Insulin Detemir in Pregnancy: A Small but Significant Step Forward?

P regnancies complicated by diabetes are at increased risk of adverse fetal and maternal outcomes and longer-term health problems in the offspring. Treatments directed at improving glycemic control reduce these risks. However, observational studies show that pregnancies complicated by either type 1 or type 2 diabetes, compared with nondiabetic pregnancies , still have more adverse outcomes, including increased perinatal mortality (1,2). The recent Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study (3) has established a continuum of risk between glycemic levels obtained during a glucose tolerance test and a variety of adverse fetal and maternal outcomes. Two large randomized controlled trials (4,5) of women with gestational diabetes mellitus, variously diagnosed, have demonstrated that treating and reducing glucose levels during pregnancy reduces many of these complications. The poor fetal outcomes in preexist-ing diabetes are largely related to the degree of maternal glycemic control. This is very well documented for the risk of miscarriage, congenital malforma-tions, and excessive fetal weight (3,6–8). Unfortunately, the currently available insulin preparations and the treatment paradigms used in an attempt to achieve normoglyce-mia are generally inadequate for the task. This is especially true for type 1 diabetes. Specifically, the current insulin therapies cannot mimic the complex physiology required to maintain normal blood glucose concentrations. In addition, exogenous insulin therapies are limited by the dangers of hypoglycemia. Many women with preex-isting diabetes cannot achieve normoglyce-mia as estimated by the ability to achieve a normal HbA 1c. It is also worth reminding ourselves that insulin use alone is rarely sufficient to achieve optimal pregnancy outcomes. Insulin must be used skillfully as part of an overall management plan. There is little evidence in the literature for the safety of the current insulin gold standards of human short-acting insulin preparations or protaphane, the long-acting/ basal insulin. There is limited information on the short-acting analogs lispro and aspart. A systematic review and meta-analysis (9) of lispro versus regular insulin identified a higher rate of large-for-gestational-age infants (.90th per-centile), despite similar HbA 1c levels in the lispro group (relative risk, 1.38 [95% CI 1.14–1.16]), but no differences in the rate of small-for-gestational-age infants. No advantage of lispro was demonstrated. Insulin aspart has been studied in a randomized control trial similar to the detemir study described in this issue of Diabetes Care. It demonstrated similar outcomes for aspart compared with regular human short-acting insulin (10). In both the lispro and aspart studies, there was a …