Human placental growth hormone, insulin-like growth factor I and -II, and insulin requirements during pregnancy in type 1 diabetes

Human placental GH (hPGH) replaces pituitary GH during pregnancy. hPGH is correlated to serum IGF-I in normal pregnancies and in pregnancies complicated by fetoplacental disorders. In gestational diabetes and type 2 diabetes no correlation between hPGH and IGF-I has been found. The relationship between hPGH and IGF-I in type 1 diabetes mellitus has not been investigated thoroughly. Furthermore, hPGH may be involved in the development of insulin resistance during pregnancy. In this prospective, longitudinal study, 51 type 1 diabetic subjects were followed with repeated blood sampling during pregnancy (median, 14 blood samples/subject; range, 8-26). Maternal concentrations of serum hPGH, IGF-I, and IGF-II were measured and compared with insulin requirements and birth characteristics. hPGH was detected from as early as 6 wk gestation. In all subjects, a rise in serum hPGH was observed during pregnancy, and the rise between wk 16 and 25 was correlated to the rise between wk 26 and 35 (P<0.001). From wk 26 onward, the increase in hPGH values was significantly correlated to the birth weight, expressed as a z-score (r(s)=0.54; P<0.001), as were the absolute hPGH values. Also, a positive influence of hPGH on placental weight was found. Serum IGF-I values decreased significantly from the first to the second trimester (P<0.021). Serum hPGH correlated to serum IGF-I from wk 24-35, and changes in IGF-I followed the increase in hPGH between wk 26-35 (r(s)=0.53; P<0.001), as did IGF-II (r(s)=0.37; P=0.008). Changes in IGF-I and IGF-II between wk 26-35 also correlated to the birth weight z-score (P<0.020), but only hPGH remained significant in multiple regression analysis. Similar results were found in the subgroup delivering at term. Interestingly, the increase in hPGH was not correlated to the increase in insulin requirements, nor was any consistent relationship revealed during each gestational period. In conclusion, our study suggests a role for hPGH in the regulation of both IGFs and fetal growth in type 1 diabetes. In contrast, the increase in insulin requirements during pregnancy in type 1 diabetic subjects could not be related to hPGH levels.