Insulin Sensitivity in Children Born Small for Gestational Age (SGA)

Geremia, Caterina; Cianfarani, Stefano

doi:10.1900/rds.2004.1.58

Cited by 26 publications

(20 citation statements)

References 58 publications

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“…Subjects born with IUGR have been reported to have an increased incidence of developing cardiovascular disease, hypertension and type 2 diabetes mellitus in adulthood compared with the general population (1). These features are shared with obese subjects, and derive primarily from increased insulin resistance (2), which is related by association with high serum concentrations of pro-inflammatory cytokines and low adiponectin concentrations (3,4).…”

Section: Introductionmentioning

confidence: 99%

Impairment of insulin receptor signal transduction in placentas of intra-uterine growth-restricted newborns and its relationship with fetal growth

Street

Viani²,

Ziveri³

et al. 2011

European Journal of Endocrinology

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Objective: Intra-uterine growth restriction (IUGR) is related to a higher incidence of type 2 diabetes mellitus. We previously reported reduced adiponectin and increased interleukin 6 (IL6) concentrations in IUGR placentas, which are features of insulin resistance. We aimed to investigate placental insulin receptor (IR) function and activation in human placenta and subsequently the relationships of insulin signalling peptides with placental protein content in IL6, insulin, resistin and adiponectin, and with parameters of fetal growth. Design and methods: Whole villous tissue was collected from 18 IUGR and 24 appropriate for gestational age (AGA) placentas of comparable gestational age. Insulin signalling peptides, suppressors of cytokine signalling-2 (SOCS2), insulin, adiponectin, resistin, and IL6 concentrations were determined by using western immunoblotting or specific research kits. Results: The amount of total IR was similar in both groups but activated IR significantly higher in IUGR. Total IR substrate-1 (IRS1) was increased in IUGR, whereas total IRS2 and activated IRS1 were similar. AKT content was reduced and activated AKT was undetectable in IUGR placentas. c-Jun N-terminal kinase content was reduced in IUGR. Total and activated ERK1/2 was similar in IUGR and AGA groups, and total SOCS2 was increased in IUGR. IL6 lysate concentrations correlated with AKT content and activated IR. Correlations were found also with adiponectin and resistin. SOCS2 correlated negatively with all growth parameters at birth. Conclusions: IR was more activated in placentas of IUGR compared with AGA; however, signal transduction downstream of the receptor was impaired. The increase in activated IR could be in favour of a compensatory mechanism to increase insulin sensitivity. Close relationships of insulin action in placenta with fetal growth were shown.

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Section: Introductionmentioning

confidence: 99%

Impairment of insulin receptor signal transduction in placentas of intra-uterine growth-restricted newborns and its relationship with fetal growth

Street

Viani²,

Ziveri³

et al. 2011

European Journal of Endocrinology

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“…Although this association is clearly established in adults (5), results in children are still conflicting (6). Some authors have suggested that IR, as a consequence of intrauterine growth retardation would be detectable as early as birth (7,8).…”

Section: Introductionmentioning

confidence: 99%

Retinol-binding protein 4 in neonates born small for gestational age

Giacomozzi

Ghirri

Lapolla

et al. 2010

J Endocrinol Invest

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ABSTRACT. Background: Retinol-binding protein 4 (RBP4) is an adipocyte-derived 'signal' that may contribute to the pathogenesis of insulin resistance and Type 2 diabetes. The relationship of RBP4 with insulin resistance and metabolic risk in human beings has been the subject of several studies. Subjects born small for gestational age (SGA) are at risk of insulin resistance and Type 2 diabetes. Though RBP4 could represent an early marker of insulin resistance, to date, none have determined RBP4 in SGA children. Aim: Our aim was to measure RBP4 concentrations in cord blood of SGA newborns compared with those in children born with a birth weight appropriate for gestational age (AGA) and to determine whether serum RBP4 levels at birth correlate with insulin sensitivity markers. Subjects and methods: Sixty-four newborns, 17 born SGA (mean gestational age: 36.4±2.1 weeks), and 47 born AGA (mean gestational age: 37.0±3.6 weeks) were studied. The main outcome measures included anthropometry, lipid profile, insulin, homeostasis model assessment, quantitative insulin-sensitivity check index, adiponectin, and RBP4. Results: RBP4 concentrations were significantly reduced in SGA newborns (p<0.002). No relationship was found between RBP4 and insulin sensitivity parameters. Stepwise regression analysis revealed that birth weight was the major predictor of RBP4 serum concentrations (p<0.001). Conclusion: RBP4 is reduced in SGA newborns, birth weight representing the major determinant of RBP4 concentrations, and is not related to insulin sensitivity. No significant difference in adiponectin levels and insulin sensitivity markers was found between SGA and AGA neonates. INTRODUCTIONRetinol-binding protein 4 (RBP4) is an adipocyte-derived 'signal' that may contribute to the pathogenesis of insulin resistance (IR) and Type 2 diabetes. RBP4 could play a role in obesity-induced IR, since chronic elevation of RBP4 in mice increases hepatic glucose production, down-regulates insulin signaling in muscle, and causes systemic IR (1). Furthermore, lowering elevated serum RBP4 levels in obese mice with a synthetic retinoid improves insulin sensitivity and normalizes glucose tolerance (1). In humans, the link between RBP4 and IR is less clear. In adulthood, serum RBP4 levels have been shown to correlate with the magnitude of IR in subjects with obesity, impaired glucose tolerance, and Type 2 diabetes (2). Moreover, elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body mass index, waist-tohip ratio, serum triglyceride levels, and systolic blood pressure and decreased HDL cholesterol levels (2). In childhood, a relationship between serum RBP4 and obesity and components of the metabolic syndrome has been described in pre-pubertal and early pubertal children (3).Increased risk of developing IR and Type 2 diabetes in adulthood is associated with low birth weight (4). Although this association is clearly established in adults (5), results in children are still conflicting (6). Some authors have sugg...

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“…pidemiologic studies in man have shown that impaired intrauterine growth is associated with an increased incidence of insulin resistance, type 2 diabetes, and cardiovascular disease in the adult (1)(2)(3)(4)(5). These observations have led to the hypothesis that adult disease arises in utero, in part, as a result of changes in the development of key endocrine and metabolic pathways during suboptimal intrauterine conditions associated with impaired fetal growth.…”

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confidence: 99%

Changes in the Expression of Hypothalamic Lipid Sensing Genes in Rat Model of Intrauterine Growth Retardation (IUGR)

et al. 2007

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Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in later life. The mechanisms underlying this phenomenon are unknown. Recent data suggest that some of the molecular defects underlying type 2 diabetes reside in the CNS. The enzyme carnitine palmitoyltransferase-1 (CPT1) regulates long-chain fatty acid (LCFA) entry into mitochondria, where LCFA undergo ␤-oxidation. Hypothalamic inhibition of CPT1 decreases food intake and suppresses endogenous glucose production. Our aim was to investigate the effects of uterine artery ligation, a procedure that mimics uteroplacental insufficiency, on the CNS expression of CPT1 and other key enzymes of LCFA metabolism. Bilateral uterine artery ligation was performed on d 19 of gestation in the pregnant rat; sham-operated pregnant rats served as controls. Hypothalamus, cerebellum, hippocampus, and cortex were dissected and analyzed at birth by real-time PCR. Nonesterified fatty acid (NEFA) serum levels were significantly higher in IUGR pups (p Ͻ 0.0001). In IUGR rats, the hypothalamic expression of CPT1 isoform C (p ϭ 0.005) and acetyl-CoA carboxylase (ACC) isoforms alpha (p Ͻ 0.05) and beta (p ϭ 0.005) were significantly decreased. The data presented here support the hypothesis that an abnormal intrauterine milieu can induce changes in hypothalamic lipid sensing. E pidemiologic studies in man have shown that impaired intrauterine growth is associated with an increased incidence of insulin resistance, type 2 diabetes, and cardiovascular disease in the adult (1-5). These observations have led to the hypothesis that adult disease arises in utero, in part, as a result of changes in the development of key endocrine and metabolic pathways during suboptimal intrauterine conditions associated with impaired fetal growth. This hypothesis has been tested experimentally in a number of species, using a range of techniques to impair fetal growth. Inducing IUGR by placental insufficiency or by undernutrition, stress, or hormone treatment of the mother leads to endocrine and metabolic alterations in the adult offspring in several species (6). These findings have led to the "fetal origins" hypothesis, which suggests that an adverse intrauterine environment would program or imprint the development of fetal tissues, permanently determining responses producing later dysfunction and disease (7).The hypothalamus is emerging as a critical site for the integration of nutritional, endocrine, and neural cues signaling the body's metabolic and nutritional status. Neurons in the hypothalamus (particularly in the arcuate nucleus) are primary targets of a number of key hormones and metabolic signals. Hypothalamic neurons, in turn, target several downstream sites to influence the coordinated autonomic, behavioral, and endocrine responses. These signals should normally activate a negative feedback loop between the availability of nutrients and their intake and metabolism (8 -10). A major breakthrough in the understanding of mechanisms leading to type 2 diabe...

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Insulin Sensitivity in Children Born Small for Gestational Age (SGA)

Cited by 26 publications

References 58 publications

Impairment of insulin receptor signal transduction in placentas of intra-uterine growth-restricted newborns and its relationship with fetal growth

Impairment of insulin receptor signal transduction in placentas of intra-uterine growth-restricted newborns and its relationship with fetal growth

Retinol-binding protein 4 in neonates born small for gestational age

Changes in the Expression of Hypothalamic Lipid Sensing Genes in Rat Model of Intrauterine Growth Retardation (IUGR)

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