Transfer of Insulin Lispro Across the Human Placenta

Abstract

OBJECTIVE—Insulin lispro (Humalog), a human insulin analog, has a more rapid onset, earlier peak, and shorter duration of glucose lowering activity than regular human insulin. However, it is not known whether insulin lispro crosses the human placenta and reaches the fetus. Therefore, the objective of the present study was to examine whether insulin lispro crosses the placenta using the technique of perfusing a human placental lobule in vitro. RESEARCH DESIGN AND METHODS—Term human placentae from uncomplicated pregnancies were obtained immediately after delivery. Insulin lispro, at concentrations ranging from 100 to 1000 μU/ml, was introduced into the maternal reservoir. The maternal side of the placenta was perfused with constant concentration of lispro insulin; the fetal circulation was closed. Samples were drawn from both the maternal and fetal circulations at regular intervals. The appearance of insulin lispro in the fetal circulation was analyzed by a specific radioimmunoassay. RESULTS—No placental transfer of lispro could be detected during perfusion with 100 and 200 μU/ml. In contrast, there was a small concentration-dependent transfer to the fetus at concentrations of 580 μU/ml and higher, detectable after at least an hour of constant concentration of insulin lispro during perfusion. The rate of placental transfer was 0.019 μU · min−1 · g tissue−1 at maternal levels of 580 μU/ml and 0.045 μU · min−1 · g−1 tissue at maternal levels of 1000 μU/ml. Measuring lispro levels in 11 pregnant women revealed that a dose of 50 units may achieve serum concentrations >200 μU/ml with apparent linear correlation between dose and levels. CONCLUSIONS—Insulin lispro is not likely to cross the placenta at a single standard dose. This study suggests that insulin lispro is unlikely to reach or harm the unborn baby.

Hypothalamic alterations in fetuses of high fat diet-fed obese female rats

“…There is evidence that maternal leptin can cross the placenta and is a significant source of fetal leptin (Smith & Waddell 2003) but there is little transplacental transfer of insulin (Boskovic et al 2003). In our previous study, we showed that HF fetuses were hyperinsulinemic due to enhanced pancreatic insulin secretion (Srinivasan et al 2006 (Fig.…”

Treatment With Insulin and Its Analogs in Pregnancies Complicated by Diabetes

“…Insulin lispro was not detectable in cord blood when patients received continuous intravenous lispro and dextrose infusions intrapartum to assess placental transfer. However, in an in vitro perfusion study using human placentas, insulin lispro was found to cross the placenta at greater than normal therapeutic concentrations, with fetal perfusate concentration of lispro reaching up to 59% of maternal concentration (7). The mechanism of how the placenta handles therapeutic concentrations of lispro warrants further study.…”

“…Maternal insulin does not cross the placenta unless it is bound to IgG antibody, which carries it through the placenta or insulin is forced through the placenta by high perfusion (6,7). Diabetic fetopathy is thought to be the result of fetal hyperinsulinemia (1)(2)(3)(4)(5)(6)(7)(8)(9). Thus, our treatment must be designed to normalize maternal blood glucose concentrations without the use of exogenous insulins that cross the placenta.…”

Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin

“…Only negligible amounts of maternal insulin and insulin analogs cross the placental barrier at therapeutic concentrations (18,19,20). This explains the lack of correlation between maternal venous insulin concentrations and umbilical venous insulin concentrations (20,21).…”