Role of Adiponectin in Matching of Fetal and Placental Weight in Mothers With Type 1 Diabetes

Nelson, Scott M.; Freeman, Dilys J.; Sattar, Naveed; Lindsay, Robert

doi:10.2337/dc07-2195

Cited by 14 publications

(16 citation statements)

References 11 publications

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“…The role of IGF-II is less clear in human studies and is likely modified by circulating IGF-II receptor (12). Adiponectin, although not directly associated with birth weight, does correlate with placental weight and contributes to the matching of fetal and placental growth in control subjects and OT1DM (11,14). Finally, leptin also correlates with placental weight in control subjects and OT1DM and has recently been proposed as an in utero signal of nutrient availability (11,15).…”

mentioning

confidence: 84%

“…Certainly, fetal hyperinsulinemia has an independent positive association with birth weight and placental weight in offspring of mothers with type 1 diabetes (OT1DM) (11). IGF-I and IGF-II also influence feto-placental growth.…”

mentioning

confidence: 99%

“…IGF-I and IGF-II also influence feto-placental growth. IGF-I has strong correlations to both birth weight and placental weight in control subjects and OT1DM (11–13). The role of IGF-II is less clear in human studies and is likely modified by circulating IGF-II receptor (12).…”

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confidence: 99%

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Placental Structure in Type 1 Diabetes

et al. 2009

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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.

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Placental Structure in Type 1 Diabetes

et al. 2009

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“…3, A-E). In humans, fetal-placental index (FPI) (birth weight divided by placental weight) can be used to indicate appropriate fetal growth in pregnancies involving multiple fetuses [24], but no difference was found in mean FPI between laboring WT and CCR2-deficient mice (Fig. 3E).…”

Section: Ccr2 In Labormentioning

confidence: 97%

The Chemokine Receptor CCR2 Is Not Required for Successful Initiation of Labor in Mice1

Menzies

Khan

Nelson

et al. 2012

Biology of Reproduction

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Chemokine-driven neutrophil and monocyte recruitment into the uterus and cervix has been proposed to initiate labor. Chemokines that bind CXCR2 direct neutrophil migration and are induced during labor in humans. The chemokine CCL2, induced in the uterus by endocrine and mechanical signals, has been proposed to drive CCR2-dependent monocyte homing to the uterus to contribute to the initiation of labor. However, no direct evidence indicates that chemokines or their receptors play indispensable roles in labor-associated inflammation, and the impact of leukocyte infiltration on labor is unclear. Here, we have quantified expression of the principal monocyte- and neutrophil-attracting chemokines in the uteri of term pregnant (Day 18) and laboring wild-type mice. None of the neutrophil attractants we assayed were up-regulated with labor. Strikingly, however, Ccl2 was markedly increased, and this was concomitant with increased expression of Ccr2, the myeloid marker Itgam (also known as Cd11b), the monocyte/macrophage marker Emr1 (also known as F4/80). Moreover, in CCR2-deficient mice, this labor-associated increase in Itgam and Emr1 was not seen, consistent with the monocyte-trafficking defects that exist in these animals. Nonetheless, laboring CCR2-deficient and wild-type uteri showed similarly enhanced expression of the myometrial activation markers Gja1 and Oxtr (commonly known as connexin 43 and oxytocin receptor, respectively), and CCR2-deficient mice had gestation lengths, litter sizes, and fetal and placental weights no different from those of their wild-type counterparts. Thus, whereas labor is associated with an inflammatory response in gestational tissues, CCR2-dependent leukocyte recruitment into the mouse uterus is dispensable for the initiation of successful labor.

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“…Measurements of plasma glucose, insulin, HbA 1c and lipid concentrations were performed in the routine clinical laboratory using an automated analyser (Abbott Diagnostics, Maidenhead, UK). Total adiponectin was determined by ELISA (R&D Systems, Abingdon, UK) as described previously by Nelson et al [29].…”

Section: Methodsmentioning

confidence: 99%

AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin: a randomised glycaemia-controlled crossover study

et al. 2011

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Aims/hypothesis The hypoglycaemic actions of metformin have been proposed to be mediated by hepatic AMP-activated protein kinase (AMPK). As the effects of metformin and the role of AMPK in adipose tissue remain poorly characterised, we examined the effect of metformin on AMPK activity in adipose tissue of individuals with type 2 diabetes in a randomised glycaemia-controlled crossover study. Methods Twenty men with type 2 diabetes (aged 50-70 years) treated with diet, metformin or sulfonylurea alone were recruited from North Glasgow University National Health Service Trusts' diabetes clinics and randomised to either metformin or gliclazide for 10 weeks. Randomisation codes, generated by computer, were put into sealed envelopes and stored by the hospital pharmacist. Medication bottles were numbered, and allocation was done in sequence. The participants and investigators were blinded to group assignment. At the end of each phase of therapy adipose biopsy, AMPK activity (primary endpoint) and levels of lipid metabolism and signalling proteins were assessed. In parallel, the effect of metformin on AMPK and insulinsignalling pathways was investigated in 3T3-L1 adipocytes. Results Ten participants were initially randomised to metformin and subsequently crossed over to gliclazide, while ten participants were initially randomised to gliclazide and subsequently crossed over to metformin. No participants discontinued the intervention and the adipose tissue AMPK activity was analysed in all 20 participants. There were no adverse events or side effects in the study group. Adipose AMPK activity was increased following metformin compared with gliclazide therapy (0. ; p< 0.005), independent of AMPK level, glycaemia or plasma adiponectin concentrations. The increase was associated with reduced levels of acetyl-CoA carboxylase (ACC) protein and increased ACC Ser80 phosphorylation. In 3T3-L1 adipocytes, metformin reduced levels of ACC protein and stimulated phosphorylation of AMPK Thr172 and hormone-sensitive lipase Ser565. Conclusions These results provide the first evidence that metformin activates AMPK and reduces ACC protein levels in human adipose tissue in vivo. Future studies are required to assess the role of adipose AMPK activation in the pharmacological effects of metformin.Trial registration ISRCTN51336867

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Role of Adiponectin in Matching of Fetal and Placental Weight in Mothers With Type 1 Diabetes

Cited by 14 publications

References 11 publications

Placental Structure in Type 1 Diabetes

Placental Structure in Type 1 Diabetes

The Chemokine Receptor CCR2 Is Not Required for Successful Initiation of Labor in Mice1

AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin: a randomised glycaemia-controlled crossover study

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