Gestational diabetes mellitus includes pre-gestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM), which may have been diagnosed before pregnancy or first diagnosed during pregnancy. With the increasing prevalence of diabetes mellitus and the widespread emphasis on the screening and diagnosis of GDM, the number of patients with gestational diabetes mellitus is increasing.
In 2007, the Obstetrics and Gynecology Section of the Chinese Medical Association and the Collaborative Group on Gestational Combined Diabetes of the Perinatal Medicine Branch of the Chinese Medical Association formulated the Draft Recommended Guidelines for the Clinical Diagnosis and Treatment of Gestational Combined Diabetes [Draft Guidelines], which have played an important role in guiding clinical management.
The Obstetrics and Gynecology Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association and the Collaborative Group on Gestational Combined Diabetes of the Perinatal Medicine Branch of the Chinese Medical Association have revised the draft guidelines and formulated the Guidelines for the Diagnosis and Treatment of Gestational Combined Diabetes (2014) (referred to as the Guidelines). This guideline is based on the current diagnostic criteria for GDM in China, the International Association of Diabetes and Pregnancy Study Group (IADPSG), the International Diabetes Federation (IDF), and the guidelines developed by the United Kingdom, Australia and Canada, as well as a large amount of evidence-based clinical studies in China and abroad. The recommended hierarchy of evidence in this guideline is shown in Table 1.
Diagnosis
For many years, there has been controversy regarding the methods and criteria for the diagnosis of GDM. For this reason, a global multicenter prospective study, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, was conducted in 2001 with the support of the National Institute of Health (NIH).
Based on the results of this study, the IADPSG proposed new criteria for the diagnosis of GDM in 2010, the American Diabetes Association (ADA) updated the diagnostic criteria for GDM in 2011, and the WHO established diagnostic criteria for hyperglycemia in pregnancy in 2013. At the same time, studies have shown that strict management of mild hyperglycemia in pregnancy significantly improves maternal and child outcomes (Level A evidence). Therefore, this guideline recommends the adoption of the new internationally and nationally recommended diagnostic criteria for GDM.
I. PGDM
The diagnosis of PGDM can be confirmed if any one of the following 2 items is met.
1.Patients who have been diagnosed with diabetes mellitus before pregnancy.
2.Pregnant women who have not undergone blood glucose examination before pregnancy, especially those with high risk factors for diabetes, need to clarify the presence of diabetes during the first prenatal examination, and should be diagnosed as PGDM if their blood glucose rises to any of the following criteria during pregnancy
(1) Fasting plasma glucose (FPG) ≥7.0mmol/L (126mg/dl).
(2) 75g oral glucose tolerance test (OGTT), blood glucose ≥ 11.1mmol/L (200mg/dl) 2h after glucose administration.
(3) With typical symptoms of hyperglycemia or hyperglycemic crisis, and random blood glucose ≥11.1mmol/L(200mg/dl).
(4) Glycohemoglobin (HbAlc) ≥6.5% [using the National glycohemoglobin standardization program (NGSP)/diabetes control and complication trial (DCCT) standardized method, but HbAlc is not recommended for routine diabetes screening in pregnancy Screening with HbAlc during pregnancy is not recommended.
Risk factors for GDM include obesity (especially severe obesity), first-degree relative with type 2 diabetes mellitus (T2DM), history of GDM or delivery of a large child, polycystic ovary syndrome, and recurrent positive fasting urine glucose in early pregnancy.
GDM
GDM refers to the abnormal glucose metabolism occurring during pregnancy, and when it is first detected during pregnancy and the elevated glucose has reached the criteria of diabetes, it should be diagnosed as PGDM instead of GDM. the diagnosis methods and criteria of GDM are as follows.
1. It is recommended that medical institutions perform OGTT for all pregnant women who have not been diagnosed with PGDM or GDM at 24-28 weeks of gestation and at the first visit after 28 weeks. 75g OGTT method: fasting for at least 8 h before OGTT, eating a normal diet for 3 days before the test, i.e. eating at least 150 g of carbohydrate per day, sitting still and abstaining from smoking during the examination. During the test, 300 ml of liquid containing 75g glucose was taken orally within 5 min, and venous blood was drawn from the pregnant woman before and 1 and 2 h after taking glucose (calculated from the time of starting to drink glucose water), and put into a test tube containing sodium fluoride to determine the blood glucose level by glucose oxidase method.
Diagnostic criteria for 75g 0GTT: The three blood glucose values should be below 5.1, 10.0 and 8.5 mmol/L (92, 180 and 153 mg/dl) before and 1 and 2 h after taking sugar, respectively. GDM is diagnosed when any of the blood glucose values reaches or exceeds the above criteria.
If FPG is ≥5.1 mmol/L, GDM can be diagnosed directly without OGTT; if FPG is <4.4 mmol/L (80 mg/dl), GDM is very unlikely to occur and OGTT can be temporarily not performed; if FPG is ≥4.4 mmol/L and <5.1 mmol/L, OGTT should be performed as soon as possible. If FPG≥4.4mmol/L and <5.1mmol/L, OGTT should be performed as soon as possible.
3, pregnant women with high risk factors for GDM, the first OGTT result is normal, if necessary, OGTT can be repeated in late pregnancy.
4.The FPG level decreases gradually with the increase of gestational weeks in early and middle pregnancy, especially in early pregnancy, therefore, the FPG level in early pregnancy cannot be used as the basis for the diagnosis of GDM.
If the first visit is after 28 weeks of gestation, it is recommended that OGTT or FPG test be performed at the first visit or as soon as possible after the visit if the test has not been performed regularly.
Monitoring during pregnancy
I. Blood glucose monitoring for pregnant women
1. Blood glucose monitoring methods.
(1) Self-monitored blood glucose (SMBG): The capillary whole blood glucose level is measured by micro glucose meter. Newly diagnosed hyperglycemic pregnant women, those with poor or unstable glycemic control and those on insulin therapy during pregnancy should monitor blood glucose seven times a day, including 30 min before three meals, 2 h after three meals and nocturnal blood glucose.
For those who have stable blood glucose control, blood glucose profile test should be performed at least once a week, and insulin dosage should be adjusted according to the blood glucose monitoring results in a timely manner.
(2) Continuous glucose monitoring system (CGMS): It can be used for PGDM with unsatisfactory blood glucose control or GDM pregnant women with obvious abnormal blood glucose and need to add insulin. Most pregnant women with GDM do not need CGMS, and it is not recommended to use CGMS as a means of routine clinical monitoring of blood glucose in pregnant women with diabetes.
2. Glucose control target during pregnancy: GDM patients’ blood glucose should be controlled to ≤5.3, 6 and 7 mmol/L (95 and 120mg/d1) before and 2h after meal respectively, and in special cases, blood glucose ≤7.8 mmol/L (140mg/dL) 1h after meal can be measured; nighttime blood glucose should not be less than 3.3 mmol/L (60mg/dl); HbAlc during pregnancy should be <5.5 HbAlc should be less than 5.5% during pregnancy.
The glycemic control of PGDM patients during pregnancy should achieve the following goals: early glucose control should not be too strict to prevent hypoglycemia; preprandial and nocturnal blood glucose and FPG should be controlled at 3.3 and 5.6 mmol/L (60-99 mg/dl) during pregnancy, peak postprandial blood glucose 5.6-7.1 mmol/L (100-129 mg/dl), and HbAlc＜6.0%. Regardless of GDM or PGDM, if the glucose during pregnancy does not reach the above standard after diet and exercise management, insulin or oral hypoglycemic drugs should be added in time to further control the glucose.
3. Measurement of HbAlc level: HbAlc reflects the average blood glucose level in the 2-3 months before blood sampling and can be a good indicator to assess the long-term control of diabetes, mostly used for the initial assessment of GDM. For pregnant women with diabetes mellitus treated with insulin, it is recommended to test once every 2 months.
Urine ketone body monitoring: Urine ketone body can help to detect the lack of carbohydrate or energy intake of pregnant women in time, and is also a sensitive indicator of early diabetic ketoacidosis (diabetes mellitus ketoacidosis, DKA), pregnant women should monitor urine ketone body in time when they have unexplained nausea, vomiting, weakness and other discomfort or when their blood glucose control is not satisfactory.
5. Monitoring of urine glucose: Since a positive urine glucose during pregnancy does not really reflect the blood glucose level of pregnant women, it is not recommended to use urine glucose as a routine monitoring means during pregnancy.
Second, the monitoring of maternal complications
1.Monitoring of hypertensive disorders in pregnancy: the blood pressure and urine protein of pregnant women should be monitored during each pregnancy checkup, and once the complication of pre-eclampsia is found, it should be treated according to the principles of pre-eclampsia.
2, monitoring of excessive amniotic fluid and its complications: pay attention to the uterine height curve and uterine tension of pregnant women, if the uterine height increases too fast or the uterine tension increases, promptly perform B ultrasound examination to understand the amount of amniotic fluid.
3, monitoring of DKA symptoms: if there is unexplained nausea, vomiting, weakness, headache or even coma during pregnancy, pay attention to checking blood glucose and urine ketone levels, and if necessary, perform blood gas analysis to clarify the diagnosis.
4.Monitoring of infection: pay attention to whether pregnant women have increased leucorrhea, vulvar itching, urinary urgency, urinary frequency, urinary pain and other manifestations, and perform regular routine urine tests.
5.Monitoring of thyroid function: perform thyroid function test when necessary to understand the thyroid function of pregnant women.
6.Monitoring of other complications: in cases of diabetes mellitus with microangiopathy combined with pregnancy, renal function, fundus examination and lipid testing should be performed in the early, middle and late stages of pregnancy respectively.
Fetal monitoring
1. Monitoring of fetal development: prenatal screening of the fetus by ultrasound is applied in the middle of pregnancy. For pregnant women whose blood sugar is not controlled in the early stage of pregnancy, it is especially important to apply ultrasound to check the development of fetal central nervous system and heart, and fetal echocardiography is recommended if available.
2. Monitoring of fetal growth rate: Ultrasound examination should be performed every 4-6 weeks during late pregnancy to monitor fetal development, with special attention to monitoring changes in fetal abdominal circumference and amniotic fluid volume.
Evaluation of fetal development in utero: pregnant women in late pregnancy should pay attention to monitoring fetal movement. For those who need insulin or oral hypoglycemic drugs, non-stress test (NST) should be performed once a week from the 32nd week of pregnancy. The fetal growth restriction should be monitored closely especially when it is suspected.
Fetal lung maturation: If the glucose control during pregnancy is unsatisfactory or if early termination of pregnancy is needed, fetal lung maturation should be promoted 48h before the planned termination of pregnancy. If possible, amniocentesis should be performed to extract amniotic fluid to understand the maturity of fetal lung, and intra-amniotic injection of dexamethasone 10mg or intramuscular injection should be given, but the latter should be followed by monitoring the change of maternal blood sugar.
Consultation and treatment
I. Before pregnancy
(i) General advice
Pre-pregnancy counseling is recommended for all women with diabetes mellitus, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG; i.e., prediabetes) who are planning to become pregnant.
The likelihood of GDM in a second pregnancy is 30% to 50% in those with a history of GDM, therefore, for those planning a pregnancy more than 1 year postpartum, OGTT should be performed before the planned pregnancy or at least early in the pregnancy, but OGTT should still be performed at 24 to 28 weeks of gestation if glucose is normal (level B evidence).
Patients with diabetes should be aware of the possible effects of pregnancy on their condition. In addition to hyperglycemia, abnormal feeding due to early pregnancy (e.g., morning sickness) may increase the risk of hypoglycemia.
Patients with diabetes need to be evaluated for complications such as diabetic retinopathy (DR), diabetic nephropathy (DN), neuropathy, and cardiovascular disease before planning pregnancy. Chronic complications of diabetes mellitus may worsen during pregnancy and need to be re-evaluated during pregnancy screening.
(ii) Evaluation of diabetic complications
1. DR: Diabetic patients with planned or definite pregnancy should undergo an eye examination and evaluation of risk factors that may aggravate or contribute to the progression of DR. When there is an indication, such as proliferative DR, taking laser treatment can reduce the risk of aggravation of DR lesions. Fundus changes should be followed closely during pregnancy until 1 year postpartum (Level B evidence). Good glycemic control before and during pregnancy may prevent progression of the disease.
2. DN: Pregnancy may result in temporary renal hypoplasia in patients with mild DN. In patients with more severe renal insufficiency (serum creatinine >265umol/l) or creatinine clearance <50ml/(min?1.73m2), pregnancy can cause permanent damage to renal function in some patients. Therefore, pregnancy is not recommended for this group of patients. DN with normal renal function will have less impact on renal function if the glycemic control during pregnancy is ideal.
3. other complications of diabetes mellitus: diabetic neurological related lesions including gastroparesis, urinary retention and postural hypotension can further increase the difficulty of diabetes mellitus management during pregnancy. If underlying cardiovascular disease is not identified and managed, pregnancy can increase the patient’s risk of death, and evidence of cardiovascular disease should be carefully examined and managed prior to pregnancy. Women with diabetes who are planning to become pregnant should have cardiac function at a level that can tolerate exercise testing.
(iii) Rational use of pre-pregnancy medications
Drugs contraindicated during pregnancy, such as angiotensin converting enzymes inhibitor (ACEI) and angiotensin II receptor antagonist, should be stopped before pregnancy in women with PGDM. If ACEI is used to treat DN before pregnancy, it should be discontinued as soon as pregnancy is detected. Patients should be informed during prenatal counseling that proteinuria may be significantly worsened after discontinuation of ACEI before or during pregnancy.
In pregnant women with diabetes combined with chronic hypertension, the goal of blood pressure control during pregnancy is 110-129 mmHg (1 mmHg=0.133 kPa) for systolic blood pressure and 65-79 mmHg for diastolic blood pressure. available evidence suggests that the application of labetalol and calcium channel blockers in early pregnancy do not significantly increase the risk of fetal teratogenicity and can be applied before as well as during pregnancy. acei ACEIs and angiotensin II receptor antagonists are contraindicated in mid- and late pregnancy (Level E evidence).
2. Pre-pregnancy and early pregnancy in diabetic patients should be supplemented with multivitamins containing folic acid.
3. Patients with T2DM on metformin need to consider the possible benefits or adverse effects of the drug. If the patient wishes, the application can be continued under the guidance of the physician.
(iv) Pre-pregnancy glycemic control
The risk of miscarriage and fetal malformation in early pregnancy is significantly increased in pregnant women with diabetes mellitus with suboptimal glycemic control. Diabetic patients planning pregnancy should try to control their blood glucose so that HbAlc is less than 6.5%, and for those using insulin, HbAlc can be less than 7% (level B evidence).
II. Pregnancy
(i) Medical nutrition therapy
The purpose of medical nutrition therapy is to keep the blood glucose of pregnant women with diabetes mellitus within the normal range, ensure reasonable nutritional intake of pregnant women and fetus, and reduce the occurrence of maternal and fetal complications. 2 randomized controlled trials since 2005 have provided strong evidence for nutritional therapy and management of GDM. Once GDM is diagnosed, patients should be given immediate medical nutrition therapy and exercise instruction, as well as education on how to monitor blood glucose. After medical nutrition therapy and exercise instruction, if FPG and 2h postprandial glucose are still abnormal, timely application of insulin is recommended.
(II) Nutritional intake recommendation
The total daily energy intake should be determined according to the body mass before pregnancy and the growth rate of body mass during pregnancy. Although it is necessary to control the total daily energy intake of pregnant women with diabetes, excessive energy restriction should be avoided, ensuring that it is not less than 1500 kcal/d (1kcal=4.184kJ) in early pregnancy and not less than 1800kcal/d in late pregnancy. insufficient carbohydrate intake may lead to the development of ketosis, which may have adverse effects on both the pregnant woman and the fetus.
2, carbohydrates: recommended dietary carbohydrate intake of 50% to 60% of the total energy is appropriate, not less than 150g of carbohydrates per day is more appropriate to maintain normal blood sugar during pregnancy. Refined sugars such as sucrose should be avoided as much as possible, and low glycemic index foods should be preferred when choosing equal carbohydrate foods. Monitoring carbohydrate intake is a key strategy for achieving glycemic control, whether by carbohydrate counting, food exchange or empirical estimation (Level A evidence). When only total carbohydrate is considered, glycemic index and glycemic load may be more helpful in glycemic control (Level B evidence).
3. Protein: The recommended dietary protein intake should account for 15% to 20% of total energy to meet the needs of physiological regulation during pregnancy and fetal growth and development.
4. fat: the recommended dietary fat intake accounts for 25% to 30% of the total energy is appropriate. However, foods with high saturated fatty acid content, such as animal fats, red meat, coconut milk and full-fat dairy products, should be appropriately limited. The intake of saturated fatty acids for pregnant women with diabetes should not exceed 7% of the total energy intake (Level A evidence); while monounsaturated fatty acids, such as olive oil and camellia oil, should account for more than 1/3 of the fat energy supply. Reducing the intake of trans fatty acids can lower LDL cholesterol and increase HDL cholesterol levels (Level A evidence), so pregnant women with diabetes should reduce the intake of trans fatty acids (Level B evidence).
5. Dietary fiber: It is a polysaccharide that does not produce energy. Pectin in fruits, algae gum in kelp and nori, guanidine gum in some beans and konjac flour have the function of controlling the rise of blood sugar after meals, improving glucose tolerance and lowering blood cholesterol. The recommended daily intake is 25-30 g. The diet can be rich in dietary fiber oatmeal, buckwheat noodles and other coarse grains, as well as fresh vegetables, fruits, algae food, etc.
6, vitamins and minerals: during pregnancy, the need for iron, folic acid and vitamin D increased by a factor of one, calcium, phosphorus, thiamine, vitamin B6 increased by 33% to 50%, zinc, riboflavin increased by 20% to 25%, vitamin A, B12, C, selenium, potassium, biotin, niacin and total daily energy needs increased by about 18%. Therefore, it is recommended that foods rich in vitamin B6, calcium, potassium, iron, zinc and copper, such as lean meat, poultry, fish, shrimp, dairy products, fresh fruits and vegetables, be increased systematically during pregnancy.
7. Use of non-nutritive sweeteners: The ADA recommends that only non-nutritive sweeteners approved by the U.S. Food and Drug Administration (FDA) be used by pregnant women, and recommends them in moderation. Currently, there are very limited studies (Level E evidence). The five FDA-approved non-nutritive sweeteners are potassium acetyl sulfonate, aspartame, neotame, saccharin, and sucralose.
(3) Reasonable arrangement of meals
Small and frequent meals and regular meals are very important for blood sugar control. The energy of breakfast, lunch and dinner should be controlled at 10%-15%, 30% and 30% of the total daily energy intake, and the energy of each additional meal can account for 5%-10% to help prevent excessive hunger before meals.
The process of medical nutrition therapy should be closely coordinated with insulin application to prevent the occurrence of hypoglycemia. Meal plan must be individualized, and reasonable meal arrangement and corresponding nutrition education should be carried out according to cultural background, lifestyle, economic condition and education level.
(D) Exercise therapy for GDM
1, the role of exercise therapy: exercise therapy can reduce the basal insulin resistance during pregnancy, is one of the comprehensive treatment measures of GDM, after 30min of each meal, moderate intensity exercise has no adverse effects on the mother and child.
2, the method of exercise therapy: choose a low to moderate intensity aerobic exercise (also known as endurance exercise), mainly refers to the body’s large muscle groups to participate in continuous exercise. Walking is a simple aerobic exercise commonly used.
3, the duration of exercise: can start from 10min, gradually extended to 30min, which can be interspersed with the necessary intervals, it is recommended that the exercise after meals.
4, the frequency of exercise: the appropriate frequency is 3 to 4 times / week.
5, exercise treatment precautions.
(1) Electrocardiogram should be performed before exercise to exclude cardiac disorders and to confirm the presence of macrovascular and microvascular complications.
(2) Contraindications to exercise therapy for GDM: type 1 diabetes combined with pregnancy, heart disease, retinopathy, multiple pregnancy, cervical insufficiency, preterm labor or miscarriage, fetal growth restriction, placenta praevia, hypertensive disease during pregnancy, etc.
(3) Prevention of hypoglycemic reaction and delayed hypoglycemia: Exercise after 30 minutes of eating, 30-40 minutes per exercise, and 30 minutes of rest after exercise; stop exercise if blood glucose level is <3.3mmol/L or >13.9mmol/L. Carry cookies or candies with you when you exercise, so that you can eat them in time when there are signs of hypoglycemia.
(4) Seek medical attention if the following conditions occur during exercise: abdominal pain, vaginal bleeding or watering, breath-holding, dizziness, severe headache, chest pain, muscle weakness, etc.
(5) Avoid exercising in the early morning on an empty stomach before insulin injection.
(V) Insulin therapy
1. Commonly used insulin preparations and their characteristics.
(1) Ultra-short-acting human insulin analogues: Menthol insulin has been approved by the State Food and Drug Administration (SFDA) in China for use in pregnancy. It is characterized by rapid onset of action and short duration of maintenance of drug effect. It has the strongest or best effect of lowering postprandial blood glucose and is not easy to occur hypoglycemia, and is used to control postprandial blood glucose level.
(2) Short-acting insulin: It is characterized by rapid onset of action and easy dose adjustment, and can be used subcutaneously, intramuscularly and intravenously. After intravenous injection of insulin, it can make blood glucose drop rapidly with a half-life of 5-6 min, so it can be used to rescue DKA.
(3) Medium-acting insulin: It is a suspension containing fisetin, short-acting insulin and zinc ion, which can only be injected subcutaneously but not intravenously. After injection, insulin must be separated from fisetin by the decomposition of protease in tissues, and then insulin is released to exert biological effects. It is characterized by slow onset and long duration of effect, and its strength of lowering blood sugar is weaker than that of short-acting insulin.
(4) Long-acting insulin analogues: Dietary insulin has also been approved by SFDA for use in pregnancy, and can be used to control nocturnal blood glucose and preprandial blood glucose. The various insulin preparations commonly used in pregnancy and their action characteristics are shown in Table 3.
2. Timing of insulin application: After diabetic pregnant women are treated with diet for 3-5 d, the 24-h terminal blood glucose (blood glucose profile test) is measured, including nocturnal blood glucose, blood glucose 30 min before and 2 h after three meals, and urinary ketone bodies. If fasting or pre-meal glucose is ≥5.3mmol/L (95mg/dl), or 2h post-meal glucose is ≥6.7mmol/L (120mg/d1), or if starvation ketosis occurs after diet adjustment and glucose exceeds the pregnancy standard after increasing caloric intake, insulin therapy should be added promptly.
3. Insulin treatment regimen: The insulin treatment regimen that best meets the physiological requirements is: basal insulin combined with pre-meal ultra-short-acting or short-acting insulin. The replacement effect of basal insulin can last 12~24h, while pre-meal insulin has fast onset and short duration, which is conducive to the control of postprandial blood glucose. The individualized insulin treatment plan should be selected according to the results of blood glucose monitoring.
(1) Basal insulin therapy: choose medium-acting insulin for subcutaneous injection before bedtime, which is suitable for pregnant women with high fasting glucose; for those whose fasting glucose has reached the standard after medium-acting insulin injection before bedtime but whose glucose is not well controlled before dinner, choose 2 injections before breakfast and before bedtime, or long-acting insulin injection before bedtime.
(2) Pre-meal ultra-short-acting or short-acting insulin therapy: pregnant women with elevated postprandial glucose should have ultra-short-acting or short-acting human insulin injected at mealtime or 30 min before meal.
(3) Insulin combination therapy: The combination of medium-acting insulin and ultra-short-acting or short-acting insulin is the most commonly used method, that is, short-acting insulin is injected before three meals and medium-acting insulin is injected before bedtime. Due to the significant increase in postprandial glucose during pregnancy, the routine application of premixed insulin is generally not recommended.
4. Precautions for insulin application during pregnancy.
(1) The initial use of insulin should start with a small dose, 0.3 to O.8 U/(kg?d). The total amount of insulin planned for daily application should be allocated for use before three meals, and the principle of allocation is the most before breakfast, the least before Chinese food, and the middle amount before dinner. After each adjustment, the efficacy should be judged by observation for 2-3 d. Each time, it is appropriate to increase or decrease 2-4 u or not more than 20% of the daily insulin dosage until the goal of blood glucose control is achieved.
(2) Treatment of early morning or fasting hyperglycemia during insulin therapy: Insufficient insulin action at night, dawn phenomenon and Somogyi phenomenon can all lead to hyperglycemia. In the first 2 cases, the amount of intermediate-acting insulin must be increased at bedtime, while the amount of intermediate-acting insulin at bedtime should be reduced in case of Somogyi phenomenon.
(3) Changes in the body’s insulin requirement during pregnancy: the insulin requirement increases to different degrees in the middle and late stages of pregnancy; the insulin requirement peaks from 32 to 36 weeks of gestation and decreases slightly after 36 weeks of gestation, and the insulin dosage should be adjusted continuously according to individual blood glucose monitoring results.
(vi) Application of oral hypoglycemic drugs in pregnant women with GDM Most pregnant women with GDM can achieve the blood glucose standard through lifestyle interventions, and those who cannot achieve the standard should first be recommended to apply insulin to control blood glucose. At present, the safety and efficacy of oral hypoglycemic drugs metformin and glibenclamide in pregnant women with GDM have been continuously confirmed. However, there is a lack of relevant studies in China, and these 2 oral hypoglycemic agents are not included in the registration indications for the treatment of diabetes mellitus during pregnancy in China.
However, considering the potential risk of applying the above oral hypoglycemic agents in pregnant women with high insulin dosage or refusal to apply insulin is much less than the risk of uncontrolled gestational hyperglycemia itself to the fetus. Therefore, on the basis of informed consent, some pregnant women with GDM can be used with caution. The classification of oral hypoglycemic drugs and their characteristics are shown in Table 4.
1.Glibenclamide: It is the most widely used oral hypoglycemic drug for the treatment of GDM, and the target organ is the pancreas. 99% of it exists in protein-bound form and rarely passes the placental barrier. The current clinical study shows that the efficacy of glibenclamide compared with insulin therapy in pregnant women with GDM in the middle and late stages of pregnancy is the same, but the former is easy to use and cheap. However, the risk of preeclampsia and neonatal jaundice requiring phototherapy is increased after the use of the drug, and a small number of pregnant women have nausea, headache and hypoglycemic reactions.
2, metformin: can increase the sensitivity of insulin, the current data show that the application of early pregnancy is not teratogenic to the fetus, and has an important role in the maintenance of early pregnancy in the treatment of polycystic ovary syndrome. Since the drug can cross the placental barrier, the long-term safety of the drug for the fetus in the middle and late pregnancy has yet to be confirmed.
Timing and mode of delivery
(I) Time of delivery
1.Pregnant women with GDM who do not need insulin therapy and whose blood glucose control is up to standard can wait for the expected date of delivery under close monitoring if there are no maternal and fetal complications, and those who are not in labor by the expected date of delivery can be induced to terminate the pregnancy.
2.Pregnant women with PGDM and insulin treated GDM, if they have good glycemic control and no maternal and child complications, the pregnancy can be terminated after 39 weeks of gestation under close monitoring; if the glycemic control is unsatisfactory or maternal and child complications occur, they should be admitted to hospital for observation in time and the timing of pregnancy termination should be decided according to their condition.
3. Those with diabetes mellitus with microangiopathy or previous history of adverse delivery should be closely monitored and the timing of termination of pregnancy should be individualized.
(ii) Mode of delivery
Diabetes mellitus itself is not an indication for cesarean delivery. For those who decide to deliver vaginally, a delivery plan should be made and the pregnant woman’s blood glucose, contractions and fetal heart rate changes should be closely monitored during labor to avoid prolonged labor. Indications for elective cesarean delivery are diabetes mellitus with severe microangiopathy, or other obstetric indications. The indications for cesarean delivery should be relaxed in cases of poor glucose control during pregnancy, large fetus (especially if the estimated fetal mass is ≥ 4250 g) or history of stillbirth or stillbirth.
Management of special cases
I. Principles of insulin use during labor and perioperative period
1. Principles of use: All subcutaneous insulin injections should be stopped before and after surgery, during labor and delivery, and during the postpartum period when the diet is not normal, and intravenous insulin drips should be used instead to avoid hyperglycemia or hypoglycemia. The mother should be provided with sufficient glucose to meet the basal metabolic needs and energy consumption under stress; insulin should be supplied to prevent the occurrence of DKA, control hyperglycemia and facilitate the utilization of glucose; and proper blood volume and electrolyte metabolic balance should be maintained.
2. Examination during labor or before surgery: blood glucose and urinary ketone body levels must be detected. Electrolytes, blood gas analysis and liver and kidney function must also be checked for elective surgery.
3. Insulin use: monitor blood glucose every 1-2 hours and maintain small doses of insulin intravenously according to blood glucose values. When insulin is used to control blood glucose during pregnancy and delivery is planned, medium-acting insulin should be used normally at bedtime 1d before induction of labor; insulin before breakfast should be stopped on the day of induction of labor, and 0.9% sodium chloride injection should be given intravenously.
When labor is officially approaching or blood glucose level is <3,9 mmol/L, change the intravenous 0.9% sodium chloride injection to 5% glucose and lactated Ringer's solution and drip at a rate of 100-150 ml/h to maintain blood glucose level at 5.6mmol/L (100mg/d1); if blood glucose level is >5,6mmol/L, use 5% glucose solution plus short-acting insulin and drip intravenously at a rate of 1-4 U/h. Blood glucose level was monitored once an hour using a rapid glucose meter, which was used to adjust the rate of insulin or glucose infusion. Blood glucose can also be regulated according to the method in Table 5.
Management of combined DKA in pregnancy
1. Clinical manifestations and diagnosis of pregnancy-associated DKA: nausea, vomiting, weakness, thirst, excessive drinking, polyuria, a few with abdominal pain; dry skin and mucous membrane, sunken eyes, ketone odor in the breath, consciousness impairment or coma in severe cases; laboratory tests show hyperglycemia > 13,9 mmol/L (250 mg/dl), positive urine ketone bodies, blood pH <7,35, carbon dioxide binding capacity <13,8 mmol/L, and carbon dioxide binding capacity <3,8 mmol/L. 13, 8 mmol/L, blood ketone body > 5 mmol/L, electrolyte disorders.
2. Causes: Diabetes mellitus missed during pregnancy, not diagnosed or treated in time; irregular insulin treatment; unreasonable dietary control; stressful conditions during labor and before and after surgery; co-infection; use of glucocorticoids, etc.
3.Treatment principle: give insulin to lower blood glucose, correct metabolic and electrolyte disorders, improve circulation, and remove causative factors.
4.Specific steps and precautions for treatment.
(1) If the blood sugar is too high (>16,6mmol/L), insulin 0,2-0,4u/kg should be given as a one-time static injection.
(1) If the blood glucose is too high (>16,6 mmol/L), insulin should be given as a single intravenous injection of 0,2-0,4 u/kg.
(2) Continuous intravenous insulin infusion: 0.9% sodium chloride injection + insulin at the rate of 0.1U/(kg?h) or 4-6U/h of insulin.
(3) Blood glucose monitoring: monitor blood glucose once an hour from the beginning of insulin use, and adjust according to the blood glucose decrease.
The average hourly blood glucose drop should be 3.9~5.6 mmol/L or more than 30% of the blood glucose level before intravenous drip. Those who cannot reach this standard may have insulin resistance, and the insulin dosage should be doubled.
(4) When the blood glucose drops to 13,9mmol/L, change 0,9% sodium chloride injection to 5% glucose solution or glucose saline, and add 1U of insulin for every 2,4g of glucose until the blood glucose drops to 11,1mmol/L or less, the urine ketone body is negative, and the rehydration can be stopped when the treatment can be smoothly transitioned to subcutaneous injection before meal.
(5) Precautions: The principle of rehydration is first fast and then slow, salt first and then sugar; pay attention to the balance of the output. After starting intravenous insulin therapy and the patient has urine, potassium should be replenished in time to avoid severe hypokalemia. When pH＜7,1, carbon dioxide binding force＜10mmol/L, HCO3-＜10mmol/L can be supplemented with alkali, generally with 5% NaHCO3- 100ml + 400ml of water for injection, intravenous drip at the rate of 200ml/h, until pH≥7,2 or dioxide