INSULIN-LIKE GROWTH-FACTOR-I AND GROWTH-FACTOR-II PEPTIDE AND MESSENGER-RNA LEVELS IN MACROSOMIC INFANTS OF DIABETIC PREGNANCIES

OBJECTIVE: Fetal macrosomia is a common complication of maternal diabe tes mellitus and is associated with substantial morbidity, but the pre cise cellular and molecular mechanisms that induce fetal macrosomia ar e not well understood. We hypothesized that the macrosomia or accelera ted fetal growth seen in infants of diabetic mothers is due to a pertu rbation of a putative placental-fetal growth axis involving growth hor mone and insulin-like growth factors. Insulin-like growth factors I an d II (IGF-I and IGF-II) am ubiquitous peptides that share structural h omology with insulin and have been implicated in processes that contro l fetal growth. Studies of IGF levels in pregnancies complicated by di abetes and macrosomia have shown conflicting results. We set out to re solve these inconsistencies using molecular techniques to measure the placental IGF-I and IGF-II messenger RNA levels in placentas and a spe cific radioimmunoassay to measure IGF-I and IGF-II peptide levels in c ord serum of normal and diabetic pregnancies. METHODS: Placentas and c ord blood were collected immediately after delivery at term from patie nts from each of three study groups: 1) nonmacrosomic infants of nondi abetic nondiabetic mothers (controls), 2) macrosomic infants of diabet ic mothers, and 3) nonmacrosomic infants of diabetic mothers. Both IGF -I and IGF-II levels were measured in cord serum and placental tissue by a specific radioimmunoassay. Total RNA war extracted and analyzed b y Northern gels hybridized to IGF-I or IGF-II riboprobes. RESULTS: Lev els of IGF-I in cord serum from the macrosomic diabetic group (83 +/- 4.2 ng/mL) were significantly higher than levels from either the nonma crosomic nondiabetic group (38 +/- 1.9 ng/mL) or the nonmacrosomic dia betic group (13 +/- 3.5 ng/mL). There tons a direct linear correlation between cord serum IGF-I and infant birth weight, independent of diab etes (r(2) = 0.61, P < .01). On the other hand, IGF-II cord serum leve ls were elevated in diabetic pregnancies (337 +/- 12.2 ng/mL) compared with nondiabetic women (172 +/- 19.8 ng/mL), but there was no correla tion with birth weight (r(2) = 0.035, P = .52). In contrast to cord bl ood levels, IGF-ll peptide levels weve significantly, decreased in the placentas from mothers with diabetes compared with nondiabetic contro ls (116 +/- 3.2 venus 158 +/- 5.3 ng/mL, respectively. Levels of IGF-I peptide in placentas from both nondiabetic controls and diabetic moth ers were below the sensitivity of the assail. Levels of IGF-I and IGF- II mRNA did not differ in placentas from diabetic mothers versus nondi abetic controls. CONCLUSION: Cord serum IGF-II levels are elevated in diabetic pregnancies without a concomitant increase in placental IGF-I I levels. This novel finding, combined with the finding that IGF-I lev els ave correlated with macrosomia independent of the diabetic state, contributes to our understanding of the possible mechanisms involved i n fetal growth in pregnancies complicated by diabetes.