Pregnancy induces molecular alterations reflecting impaired insulin control over glucose oxidative pathways that only in women with a family history of Type 2 diabetes last beyond pregnancy

Abstract

In circulating lymphomonocytes (CLM) of patients with Type 2 diabetes (DM2) pyruvate dehydrogenase (PDH), the major determinant of glucose oxidative breakdown, is affected by a cohort of alterations reflecting impaired insulin stimulated glucose utilization. The cohort is also expressed, although incompletely, in 40% of healthy young subjects with a DM2-family history (FH). Pregnancy restrains glucose utilization in maternal peripheral tissues to satisfy fetal requirements. Here we explore whether pregnant women develop the PDH alterations and, if so, whether there are differences between women with and without FH (FH+, FH-). Ten FH+ and 10 FH- were evaluated during pregnancy (12-14, 24-26, and 37-39 weeks) and 1 yr after (follow-up) for fasting plasma glucose and insulin as well as body mass index (BMI), and for the PDH alterations. Twenty FH- and 20 FH+ non-pregnant women served as controls. All FH+ and FH- controls exhibited normal clinical parameters and 8 FH+ had an incomplete cohort of PDH alterations. In FH- and FH+ pregnant women at 12-14 weeks clinical parameters were normal; from 24-26 weeks, with unvaried glucose, insulin and BMI rose more in FH- and only in the latter recovered the 12-14 weeks values at follow-up. In all FH-, the cohort of PDH alterations was incomplete at 24-26 weeks, complete at 37-39 weeks, and absent at follow-up but complete from 12-14 weeks including follow-up in all FH+. In FH-, the cohort is an acquired trait restricted to pregnancy signaling transiently reduced insulin-stimulated glucose utilization; in FH+, instead, it unveils the existence of an inherited DM2-related background these women all have, that is awakened by pregnancy and as such lastingly impairs insulin-stimulated glucose utilization.

A novel role of cellular interactions in vascular calcification

“…Recent discovery of OPG/receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL) system builds a physiopathological link between bone loss and VC [44]. In mice, OPG knockdown presented severe osteoporosis and VC, but OPG overexpression reduced osteoclast differentiation from precursor cells and increased bone mass [45, 46].…”

“…It seemed inconsistent that serum OPG levels were increased in the presence of VC [48], but this may be a reflection of noxious OPG activity or a compensatory mechanism. Growing evidence have demonstrated the vascular OPG/RANK/RANKL axis plays an important role in the cellular interactions under pro-calcific setting [44]. …”

Less Vertebral Bone Mass after Treatment with Macitentan in Mice: A Pilot Study

“…Blood vessels and the skeleton are closely connected [1]. Vascular diseases and bone remodeling disorders (e.g., osteoporosis, osteoarthritis) may share common biological mechanisms [2], including dysfunction of OPG/RANK/RANKL system [3, 4], altered PTH level [5, 6], and aberrant WNT [7] and BMP signaling pathways [8–11]. Additionally, human mesenchymal stem cells (hMSCs), including the newly identified human skeletal stem cells (hSSCs) [12] that give rise to the skeleton, are derived from perivascular cells [13].…”