Type 1 Diabetes & Pregnancy

Essentials of Diagnosis

  • Hyperglycemia requiring exogenous insulin.
  • Onset earlier than 30 years of age.
  • Profound thirst, increased urination, weight loss.
  • Ketoacidosis.

Etiology

Type 1 diabetes, previously known as insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, results from a cellular-mediated autoimmune destruction of the β cells of the pancreas. Autoantibodies, such as those specific to islet cells or insulin can be found in 85-90% of individuals when fasting hyperglycemia is detected. The rate of β-cell destruction by autoantibodies is variable, but eventually this condition leads to elevated glucose and elevated free fatty acids due to lack of sufficient insulin production in the β islet cells of the pancreas.

Type 1 diabetes has multiple genetic predispositions. Susceptibility to this form of diabetes is noted to be increased by a gene or genes located near or within the HLA locus on the short arm of chromosome 6 (6p). The risk to offspring of developing type 1 diabetes with an affected sibling is 5% if one haplotype is shared, 13% for two haplotypes, and 2% for no shared haplotypes. If both parents are affected, the incidence of type 1 diabetes is 33%.

Incidence

The incidence of type 1 diabetes in the general population is 0.1-0.4% in various age groups under 30 years of age. Diabetes mellitus represents one of the most common maternal illnesses resulting in anomalous offspring. The incidence of major congenital anomalies among infants of type 1 diabetic mothers has been estimated at 6-10%, representing a 2- to 3-fold increase over the incidence in the general population, and accounting for 40% of all perinatal deaths among these infants. The incidence of malformations is directly related to the level of glucose elevation over the embryonic period as measured by a hemoglobin A1c level in the first trimester. In addition, if not well controlled, type 1 DM results in a comparable increase in abortions.

Pathophysiology

Insulin is an anabolic hormone with crucial roles in carbohydrate, fat, and protein metabolism. It promotes uptake and utilization of amino acids, lipogenesis, glucose uptake, and storage as glycogen. Lack of insulin results in elevated levels of glucose, and lipolysis with elevation of free fatty acids leading to increased formation of ketone bodies, acetoacetate and β-hydroxybutyrate. Blood glucose levels exceeding the renal capability of absorption produce an osmotic diuresis with dehydration and electrolyte loss. Ketoacidosis, a life-threatening condition for both mother and fetus, results from a paucity of insulin.

Elevated glucose levels are toxic to the developing fetus, producing an increase in serious midline defects in direct proportion to the elevation. These birth defects (Table 18-1) are fatal or seriously deleterious to quality of life and are preventable by preconception glucose control. The presence of ketones significantly reduces the hyperglycemia necessary to produce defects. These anomalies occur within the first 8 weeks of gestation, when most women are just initiating prenatal care. Hemoglobin A1c, a particular fraction of a glycosylated hemoglobin molecule, when drawn in the first trimester can indicate the risk of fetal anomalies (Table 18-2).

    Hypertensive States of Pregnancy

    Hypertensive States of Pregnancy

    Hypertensive states in pregnancy include preeclampsia-eclampsia, chronic hypertension (either essential or secondary to renal disease, endocrine disease, or other causes), chronic hypertension with superimposed preeclampsia, and gestational hypertension ...

    Contraception for Adolescents

    Contraception for Adolescents

    Adolescents today represent a significant proportion of the world population ...

    Endometriosis

    Endometriosis

    Endometriosis is a disorder in which abnormal growths of tissue, histologically resembling the endometrium, are present in locations ...

    Delayed Puberty

    Delayed Puberty

    Developmental changes during puberty in girls occur...

    Urinary Incontinence

    Urinary Incontinence

    Millions of women experience involuntary loss of urine called urinary incontinence (UI). Some women may lose a few drops ...

    Medical conditions complicating pregnancy

    Complications of pregnancy are health problems ...

    Teenage Pregnancy

    U.S. pregnancy rate among girls between 15 and 19 ...

    Diabetes Mellitus & Pregnancy

    Diabetes Mellitus & Pregnancy

    Diabetes mellitus, a clinical syndrome characterized by ...

    Diagnosis

    Type 1 diabetes has an early age of onset with deficient insulin production. Profound thirst, increased urination, and weight loss or even overt diabetic ketoacidosis are the usual symptoms triggering medical evaluation.

    Initial evaluation, if the patient was not seen preconceptionally, includes assessment for other organ damage. This allows more individualized and effective prenatal care as well as classification based on White's criteria (Table 18-3). The usual evaluation includes an ophthalmologic examination for evidence of retinopathy. Retinal hemorrhages may increase in the initial stages of improved glucose control as blood flow increases to these terminal vessels, clearing atherosclerotic plaques. The negative impact of this can be controlled by frequent visits with early laser treatment as needed. The renal status is evaluated by a 24-hour urine test for creatinine clearance and total protein. If the protein value is less than 200 mg, a 24-hour urine test for microalbuminuria should be considered, because microalbuminuria is associated with increased future vascular disease. An electrocardiogram should be done on patients with disease duration of 5 years or those who are over the age of 30. Thyroid status should also be evaluated due to the potential multiendocrine impact of diabetes.

    All patients should have a detailed ultrasound examination with fetal echocardiography at 18-20 weeks to rule out anomalies, as well as an AFP (alpha-fetoprotein) or TriScreen at 16-18 weeks' gestation due to the increased rate of congenital anomalies in the offspring of diabetics.

    Fetal surveillance is increased at 32 weeks' gestation if vascular disease is present. This is accomplished with ultrasound amniotic fluid assessments until 36 weeks, then biweekly unless contraction stress tests are done weekly. Serial ultrasound testing for growth is done at 28-32 weeks and at 36 weeks. Polyhydramnios (AFI ≥ 20) or increased abdominal girth should alert the practitioner to less-than-ideal glucose control. If glucose values remain labile despite all attempts at management, then it is best to deliver the fetus as soon as lung maturity is established by L:S and prostaglandin by amniocentesis at 37 weeks.

    Approach to the Type 1 Diabetic

    Care of the insulin-dependent diabetic must be intensive. Support personnel should be identified and constructively involved with the therapy wherever possible. However, it is extremely important to stress that the patient herself is solely responsible for her actions. The educational focus is to develop the patient's understanding of her disease to a point at which she can balance activity, diet, and insulin, with further guidance only as needed to assist her to cease self-destructive behaviors.

    If not seen preconceptionally, prenatal vitamins should be started and additional folate should be given, 0.5 mg twice daily, due to the interaction of hyperglycemia with folate receptors.

    Education

    The education necessary to maximize the diabetic's chances for a successful pregnancy is ideally accomplished through a multidisciplinary team of health care professionals consisting of a physician trained in managing diabetes and pregnancy, a dietician, a diabetes educator, and a social worker. The education process is ongoing and carries the committed woman from a dependent state to one of interdependence. Such a program will result in a successful pregnancy outcome in 96% of patients with preconception control.

    A careful review of the patient's existing knowledge of diabetes and her care is necessary. This may be accomplished by any knowledgeable member of the health care team, but is ideally done by a diabetes educator. Each step from diet, glucose monitoring, insulin administration, exercise, and self-care during illnesses is reviewed, assessing her knowledge and correcting inappropriate information. Ideally, the patient then identifies areas that she can correct to improve glucose control. These areas are summarized, and the care goals are written in an individualized form with patient input and given to her for review at home as well as remaining in the chart so that progress toward the goals can be monitored.

    The patient is thoroughly instructed on how to properly use a home glucose monitor, including running control solutions, cleaning, troubleshooting, and proper technique of sample collection. It is important not to squeeze the area of lancet puncture because the sample may become diluted by tissue fluids, resulting in lowered values. This is so common that the care providers must constantly assess the patient's technique when values vary.

    When the team approach is taken, with active patient cooperation, cesarean delivery is rarely necessary, and most patients go into spontaneous labor or are induced at 40 weeks, thus decreasing the cesarean section rate.

    It is hoped that educational efforts result in a lifelong program designed to prevent the development of diabetic complications and retard the progression of complications. Indeed, the recent CDDT trials clearly indicate this to be the attainable goal. Some 20 years after the pioneering work of Karlsson and Kjellmer, which showed a linear relationship between glycemic control and perinatal mortality, the same reduction in complications has been seen in patients with new-onset diabetes, as well as those with early organ damage (eg, eye, kidney).

    Normalization of Blood Glucose

    Prevention of hyperglycemia and ketoacidosis through rigorous control of blood glucose is mandatory in the pregnant woman with type 1 DM. This is best accomplished by careful preconceptual analysis and counseling, achievement of normal levels of glycosylated hemoglobin before pregnancy, frequent (usually 4-5 times a day) home glucose monitoring, thoughtful control of diet (the diabetic should have the usual weight gain of pregnancy), and stabilization of exercise. Obviously this can be accomplished only by focusing the health care team's efforts on education and by including the patient as an active participant in the care of herself and her fetus.

    Optimal glucose levels before and during pregnancy are fasting levels of 70-90 mg/dL and 1-hour postprandial values of 100-130 mg/dL, or 2-hour postprandial values of 90-120 mg/dL.

    To achieve these levels, the patient must carry a reliable, portable glucose meter at all times to allow independence and to provide protection from adverse outcomes. It is best if the meter has a large-capacity memory. The memory meter not only records times and values but also allows a review of glucose level changes over time. Unfortunately, good glucose levels are invariably associated with being a "good patient" and vice versa. The team, including the patient, must focus on the goal of glucose normalization and assist in changing behavior while always recognizing the difficulties imposed by society on obtaining this goal.

    All patients and significant others should be instructed on treatment of hypoglycemia and have symptoms reviewed. Nocturnal hypoglycemia episodes with nightmares, sleep walking, tossing and turning in bed, and waking with headaches are significant and should be asked about during prenatal visits. After a change in the evening intermediate insulin dose, the efficacy of the dose should be checked with a 2 AM glucose reading. If the value is below 90 mg/dL in a patient with type 1 DM, a snack should be taken, and the health care provider should be contacted in the morning to readjust the dose.

    As noted previously, women with diabetes may optimize their reproductive outcomes by normalization of glucose before pregnancy. Correction of glucose levels to normal as well as replacement of vitamins and minerals depleted during periods of diuresis result in anomaly rates similar to those seen in the general population. Counseling of the diabetic woman must include the family and the lifestyle changes necessary to attain this goal of normalization of glucose levels.

    A. Diet
    The patient should be instructed on an ADA diet, with caloric intake of 25-35 kcal/kg body weight, but no greater than 2400 kcal or less than 1800 kcal. Actual weight gain with confirmation of actual caloric intake will further aid in adjusting the patient's caloric needs to allow appropriate weight gain. Women who are under their ideal weight have additional weight to gain in addition to the recommended 11-kg weight gain (a minimum of 7 kg for obese patients). The diet should be 40-50% carbohydrate, 30% fat, and 20-30% protein. Women with renal disease should have protein limited to 90 g of protein to minimize the impact of pregnancy on their disease. The calories are divided into 3 meals and 3 snacks, with the evening snack recommended to be a half-sandwich. The protein in meat provides calories in the early morning hours, when intermediate insulin is peaking and fetal glucose utilization is maximized due to increased movements during sleep.

    The snack for hypoglycemia should be milk or peanut butter with crackers. Orange juice should be discouraged unless it is the only food available, because it causes an abrupt rise in glucose that is not sustained. Glucagon emergency kits should be given to all type 1 patients and their spouses taught how to use it if the patient is found unresponsive.

    Soluble fiber assists in satiating hunger, but more importantly, it helps reduce glycemic swings. The patient should note exactly what she ate, the amount, and the mode of preparation when she has a postprandial glucose level over 130 mg/dL. Attention should be directed to the bedtime snack when there is elevation or lowering of the fasting glucose.

    The dietitian is a crucial team member in the care of a type 1 diabetic pregnant patient. Visits should occur as often as needed to obtain proper compliance. The dietitian should make a concerted effort to individualize the diet, respecting different lifestyles and ethnicity. A minimum of two visits is always necessary, and family involvement is encouraged to improve compliance.

    B. Insulin
    All patients should undergo a review of insulin administration technique, including mixing of regular and intermediate insulin, as well as injection. All patients should be started on human insulin or switched from older animal products to reduce antibody formation. Patients should be advised that regular insulin may have a more profound hypoglycemic effect due to a lack of blocking antibodies, but generally only a slight decrease in dose is necessary. Because of the increased purity of the human insulin preparations, the duration of action is shorter, and most patients require three injections daily for ideal glucose control, with the intermediate insulin being given at bedtime.

    Initially, the injection sites should be noted, and these should be reevaluated if anomalous glucose readings are seen. The intermediate insulin at bedtime should be given in the fatty area of the thigh for the most prolonged and even absorption. Injections with regular insulin should be given a minimum of 30 minutes prior to a meal.

    Although current studies do not support an improvement in glycemic control or outcome in pregnancy using subcutaneous insulin pumps, some experienced investigators advocate their use in selected patients. Indeed, no research has been conducted using the newer improved pumps. Even advocates of the insulin pump note that initiation with appropriate training is tricky during pregnancy and is probably best done prior to conception.

    Severe Hyperglycemia & Ketoacidosis

    During pregnancy severe hyperglycemia and ketoacidosis are treated exactly the same as in the nonpregnant state. Insulin therapy, careful monitoring of potassium, and fluid replacement are crucial for maternal survival. Fetal status and survival are enhanced by administration of maternal oxygen, lateral recumbency, and slow but decisive lowering of the blood glucose. Fetal heart rate monitoring often demonstrates late decelerations (indicative of uteroplacental insufficiency), in addition to decreased beat-to-beat variability (due to maternal acidosis combined with limited fetal placental clearance and buffering capabilities).

    Postpartum

    The postpartum patient should be started back on an ADA diet as soon as clinically indicated. The dose of insulin should be reduced because the rapid clearing of HPL results in increased insulin receptor sensitivity. The general rule is two-thirds of the prepregnant dose or one- to two-thirds to one-half of the present dose with careful observation for hypoglycemia. If the patient underwent surgery, the insulin infusion is continued until oral intake can be established. The glucose levels should be kept relatively controlled to assist the patient in healing. Infections should be aggressively treated in the postpartum patient, and she should be mobilized as soon as possible because of an increased risk of thrombotic events.

    The patient may experience a "honeymoon" period with a significant reduction in insulin requirement as the energy expenditure of breastfeeding increases. Breastfeeding is encouraged, and insulin is managed accordingly.

    Contraception

    Use of a reliable form of contraception is necessary for the patient until she desires pregnancy or until glucose values are in the desired range. The choices are limited but should be presented to the patient. Low-dose oral contraceptives cause a minimal increase in thromboembolic events, but much less than that experienced during pregnancy. Their use offers the most complete protection from pregnancy. Barrier contraceptive methods may be useful in the properly motivated patient. Currently, studies do not indicate an added risk of infection in women with diabetes who use an intrauterine device (IUD). Indeed, the IUD may be a good choice in a woman who has vascular complications. However, if the diabetic woman is not in a monogamous relationship, the use of both oral contraception and condoms might be advisable, to decrease the possibility of infection by sexually transmitted diseases such as human papillomavirus, herpes, and HIV.

    Prognosis

    Prognosis is primarily dependent on the level of glucose control. Good control requires a motivated patient, an active management approach (education, diet, insulin, and exercise) with trained health care providers, and frequent patient-provider interactions. Another factor influencing prognosis is the amount of degenerative changes. With diligent antenatal care, the patient can anticipate a normal labor and delivery experience. Severe hypoglycemia and diabetic ketoacidosis can result in maternal compromise and even death. The fetus, if spared from congenital malformation or death in utero, may suffer significant impairment in the hostile uterine environment, with poor glucose control affecting brain development as well as that of other organs.

    Considerations

    There are no data to support a shortening of the woman's lifespan or a worsening of renal disease as a result of pregnancy. Retinal complications might be worsened by pregnancy, and there should be no evidence of macular edema or proliferative retinopathy present before proceeding with a pregnancy. Persons in renal failure should be advised to undergo a transplant prior to a pregnancy, because of the impact of elevated creatinine on pregnancy outcome. A history of severe or frequent maternal hypoglycemia is a major concern during pregnancy and should be addressed with the family in detail, since symptoms of hypoglycemia are blunted during pregnancy. It is especially important to establish appropriate guidelines for operating a motor vehicle by advising the patient to use common sense (eg, avoid taking insulin without eating) and evaluate her glucose prior to driving if the level has not been checked recently.