DIABETES AND THE USE OF INSULIN IN PREGNANCY

Diabetes mellitus is a group of conditions characterised by high levels of blood glucose. Type 1 diabetes results from failure to produce insulin (a hormone produced by the pancreas to regulate carbohydrate and fat metabolism) necessitating administration of exogenous insulin which may be derived from human, porcine or recombinant sources and administered via subcutaneous injection or continuous subcutaneous infusion. In type 2 diabetes, insulin is produced but cannot be utilised by the body. Lifestyle changes (including diet and exercise) are the first-line treatment for type 2 diabetes, although oral hypoglycaemic agents and insulin may be necessary. Gestational diabetes occurs during pregnancy and usually resolves spontaneously after delivery. Treatment of gestational diabetes is the same as for type 2 diabetes.

Whereas maternal pregestational diabetes is associated with an increased risk of congenital malformations (typically CNS, cardiovascular, urogenitary, musculoskeletal and gastrointestinal), studies have not demonstrated an increased malformation rate in infants born to women who develop gestational diabetes. Both conditions are, however, associated with increased risks of large for gestational age infants and fetal macrosomia which are in turn associated with delivery complications (such as shoulder dystocia) and increased perinatal mortality. Good maternal glycaemic control during fetal organogenesis is vital to reduce teratogenicity, but should be balanced against the risk of hypoglycaemic episodes which are associated with significant maternal and fetal risks. Some studies have estimated that the risk of congenital malformations with untreated or poorly controlled pregestational diabetes is up to 10-fold higher than the background risk, while the risk for intrauterine death is five times higher, and neonatal death three times higher.

Increasing maternal hyperglycaemia is directly correlated with both maternal and fetal adverse outcomes, therefore glycaemic control during pregnancy is of particular importance. However, even with good glycaemic control, infants of diabetic mothers remain at increased risk of congenital malformation. The risks of uncontrolled or poorly controlled diabetes should ideally be discussed with the patient prior to conception, along with maternal diet and exercise regimes. Women with poorly controlled diabetes and glycosylated haemoglobin (HbA1c) above 10% should be strongly advised to improve diabetic control prior to conception in light of the associated increased risk of congenital malformations in the fetus and other adverse pregnancy outcomes. Preconception and antenatal high dose folic acid (5mg/day) is advised for all women with pregestational diabetes. Insulin does not cross the placenta and has not been associated with fetal teratogenesis. NICE guidance at the time of writing recommends that oral blood glucose lowering agents other than metformin are discontinued before pregnancy and insulin substituted. 

Management of diabetes in pregnancy is complex. Readers are advised to refer directly to NICE guidance. NICE recommend that women with pre-existing diabetes are seen by members of the joint diabetes and antenatal care team within one week of their pregnancy being confirmed. The importance of preconception education and care cannot be emphasised enough.