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1.
Diabetes Care ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601636

RESUMO

OBJECTIVE: Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS: Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, using DNA methylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations between GDM and DNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS: Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05. CONCLUSIONS: Maternal GDM was associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31483758

RESUMO

Background Sex differences in body composition are appreciated throughout the lifespan with probable contributions from sex steroids: testosterone and estrogen. The purpose of this longitudinal observational study was to determine if sex differences in body composition emerge during the first months of life in healthy infants, corresponding to the age at which male infants produce endogenous testosterone. Methods Linear growth and body composition parameters using air displacement plethysmography were obtained from 602 healthy infants after birth and again at 5 months of age. Rate of change in body composition parameters were compared between sexes. Results Sex differences in length, total mass, fat free mass (FFM), and percent fat mass (%FM) were present both at birth and at 5 months (p < 0.001 for all), with males having greater total mass and FFM but lower %FM. Gain in %FM over the first 5 months was significantly lower in males (p = 0.0004). This difference was secondary to a gain of 17 g/week more in FFM in males compared to females. Conclusions Sex differences in body composition emerge in the first months of life, with lower adiposity accumulation in males. Endogenous testosterone production in males ~1-4 months of age may account for findings and may have lifelong implications for sex differences in body composition.

5.
Diabetologia ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444527

RESUMO

AIMS/HYPOTHESIS: We previously showed that intrauterine exposure to gestational diabetes mellitus (GDM) increases selected markers of adiposity in pre-pubertal adolescents. In the present study, we examined these associations in adolescence, and explored whether they are strengthened as the participants transition through puberty. METHODS: Data from 597 individuals (505 unexposed, 92 exposed) participating in the longitudinal Exploring Perinatal Outcomes among Children (EPOCH) study in Colorado were collected at two research visits when the participants were, on average, 10.4 and 16.7 years old. Adiposity measures included BMI, waist/height ratio, and visceral and subcutaneous adipose tissue (as determined by MRI). Separate general linear mixed models were used to assess the longitudinal relationships between exposure to maternal GDM and each adiposity outcome. We tested whether the effect changed over time by including an interaction term between exposure and age in our models, and whether the associations were explained by postnatal behaviours. RESULTS: Compared with unexposed participants, those exposed to maternal GDM had higher BMI (ß = 1.28; 95% CI 0.35, 2.21; p < 0.007), waist/height ratio (ß = 0.03; 95% CI 0.01, 0.04; p = 0.0004), visceral adipose tissue (ß = 4.81; 95% CI 1.08, 8.54; p = 0.01) and subcutaneous adipose tissue (ß = 35.15; 95% CI 12.43, 57.87; p < 0.003). The magnitude of these differences did not change over time and the associations did not appear to be explained by postnatal behaviours. CONCLUSIONS/INTERPRETATION: Our data provide further evidence that intrauterine exposure to maternal GDM is associated with increased offspring adiposity, an effect that appears early in life and tracks throughout adolescence. Efforts to prevent childhood obesity following intrauterine exposure to maternal GDM should target the prenatal or early life periods.

6.
Nutrients ; 11(8)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366063

RESUMO

The relationship between added sugar and arterial stiffness in youth with type 1 diabetes (T1D) has not been well-described. We used data from the SEARCH for Diabetes in Youth Study (SEARCH), an ongoing observational cohort study, to determine the association between added sugar and arterial stiffness in individuals diagnosed with T1D <20 years of age (n = 1539; mean diabetes duration of 7.9 ± 1.9 years). Added sugar intake was assessed by a food frequency questionnaire, and arterial stiffness measures included pulse wave velocity (PWV) and augmentation index. Separate multivariate linear regression models were used to evaluate the association between added sugar and arterial stiffness. Separate interaction terms were included to test for effect modification by body mass index (BMI) z-score and physical activity (PA). Overall, there was no association between added sugar and arterial stiffness (P > 0.05); however, the association between added sugar and arterial stiffness differed by BMI z-score (P for interaction = 0.003). For participants with lower BMI z-scores, added sugar intake was positively associated with PWV trunk measurements, whereas there was no association for those who had a higher BMI z-score. PA did not significantly modify the association between added sugar and arterial stiffness. Further research is needed to determine the longitudinal relationship and to confirm that obesity differentially affects this association.

7.
Diabetologia ; 62(10): 1779-1788, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31451868

RESUMO

Childhood obesity has reached pandemic proportions, and youth-onset type 2 diabetes is following suit. This review summarises the literature on the influence of developmental overnutrition, resulting from maternal diabetes, obesity, maternal dietary intake during pregnancy, excess gestational weight gain, and infant feeding practices, on the aetiology of obesity and type 2 diabetes risk during childhood and adolescence. Key goals of this review are: (1) to summarise evidence to date on consequences of developmental overnutrition; (2) describe shared and distinct biological pathways that may link developmental overnutrition to childhood obesity and youth-onset type 2 diabetes; and (3) to translate current knowledge into clinical and public health strategies that not only target primary prevention in youth, but also encourage primordial prevention during the perinatal period, with the aim of breaking the intergenerational cycle of obesity and diabetes.

8.
Ann Epidemiol ; 37: 37-42, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31383511

RESUMO

PURPOSE: Most surveillance efforts in childhood diabetes have focused on incidence, whereas prevalence is rarely reported. This study aimed to assess whether a mathematical illness-death model accurately estimated future prevalence from baseline prevalence and incidence rates in children. METHODS: SEARCH for Diabetes in Youth is an ongoing population-based surveillance study of prevalence and incidence of diabetes and its complications among youth in the United States. We used age-, sex-, and race/ethnicity-specific SEARCH estimates of the prevalence of type I and type II diabetes in 2001 and incidence from 2002 to 2008. These data were used in a partial differential equation to estimate prevalence in 2009 with 95% bootstrap confidence intervals. Model-based prevalence was compared with the observed prevalence in 2009. RESULTS: Most confidence intervals for the difference between estimated and observed prevalence included zero, indicating no evidence for a difference between the two methods. The width of confidence intervals indicated high precision for the estimated prevalence when considering all races/ethnicities. In strata with few cases, precision was reduced. CONCLUSIONS: Future prevalence of type I and type II diabetes in youth may be accurately estimated from baseline prevalence and incidence. Diabetes surveillance could benefit from potential cost savings of this method.

9.
Environ Int ; 132: 105064, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31419765

RESUMO

BACKGROUND: Evidence remains equivocal regarding the association of inflammation, a precursor to cardiovascular disease, and acute exposures to ambient air pollution from traffic-related particulate matter. Though youth with type 1 diabetes are at higher risk for cardiovascular disease, the relationship of inflammation and ambient air pollution exposures in this population has received little attention. OBJECTIVES: Using five geographically diverse US sites from the racially- and ethnically-diverse SEARCH for Diabetes in Youth Cohort, we examined the relationship of acute exposures to PM2.5 mass, Atmospheric Dispersion Modeling System (ADMS)-Roads traffic-related PM concentrations near roadways, and elemental carbon (EC) with biomarkers of inflammation including interleukin-6 (IL-6), c-reactive protein (hs-CRP) and fibrinogen. METHODS: Baseline questionnaires and blood were obtained at a study visit. Using a spatio-temporal modeling approach, pollutant exposures for 7 days prior to blood draw were assigned to residential addresses. Linear mixed models for each outcome and exposure were adjusted for demographic and lifestyle factors identified a priori. RESULTS: Among the 2566 participants with complete data, fully-adjusted models showed positive associations of EC average week exposures with IL-6 and hs-CRP, and PM2.5 mass exposures on lag day 3 with IL-6 levels. Comparing the 25th and 75th percentiles of average week EC exposures resulted in 8.3% higher IL-6 (95%CI: 2.7%,14.3%) and 9.8% higher hs-CRP (95%CI: 2.4%,17.7%). We observed some evidence of effect modification for the relationships of PM2.5 mass exposures with hs-CRP by gender and with IL-6 by race/ethnicity. CONCLUSIONS: Indicators of inflammation were associated with estimated traffic-related air pollutant exposures in this study population of youth with type 1 diabetes. Thus youth with type 1 diabetes may be at increased risk of air pollution-related inflammation. These findings and the racial/ethnic and gender differences observed deserve further exploration.

10.
Clin Endocrinol (Oxf) ; 91(4): 525-533, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31278867

RESUMO

OBJECTIVE: It is unclear how childhood adipose tissue deposition influences sex hormone profiles in later adolescence. DESIGN: Prospective cohort study. PARTICIPANTS: Children (n = 418) with a mean age of 10.5 (1.5) years at visit 1 and 16.7 (1.2) at visit 2 in the Exploring Perinatal Outcomes among Children (EPOCH) Study. MEASUREMENTS: We used reverse-scale Cox proportional hazard models to assess associations between pubertal dehydroepiandrosterone (DHEA), testosterone (T), and oestradiol (E2) and childhood-to-puberty rate of change in visceral (VAT) and subcutaneous adipose tissue (SAT). Models stratified by sex and adjusted for childhood adiposity, maternal factors, birthweight and pubertal onset, and then further adjusted for insulin, luteinizing hormone (LH), leptin and hepatic fat fraction. RESULTS: Among boys, more rapid accumulation of either VAT or SAT was associated with lower testosterone at visit 2 (HR 0.86, and .96, respectively, both P < .0001), independently of race/ethnicity, LH, leptin and hepatic fat fraction. Among boys, more childhood VAT was associated with lower testosterone in adolescence (HR 0.98, P = .003), but this association did not persist after adjustment for leptin or insulin. No associations were observed between either fat measure and oestradiol or DHEA in boys. In girls, no associations between childhood fat or fat accumulation and sex hormones were observed. CONCLUSIONS: More rapid accumulation of fat is associated with lower testosterone in boys. These associations suggest that fat growth influences androgen profiles in adolescent boys. Since fat accumulation is a modifiable risk factor, the study results provide a possible intervention target and time period for improving adult health.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31290977

RESUMO

CONTEXT: Subclinical and clinical complications emerge early in type 1 diabetes and may be associated with obesity and hyperglycemia. OBJECTIVE: Test how longitudinal 'weight-glycemia' phenotypes increase susceptibility to different patterns of early/subclinical complications among youth with type 1 diabetes. DESIGN: SEARCH for Diabetes in Youth observational study. SETTING: Population-based cohort. PARTICIPANTS: Youth with type 1 diabetes (n=570) diagnosed 2002-2006 or 2008. MAIN OUTCOME MEASURES: Participants were clustered based on longitudinal BMI z-score and hemoglobin A1c from a baseline visit and 5+ year follow-up visit (mean diabetes duration: 1.4±0.4 years and 8.2±1.9 years, respectively). Logistic regression modeling tested cluster associations with seven early/ subclinical diabetes complications at follow-up, adjusting for sex, race/ethnicity, age, and duration. RESULTS: Four longitudinal weight-glycemia clusters were identified: The Referent Cluster (n=195, 34.3%), the Hyperglycemia Only Cluster (n=53, 9.3%), the Elevated Weight Only Cluster (n=206, 36.1%), and the Elevated Weight with Increasing Hyperglycemia "EWH" Cluster (n=115, 20.2%). Compared to the Referent Cluster, the Hyperglycemia Only Cluster had elevated odds of dyslipidemia (adjusted odds ratio (aOR) 2.22, 95% CI 1.15-4.29), retinopathy (aOR 9.98, 95% CI 2.49-40.0) and diabetic kidney disease (DKD) (aOR 4.16, 95% CI 1.37-12.62). The EWH Cluster had elevated odds of hypertension (aOR 2.18, 95% CI 1.19-4.00), dyslipidemia (aOR 2.36, 95% CI 1.41-3.95), arterial stiffness (aOR 2.46, 95% CI 1.09-5.53), retinopathy (aOR 5.11, 95% CI 1.34-19.46), and DKD (aOR 3.43, 95% CI 1.29-9.11). CONCLUSIONS: Weight-glycemia phenotypes show different patterns of complications, particularly markers of subclinical macrovascular disease, even in the first decade of type 1 diabetes.

12.
BMC Pregnancy Childbirth ; 19(1): 267, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349808

RESUMO

BACKGROUND: Improved understanding of vegetable intake changes between pregnancy and postpartum may inform future intervention targets to establish healthy home food environments. Therefore, the goal of this study was to explore the changes in vegetable intake between pregnancy and the postnatal period and explore maternal and sociodemographic factors that are associated with these changes. METHODS: We examined sociodemographic, dietary, and health characteristics of healthy mothers 18-43y from the prospective Infant Feeding Practices II cohort (n = 847) (2005-2012). Mothers completed a modified version of the diet history questionnaire, a food-frequency measure, developed by the National Cancer Institute. We created four categories of mothers, those that were: meeting vegetable recommendations post- but not prenatally (n = 121; improved intake), not meeting vegetable recommendations during pregnancy and postnatally (n = 370; stable inadequate), meeting recommendations pre- but not postnatally (n = 123; reduced intake), and meeting recommendations at both time points (n = 233; stable adequate). To make our results more relevant to public health recommendations, we were interested in comparing the improved vegetable intake group vs. stable inadequate vegetable intake group, as well as those that reduced their vegetable intake compared to the stable adequate vegetable intake group. Separate multivariable-adjusted logistic regression were used to examine sociodemographic predictors of improved vs. stable inadequate and reduced vs. stable adequate vegetable intake. RESULTS: Women with improved vegetable intake vs. stable inadequate smoked fewer cigarettes while women with reduced vegetable intake vs. stable adequate were more likely to experience less pregnancy weight gain. In adjusted models, employed women had greater odds of reduced vegetable intake (OR = 1.64 95% CI 1.14-2.36). In exploratory analyses, employment was associated with greater odds of reduced vegetable intake among low-income (OR = 1.79; 95% CI 1.03-3.1), but not higher income women (OR = 1.31; 95% CI 0.94-1.84). After further adjustment for paid maternity leave, employment was no longer associated with vegetable intake among lower income women (OR: 1.53; 95% CI: 0.76-3.05). CONCLUSIONS: More women with reduced vs. stable adequate vegetable intake were lower income and worked full time. Improved access to paid maternity leave may help reduce disparities in vegetable quality between lower and higher income women.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31285833

RESUMO

Obesity is a disease with a complex etiology and variable prevalence across different populations. While several studies have reported gut microbiota composition differences associated with obesity in humans, there has been a lack of consistency in the nature of the reported changes; it has been difficult to determine whether methodological differences between studies, underlying differences in the populations studied, or other factors are responsible for this discordance. Here we use 16 S rRNA data from previously published studies to explore how the gut microbiota-obesity relationship varies across heterogeneous Western populations, focusing mainly on the relationship between (1) alpha diversity and (2) Prevotella relative abundance with BMI. We provide evidence that the relationship between lower alpha diversity and higher BMI may be most consistent in non-Hispanic white (NHW) populations and/or those with high socioeconomic status, while the relationship between higher Prevotella relative abundance and BMI may be stronger among black and Hispanic populations. We further examine how diet may impact these relationships. This work suggests that gut microbiota phenotypes of obesity may differ with race/ethnicity or its correlates, such as dietary components or socioeconomic status. However, microbiome cohorts are often too small to study complex interaction effects and non-white individuals are greatly underrepresented, creating substantial challenges to understanding population-level patterns in the microbiome-obesity relationship. Further study of how population heterogeneity influences the relationship between the gut microbiota and obesity is warranted.

14.
Environ Int ; 131: 104983, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31284113

RESUMO

BACKGROUND: Prenatal exposures to certain per- and polyfluoroalkyl substances (PFAS) have been linked to lower weight and adiposity at birth but greater weight and adiposity in childhood. We hypothesized that faster growth in early infancy may be associated with maternal PFAS concentrations. METHODS: Among 415 mother-infant pairs in a longitudinal cohort study, we estimated associations between maternal pregnancy serum concentrations of six PFAS and offspring weight and adiposity at ~5 months of age, and growth in early infancy. Linear and logistic regression models were adjusted for potential confounders including maternal pre-pregnancy body mass index. Effect modification by infant sex was evaluated. We evaluated potential confounding by correlated exposures via multipollutant linear regression and elastic net penalized regression. RESULTS: Associations between maternal PFAS concentrations and infant weight and adiposity differed by offspring sex. In male infants, maternal perfluorooctanoate and perfluorononanoate were positively associated with adiposity, with percent fat mass increases of 1.5-1.7% per ln-ng/mL increase in PFAS (median adiposity at ~5 months: 24.6%). Maternal perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with lower weight-for-age z-score among female infants only (-0.26 SD per ln-ng/mL PFOS, 95% CI -0.43, -0.10; -0.17 SD per ln-ng/mL PFHxS, 95% CI -0.33, -0.01). In analyses pooled by sex, 2-(N-methyl-perfluorooctane sulfonamido) acetate above vs. below the limit of detection was associated with greater odds of rapid growth in weight-for-age (odds ratio [OR] 2.2, 95% CI 1.1, 4.3) and weight-for-length (OR 3.3, 95% CI 1.8, 6.2). Multipollutant models generally confirmed the results and strengthened some associations. DISCUSSION: We observed sex- and chemical-specific associations between maternal serum PFAS concentrations and infant weight and adiposity. Multipollutant models suggested confounding by correlated PFAS with opposing effects. Although maternal PFAS concentrations are inversely associated with infant weight and adiposity at birth, rapid gain may occur in infancy, particularly in fat mass.

15.
Pediatr Diabetes ; 20(7): 815-820, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31260152

RESUMO

AIM: SEARCH has recently reported that both prevalence and incidence of youth onset type 2 diabetes (YT2D) increased among most US race/ethnic groups in the early 2000s. This study reports on the incidence (2002-2013) and prevalence (2001, 2009) of YT2D in the Navajo Nation among youth age < 20 years from 2001 to 2013. METHODS: SEARCH sought to identify prevalent YT2D cases in 2001 (N = 75) and 2009 (N = 70) and all incident YT2D cases in three periods: 2002 to 2005 (N = 53), 2006 to 2009 (N = 68), and 2010 2013 (N = 90) in Navajo Nation. Denominators were based on the active Indian Health Service user population for eligible health care facilities. Prevalence (per 100 000) and period-specific incidence rates (per 100 000 person-years) were computed for youth aged 10 to 19 years. Changes in prevalence were tested with a two-sided skew-corrected inverted score test, while changes in incidence were tested with Poisson regression. RESULTS: YT2D prevalence was high but stable in 2001 and 2009, overall [146.6 (116.8, 184.0) vs 141.5 (112.0, 178.8), P = .65) and in all subgroups. In contrast, incidence rates increased particularly between the second and third periods overall and in most subgroups by age and by sex. CONCLUSIONS: These data confirm the high burden of YT2D among Navajo youth and suggest an increasing risk in more recent years. However, recent improvements in obesity reduction in this population demonstrate optimism for potential reductions in YT2D in Navajo Nation.

16.
Diabetes Care ; 42(9): 1809-1815, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31320445

RESUMO

OBJECTIVE: Regression from prediabetes to normal glucose regulation (NGR) was associated with reduced incidence of diabetes by 56% over 10 years in participants in the Diabetes Prevention Program Outcomes Study (DPPOS). In an observational analysis, we examined whether regression to NGR also reduced risk for microvascular disease (MVD). RESEARCH DESIGN AND METHODS: Generalized estimating equations were used to examine the prevalence of aggregate MVD at DPPOS year 11 in people who regressed to NGR at least once (vs. never) during the Diabetes Prevention Program (DPP). Logistic regression assessed the relationship of NGR with retinopathy, nephropathy, and neuropathy, individually. Generalized additive models fit smoothing splines to describe the relationship between average A1C during follow-up and MVD (and its subtypes) at the end of follow-up. RESULTS: Regression to NGR was associated with lower prevalence of aggregate MVD in models adjusted for age, sex, race/ethnicity, baseline A1C, and treatment arm (odds ratio [OR] 0.78, 95% CI 0.65-0.78, P = 0.011). However, this association was lost in models that included average A1C during follow-up (OR 0.95, 95% CI 0.78-1.16, P = 0.63) or diabetes status at the end of follow-up (OR 0.92, 95% CI 0.75-1.12, P = 0.40). Similar results were observed in examination of the association between regression to NGR and prevalence of nephropathy and retinopathy, individually. Risk for aggregate MVD, nephropathy, and retinopathy increased across the A1C range. CONCLUSIONS: Regression to NGR is associated with a lower prevalence of aggregate MVD, nephropathy, and retinopathy, primarily due to lower glycemic exposure over time. Differential risk for the MVD subtypes begins in the prediabetes A1C range.

17.
Pediatr Obes ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31274243

RESUMO

BACKGROUND: Intrauterine exposure to gestational diabetes (GDM) is associated with increased adiposity; however, not all offspring exposed to GDM exhibit excess adiposity. OBJECTIVES: Examine whether optimal diet and activity behaviours in infancy, childhood, and adolescence modify the association between GDM exposure and adiposity. METHODS: In 564 offspring (84 exposed to GDM), we assessed breastfeeding (maternal recall), dietary intake (food frequency questionnaire), physical activity (3-day recall), and adiposity (BMI, waist-to-height ratio, visceral and subcutaneous adipose tissue, and subscapular-to-triceps skinfold ratio) at 10.4 (SD, 1.5) and 16.7 (SD, 1.2) years. Optimal behaviours were defined as >6 breastmilk months, Healthy Eating Index score >60, and daily vigorous activity >1 hour. Linear mixed models assessed the association between GDM exposure and adiposity among those with optimal versus suboptimal health behaviours, adjusting for sex, race/ethnicity, age, and pubertal status. RESULTS: GDM exposure was associated with increased skinfold ratio, visceral and subcutaneous adipose tissue among those with <6 breastmilk months (all Ps < .05), but only associated with increased skinfold ratio among those with >6 breastmilk months (P = .01). GDM exposure was associated with increases in all adiposity measures among those with Healthy Eating Index scores <60 (P < .01), but not those with scores >60 (P > .10). GDM exposure was associated with increased BMI and subcutaneous adipose tissue among those with >1 hour of vigorous activity (P < .05) but not among those with <1 hour of vigorous activity (P > .30). CONCLUSIONS: The association of GDM exposure with excess adiposity is attenuated in offspring with more optimal diet and activity behaviours in infancy, childhood, and adolescence.

18.
J Am Heart Assoc ; 8(13): e010150, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31213111

RESUMO

Background The incidence of type 1 diabetes mellitus (T1DM) in children is increasing, resulting in higher burden of cardiovascular diseases due to diabetes mellitus-related vascular dysfunction. Methods and Results We examined cardiovascular risk factors ( CVRF s) and arterial parameters in 1809 youth with T1DM. Demographics, anthropometrics, blood pressure, and laboratory data were collected at T1DM onset and 5 years later. Pulse wave velocity and augmentation index were collected with tonometry. ANOVA or chi-square tests were used to test for differences in measures of arterial parameters by CVRF . Area under the curve of CVRF s was entered in general linear models to explore determinants of accelerate vascular aging. Participants at the time of arterial measurement were 17.6±4.5 years old, 50% female, 76% non-Hispanic white, and duration of T1DM was 7.8±1.9 years. Glycemic control was poor (glycated hemoglobin, 9.1±1.8%). All arterial parameters were higher in participants with glycated hemoglobin ≥9% and pulse wave velocity was higher with lower insulin sensitivity or longer duration of diabetes mellitus. Differences in arterial parameters were found by sex, age, and presence of obesity, hypertension, or dyslipidemia. In multivariable models, higher glycated hemoglobin, lower insulin sensitivity, body mass index, blood pressure, and lipid areas under the curve were associated with accelerated vascular aging. Conclusions In young people with T1DM, persistent poor glycemic control and higher levels of traditional CVRF s are independently associated with arterial aging. Improving glycemic control and interventions to lower CVRF s may prevent future cardiovascular events in young individuals with T1DM.

19.
Hypertension ; 74(2): 375-383, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31230546

RESUMO

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.

20.
J Pediatr ; 211: 92-97, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31060808

RESUMO

OBJECTIVE: To evaluate the hypothesis that metabolic measures (fasting glucose, insulin, and Homeostatic Model of Assessment for Insulin Resistance [HOMA-IR] levels) are inversely associated with performance on cognitive tasks using data from young (4- to 6-year-old), typically developing, healthy children. STUDY DESIGN: Data were obtained from children participating in the Healthy Start study, a pre-birth cohort in Colorado. HOMA-IR, glucose, and insulin values were centered and scaled using the study sample means and SD. Thus, they are reported in number of SD units from the mean. Fully corrected T scores for inhibitory control (Flanker task), cognitive flexibility (Dimensional Change Card Sort test), and receptive language (Picture Vocabulary test) were obtained via the National Institutes of Health Toolbox cognition battery. RESULTS: Children included in this analysis (n = 137) were 4.6 years old, on average. Per 1-SD unit, fasting glucose (B = -2.0, 95% CI -3.5, -0.5), insulin (B = -1.7, 95% CI -3.0, -0.4), and HOMA-IR values (B = -1.8, 95% CI -3.1, -0.5) were each significantly and inversely associated with inhibitory control (P < .05 for all, respectively). Fasting glucose levels were also inversely associated with cognitive flexibility (B = -2.0, 95% CI -3.7, -0.2, P = .03). CONCLUSIONS: Our data suggest that metabolic health may impact fluid cognitive function in healthy, young children.

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