Approximately 5 percent of pregnancies are complicated by diabetes. The importance of good glycemic control before conception in diabetic women and as early as possible in women with gestational diabetes has recently been emphasized. Studies in nonpregnant patients have advocated intensive insulin regimens, often involving multiple daily injections, to optimize glycemic levels. Nevertheless, the most widely used regimens for diabetes in pregnancy depend on twice-daily dosing. Nachum and colleagues compared glycemic control and perinatal outcome in pregnant diabetic patients receiving four injections of insulin per day with the same outcomes in similar patients using two daily injections.
They enrolled patients with singleton pregnancies who were beginning treatment before 35 weeks of gestation at an obstetric referral center. The standard criteria of the National Diabetes Data Group were used to define diabetes. The study included 274 women with gestational diabetes and 118 women who had pregestational diabetes. These women were randomly assigned to receive insulin two or four times daily. In the twice-daily regimen, the morning dosage contained two thirds of the calculated total daily insulin requirement and was composed of one third human regular insulin and two thirds human intermediate insulin. The afternoon dosage contained equal parts of regular and intermediate insulin. In the four-times-daily insulin regimen, the first three dosages were of regular insulin given 30 minutes before a meal, and the final dosage, given at bedtime, was of intermediate insulin. All participants received the same dietary and glycemic monitoring advice. Glucose levels were initially self-monitored seven times daily, but this changed to at least twice daily when control was established. Home monitors were checked at monthly clinic visits. Blood was also checked at these visits for glycosylated hemoglobin A1c (HbA1c) and fructosamine. Whenever possible, infants were delivered at term, and neonatal blood samples were taken six times during the first day of life to monitor glucose levels.
The women treated by the different regimens did not differ significantly in any important variables. The twice-daily regimen was followed by 136 women with gestational diabetes and 60 women with pregestational diabetes. The four-times-daily regimen was followed by 138 gestational and 58 pregestational diabetic women. Overall glycemic control, measured by daily glucose measurements and determination of HbA1c and fructosamine levels, was significantly better in the four-times-daily group. Although women in the intensive group received significantly greater amounts of daily insulin, no increase in episodes of hypoglycemia was noted. In women with gestational diabetes, the overall rate of neonatal morbidity was significantly reduced in the four-times-daily group, to almost one half of that in infants born to mothers in the twice-daily group. The most significant reductions were in hypoglycemia and hyperbilirubinemia. Both groups had low rates of macrosomia. In mothers with pregestational diabetes, the more intensive regimen also reduced morbidity, but this reduction did not achieve statistical significance. Hypoglycemia was significantly reduced in infants of mothers with pregestational diabetes who were treated with the four-times-daily regimen.
The authors conclude that using insulin four times daily improved glycemic control and perinatal outcome in mothers with gestational or pregestational diabetes. The more intensive regimens do not appear to result in adverse effects, particularly of hypoglycemia, in the mother.