Diabetes in pregnancy

• Diabetes in pregnancy is any diabetes present during pregnancy. It includes pregestational diabetes (type 1, type 2 or other diabetes diagnosed before pregnancy) and gestational diabetes mellitus (GDM): glucose intolerance first recognised in pregnancy, usually in the second or third trimester.
• Good glucose control before conception and throughout pregnancy reduces miscarriage, congenital anomalies, stillbirth, pre-eclampsia, macrosomia, birth injury and neonatal hypoglycaemia, but it does not remove the risk entirely.
• Most women with GDM have no symptoms; screening uses risk factors and an oral glucose tolerance test (OGTT) at 24 to 28 weeks. GDM often responds to nutrition and activity alone; insulin is the preferred drug if targets are not met.
• Pregestational diabetes needs preconception optimisation to an HbA1c under 6.5 percent, continuation of safe medicines only, and delivery planned at 37 to 38 weeks plus 6 days unless complications arise.
• Both conditions usually resolve after birth, but they leave a higher lifetime risk of type 2 diabetes and cardiovascular disease in the mother, and of obesity, hypertension and type 2 diabetes in the child. ^[6]

By the end of this page you should be able to:

1. Define diabetes in pregnancy, GDM and diabetes in pregnancy, and state how they are classified.
2. State the risk factors, explain the physiology of insulin resistance in pregnancy, and outline the maternal and fetal complications.
3. Plan screening and diagnosis using the WHO/IADPSG, NICE and ACOG pathways and their cut-offs.
4. Set glucose targets, explain nutrition and activity advice, and state when to start insulin, metformin or glyburide.
5. Plan antenatal surveillance, fetal monitoring, intrapartum care and timing of delivery.
6. Arrange postnatal testing, future-pregnancy planning and long-term follow-up for mother and child.

• Pregestational diabetes is diabetes diagnosed before pregnancy. It may be type 1, type 2, or another form (for example monogenic diabetes or pancreatic disease). It carries the risks of diabetic embryopathy and of vascular and renal complications. ^[1]
• Diabetes mellitus in pregnancy is asymptomatic hyperglycaemia first found in pregnancy that meets the non-pregnant WHO criteria for diabetes (fasting glucose of 7.0 mmol/L (126 mg/dL) or more, or 2-hour glucose of 11.1 mmol/L (200 mg/dL) or more after 75 g of glucose, or a random glucose of 11.1 mmol/L (200 mg/dL) or more with symptoms). ^[3]
• Gestational diabetes mellitus (GDM) is lesser hyperglycaemia first found in the second or third trimester, in a woman who did not have diabetes before pregnancy. ^[2]

GDM is best thought of as a stress test of pancreatic beta-cell reserve: the placenta produces hormones that induce insulin resistance, and GDM develops when the pancreas cannot raise insulin enough to overcome it.

GDM is common and is becoming more common as maternal age rises and obesity and type 2 diabetes become more prevalent. ^[1][7] Around 4 to 5 in 100 women in the United Kingdom develop GDM. ^[6] Worldwide, the reported rates of GDM have risen in parallel with the obesity epidemic. ^[2] Gestational or pregestational diabetes together are among the commonest medical complications of pregnancy in many populations. ^[4]

• Age, obesity and ethnicity. Older maternal age, overweight before pregnancy, non-white ethnicity, first-degree family history of diabetes and polycystic ovary syndrome all raise risk.
• Recurrence. A woman who has had GDM has a high chance of recurrence in a future pregnancy. ^[6]
• Trend. Prevalence is rising in parallel with the worldwide obesity epidemic. ^[7]

GDM is caused by an inadequate insulin secretory response to the insulin resistance of pregnancy; there is no single known external cause other than the unmasking of limited beta-cell reserve. Risk factors should be recorded at the booking appointment and used to decide whom to test. ^[1]

NICE lists the following risk factors for GDM (any one is an indication for testing): ^[1]

• body mass index (BMI) of 30 kg/m2 or above
• previous macrosomic baby weighing 4.5 kg or more ^[2]
• previous gestational diabetes
• family history of diabetes (first-degree relative with diabetes)
• an ethnicity with a high prevalence of diabetes

Other risk factors used in US guidance include age 25 years or over, overweight before pregnancy, non-white race or ethnicity, history of abnormal glucose tolerance, poor obstetric outcome and medical conditions such as polycystic ovary syndrome. ^[7]

Pregestational diabetes carries additional risks related to its duration and complications: nephropathy, retinopathy, hypertension, autonomic neuropathy and coronary disease may all worsen in pregnancy, and retinopathy may progress when glucose is lowered rapidly. ^[2][5]

• Early pregnancy is a time of enhanced insulin sensitivity; fasting glucose is lower and postprandial excursions are mild. ^[2]
• From mid-pregnancy the placenta produces hormones that progressively raise insulin resistance in the second and third trimesters. ^[2]
• After delivery insulin resistance drops rapidly once the placenta is delivered. ^[2]
• The Pedersen hypothesis still explains the fetal complications: maternal hyperglycaemia crosses the placenta, the fetal pancreas makes insulin, and fetal hyperinsulinaemia drives macrosomia, adiposity and neonatal hypoglycaemia once the maternal glucose supply stops at birth. ^[7]
• In pregestational type 1 diabetes, the islets do not function at all, so control depends on exogenous insulin and care must begin before conception. ^[1][2]
• In pregestational type 2 diabetes, pre-existing insulin resistance and beta-cell failure worsen with the added resistance of pregnancy, often requiring much more insulin. ^[2]

Most women with GDM have no symptoms; GDM is found because of risk factors, urine glucose or screening. ^[1] The classic symptoms of diabetes (polyuria, polydipsia, weight loss, fatigue) are uncommon and may be masked by pregnancy. A history of glycosuria on routine antenatal testing, or of a previous large baby or stillbirth, should prompt testing. ^[1]

Examination is usually unremarkable. Look for:

• obesity and blood pressure (pre-eclampsia risk is raised)
• signs of polyhydramnios or a large-for-gestational-age fetus (rapid uterine growth, a fetus easily palpable through the abdominal wall)
• in pregestational diabetes, signs of long-term complications: retinal changes (arrange digital retinal photography with mydriasis), albuminuria or neuropathy

A focused history should include the types and duration of pregestational diabetes, HbA1c and retinal or renal results, self-monitoring records, hypoglycaemia awareness, medicines (including metformin, insulin, ACE inhibitors, statins and GLP-1 receptor agonists), and the outcome of every previous pregnancy.

Red flags that demand same-day specialist review include diabetic ketoacidosis, severe hyperglycaemia, hyperemesis with ketonaemia, significant ketones in pregnancy, or any sign of fetal compromise.

Women without known diabetes are screened for GDM at 24 to 28 weeks. ^[2] NICE recommends testing women with risk factors using a 75 g 2-hour OGTT; women with previous GDM can be offered early self-monitoring of blood glucose or an early OGTT at booking and again at 24 to 28 weeks if that result is normal. ^[1] WHO promotes one-step testing and uses one abnormal value; US centres often use a two-step approach. ^[3][7]

Whenever a woman is diagnosed, also measure HbA1c to identify those whose GDM may actually be pre-existing type 2 diabetes; an HbA1c of 48 mmol/mol (6.5 percent) or more at diagnosis supports this. ^{[1] [2]}

The approach is the same whatever the type: set targets, start medical nutrition therapy and physical activity, add insulin if targets are not met, monitor fetal growth, and plan delivery and postnatal follow-up.

The aim is to enter pregnancy with glucose as close to normal as safely possible. ^[2] Conception should be delayed until control is good, especially when the HbA1c is above 86 mmol/mol (10 percent), because of the greatly increased risk of congenital anomaly. ^[1]

• Glucose targets before conception. Type 1 diabetes: fasting 5 to 7 mmol/L (90 to 126 mg/dL) on waking and 4 to 7 mmol/L (72 to 126 mg/dL) before other meals; HbA1c under 48 mmol/mol (6.5 percent) if achievable without troublesome hypoglycaemia. ^{[1] [2] [6]}
• Folic acid 5 mg daily until 12 weeks of gestation to reduce neural tube defect risk. ^{[1] [2]}
• ** Medicines.** Metformin may be used in the preconception period and in pregnancy if benefits outweigh risks; stop all other oral glucose-lowering agents before pregnancy and use insulin instead. ^[1] Stop ACE inhibitors, angiotensin receptor blockers and statins before conception or as soon as pregnancy is confirmed. ^[1] GLP-1 receptor agonist and dual GIP and GLP-1 receptor agonist therapy must be stopped before pregnancy; semaglutide at least 2 months before, with insulin started to reach preconception targets. ^[2]
• Insulin analogue choice. Rapid-acting analogues (aspart, lispro) can be used; isophane (NPH) insulin is the first-choice long-acting insulin. ^[1]
• Retinal assessment before (or at first contact if in the last 6 months) because rapid optimisation can worsen retinopathy; defer rapid glucose lowering until treatment is complete. ^[1]
• Renal assessment (albuminuria, creatinine, eGFR) before stopping contraception; refer if creatinine is 120 micromol/L or more, urinary albumin to creatinine ratio is above 30 mg/mmol, or eGFR is below 45 mL/min/1.73 m2. ^{[1] [2]}
• Weight. BMI above 27 kg/m2: offer weight-loss advice. ^{[1] [2]}
• Education and support. Structured education, contraception advice and a supportive environment; record pregnancy plans from adolescence onwards. ^[1]

• Targets (capillary plasma glucose), if achievable without problematic hypoglycaemia: fasting 5.3 mmol/L (95 mg/dL) or less; 1 hour after meals 7.8 mmol/L (140 mg/dL) or less, or 2 hours after meals 6.4 mmol/L (115 mg/dL) or less. ^{[1] [6]}
• Insulin-treated women should keep glucose above 4 mmol/L (72 mg/dL) at all times to avoid severe hypoglycaemia. ^[1]
• ADA glucose goals for GDM and pre-existing diabetes are similar: fasting 70 to 95 mg/dL (3.9 to 5.3 mmol/L), and either 1-hour postprandial 110 to 140 mg/dL (6.1 to 7.8 mmol/L) or 2-hour postprandial 100 to 120 mg/dL (5.6 to 6.7 mmol/L). For women with GDM not taking insulin, ADA uses fasting under 95 mg/dL, 1-hour under 140 mg/dL and 2-hour under 120 mg/dL. ^{[2] [1][6]}
• A1c is secondary in pregnancy; ideally under 6 percent (42 mmol/mol) if achievable without significant hypoglycaemia, relaxed to under 7 percent (53 mmol/mol) if needed. Do not use A1c routinely in the second and third trimesters for control. ^[2][1]
• Continuous glucose monitoring is recommended for all pregnant women with type 1 diabetes; its value in type 2 and GDM is less certain. ^[1][2]
• Monitoring frequency: six to eight or more tests a day. Type 1 diabetes: fasting, pre-meal, 1 hour after every meal and bedtime daily. Multiple-dose insulin type 2 or GDM: same schedule. GDM on diet or single-dose insulin: fasting and 1 hour after meals daily. ^[1]

• Refer to a dietitian; individualised plan; the National Academy of Medicine reference intakes suggest at least 175 g of carbohydrate daily, 71 g of protein and 28 g of fibre, with emphasis on high-quality carbohydrates. ^{[2] [1]}
• A minimum daily carbohydrate intake of about 175 g is advised to avoid starvation ketosis. ^[1]
• Avoid diets that severely restrict any macronutrient class, especially ketogenic diets, because they increase ketones. ^[2]
• 150 minutes of moderate-intensity activity weekly, spread across days, is recommended; a 30-minute walk after a meal is a simple starting point. ^[2][1]
• In GDM, 70 to 85 percent of women diagnosed under the older (Carpenter-Coustan) thresholds can achieve targets with lifestyle measures alone. ^{[2] [1]}

• Insulin is preferred for pregestational diabetes in pregnancy and for GDM. ^[2] Use isophane (NPH) insulin for basal dosing; rapid-acting analogues for meals. ^[1]
• Metformin and glyburide should not be used first line because both cross the placenta and may not be sufficient to achieve targets. ^[2] Glyburide produces higher neonatal hypoglycaemia and macrosomia rates than insulin in systematic reviews. ^{[2] [1]}
• Metformin is nonetheless used: NICE offers it when diet and exercise fail, and for women with pregestational diabetes if the benefits outweigh risks. ^[1]
• Doses are individual and by glucose profile; typical starting doses described in reviews include 0.2 units per kg body weight of evening NPH for a high fasting glucose, 1.5 units per 10 g carbohydrate for breakfast and 1.0 units per 10 g for lunch and dinner for postprandial rises, or split-dose regimens if both are raised. ^[7] Check and titrate to glucose and local formulary.
• Medicines for complications: ACE inhibitors, ARBs, statins and, in most cases, other oral glucose-lowering agents stop at conception; metformin may continue in breastfeeding type 2 diabetes. ^[1]

NICE stepwise algorithm for GDM diagnosed with fasting glucose under 7.0 mmol/L: ^[1]

1. Offer advice on diet and exercise changes.
2. If targets are not met in 1 to 2 weeks, offer metformin.
3. If metformin is contraindicated or unacceptable, offer insulin.
4. If targets are still not met on metformin, add insulin.
5. If fasting glucose is 7.0 mmol/L or more at diagnosis, start insulin (with or without metformin) and diet and exercise at once.
6. If fasting glucose is 6.0 to 6.9 mmol/L and there are complications such as macrosomia or hydramnios, consider starting insulin (with or without metformin) with diet and exercise. ^[2]

• Retinal assessment each trimester for pregestational diabetes; offer retinal photography at booking unless assessed in the last 3 months. ^[1]
• Renal assessment at first contact if not done in the last 3 months. ^[1]
• Fetal anomaly screening with a detailed 20-week scan including the fetal heart (four chambers, outflow tracts, three vessels). ^[1]
• Growth scans every 4 weeks from 28 to 36 weeks for diabetic pregnancies. ^[1]
• No routine fetal well-being testing before 38 weeks unless growth restriction is suspected. ^[1]
• Pre-eclampsia prevention: aspirin and blood pressure management as in the hypertension guideline (low-dose aspirin recommended by many authorities for all diabetic pregnancies). ^[1]
• Antenatal contact every 1 to 2 weeks with the joint diabetes and antenatal clinic. ^[1]
• Steroids for fetal lung maturation require careful insulin dose adjustment; beta-mimetic tocolysis is avoided; tocolysis and steroids are not contraindicated by diabetes itself. ^[1]
• Fetal growth monitoring includes regular ultrasound assessment of fetal growth and amniotic fluid volume; rising fetal abdominal circumference is a marker of fetal hyperinsulinaemia and warrants intensified control. ^[4]

• Type 1 or type 2 diabetes: advise elective birth by induction or (if indicated) caesarean section between 37 weeks and 38 weeks plus 6 days; consider delivery before 37 weeks if there are metabolic or other maternal or fetal complications. ^{[1] [2]}
• GDM: advise women to give birth no later than 40 weeks plus 6 days; offer induction or caesarean section if not delivered by then; consider earlier delivery if complications exist. ^{[1] [2]}
• Glucose in labour: maintain capillary plasma glucose at 4 to 7 mmol/L (72 to 125 mg/dL) and monitor hourly. ^{[1] [2]}
• Insulin delivery: intravenous dextrose and insulin infusion during labour; consider IV dextrose and insulin from the onset of established labour for type 1 diabetes. Consultant-level neonatal resuscitation should be available 24 hours. ^[1]
• After delivery: women with pregestational insulin-treated diabetes reduce insulin immediately; GDM women stop glucose-lowering therapy immediately. ^{[1] [2]}
• Neonatal care: feed within 30 minutes of birth and 2 to 3 hourly; routine glucose test 2 to 4 hours after birth; neonatal unit admission criteria as per NICE. ^{[1] [2]}

• Miscarriage, congenital malformation, stillbirth and neonatal death are all more common with suboptimal preconception control; risk rises across the range of HbA1c even below the diabetic threshold. ^[1][2]
• Pre-eclampsia and gestational hypertension occur more often; all three glucose values, fasting, 1-hour and 2-hour, independently raise risk. ^{[7] [1]}
• Preterm birth and caesarean delivery rates are raised, partly because of fetal macrosomia and labour complications. ^[7]
• Lifelong: women with GDM are at high risk of type 2 diabetes and need annual surveillance. ^[1][6]
• Progression of diabetic complications (retinopathy, nephropathy) in pregestational diabetes; rapid tightening of control can transiently worsen retinopathy.

• Macrosomia (abnormally large baby) and large-for-gestational-age infants, which raise shoulder dystocia, instrumental and caesarean delivery, perineal trauma and postpartum haemorrhage. ^[1][7]
• Neonatal hypoglycaemia in the first hours after birth (2.1 percent of babies in HAPO by clinical definitions), hyperbilirubinaemia and neonatal respiratory distress. ^[7]
• Congenital malformations, especially cardiac, renal and neural tube, following hyperglycaemia in early pregnancy when organogenesis occurs. ^[2]
• Stillbirth (still four-fold higher in untreated GDM in older series). ^[7]
• Shoulder dystocia (1.3 percent in HAPO) and birth trauma. ^[7]

Exposure to maternal hyperglycaemia raises the child's risk of obesity, hypertension, impaired glucose tolerance and type 2 diabetes later in life. ^{[2][7] [1]}

• With good control, most women with type 1, type 2 or gestational diabetes have healthy pregnancies and healthy babies; GDM usually resolves after delivery. ^[6]
• Miscarriage, anomaly, stillbirth and neonatal complication rates can be brought close to background, but not to the level of a woman without diabetes, even at optimal control. ^[1]
• After GDM, the risk of type 2 diabetes is greatly increased and cardiovascular risk is raised. Intensive lifestyle change (weight reduction of 7 percent with increased activity) substantially reduces conversion. ^{[7] [6]}
• Offspring of diabetic pregnancies carry a higher lifelong risk of metabolic disease. ^[7]
• Pregestational diabetes in pregnancy is increasingly survivable with modern care, but it remains one of the most challenging medical complications of pregnancy. ^[5]

• Primary prevention: preconception glucose control, weight management and, in high-risk women, metformin and lifestyle change before and between pregnancies. A history of GDM itself is a marker for future type 2 diabetes and should trigger lifestyle counselling even when fasting glucose is normal. ^[2][7]
• Risk-factor screening at booking: record BMI 30 kg/m2 or more, previous macrosomic baby of 4.5 kg or more, previous GDM, family history of diabetes and high-prevalence ethnicity; test anyone with at least one factor. ^[1]
• Urine glucose screening is not diagnostic; glycosuria of 2+ on one occasion or 1+ on two or more occasions should prompt further testing. ^[1]
• Testing window: women with previous GDM: early self-monitoring or an OGTT at booking, repeated at 24 to 28 weeks if normal; other risk factors: 75 g 2-hour OGTT at 24 to 28 weeks. ^[1]
• Early-pregnancy hyperglycaemia below the diabetes threshold: in the TOBOGM trial of early screening and treatment (mean 15.6 weeks) there was a modest reduction in a composite neonatal outcome, but benefit appears concentrated in higher glucose ranges and in women screened under 14 weeks; almost one-third of observed women's GDM regressed by 24 to 28 weeks with similar outcomes. Treatment of all early abnormal glucose is therefore still debated. ^[2]
• Postnatal: fasting plasma glucose 6 to 13 weeks after birth; annual HbA1c for women whose postnatal result is negative; refer to diabetes prevention programmes if results are high. ^[1]
• Future pregnancies: offer early self-monitoring or an OGTT in the next pregnancy, plus preconception care. ^[1]

• Pregnancy (the condition itself): early pregnancy may improve insulin sensitivity and cause hypoglycaemia, especially in type 1 diabetes; from mid-pregnancy glucose targets tighten and insulin doses rise.
• Children of diabetic mothers: hypoglycaemia, macrosomia, congenital malformations in early-pregnancy hyperglycaemia, and long-term cardiometabolic risk.
• Older women and multiparous women: more likely to have type 2 diabetes and GDM; nephropathy and retinopathy assessment is especially important.
• Type 1 diabetes: start preconception care early, use rtCGM, plan off-loading for hypoglycaemia, and give glucagon prescriptions to family members. ^[1][2]
• Low-resource settings: WHO does not state how to screen, and a full 75 g OGTT may not be available; fasting plasma glucose alone, or a simpler two-step approach, may be used where resources are limited, and insulin should be available even though oral agents are cheaper. ^[3]
• Ethnicity: many UK guidelines adjust BMI thresholds for South Asian and other higher-risk ethnic groups; screening thresholds for diabetes diagnosis remain universal.

• Diabetes in pregnancy means any diabetes present in pregnancy; classify as pregestational, GDM, or diabetes in pregnancy.
• Poor preconception control increases miscarriage, anomalies, stillbirth and neonatal death; risk falls with every improvement but is not eliminated.
• Risk factors alone guide whom to screen; the diagnostic test is usually a 75 g 2-hour OGTT at 24 to 28 weeks.
• Thresholds differ: NICE uses fasting 5.6 or 2-hour 7.8 mmol/L; WHO/IADPSG uses lower thresholds of 5.1, 10.0 and 8.5 mmol/L; ACOG's two-step uses Carpenter-Coustan thresholds (cut-offs of 95 mg/dL fasting, then 180, 155 and 140 mg/dL at 1, 2 and 3 hours).
• Pregnancy control targets are fasting 5.3 mmol/L or less and postprandial 7.8 mmol/L (1-hour) or 6.4 mmol/L (2-hours) or less; optimally lower for type 1. ^[1]
• A1c goal is under 6 percent if achievable without hypoglycaemia; under 7 percent if not; do not use A1c to assess control in the second and third trimesters.
• Medical nutrition therapy, activity and weight management come first; insulin is preferred when targets are not met.
• Metformin and glyburide are not first line because they cross the placenta and may not suffice; glyburide causes more neonatal hypoglycaemia and macrosomia.
• Type 1 and type 2 diabetes: delivery planned at 37 + 0 to 38 + 6 weeks; GDM: by 40 + 6 weeks; glucose in labour kept at 4 to 7 mmol/L.
• Pregestational women reduce insulin after delivery; GDM women stop their glucose-lowering drugs.
• Neonatal glucose is checked at 2 to 4 hours and feeding starts within 30 minutes.
• Postnatal testing and annual HbA1c are essential; women with GDM have a high risk of future type 2 diabetes.
• GDM is often asymptomatic; risk-factor screening and OGTT are essential.
• Always check for and manage diabetic complications (eyes, kidneys, pressure) before and in pregnancy.

Read first and related MedGrasp topics (pending verified entries linked as plain text): type 1 diabetes mellitus, type 2 diabetes mellitus, diabetes chronic complications, hyperemesis gravidarum, antepartum fetal surveillance, neonatal hypoglycaemia, gestational and chronic hypertension in pregnancy, pre-eclampsia, HELLP and eclampsia, antepartum haemorrhage, neonatal resuscitation, gestational hypertension.