Introduction: Macrosomia in diabetic pregnancy is an ubiquitous finding and implies both maternal and fetal issues. Its incidence surpasses other critical obstetrical morbidity in diabetic pregnancy with increased placental size and polyhydramnios as comorbidity. The studies on the underlying factors contributing to macrosomia have focused on growth stimuli like IGF, glycemia, and insulin and their effects on regional organ function. IGF-I and -II in maternal serum are associated with birth weight and the bioavailabiliy is modulated by IGF-binding-proteins (IGFBP) and phosporylated isoforms of IGFBP and the presence of proteases and IGF split products. Human placental growth hormone regulates the effect of IGF-I in pregnancy. Methods: The literature on the IGF system′s possible effect on fetal growth in diabetic pregnancy is reviewed before our current studies and updated with respect to later findings. Regulation on bioavailability by proteolysis and phosporylation is described. The review discusses briefly the studies on pregnant women with type 1 diabetes with respect to vasculopathy. Results: The data show good correlation of IGF-1/2 levels with birth weight. No such correlation with IGFBP-1 and -3 is found. Fetal growth deviation in diabetic pregnancy is not uniform. In first trimester, growth delay is documented in fetal growth curves compared to non-diabetic controls. Accordingly, a shift in IGF-IGFBP regulation in second trimester is found with less proteolysis of IGFBPs and relative increase in total binding capacity. In third trimester, free IGF further increases as IGFBP binding decreases by proteolysis and modulation. The first trimester values may be used as predictor of fetal weight at term. Diabetic women show a two-to threefold increase in the in vitro IGFBP-3 proteolytic activity during pregnancy as compared to post-partum values. Conclusions: Prominent proteolysis of binding proteins and the modulation by insulin account for the mechanism leading to macrosomia. The two factors combined guarantee the stimulation by more bioavailable IGF and the glycemic levels reveal whether insulin dose are optimal. Structural factors of diabetes i.e. microangiopathy further modulate the sum of effects on fetal growth. In contrast to macrosomia, fetal growth restriction is associated with prominent maternal vascular endothelial complications, such as overt nephropathy, proliferative retinopathy, preeclampsia, and hypertension. In parallel to the growth inhibition, stimulatory effects are exerted by the GH axis including the placental growth hormones and occur probably as compensatory mechanism, similar to the increased IGFBP-3 proteolysis in late pregnancy found in growth retardation. This influence may in part explain the disproportionate growth in different tissue components occurring in the various stages of diabetic pregnancy.

No abstract

No abstract

No abstract

Aim: The arterial wall elasticity and genetic setting is a potential risk factor for dysfunction of vas¬cular endothelial cells and the clinical expression of retinopathy. The prevalence was evaluated of polymorphism in the genes of methylene-tetrahydro-folate-reductase (MTFHR), Factor V, glycoprotein IIb/IIIa (Gp2b3a), and prothrombin in a cohort of pregnant women with type 1 diabetes. The role of hyperhomo¬cysteinemia in microangiopathy in diabetes mellitus has been debated and is mainly seen with reduced activity of the MTHFR gene. The arterial resistance index (AASI) has been used to detect arterial dysfunction and correlate with cardiovascular morbidity and mortality in patients with hypertension.Design: Two-hundred-and-thirty-three women with type 1 diabetes mellitus were analyzed for MTHFR gene polymorphism and Factor V Leiden. In 176 of these women AASI was further evaluated. In a sub-cohort of 40 women with preeclampsia, mutations in glycoprotein IIb/IIIa (Gp2b3a) and prothrombin was measured. The pregnancy and ophthalmological examination data charts were reviewed retrospectively.Results: Retinopathy was associated with higher AASI during pregnancy (p<0.01, in all three trimesters) and preeclampsia (p<0.05). The stiffness increased with higher grades of retinopathy. AASI in women with simplex and proliferative retinopathy followed different patterns during the three trimesters, even when adjusted for age, BMI, and glycemic regulation (p<0.01). None of the studied coagulation genes (MTHFR, Factor V, Gp2b3a, and prothrombin) were found associated with retinopathy or preeclampsia. Conclusion:Retinopathy showed a strong association with AASI during pregnancy and not outside pregnancy in women with type 1 diabetes. This suggests a pregnancy-related functional change in the vascular bed.A common polymorphism in methylene-tetrahydro-folate-reductase (MTFHR 677C>T, a C to T substitution at nucleotide 677, which converts alanine to a valine residue) has been identified as responsible for reduced MTHFR activity and increased plasma homocysteine [10,11].Factor V Leiden is a mutated form of human factor V that causes an increase in blood clotting. With this mutation, the anticoagulant protein secreted is inhibited, leading to an increased tendency to form dangerous, abnormal blood clots. Factor V Leiden is the most common hereditary hypercoagulability disorder amongst ethnic Europeans and linked with increased risk of preeclampsia, abortions, intrauterine growth restriction, placental abruption, and thrombosis [12][13][14].Glycoprotein IIb/IIIa (Gp2b3a, also known as integrin αIIbβ3) is a complex found on platelets. It is a receptor for fibrinogen and von Lauszus FF (2017) Retinopathy in pregnancy in women with type 1 diabetes -a study of associations with arterial wall elasticity and mutation in coagulation genes