bubble_chart Overview

Diabetes is a common endocrine and metabolic disorder with a certain genetic predisposition, and its exact cause remains incompletely understood. The fundamental pathophysiological changes involve metabolic disturbances of carbohydrates, proteins, fats, water, and electrolytes due to relative or absolute insulin deficiency, characterized by "hyperglycemia." Some other conditions also present with hyperglycemia, known as symptomatic or secondary diabetes, which account for a very small proportion of cases, such as pancreatitis, post-pancreatectomy, acromegaly, Cushing's syndrome, etc.

bubble_chart Pathogenesis

Normal individuals experience an increase in blood insulin levels after oral glucose administration. Fasting insulin levels are below 179 pmol/L (25 μU/ml), peaking at around 359 pmol/L (50 μU/ml) 30 minutes after oral glucose intake, then gradually declining and returning to fasting levels after 2 hours.

In ketoacidosis-type diabetes, the lack of circulating insulin results in no response to oral glucose. However, grade I obesity-type diabetes exhibits a delayed response, with insulin levels rising to abnormally high levels, indicating that pancreatic islet cells in mild diabetes have a slow but excessive reaction. During pregnancy, the sensitivity to diabetes changes: in early pregnancy, fasting and peak insulin levels after oral glucose are similar to non-pregnant states, but in advanced pregnancy, fasting and peak insulin levels are higher than in non-pregnant states. Combined with the tendency for postprandial hyperglycemia in advanced pregnancy, it is clear that insulin sensitivity decreases in late pregnancy. Therefore, to maintain normal glucose homeostasis, pregnant women must produce and secrete more insulin. Most women have sufficient pancreatic β-cell reserves, while a minority develop diabetes. For women with pre-existing diabetes, the decline in insulin sensitivity means that exogenous insulin requirements may sometimes increase 2–3 times as pregnancy progresses.

The reasons for changes in insulin sensitivity during pregnancy are not fully understood but may involve several factors, including placental insulin degradation, elevated levels of circulating free cortisol, estrogen, and progesterone, as well as the antagonistic effects of placental lactogen (HPL) on insulin.

During pregnancy, as the fetal-placental unit grows, insulin resistance develops alongside hyperinsulinemia, both of which disappear immediately after delivery. These observations suggest that pancreatic activity during pregnancy is linked to elevated levels of placental hormones such as HPL, estrogen, and progesterone. HPL, also known as human chorionic somatomammotropin, is immunologically and biologically similar to growth hormone. In well-nourished pregnant women, HPL secretion parallels the fetal-placental growth curve but does not fluctuate with changes in circulating glucose levels. HPL has been shown to have both insulinotropic and anti-insulin properties, though its primary role is insulin antagonism.

In addition to HPL's dual effects on insulin secretion and antagonism, placental estrogen and progesterone also participate in glucose-insulin homeostasis regulation. Human and animal studies have shown that administering estradiol and progesterone leads to excessive insulin secretion and pancreatic islet hypertrophy, but their effects on glucose differ significantly. Estradiol enhances the insulin response to glucose and lowers blood glucose levels, whereas progesterone reduces insulin's hypoglycemic sensitivity. Thus, while progesterone can cause a several-fold increase in insulin, it does not alter glucose levels. These findings indicate that both estrogen and progesterone stimulate insulin secretion, but progesterone has an antagonistic effect on insulin.

bubble_chart Clinical Manifestations

Pregnant women with diabetes may experience sudden weight gain, significant obesity, or symptoms of "three excesses and one deficiency" (polyphagia, polydipsia, polyuria, and weight loss) during pregnancy. They may also develop vulvar cutaneous pruritus, vaginal and vulvar Candida infections. In severe cases, ketoacidosis with unconsciousness may occur, which can even be life-threatening.

bubble_chart Diagnosis

1. The Importance of Early Diagnosis: Malformations no longer occur after organs are fully differentiated. Congenital malformations in infants of diabetic pregnancies often occur before the 7th week of embryonic development, making early diagnosis and intervention crucial.

2. Medical History and Physical Examination: Although important, they may yield negative results. Therefore, the possibility of diabetes should be considered under the following circumstances:

(1) Family history of diabetes: The more relatives with diabetes, the higher the likelihood of the pregnant woman developing the condition.

(2) Multiparous women with a history of recurrent late abortion, unexplained dead fetus or stillbirth, neonatal death, macrosomia, polyhydramnios, or fetal malformations may have an association with diabetes. These patients should undergo urine glucose, blood glucose, and glucose tolerance tests to confirm the diagnosis promptly.

3. Clinical Manifestations (as follows)

4. Laboratory Tests

(1) Urine glucose test: All first-visit pregnant women should undergo urine glucose testing. If the result is negative in early pregnancy, the test should be repeated in the middle and advanced stages. During normal pregnancy, especially after 4 months, the renal tubules' ability to reabsorb glucose decreases. Sometimes, even with normal blood glucose levels, glycosuria may occur due to a lowered renal glucose excretion threshold. Physiological lactosuria may also occur during postpartum lactation. Therefore, a positive urine glucose test requires further fasting blood glucose and glucose tolerance tests for a definitive diagnosis.

(2) Blood glucose test: Normal pregnant women generally have lower blood glucose levels, rarely exceeding 5.6 mmol/L (100 mg/dl), with fasting blood glucose typically ranging from 3.3–4.4 mmol/L (60–80 mg/dl).

(3) Hemoglobin A₁ (HbA₁) test: Blood glucose, glycated serum protein, and glycated HbA₁ can all serve as indicators of diabetes control, though their implications differ. Blood glucose concentration reflects the current blood glucose level; glycated serum protein reflects the average (total) blood glucose level over the past 1–2 weeks; glycated HbA₁ and HbA_1c reflect the average (total) blood glucose level over the past 8–12 weeks. During the red blood cell life cycle, hemoglobin undergoes slow glycosylation to produce HbA₁. The extent of HbA change depends on the average blood glucose level. In non-diabetic individuals, HbA₁ levels are about 4%, while in diabetic patients, they can reach up to 20%. However, with treatment and control, blood glucose levels may decrease. HbA₁ can be further subdivided into HbA_1a, HbA_1b, and HbA_1c. HbA_1c constitutes the largest proportion, and measuring HbA_1c can substitute for HbA₁ levels. During normal pregnancy, HbA₁ levels average 6%, but they may rise in diabetic pregnancies. With better diabetes control as pregnancy progresses, levels may decline. Therefore, HbA₁ testing can serve as a supplementary method to blood glucose measurement. Miller (1982) reported that elevated HbA_1c is associated with a significantly higher incidence of congenital malformations in offspring of diabetic mothers, indicating poor diabetes control.

5. Diagnostic Criteria for Diabetes

(1) World Health Organization (WHO) Diagnostic Criteria for Diabetes (1980)

1) Diagnostic criteria for diabetes mellitus (venous plasma true glucose): ① Presence of diabetes symptoms, without the need for an oral glucose tolerance test (75g) (OGTT), blood glucose at any time of the day >11.1mmol/L (200mg/dl) or fasting blood glucose >7.8mmol/L (140mg/dl); ② With or without diabetes symptoms, fasting blood glucose on more than one occasion >7.8mmol/L (140mg/dl); ③ Presence of diabetes symptoms but blood glucose does not meet the above diagnostic criteria, after overnight fasting and oral administration of 75g glucose, 2-hour blood glucose ≥11.1mmol/L (200mg/dl); ④ For individuals without diabetes symptoms requiring an OGTT, 2-hour blood glucose ≥11.1mmol/L (200mg/dl), with 1-hour blood glucose also ≥11.1mmol/L (200mg/dl), or repeat OGTT with 2-hour blood glucose ≥11.1mmol/L (200mg/dl), or fasting blood glucose ≥7.8mmol/L (140mg/dl).

2) Diagnostic criteria for impaired glucose tolerance: fasting blood glucose <7.8mmol/L (140mg/dl), OGTT 2-hour blood glucose >7.8mmol/L (140mg/dl) but <11.1mmol/L (200mg/dl). Among individuals with impaired glucose tolerance, approximately 50% may develop diabetes within 10 years, and they have a higher risk of coronary heart disease compared to normal individuals, thus requiring regular follow-up. The above diagnostic criteria can be applied to pregnant women, but those with impaired glucose tolerance during pregnancy should be treated as having diabetes.

(2) Domestic diagnostic criteria for diabetes: The National Diabetes Research Collaborative Group proposed diagnostic criteria for diabetes at its expanded meeting in 1982, as shown in Table 23-1.

Table 23-1 Diagnostic Criteria for Diabetes After Oral Glucose (100g) Tolerance Test

Time (h)	0	0.5	1	2	3
Venous Plasma Glucose (mmol/L)	6.9	11.1	10.5	8.3	6.9
(mg/dl)	125	200	190	150	125

Notes: ① If typical diabetes symptoms or complications such as diabetic ketoacidosis are present, and fasting blood glucose >7.2mmol/L (130mg/dl) and/or 2-hour postprandial blood glucose >8.9mmol/L (160mg/dl), diabetes can be diagnosed without performing an OGTT. ② The highest value at 0.5 or 1 hour is taken as one point, and the values at other time points are each taken as one point, totaling four points. ③ If three out of the four points meet or exceed the above criteria at the respective time points, diabetes is diagnosed. ④ If blood glucose values during OGTT exceed the upper limit of the normal range but do not meet the diagnostic criteria, it is termed impaired glucose tolerance. ⑤ Blood glucose measurement is performed using the ortho-toluidine boric acid (TB) method.

bubble_chart Treatment Measures

1. Pregnancy Examination: In early pregnancy, if accompanied by hypertension, coronary artery sclerosis, renal function decline, or proliferative retinal lesions, termination of pregnancy should be considered. If the pregnancy is allowed to continue, the patient should be examined and followed up in a high-risk outpatient clinic. Before 28 weeks of pregnancy, examinations should be conducted once a month; after 28 weeks, every two weeks. Each examination should include tests for urine glucose, urine ketones, urine protein, as well as measurements of blood pressure and weight. Diabetic pregnant women should generally be hospitalized at 34–36 weeks of pregnancy, and those with severe conditions should be hospitalized even earlier.

2. Dietary Therapy: This is a fundamental treatment for diabetes. Regardless of the type of diabetes, severity of the condition, presence of complications, or whether insulin therapy is being used, strict and long-term dietary control should be implemented.

(1) Total Calories and Food Composition: First, calculate the standard weight based on the patient's height. Formula: [Height (cm) - 100] × 0.9 = Standard Weight (kg). Based on the standard weight and occupation, estimate the daily total calorie requirement: - Sedentary individuals: 105–126 kJ (25–30 kcal) per kg per day; - Light physical laborers: 126–146 kJ (30–35 kcal); - Grade II physical laborers: 146–167 kJ (35–40 kcal); - Heavy physical laborers: 167 kJ (40 kcal) or more. Pregnant women, lactating mothers, and malnourished individuals should increase intake appropriately, while those with obesity should reduce it, possibly to less than 5,020 kJ (1,200 kcal) per day, aiming for a body weight reduction to about 5% below the normal standard, which often achieves satisfactory control of the condition. The daily protein intake should be 0.8–1.2 g per kg of standard body weight, increasing to 1.5–2.0 g/kg for pregnant and lactating women. Fat intake should be 0.6–1.0 g per kg of body weight per day, with the remainder consisting of carbohydrates. Carbohydrates should account for about 60% of the total dietary calories, proteins 12–15%, and fats 30%, with saturated fatty acids constituting less than 10% of total calories and cholesterol intake limited to less than 300 mg per day. These calorie and nutrient requirements should then be translated into a meal plan, with calorie distribution across three meals roughly at 1/5, 2/5, and 2/5. In early pregnancy, a regular diet is sufficient, but in advanced pregnancy, carbohydrate intake should be increased to about 150–250 g per day.

(2) Plant Fiber: The diabetic diet should include an appropriate amount of plant fiber, such as wheat bran, corn bran, pumpkin powder, seaweed polysaccharides, etc. For mild cases, long-term consumption can help control the condition and improve glucose tolerance test (OGTT) results.

3. Drug Therapy: Approximately 90% of diabetic patients require insulin during pregnancy, while the remaining patients can manage with dietary control alone. Although the teratogenic effects of oral hypoglycemic agents are not yet confirmed, these drugs can cross the placenta and cause severe neonatal hypoglycemia, especially long-acting agents like chlorpropamide. Therefore, oral hypoglycemic agents should not be used during pregnancy. When dietary control fails, insulin is the best option for maintaining blood glucose levels. Insulin requirements progressively increase after early pregnancy, often rising by 50–100% by full term. Maintaining blood glucose levels is crucial for diabetic pregnant women, as diabetic ketoacidosis is highly dangerous and often leads to fetal death. Thus, blood glucose levels should be kept close to normal without causing hypoglycemia.

4. Obstetric Management

(1) Obstetric management: includes monitoring of the fetus and mother throughout the pregnancy. For pregnant women with well-controlled diabetes, the incidence of pregnancy complications such as preeclampsia, polyhydramnios, and premature labor will not increase. Prenatal monitoring of the fetus includes abdominal palpation and routine ultrasound measurement of the fetal biparietal diameter to assess fetal growth. At 16 weeks of pregnancy, the fetal body is examined by ultrasound to exclude congenital malformations. Starting at 36 weeks of pregnancy, regular non-stress tests (NST) are performed, along with B-ultrasound biophysical scoring and Doppler measurement of fetal umbilical blood flow. The L/S ratio is measured 48 hours before planned childbirth.

(2) Issues regarding termination of pregnancy: ① Maternal aspects: If diabetes cannot be effectively controlled after treatment, or is accompanied by preeclampsia, polyhydramnios, retinal arteriosclerosis, or decreased renal function, termination of pregnancy should be considered; ② Fetal aspects: In pregnancies complicated by diabetes, the fetus often dies between 36 and 38 weeks of gestation. Therefore, to minimize the incidence of intrauterine fetal death, it is generally recommended to terminate the pregnancy around 37 weeks. Some reports suggest that for cases classified as White Class A without complications, waiting for full-term natural childbirth is acceptable.

(3) Mode of childbirth: If the diabetes is mild, well-controlled with medication, the condition is stable, placental function is good, and the fetus is not excessively large, the pregnancy can proceed to full term for vaginal childbirth. For diabetic patients who opt for induced labor or vaginal childbirth, the childbirth process should be concluded within 12 hours unless it is certain that vaginal childbirth can be achieved within the next 4 hours. This is because labor exceeding 16 hours makes it difficult to control the mother's diabetes, increasing the risk of ketoacidosis. During childbirth, close monitoring of the fetus is essential, and cesarean section should be considered if necessary to conclude the childbirth.

If the patient has a history of diabetes for more than 10 years, the condition is severe, the fetus is excessively large, there is relative cephalopelvic disproportion, poor placental function, a history of dead fetus or stillbirth, or failed induction, cesarean section should be considered.

5. Neonatal management: A neonatologist should be present during the delivery of a diabetic mother's baby, as these infants often experience asphyxia and require mucus suction, tracheal intubation, and pressurized oxygen. The infant should be minimally exposed and kept warm to prevent hypothermia. Infants with intrapartum hypoxia or low Apgar scores at birth should be sent to the intensive care unit. Capillary blood should be drawn every 2 hours to measure hematocrit and blood glucose, maintaining blood glucose above 2.2 mmol/L (40 mg/dl). If the hematocrit exceeds 0.70 (70%), 5–10% of the blood can be withdrawn via peripheral vein and replaced with an equal volume of plasma.

If the infant exhibits decreased muscle tone, limb agitation, cyanosis, asphyxia, or convulsions, blood calcium, magnesium, glucose, and hematocrit should be measured. For infants with severe birth trauma, phenobarbital should be administered at 2.5–5 mg/kg in three divided doses daily to prevent severe jaundice. Phototherapy is required if bilirubin levels exceed 170 μmol/L.

Feed the infant 10–30 ml of glucose water within the first hour after birth, then every 4 hours for 24 hours. If necessary, administer 10% glucose solution intravenously at 60 ml/kg daily. Breastfeeding should begin 24 hours after delivery.

bubble_chart Complications

Diabetic ketoacidosis unconsciousness is an acute complication of diabetes. When diabetic patients encounter acute stress situations, such as various infections, acute myocardial infarction, cerebrovascular accidents, etc., the disorder of glucose metabolism in the body worsens, fat decomposition accelerates, and urine ketones become positive, which is called diabetic ketosis. When ketones further {|###|}abdominal mass, protein decomposition increases, and acidic metabolites accumulate, leading to a decrease in blood pH, acidosis occurs, which is called diabetic ketoacidosis.

Diabetic hyperosmolar unconsciousness occurs when diabetes is not diagnosed and treated in time, leading to the development of diabetic hyperosmolar unconsciousness. Additionally, oral thiazide diuretics, glucocorticoids, hyperthyroidism, severe burns, high-concentration glucose therapy causing excessive dehydration and hyperglycemia, various severe {|###|}vomiting, diarrhea, and other conditions causing severe dehydration can also lead to diabetic hyperosmolar unconsciousness.

Diabetic lactic acidosis: Lactic acid is an intermediate metabolite of glucose. The catabolism of glucose includes aerobic oxidation and anaerobic glycolysis of glucose. The former refers to the complete oxidation of glucose under normal aerobic conditions to produce carbon dioxide and water, which is the main pathway for glucose decomposition and energy production in the body. Most tissues can obtain sufficient oxygen for aerobic oxidation and rarely undergo anaerobic glycolysis; the latter refers to the decomposition of glucose into lactic acid under anaerobic conditions.

Insulin hypoglycemic unconsciousness is more common in brittle type I diabetes or moderate to severe type II diabetes. It is generally caused by excessive insulin {|###|}dose, especially when diabetic pregnant women experience vomiting, diarrhea, or insufficient food intake, as well as during the late stage [third stage] of labor.