OBJECTIVEThe goals of this study were to examine the influence of maternal type 1 diabetes during pregnancy on offspring adiposity and glucose tolerance at age 7 years and to assess whether metabolic factors at birth (neonatal leptin and insulin) predict adverse outcomes.RESEARCH DESIGN AND METHODSWe examined 100 offspring of mothers with type 1 diabetes (OT1DM) and 45 offspring of control mothers. Mothers had previously been recruited during pregnancy, and, where possible, birth weight, umbilical cord insulin, and leptin were measured. Children were classed as overweight and obese using age-specific reference ranges.RESULTSOT1DM had similar height (control, 1.25 ± 0. 06 m; OT1DM, 1.24 ± 0.06 m; P = 0.81) but were heavier (control, 25.5 ± 3.8 kg; OT1DM, 27.1 ± 5.7 kg; P = 0.048) and had an increased BMI (control, 16.4 kg/m2; OT1DM, 17.4 ± 2.6 kg/m2, P = 0.005). Waist circumference (control, 56.0 ± 3.7 cm; OT1DM, 58 ± 6.8 cm; P = 0.02) and sum of skinfolds were increased (control, 37.5 ± 17.0 mm [n = 42]; OT1DM, 46.1 ± 24.2 mm [n = 91]; P = 0.02), and there was a marked increase in the prevalence of overweight and obese children (OT1DM, 22% overweight and 12% obese; control, 0% overweight and 7% obese; χ2 P = 0.001). Glucose tolerance was not different compared with that in control subjects. BMI at age 7 years correlated with cord leptin (OT1DM, r = 0.25; n = 61, P = 0.047), weakly with adjusted birth weight (r = 0.19; P = 0.06) and hematocrit (r = 0.25; n = 50, P = 0.07), but not cord insulin (OT1DM, r = −0.08; P = 0.54).CONCLUSIONSOT1DM are at increased risk of overweight and obesity in childhood. This risk appears to relate, in part, to fetal leptin and hematocrit but not insulin.

Patients with end‐stage renal disease (ESRD) have elevated circulating calcium (Ca) and phosphate (Pi), and exhibit accelerated progression of calcific aortic valve disease (CAVD). We hypothesized that matrix vesicles (MVs) initiate the calcification process in CAVD. Ca induced rat valve interstitial cells (VICs) calcification at 4.5 mM (16.4‐fold; p < 0.05) whereas Pi treatment alone had no effect. Ca (2.7 mM) and Pi (2.5 mM) synergistically induced calcium deposition (10.8‐fold; p < 0.001) in VICs. Ca treatment increased the mRNA of the osteogenic markers Msx2, Runx2, and Alpl (p < 0.01). MVs were harvested by ultracentrifugation from VICs cultured with control or calcification media (containing 2.7 mM Ca and 2.5 mM Pi) for 16 hr. Proteomics analysis revealed the marked enrichment of exosomal proteins, including CD9, CD63, LAMP‐1, and LAMP‐2 and a concomitant up‐regulation of the Annexin family of calcium‐binding proteins. Of particular note Annexin VI was shown to be enriched in calcifying VIC‐derived MVs (51.9‐fold; p < 0.05). Through bioinformatic analysis using Ingenuity Pathway Analysis (IPA), the up‐regulation of canonical signaling pathways relevant to cardiovascular function were identified in calcifying VIC‐derived MVs, including aldosterone, Rho kinase, and metal binding. Further studies using human calcified valve tissue revealed the co‐localization of Annexin VI with areas of MVs in the extracellular matrix by transmission electron microscopy (TEM). Together these findings highlight a critical role for VIC‐derived MVs in CAVD. Furthermore, we identify calcium as a key driver of aortic valve calcification, which may directly underpin the increased susceptibility of ESRD patients to accelerated development of CAVD.

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SUMMARY Using an enzyme-bridge immunoperoxidase method, pregnancy specific fl,-glycoprotein (PS/G) has been demonstrated in the cytoplasm of the trophoblast in several formalin-fixed tissues, namely, implantation sites of ovum, normal placentae, hydatidiform moles, invasive moles, and choriocarcinomata of uterus and testis. It is suggested that this technique may prove helpful in the detection of choriocarcinomatous elements in malignant tumours.We have recently shown , by a variety of techniques that the trophoblast produces pregnancy specific fl-glycoprotein (PS,BG), first described by Bohn (1972) and referred to by him as SP,. Electron microscopic studies of fixed first trimester placentae clearly demonstrated that, at least in vivo, the syncytiotrophoblast and not the cytotrophoblast is the source of this protein . Subsequent to these observations we found that it was possible to demonstrate the presence of PS,BG in formalin-fixed paraffinembedded normal placentae using an established enzyme-bridge immunoperoxidase technique (Mason et al., 1969;Streefkerk, 1972).In this paper we present evidence for the distribution of PS/3G in normal placentae, implantation sites of ovum, hydatidiform moles, invasive moles, and choriocarcinomata, including cases of choriocarcinoma arising in malignant teratoma of testis. Material and methodsParaffin-embedded blocks of placental tissue and trophoblastic tumours which had been stored for up to eight years were obtained from our own departmental files. Unstained sections of trophoblastic tumours (10 cases) were also kindly provided by