Metabolic Syndrome in Childhood: Association With Birth Weight, Maternal Obesity, and Gestational Diabetes Mellitus
ABSTRACT Childhood obesity has contributed to an increased incidence of type 2 diabetes mellitus and metabolic syndrome (MS) among children. Intrauterine exposure to diabetes and size at birth are risk factors for type 2 diabetes mellitus, but their association with MS in childhood has not been demonstrated. We examined the development of MS among large-for-gestational-age (LGA) and appropriate-for-gestational age (AGA) children.
The major components of MS (obesity, hypertension, dyslipidemia, and glucose intolerance) were evaluated in a longitudinal cohort study of children at age 6, 7, 9, and 11 years who were LGA (n = 84) or AGA (n = 95) offspring of mothers with or without gestational diabetes mellitus (GDM). The cohort consisted of 4 groups, ie, LGA offspring of control mothers, LGA offspring of mothers with GDM, AGA offspring of control mothers, and AGA offspring of mothers with GDM. Biometric and anthropometric measurements were obtained at 6, 7, 9, and 11 years. Biochemical testing included measurements of postprandial glucose and insulin levels and high-density lipoprotein (HDL) cholesterol levels at 6 and 7 years and of fasting glucose, insulin, triglyceride, and HDL cholesterol levels at 9 and 11 years. We defined the components of MS as (1) obesity (BMI >85th percentile for age), (2) diastolic or systolic blood pressure >95th percentile for age, (3) postprandial glucose level >140 mg/dL or fasting glucose level >110 mg/dL, (4) triglyceride level >95th percentile for age, and (5) HDL level <5th percentile for age.
There were no differences in baseline characteristics (gender, race, socioeconomic status, and maternal weight gain during pregnancy) for the 4 groups except for birth weight, but there was a trend toward a higher prevalence of maternal obesity before pregnancy in the LGA/GDM group. Obesity (BMI >85th percentile) at 11 years was present in 25% to 35% of the children, but rates were not different between LGA and AGA offspring. There was a trend toward a higher incidence of insulin resistance, defined as a fasting glucose/insulin ratio of <7, in the LGA/GDM group at 11 years. Analysis of insulin resistance at 11 years in a multivariate logistic regression revealed that childhood obesity and the combination of LGA status and maternal GDM were associated with insulin resistance, with odds ratios of 4.3 (95% confidence interval [CI]: 1.5-11.9) and 10.4 (95% CI: 1.5-74.4), respectively. The prevalence at any time of > or =2 components of MS was 50% for the LGA/GDM group, which was significantly higher than values for the LGA/control group (29%), AGA/GDM group (21%), and AGA/control group (18%). The prevalence of > or =3 components of MS at age 11 was 15% for the LGA/GDM group, compared with 3.0% to 5.3% for the other groups. Cox regression analysis was performed to determine the independent hazard (risk) of developing MS attributable to birth weight, gender, maternal prepregnancy obesity, and GDM. For Cox analyses, we defined MS as > or =2 of the following 4 components: obesity, hypertension (systolic or diastolic), glucose intolerance, and dyslipidemia (elevated triglyceride levels or low HDL levels). LGA status and maternal obesity increased the risk of MS approximately twofold, with hazard ratios of 2.19 (95% CI: 1.25-3.82) and 1.81 (95% CI: 1.03-3.19), respectively. GDM and gender were not independently significant. To determine the cumulative hazard of developing MS with time, we plotted the risk according to LGA or AGA category for the control and GDM groups from 6 years to 11 years, with Cox regression analyses. The risk of developing MS with time was not significantly different between LGA and AGA offspring in the control group but was significantly different between LGA and AGA offspring in the GDM group, with a 3.6-fold greater risk among LGA children by 11 years.
We showed that LGA offspring of diabetic mothers were at significant risk of developing MS in childhood. The prevalence of MS in the other groups was similar to the prevalence (4.8%) among white adolescents in the 1988-1994 National Health and Nutrition Examination Survey. This effect of LGA with maternal GDM on childhood MS was previously demonstrated for Pima Indian children but not the general population. We also found that children exposed to maternal obesity were at increased risk of developing MS, which suggests that obese mothers who do not fulfill the clinical criteria for GDM may still have metabolic factors that affect fetal growth and postnatal outcomes. Children who are LGA at birth and exposed to an intrauterine environment of either diabetes or maternal obesity are at increased risk of developing MS. Given the increased obesity prevalence, these findings have implications for perpetuating the cycle of obesity, insulin resistance, and their consequences in subsequent generations.
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- "Subsequent studies of maternal under-nutrition and, more recently, maternal over-nutrition have demonstrated that the maternal nutritional environment and foetal and neonatal growth, collectively known as the first 1000 days of life, are key determinants of health in the next generation (de Rooij et al., 2006; Lumey and Stein, 1997; Ravelli et al., 1976, 1999). In humans, maternal obesity is associated with low and high birth weight (Cedergren, 2004; Gaudet et al., 2014) and increased risk of obesity and metabolic dysfunction in the offspring both in childhood (Boney et al., 2005; Whitaker, 2004) as well as in adulthood (Brisbois et al., 2012; Cooper et al., 2010). Maternal obesity is also associated with increased risk of offspring cardiovascular disease (Drake and Reynolds, 2010), type 2 diabetes (Berends and Ozanne, 2012), and neurodevelopmental and psychiatric disorders, including ADHD, autism, schizophrenia, and mood disorders (Mehta et al., 2014; Rodriguez, 2010). "
ABSTRACT: Obesity in women of child-bearing age is a growing problem in developed and developing countries. Evidence from human studies indicates that maternal BMI correlates with offspring adiposity from an early age and predisposes to metabolic disease in later life. Thus the early life environment is an attractive target for intervention to improve public health. Animal models have been used to investigate the specific physiological outcomes and mechanisms of developmental programming that result from exposure to maternal obesity in utero. From this research, targeted intervention strategies can be designed. In this review we summarise recent progress in this field, with a focus on cardiometabolic disease and central control of appetite and behaviour. We highlight key factors that may mediate programming by maternal obesity, including leptin, insulin and ghrelin. Finally, we explore potential lifestyle and pharmacological interventions in humans and the current state of evidence from animal models. Copyright © 2015. Published by Elsevier Inc.Hormones and Behavior 07/2015; DOI:10.1016/j.yhbeh.2015.06.015 · 4.51 Impact Factor
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- "Concentration-response curves to the NOS-dependent agent CGRP in chorionic arteries from control (A), IUGR (B) and LOOM (C) placentae, in basal (circle) conditions and in the presence of the glutathione peroxidase inhibitor mercaptosuccinic acid (MS, square) and the Cu/Zn-SOD inhibitor diethyldithiocarbamate (DDC, triangle). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 versus basal, ANOVA. of fetal macrosomia and/or large for gestational age (LGA) fetuses, all of which present higher cardiometabolic risk during lifecourse   . Several studies show that placentae from obese women present increased markers of oxidative stress  , however there is no evidence whether placental vascular function is impaired in this condition. "
ABSTRACT: Fetal macrosomia and intrauterine growth restriction (IUGR) associate with increased morbidity in the neonate. Placental vascular relaxation is impaired in fetal macrosomia, as well as in IUGR, and this could result from increased oxidative stress present in both conditions. We determined the role of pro- and anti-oxidants on NOS dependent relaxation in placental chorionic arteries from pregnancies with LGA babies from overweight and/or obese mothers (LOOM) and IUGR fetuses from normal BMI women. Chorionic arteries were mounted in a wire-myograph, where responses to the NOS-dependent agent CGRP in presence or absence of the antioxidant N-acetyl cysteine (NAC), the pro-oxidant SIN-1, the SOD inhibitor DDC, and the GPx inhibitor MS were determined. Additionally the presence of pro- and antioxidant enzymes (NOX-4, SOD-1, SOD-2 and GPx-1) and eNOS in chorionic and umbilical vessels were addressed by immunohistochemistry. Maximal CGRP-induced relaxation was comparable to controls but presented a reduced potency in chorionic arteries from LOOM placentae, whilst in IUGR vessels both maximal response and potency were reduced. NAC increased maximal relaxation in controls, IUGR and LOOM arteries, whilst SIN-1 completely abolished the CGRP-induced relaxation only in IUGR and LOOM samples, the later effect was paralleled by SOD or GPx inhibition. These responses associated with the presence of NOX-4, SOD-1 and GPx-1 in the endothelium and vascular wall of chorionic and umbilical arteries in the different groups studied. These data suggest that NOS dependent relaxation in placental vessels from IUGR and LOOM pregnancies present a higher sensitivity to oxidative stress. Copyright © 2015 Elsevier Ltd. All rights reserved.Placenta 02/2015; 36(5). DOI:10.1016/j.placenta.2015.02.003 · 3.29 Impact Factor
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- "Pathways leading to LGA may include lack of access to nutritious food or opportunities for exercise in disadvantaged neighborhoods (Diez Roux and Mair, 2010; Schempf et al., 2009; Daniel et al., 2008; Culhane and Elo, 2005), creating environments that promote obesity and diabetes (Vinikoor-Imler et al., 2011; Elo et al., 2009; Metcalfe et al., 2011), which in turn contribute to accelerated fetal growth (Yessoufou and Moutairou, 2011; Boney et al., 2005; Janghorbani et al., 2006; Clausen et al., 2006; Baptiste- Roberts et al., 2012; Lu et al., 2001). "
ABSTRACT: Neighborhood deprivation is consistently associated with greater risk of low birthweight. However, large birth size is increasingly relevant but overlooked in neighborhood health research, and proximity within which neighborhood deprivation may affect birth outcomes is unknown. We estimated race/ethnic-specific effects of neighborhood deprivation index (NDI) within 1, 3, 5, and 8km buffers around Oregon Pregnancy Risk Assessment Monitoring System (n=3716; 2004-2007) respondents׳ homes on small and large for gestational age (SGA, LGA). NDI was positively associated with LGA and SGA in most race/ethnic groups. The results varied little across the four buffer sizes.Health & Place 09/2014; 30C:98-106. DOI:10.1016/j.healthplace.2014.08.010 · 2.44 Impact Factor