressively increases, often requiring higher insulin doses in individuals previously using insulin to control blood glucose. During labor, due to increased physical exertion and irregular food intake, failure to adjust insulin dosage in a timely manner may lead to blood glucose abnormalities. After delivery, the removal of the placenta results in the rapid elimination of insulin-antagonistic substances, necessitating a reduction in insulin dosage.

Effects of PGDM on Maternal and Fetal Health

The adverse effects of PGDM on maternal and fetal health span the entire perinatal period. The extent of these effects depends on the severity of diabetes and the level of glycemic control. Poor glycemic control or severe diabetes may cause the following complications:

Fetal Development and Early Pregnancy Loss: Pre-pregnancy or early pregnancy hyperglycemia can lead to abnormal embryonic development, particularly affecting the fetal central nervous system, heart, and kidneys, or even fetal demise. The miscarriage rate may be as high as 15% to 30%.
Hypertension and Preeclampsia: PGDM accompanied by microvascular complications, especially diabetic nephropathy, is associated with a gestational hypertension and preeclampsia incidence of over 50%, as well as an increased risk of fetal growth restriction (FGR) and fetal distress.
Diabetic Ketoacidosis (DKA): Poor glycemic control in T1DM and T2DM during pregnancy may lead to severe hyperglycemia, accelerating fat breakdown and causing a rapid rise in serum ketone levels, which could progress to DKA. DKA significantly increases the risk of intrauterine fetal death and, in severe cases, may result in maternal mortality.
Other Hyperglycemia-Related Risks: Individuals with PGDM have a higher risk of polyhydramnios, macrosomia, and genitourinary infections compared to those with GDM. These complications further increase the risks of preterm delivery, obstructed labor, birth canal injuries, assisted vaginal delivery/cesarean delivery, prolonged labor, and postpartum hemorrhage.
Neonatal Complications: Neonates born to individuals with PGDM are more prone to hypoglycemia and respiratory distress syndrome at birth.

Clinical Presentation and Diagnosis

Clinical Presentation

Pregnant individuals with well-controlled PGDM blood glucose levels typically show no significant clinical symptoms. However, those with inadequate prenatal care or poor glycemic control may present with symptoms such as polydipsia, polyphagia, and polyuria. Other complications, such as polyhydramnios, macrosomia, or FGR, may also develop.

Diagnosis

PGDM can be diagnosed if any one of the following criteria is met:

A pre-pregnancy diagnosis of diabetes is documented.
For individuals with no prior blood glucose testing, diabetes is suspected during the first prenatal checkup if any one of the following criteria is met:
Fasting blood glucose (FBG) ≥7.0 mmol/L.
Symptoms of hyperglycemia with a random blood glucose level ≥11.1 mmol/L.
HbA1c ≥6.5%.

Classification of Diabetes Mellitus with Pregnancy

Staging (or classification) of diabetes in pregnancy is based on the age of onset, duration of diabetes, and the presence of vascular complications. This staging system (White classification) facilitates the assessment of disease severity and prognosis.

Class A: Diabetes diagnosed during pregnancy.
- Class A1: Optimal blood glucose control achieved through nutritional management and exercise guidance, with fasting glucose <5.3 mmol/L and 2-hour postprandial glucose <6.7 mmol/L.
- Class A2: Additional hypoglycemic medications are required to achieve optimal blood glucose control.
Class B: Overt diabetes with onset after age 20 and a disease duration of less than 10 years.
Class C: Onset between ages 10 and 19 or a disease duration of 10–19 years.
Class D: Onset before age 10, disease duration ≥20 years, or the presence of simple retinopathy.
Class F: Presence of diabetic nephropathy.
Class R: Presence of proliferative retinopathy or vitreous hemorrhage.
Class H: Presence of coronary artery disease.
Class T: History of kidney transplantation.

Management

Pre-Pregnancy Evaluation and Care for PGDM

Individuals with diabetes should undergo assessments of cardiovascular health, retinal status, renal function, and glucose/lipid metabolism prior to pregnancy to determine the severity of their condition. Those with mild organic complications and well-controlled blood glucose levels may proceed with a planned pregnancy under active treatment and close monitoring. For individuals with poorly controlled blood glucose and severe organ damage, pregnancy poses significant risks of maternal and fetal complications. Multidisciplinary consultations are recommended to evaluate the risks associated with pregnancy and to adjust the treatment protocol:

With support from endocrinologists, blood glucose levels should be optimized. Oral hypoglycemic agents, if being used, should be replaced with insulin to control blood glucose levels, and HbA1c should ideally be reduced to below 6.5% to lower the risks of maternal and fetal complications, including fetal congenital anomalies.
For individuals with hypertension, antihypertensive medications should be adjusted, avoiding drugs such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.
Diabetic nephropathy should be actively managed, but pregnancy is not recommended for those with severe renal insufficiency.
For individuals with proliferative diabetic retinopathy, laser treatment may be performed.

Blood Glucose Management During Pregnancy

The principles of blood glucose management for PGDM are similar to those for GDM, though most individuals with PGDM require hypoglycemic medications in addition to medical nutrition therapy and exercise guidance. Blood glucose targets are the same as those for GDM. Blood glucose monitoring should be enhanced, especially for individuals with T1DM or T2DM requiring insulin therapy. When blood glucose control is inadequate, fasting and pre- and post-meal blood glucose levels should be monitored and recorded daily, along with adjustments to insulin dosage. Once blood glucose reaches the target range, the frequency of monitoring may be adjusted. For individuals on insulin therapy, vigilance is needed to detect hypoglycemia (e.g., symptoms such as palpitations, hand tremors, or cold sweats) during irregular eating schedules or physical activity.

If symptoms such as unexplained nausea, vomiting, fatigue, thirst, abdominal pain, altered consciousness, or even coma occur during pregnancy and are accompanied by hyperglycemia, the possibility of diabetic ketoacidosis (DKA) should be strongly suspected. When random blood glucose exceeds 11.1 mmol/L, blood ketones and urine ketones should be assessed. A diagnosis of DKA is confirmed when blood glucose exceeds 13.9 mmol/L with blood ketones ≥3 mmol/L or urine glucose and ketones are strongly positive (++ or higher), accompanied by a reduction in blood pH (pH <7.3) and/or bicarbonate (HCO₃^- <18 mmol/L). Upon confirmation of DKA, urgent multidisciplinary consultation and treatment should be initiated:

Fluid Replacement: Fluid replacement is the first-line therapeutic measure, with normal saline (0.9% sodium chloride) being preferred. The initial infusion rate is 15–20 ml/(kg·h) during the first hour, followed by adjustment of the rate based on the extent of dehydration, electrolyte levels, and urine output. The estimated fluid deficit should be replenished within the first 24 hours.
Insulin Therapy: Insulin is administered intravenously in normal saline at a continuous infusion rate of 0.1 U/(kg·h). For individuals with an arterial blood pH <7.0 and/or HCO3- <10 mmol/L, an initial intravenous bolus of 0.1 U/kg insulin is given, followed by a continuous infusion at 0.1 U/(kg·h), with monitoring of blood glucose, blood ketones, or urine ketones. When blood glucose levels fall to 11.1 mmol/L, the infusion is switched to insulin combined with 5% glucose solution.
Correction of Electrolyte Imbalance: On the basis of insulin therapy and fluid replacement, intravenous potassium supplementation is recommended when blood potassium levels are <5.2 mmol/L and urine output is normal.
Correction of Acidosis: Severe acidosis (pH ≤6.9) may require bicarbonate supplementation.

Maternal and Fetal Monitoring During Pregnancy

The principles of maternal and fetal monitoring for PGDM during pregnancy are consistent with those for GDM, with additional considerations:

For individuals with PGDM and suboptimal blood glucose control before or during early pregnancy, ultrasound examination should assess fetal central nervous system and cardiac development, with fetal echocardiography performed if conditions allow.
HbA1c levels should be assessed at least once each during early, mid, and late pregnancy.
PGDM complicated by microvascular disease increases the risk of hypertensive disorders of pregnancy. Low-dose aspirin may be used to reduce the risk of preeclampsia. Indicators such as blood pressure, weight, and urine protein should be monitored at each prenatal visit, along with periodic assessments of renal function and fundoscopic examination.
Ultrasound should be performed every 2–4 weeks during late pregnancy to evaluate fetal growth and monitor amniotic fluid levels. Fetal heart monitoring should begin at 32 weeks of gestation or earlier if additional high-risk factors are present.
For individuals with hyperglycemia-related complications such as hypertension or renal impairment, multidisciplinary consultations and treatment are appropriate. Those with poorly controlled blood glucose or serious complications during monitoring should be hospitalized for further management.

Timing and Mode of Delivery

For individuals with well-controlled blood glucose levels and no maternal or fetal complications, pregnancy may continue under careful monitoring until 39 weeks, when delivery is initiated. Those with poor glycemic control or maternal-fetal complications require hospitalization for close monitoring, with individualized treatment plans determining the timing of delivery. PGDM itself is not an indication for cesarean delivery, though cesarean delivery is warranted for severe microvascular complications or obstetric indications.

Management During Labor and the Postpartum Period

The management principles during labor and the postpartum period are similar to those for GDM. Special considerations include the reduction of insulin requirements postpartum. Regular blood glucose monitoring is required, and insulin dosage is adjusted based on blood glucose levels once dietary intake resumes. Breastfeeding is encouraged, and postpartum follow-up in endocrinology clinics is recommended.