Placental Structure in Type 1 Diabetes

Abstract

OBJECTIVEAlteration of placental structure may influence fetal overgrowth and complications of maternal diabetes. We examined the placenta in a cohort of offspring of mothers with type 1 diabetes (OT1DM) to assess structural changes and determine whether these were related to maternal A1C, fetal hematocrit, fetal hormonal, or metabolic axes.RESEARCH DESIGN AND METHODSPlacental samples were analyzed using stereological techniques to quantify volumes and surface areas of key placental components in 88 OT1DM and 39 control subjects, and results related to maternal A1C and umbilical cord analytes (insulin, leptin, adiponectin, IGF-I, hematocrit, lipids, C-reactive protein, and interleukin-6).RESULTSIntervillous space volume was increased in OT1DM (OT1DM 250 ± 81 cm3 vs. control 217 ± 65 cm3; P = 0.02) with anisomorphic growth of villi (P = 0.025). The placentas showed a trend to increased weight (OT1DM 690 ± 19 g; control 641 ± 22 g; P = 0.08), but villous, nonparenchymal, trophoblast, and capillary volumes did not differ. Villous surface area, capillary surface area, membrane thickness, and calculated morphometric diffusing capacity were also similar in type 1 diabetic and control subjects. A1C at 26–34 weeks associated with birth weight (r = 0.27, P = 0.03), placental weight (r = 0.41, P = 0.0009), and intervillous space volume (r = 0.38, P = 0.0024). In multivariate analysis of cord parameters in OT1DM, fetal IGF-I emerged as a significant correlate of most components (intervillous space, villous, trophoblast, and capillary volumes, all P < 0.01). By contrast, fetal insulin was only independently associated with capillary surface area (positive, r2 = 6.7%; P = 0.02).CONCLUSIONSThere are minimal placental structural differences between OT1DM and control subjects. Fetal IGF-I but not fetal insulin emerges as a key correlate of placental substructural volumes, thereby facilitating feedback to the placenta regarding fetal metabolic demand.

Placental volume relative to fetal weight estimated by sonography in diabetic pregnancies

“…Our data may be consistent with the report stating that diabetic mothers have larger placenta at birth, their offsprings' weight and placental ratio are increased (1,6).…”

“…Placental volumetry is the most common way to characterize placental growth and it is a summary of many dimensions of placental growth. Diabetic state has a profound effect on the microvasculature of developing placenta leading to increased volume of terminal villi and to non-branching angiogenesis in type I diabetes (DM type I) (4)(5) or to degenerative lesions induced by chronic hypoxia in gestational diabetes mellitus (GDM) (6) irrespective of the adequacy of glycemic control (5).…”

Role of leptin in female reproduction

“…This may be relevant in gestational diabetes [6,86,112,127], a state of greater insulin resistance and hyperinsulinemia than normal pregnancies. In this line, numerous studies have reported that circulating leptin levels, as well as placental leptin and LEPR expression are significantly higher in pregnant women with GDM compared to healthy control women with uncomplicated pregnancy [128,129], providing, at least, a molecular mechanism for the placenta overgrowth previously observed in GDM [99,100]. Others common complications of pregnancy, such as type 1 diabetes mellitus (T1DM) and preeclampsia are also associated with an increase in the concentration of leptin in the maternal blood as well as an increase in placental leptin gene expression [130,131].…”

Obesity, pregnancy, inflammation, and vascular function

“…Virtually, all known cytokines are capable of being synthesized and released by cytotrophoblast, syncytiotrophoblast, and resident placental macrophages or Over the last decade, significant advances in our understanding of placental biology have established that placental function is dynamic and influenced by maternal health, and has an important regulatory role in maternal well-being during pregnancy. For example, in women with type 1 diabetes, there is upregulation of placental glycosylation and acylation pathways and a trend toward increased placental weight (Nelson et al 2009, Radaelli et al 2009). Moreover, the progressive development of insulin resistance during pregnancy is due in part to placentally derived cytokines (Rusterholz et al 2007) such as TNF (Kirwan et al 2002) and leptin (Hauguel-de Mouzon & Guerre-Millo 2006).…”