Diabetes, a metabolic disorder, encompasses a group of diseases marked by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. Approximately 2 to 5% of all pregnancies are complicated by diabetes. While 90% of these are detected during pregnancy (gestational diabetes mellitus/GDM), the rest are pregestational and are referred to as pregnancy with pregestational diabetes mellitus (PGDM).

Pregnant women with high blood sugar values should aim to maintain their capillary plasma glucose below the following levels, avoiding hypoglycemia at the same time:

Alongside diet control, pregnant women with type 1 diabetes are advised to test their blood glucose at fasting, pre meal, 1 hour post meal, and bedtime blood glucose levels daily. Pregnant women with type 2 diabetes or gestational diabetes who are on insulin should test their fasting, pre meal, 1 hour post meal, and bedtime blood glucose levels daily. The level of risk for the pregnancy in women with pre existing diabetes increases with an HbA1c level > 6.5% .

Because of the several fetal and maternal complications associated with diabetic pregnancy, every effort should be made to achieve normoglycaemia throughout pregnancy to prevent adverse pregnancy outcomes. This would involve a multidisciplinary approach with a health care team as mentioned below. The team members should ideally be present in a combined clinic or at least a ready access to all these services at frequent intervals should be provided.

1. •Diabetologist
2. •Obstetrician
3. •Diabetes Specialist Nurse
4. •Dietitian
5. •Neonatal Paediatrician
6. •Motivated Patient

Proper management also requires increased awareness and close cooperation of the patient and her relations. There is a need for continuing education of the general practitioners and obstetricians working at the district levels.The main principles of management are:

1. •Good glycemic control
2. •Prevention of obstetric complications
3. •Early detection and prompt treatment of medical problems
4. •Optimal time and mode of delivery
5. •Arrangement for the care of the newborn

Glycaemic Control During Pregnancy:

Glycaemic control during pregnancy is achieved by modifications in the diet, insulin dose, and regimen (where required) and appropriate advice on exercise as follows:

DIET:

A regulated diet is a prerequisite to allowing predictable and smooth glycaemic control. Caloric restrictions should be applied to obese patients as far as possible. The diet should consist of less than 40% of complex carbohydrates and less than 30% of fats with saturated fats restricted to 10%. Caloric requirements are as shown in the table below:

EXERCISE:

The women with pregnancy can use arm ergometry or undertake walks as permissible by the obstetrician and such a program results in a lower level of glycemia than diet alone. Exercise improves both hepatic glucose output and peripheral glucose utilization and is particularly useful in overweight pregnant diabetics. Most advises of exercise in diabetic pregnancies have to be supervised closely. Diet and exercise may obviate the need for insulin treatment in many patients with gestational diabetes mellitus (GDM).

INSULIN:

Insulin therapy is instituted when diet therapy does not achieve good metabolic control. Due to a decrease in insulin sensitivity, the insulin requirement goes up especially during the latter half of pregnancy. Requirements may range from 0.7 u/kg/day in the first trimester to about 1.0 U/kg/day in the third trimester. A split-mix regimen may be sufficient for a few patients while most patients require multiple dose injections (MDI) i.e. intermediate or long-acting insulin at bedtime and regular insulin before each meal. Patients of GDM may be controlled with simpler regimens. Human insulin is preferable but there is no teratogenicity with purified animal insulin. There is no transplacental passage of insulin as it degraded by the placenta. The dose of insulin is modified as per the results of self-monitoring of blood glucose. The use of oral hypoglycemic agents is yet debatable as they cross the placental barrier and may cause severe neonatal hypoglycemia.

PHARMACOTHERAPY – USE OF ORAL HYPOGLYCEMIC AGENTS

The need for multiple daily injections, the potential for hypoglycemia, and an increase in appetite and weight make this therapeutic option cumbersome for many pregnant women. Amongst the oral hypoglycemic agents, Glibenclamide and Metformin are the two drugs that have been extensively studied for the management of GDM. The added risk of these drugs in the pregnant state is determined by the transplacental passage, association with fetal anomalies, the potential for maternal adverse effects; and the safety of the medications during breastfeeding.

Glibenclamide ( category C in pregnancy )

Glibenclamide is a second-generation oral sulfonylurea, which acts by enhancing the release of insulin from the pancreatic beta cells in normal and diabetic patients. While 1 – 5 % of cases may have hypoglycemia with Glibenclamide, the most common adverse effects are gastrointestinal (nausea, vomiting, dyspepsia) and dermatologic ( pruritus, urticaria, erythema, and maculopapular eruptions). Though elevations of liver function tests have been reported, the incidence of jaundice is rare. It is well absorbed, independent of food intake, and is metabolized by the liver, and time to peak concentration is 2-3 hours with a half-life of 7-10 hours.

The initial dose of Glibenclamide is 2.5 mg once or twice a day and can be increased after titration with blood glucose values up to a maximum of 20 mg/day. Care should be taken that no more than 7.5 mg should be taken at each time. Prescribing glibenclamide rather than insulin during pregnancy may increase patient compliance and overall maternal and neonatal outcome. Unlike other sulfonylureas, there is substantial evidence demonstrating the lack of transplacental passage of glibenclamide to the fetus suggesting insignificant fetal exposure with this drug and its safety in pregnancy. Possible explanations for such lack of placental transport include the extensive plasma protein binding and short elimination half-life.

Metformin(category B medication in pregnancy)

Metformin is a biguanide that improves insulin sensitivity and reduces both fasting and postprandial plasma glucose. It functions by decreasing hepatic glucose output by inhibition of gluconeogenesis and enhances peripheral glucose uptake in the muscles and adipose tissues It also decreases intestinal glucose absorption and increases insulin sensitivity. It is metabolized by the CYP 450 pathway with a half-life of 6 hours and is excreted in the urine. Metformin is available in 250 mg, 500 mg, 850mg, and 1000 mg tablets in both regular-release and extended-release forms. The usual starting dose is 500-1000 mg/day, which can be increased gradually to a maximum dose of 2500 mg/day.

Hypoglycemia related to metformin may occur in 0-21% of pregnant women. The frequently observed gastrointestinal adverse effects include diarrhea, flatulence, nausea, and vomiting, with the incidence ranging from 2 to 63%. Hence metformin is started at a low dose and increased gradually.

Metformin is considered to be safe for breastfed infants. The mean infant exposure to the drug is less than 1% of the weight-normalized maternal dose, which is much below the 10% level of concern for breastfeeding

Alpha-glucosidase inhibitor delays the absorption of carbohydrate in the gut.No systematic review available

Fetal monitoring is essential in both GDM and pregestational diabetes. The frequency and type of testing depends upon the severity of glucose intolerance, associated medical complications, and patient compliance.

ACOG recommends the need for antenatal fetal monitoring in patients with pregestational diabetes, gestational diabetes with poor glycemic control, and patients with other obstetrical complications.

Twice weekly NST should be started at a gestational age of 32 weeks. In patients with IUGR and preeclampsia, testing should be started at 28 weeks of gestation.

Gestational diabetics controlled on diet alone can be managed by fetal kick counting only starting at 32 weeks POG. NST is optional and it can be started any time between 32 – 40 weeks of gestation. Patients on oral hypoglycemic drugs and/ or insulin should be managed with a twice-weekly biophysical profile from 32 weeks onwards. The presence of IUGR, preeclampsia, and oligohydramnios necessitates starting these tests at 28 weeks

POG:

Poor glycemic control in the mother leads to fetal hyperglycemia, which stimulates fetal pancreas for increased insulin release. This leads to fetal macrosomia. Macrosomia is associated with antenatal and intrapartum complications.

Prolongation of pregnancy beyond 38 weeks increases the risk of macrosomia without reducing the cesarean section rates. Therefore, it is advisable to induce the patients with diabetes at 38 completed weeks POG.

Patients controlled on diet only with no other complication can be managed by expectant management until term.

Management during labour and postpartum

Patients with good metabolic control can be carried to term and normal vaginal delivery. Patients who did not have good control can be delivered at 36-37 weeks after assessment of fetal well being. It is advisable to deliver insulin-dependant diabetics at 38 weeks of gestation as there is a little fetal benefit after 38 weeks in utero. The major disadvantage is the risk of failure of induction due to unfavorable cervix. Spontaneous vaginal delivery may be contemplated in the absence of other obstetric indications and fetal Macrosomia. The risk of shoulder dystocia is 0.07% in vaginal deliveries of infants weighing less than 4000gm and 23% in infants weighing more than 4000gm.

Patients who are to be induced benefit from regular monitoring of blood glucose values. An intravenous line is placed for administering oxytocin and fluids. Generally, Ringer’s lactate is administered at 100ml/hour through a controlled infusion pump. Maternal capillary blood sugar should be checked hourly, and if the value is above 120 mg/dl intravenous insulin infusion can be initiated. Usually, ten units of regular insulin are added to 100 ml of normal saline and infused in a controlled manner. A bolus dose of glucose(5gm/hour of glucose) solution should be avoided. The aim is to maintain blood glucose around 100 mg/dl.

Before the elective Cesarean section, approximately one-third of the patient’s pre-pregnancy dose of insulin is given as intermediate-acting insulin in the morning of the day of surgery. Infusion of glucose solutions should be avoided during surgery unless there is a delay between insulin administration and surgery. In the latter event, a glucose infusion drip, as described previously, should be instituted. A neonatologist should be present to take care of a newborn.

Postpartum insulin resistance is decreased and insulin requirement goes down suddenly in pre-gestational diabetes while GDM women may not require insulin at all. The insulin dose should be adjusted accordingly. These patients should be advised to undergo an OGTT at 6 weeks and also counseled regarding recurrence in subsequent pregnancy and increased risk of developing Diabetes mellitus in later life.

The outlook for the pregnant woman with high blood glucose values has improved considerably with meticulous metabolic control from the pre-conception stage and throughout pregnancy.