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1.
Diabetes ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414248

RESUMO

An adverse intrauterine environment is associated with the future risk of obesity and type 2 diabetes. Changes in placental function may underpin the intrauterine origins of adult disease, but longitudinal studies linking placental function with childhood outcomes are rare. Here, we determined the abundance and phosphorylation of protein intermediates involved in insulin signaling, inflammation, cortisol metabolism, protein glycosylation, and mitochondrial biogenesis in placental villus samples from healthy mothers from the Healthy Start cohort. Using MANOVA, we tested the association between placental proteins and offspring adiposity (percent fat mass) at birth (n=109) and infancy (4-6mo, n=104), and adiposity, skinfold thickness, triglycerides, and insulin in children (4-6y, n=66). Placental IGF-1 receptor protein was positively associated with serum triglycerides in children. GSK3ß phosphorylation at serine 9, a readout of insulin and growth factor signaling, and the ratio of phosphorylated to total JNK2 were both positively associated with midthigh skinfold thickness in children. Moreover, PGC-1α abundance was positively associated with insulin in children. In conclusion, placental insulin/IGF-1 signaling, PGC-1α, and inflammation pathways were positively associated with metabolic outcomes in 4-6-year-old children, identifying a novel link between placental function and long-term metabolic outcomes.

2.
Epigenomics ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33406918

RESUMO

Background: Gestational hyperglycemia is associated with adverse perinatal outcomes and long-term offspring metabolic programming, likely through dysregulation of DNA methylation (DNAm). Materials & methods: We tested associations between maternal HbA1c and cord blood DNAm among 412 mother-child pairs in the genetics of glucose regulation in gestation and growth (Gen3G) and implemented Mendelian randomization to infer causality. We sought replication in an independent sample from Healthy Start. Results: Higher second trimester HbA1c levels were associated with lower DNAm at cg21645848 (p = 3.9 × 10-11) near URGCP. Mendelian randomization and replication analyses showed same direction of effect between HbA1c and DNAm at cg21645848, but did not reach statistical significance. Conclusion: We found that higher maternal glycemia reflected by HbA1c is associated with cord blood DNAm at URGCP, a gene related with inflammatory pathways.

3.
PLoS One ; 16(1): e0245064, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33418560

RESUMO

Preterm birth occurs at excessively high and disparate rates in the United States. In 2016, the National Institutes of Health (NIH) launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate the influence of early life exposures on child health. Extant data from the ECHO cohorts provides the opportunity to examine racial and geographic variation in effects of individual- and neighborhood-level markers of socioeconomic status (SES) on gestational age at birth. The objective of this study was to examine the association between individual-level (maternal education) and neighborhood-level markers of SES and gestational age at birth, stratifying by maternal race/ethnicity, and whether any such associations are modified by US geographic region. Twenty-six ECHO cohorts representing 25,526 mother-infant pairs contributed to this disseminated meta-analysis that investigated the effect of maternal prenatal level of education (high school diploma, GED, or less; some college, associate's degree, vocational or technical training [reference category]; bachelor's degree, graduate school, or professional degree) and neighborhood-level markers of SES (census tract [CT] urbanicity, percentage of black population in CT, percentage of population below the federal poverty level in CT) on gestational age at birth (categorized as preterm, early term, full term [the reference category], late, and post term) according to maternal race/ethnicity and US region. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Cohort-specific results were meta-analyzed using a random effects model. For women overall, a bachelor's degree or above, compared with some college, was associated with a significantly decreased odds of preterm birth (aOR 0.72; 95% CI: 0.61-0.86), whereas a high school education or less was associated with an increased odds of early term birth (aOR 1.10, 95% CI: 1.00-1.21). When stratifying by maternal race/ethnicity, there were no significant associations between maternal education and gestational age at birth among women of racial/ethnic groups other than non-Hispanic white. Among non-Hispanic white women, a bachelor's degree or above was likewise associated with a significantly decreased odds of preterm birth (aOR 0.74 (95% CI: 0.58, 0.94) as well as a decreased odds of early term birth (aOR 0.84 (95% CI: 0.74, 0.95). The association between maternal education and gestational age at birth varied according to US region, with higher levels of maternal education associated with a significantly decreased odds of preterm birth in the Midwest and South but not in the Northeast and West. Non-Hispanic white women residing in rural compared to urban CTs had an increased odds of preterm birth; the ability to detect associations between neighborhood-level measures of SES and gestational age for other race/ethnic groups was limited due to small sample sizes within select strata. Interventions that promote higher educational attainment among women of reproductive age could contribute to a reduction in preterm birth, particularly in the US South and Midwest. Further individual-level analyses engaging a diverse set of cohorts are needed to disentangle the complex interrelationships among maternal education, neighborhood-level factors, exposures across the life course, and gestational age at birth outcomes by maternal race/ethnicity and US geography.

4.
Diabetes Obes Metab ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33394545

RESUMO

AIMS: Intensive lifestyle intervention (ILS) targeting health behaviors is efficacious for diabetes mellitus prevention, but there is heterogeneity in the effect of ILS. We tested whether diabetes genetic risk modifies the association of successful lifestyle changes with incident diabetes. MATERIALS AND METHODS: We studied 823 individuals randomized to the ILS arm of the Diabetes Prevention Program who were diabetes-free one year after enrollment. We tested additive and multiplicative interactions of a 67-variant diabetes genetic risk score (GRS) with achievement of three ILS goals at one year (≥7% weight loss, ≥150 minutes/week of moderate leisure-time physical activity, and/or a goal for self-reported total fat intake) on the primary outcome of incident diabetes over 3 years of follow-up. RESULTS: A lower GRS and achieving each or all three ILS goals were each associated with lower incidence of diabetes (all p < 0.05). Additive interactions were significant between the GRS and achievement of the weight loss goal (p < 0.001), physical activity goal (p = 0.02), and all three ILS goals (p < 0.001) for diabetes risk. Achievement of all three ILS goals was associated with 1.8 [0.3, 3.4], 3.1 [1.5, 4.7], and 3.9 [1.6, 6.2] fewer diabetes cases/100-person-years in the 1st, 2nd, and 3rd GRS tertiles (p < 0.001 for trend). Multiplicative interactions between the GRS and ILS goal achievement were significant for the diet goal (p < 0.001) but not for weight loss (p = 0.18) or physical activity (p = 0.62) goals. CONCLUSIONS: Genetic risk may identify high-risk subgroups for whom successful lifestyle modification is associated with greater absolute reduction in the risk of incident diabetes. This article is protected by copyright. All rights reserved.

5.
J Diabetes Complications ; 35(2): 107768, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33168393

RESUMO

AIMS: We sought to characterize the direction and associated factors of eGFR change following diagnosis of youth-onset type 1 and type 2 diabetes. METHODS: We assessed the direction of eGFR change at two visits (mean 6.6 years apart) in SEARCH, a longitudinal cohort study of youth-onset type 1 and type 2 diabetes. We used the CKiDCr-CysC equation to estimate GFR and categorized 'rising' and 'declining' eGFR as an annual change of ≥3 ml/min/1.73 m2 in either direction. Multivariable logistic regression evaluated factors associated with directional change in eGFR. RESULTS: Estimated GFR declined in 23.8% and rose in 2.8% of participants with type 1 diabetes (N = 1225; baseline age 11.4 years), and declined in 18.1% and rose in 15.6% of participants with type 2 diabetes (N = 160; baseline age 15.0 years). Factors associated with rising and declining eGFR (versus stable) in both type 1 and type 2 diabetes included sex, age at diagnosis, baseline eGFR and difference in fasting glucose between study visits. Additional factors in type 1 diabetes included time from baseline visit, HbA1c and body mass index. CONCLUSIONS: Over the first decade of diabetes, eGFR decline is more common in type 1 diabetes whereas eGFR rise is more common in type 2 diabetes.

6.
Diabetologia ; 64(1): 83-94, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33021691

RESUMO

AIMS/HYPOTHESIS: The aim of this work was to investigate the association of maternal HbA1c during mid-pregnancy with biomarkers of glucose-insulin homeostasis during early childhood (4-7 years of age) and to assess whether and how offspring adiposity at birth and at age 4-7 years mediates this relationship among 345 mother-child pairs in the Healthy Start Study. METHODS: The exposure was maternal HbA1c (mmol/mol) measured at 20-34 gestational weeks and categorised into tertiles. The outcomes were offspring fasting glucose, 1/insulin, HOMA2-IR, and HOMA2-B at age 4-7 years. The mediators were per cent fat mass (%FM) at birth, %FM at age 4-7 years, and the sum of the two as a metric of cumulative adiposity. Mediation analyses were conducted via a counterfactual-based approach. All models accounted for maternal race/ethnicity, offspring age and sex. RESULTS: There was a significant total effect of maternal HbA1c on offspring glucose and 1/insulin. Specifically, we observed a positive trend across tertiles of HbA1c and offspring glucose (p trend <0.001), and an inverse trend across tertiles of HbA1c and offspring 1/insulin (p trend = 0.04). For instance, compared with offspring of women in the lowest tertile of HbA1c, those whose mothers were in the second and third tertiles had 0.04 mmol/l (95% CI -0.05, 0.13) and 0.17 mmol/l (95% CI 0.08, 0.26) higher fasting glucose concentrations at age 4-7 years, respectively. Adjustment for pre-pregnancy BMI did not appreciably change the results. We found no evidence of mediation by offspring adiposity at any life stage. CONCLUSIONS/INTERPRETATION: Offspring of women with higher HbA1c during pregnancy had higher fasting glucose and lower insulin sensitivity by early childhood. These relationships were largely unaffected by the child's own adiposity. Graphical abstract.

7.
Environ Health Perspect ; 128(12): 127014, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33356526

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype. OBJECTIVES: We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators. METHODS: Among 583 mother-infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate (FDR)<0.05 and differentially methylated regions (DMRs) were identified using comb-p (Sidák-adjusted p<0.05). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin. RESULTS: Maternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correlations were observed between PFAS concentrations (ρ=0.28-0.76). Methylation at one DMP (cg18587484), annotated to the gene TJAP1, was associated with perfluorooctanoate (PFOA) at FDR< 0.05. Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth (RPTOR), lipid homeostasis (PON1, PON3, CIDEB, NR1H2), inflammation and immune activity (RASL11B, RNF39), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively (FDR< 0.1). DISCUSSION: DNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. https://doi.org/10.1289/EHP6888.

8.
Pediatr Obes ; : e12758, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296951

RESUMO

OBJECTIVES: To identify dietary patterns associated with hepatic fat fraction (HFF), a measure of liver fat content and risk factor for non-alcoholic fatty liver disease, in a prospective study of 397 multi-ethnic youth. METHODS: We obtained information on habitual dietary intake via the Block Kids Food Frequency Questionnaire at age 6 to 15 years ('T1') and 12 to 19 years ('T2'), and measured HFF using magnetic resonance imaging at T2. We derived dietary patterns via principal components analysis and examined associations with ln-transformed HFF using linear regression models that accounted for maternal education, gestational diabetes exposure and smoking habits; and child pubertal status, BMI and physical activity. RESULTS: At T1, none of the dietary patterns identified were associated with HFF measured at T2. At T2, a Prudent dietary pattern characterized by high fruit and vegetable intake was inversely associated with HFF (-0.08 [95% CI: -0.16, -0.00]). Similarly, increased adherence to the Prudent pattern across T1 and T2 corresponded with lower ln-HFF (-0.11 [-0.18, -0.04] units). On the other hand, adherence to a Western pattern comprising fried foods and refined carbohydrates at T2 correlated with higher HFF among non-Hispanic White participants (0.16 [0.06, 0.26]). These findings persisted after accounting for child BMI. CONCLUSIONS: Even in healthy youth, a diet high in fruits and vegetables is associated with lower HFF, whereas a diet high in fried foods and refined carbohydrates is related to higher HFF. Dietary changes may serve as an early preventive measure to mitigate liver fat accrual.

9.
Am J Health Promot ; : 890117120968654, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118362

RESUMO

PURPOSE: To assess adherence to the 2015-2020 Dietary Guidelines for Americans and 2018 Physical Activity Guidelines, and identify sociodemographic predictors of adherence among children. DESIGN: Cross sectional. SETTING: Colorado, United States. PARTICIPANTS: Children aged 5 (n = 482). MEASURES: Sex, race/ethnicity, maternal education, maternal employment, maternal subjective social status and household income were assessed via questionnaires. Diet was assessed via 2 interviewer-administered 24-hour dietary recalls. Physical activity was objectively-measured with accelerometry for 7 days. Adherence was defined as a Healthy Eating Index-2015 score of ≥70 and/or ≥6 hours/day of light, moderate and vigorous activity. ANALYSIS: For each predictor, logistic regression was used to estimate odds ratios for adherence to the diet guidelines only, the activity guidelines only or both guidelines. RESULTS: In the full sample, 29% of children were non-adherent to both guidelines, 6% adhered to the dietary guidelines only, 50% adhered to the activity guidelines only and 14% adhered to both. Girls had a 41% lower odds of adhering to the physical activity guidelines than boys (p = 0.01), after adjustment for race/ethnicity, household income and maternal education level, perceived social status and employment status. CONCLUSION: Efforts to improve the health of young children should promote adherence to the Dietary Guidelines for Americans among all children. Targeted interventions that increase physical activity among girls may help to mitigate health disparities.

10.
Pediatr Diabetes ; 21(8): 1403-1411, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32981196

RESUMO

BACKGROUND: Although surveillance for diabetes in youth relies on provider-assigned diabetes type from medical records, its accuracy compared to an etiologic definition is unknown. METHODS: Using the SEARCH for Diabetes in Youth Registry, we evaluated the validity and accuracy of provider-assigned diabetes type abstracted from medical records against etiologic criteria that included the presence of diabetes autoantibodies (DAA) and insulin sensitivity. Youth who were incident for diabetes in 2002-2006, 2008, or 2012 and had complete data on key analysis variables were included (n = 4001, 85% provider diagnosed type 1). The etiologic definition for type 1 diabetes was ≥1 positive DAA titer(s) or negative DAA titers in the presence of insulin sensitivity and for type 2 diabetes was negative DAA titers in the presence of insulin resistance. RESULTS: Provider diagnosed diabetes type correctly agreed with the etiologic definition of type for 89.9% of cases. Provider diagnosed type 1 diabetes was 96.9% sensitive, 82.8% specific, had a positive predictive value (PPV) of 97.0% and a negative predictive value (NPV) of 82.7%. Provider diagnosed type 2 diabetes was 82.8% sensitive, 96.9% specific, had a PPV and NPV of 82.7% and 97.0%, respectively. CONCLUSION: Provider diagnosis of diabetes type agreed with etiologic criteria for 90% of the cases. While the sensitivity and PPV were high for youth with type 1 diabetes, the lower sensitivity and PPV for type 2 diabetes highlights the value of DAA testing and assessment of insulin sensitivity status to ensure estimates are not biased by misclassification.

11.
Diabetologia ; 63(10): 2040-2048, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32894314

RESUMO

Advances in molecular methods and the ability to share large population-based datasets are uncovering heterogeneity within diabetes types, and some commonalities between types. Within type 1 diabetes, endotypes have been discovered based on demographic (e.g. age at diagnosis, race/ethnicity), genetic, immunological, histopathological, metabolic and/or clinical course characteristics, with implications for disease prediction, prevention, diagnosis and treatment. In type 2 diabetes, the relative contributions of insulin resistance and beta cell dysfunction are heterogeneous and relate to demographics, genetics and clinical characteristics, with substantial interaction from environmental exposures. Investigators have proposed approaches that vary from simple to complex in combining these data to identify type 2 diabetes clusters relevant to prognosis and treatment. Advances in pharmacogenetics and pharmacodynamics are also improving treatment. Monogenic diabetes is a prime example of how understanding heterogeneity within diabetes types can lead to precision medicine, since phenotype and treatment are affected by which gene is mutated. Heterogeneity also blurs the classic distinctions between diabetes types, and has led to the definition of additional categories, such as latent autoimmune diabetes in adults, type 1.5 diabetes and ketosis-prone diabetes. Furthermore, monogenic diabetes shares many features with type 1 and type 2 diabetes, which make diagnosis difficult. These challenges to the current classification framework in adult and paediatric diabetes require new approaches. The 'palette model' and the 'threshold hypothesis' can be combined to help explain the heterogeneity within and between diabetes types. Leveraging such approaches for therapeutic benefit will be an important next step for precision medicine in diabetes. Graphical abstract.

12.
Diabetes Care ; 43(10): 2418-2425, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32737140

RESUMO

OBJECTIVE: Diabetes surveillance often requires manual medical chart reviews to confirm status and type. This project aimed to create an electronic health record (EHR)-based procedure for improving surveillance efficiency through automation of case identification. RESEARCH DESIGN AND METHODS: Youth (<20 years old) with potential evidence of diabetes (N = 8,682) were identified from EHRs at three children's hospitals participating in the SEARCH for Diabetes in Youth Study. True diabetes status/type was determined by manual chart reviews. Multinomial regression was compared with an ICD-10 rule-based algorithm in the ability to correctly identify diabetes status and type. Subsequently, the investigators evaluated a scenario of combining the rule-based algorithm with targeted chart reviews where the algorithm performed poorly. RESULTS: The sample included 5,308 true cases (89.2% type 1 diabetes). The rule-based algorithm outperformed regression for overall accuracy (0.955 vs. 0.936). Type 1 diabetes was classified well by both methods: sensitivity (Se) (>0.95), specificity (Sp) (>0.96), and positive predictive value (PPV) (>0.97). In contrast, the PPVs for type 2 diabetes were 0.642 and 0.778 for the rule-based algorithm and the multinomial regression, respectively. Combination of the rule-based method with chart reviews (n = 695, 7.9%) of persons predicted to have non-type 1 diabetes resulted in perfect PPV for the cases reviewed while increasing overall accuracy (0.983). The Se, Sp, and PPV for type 2 diabetes using the combined method were ≥0.91. CONCLUSIONS: An ICD-10 algorithm combined with targeted chart reviews accurately identified diabetes status/type and could be an attractive option for diabetes surveillance in youth.

13.
Pediatr Diabetes ; 21(7): 1277-1284, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32738012

RESUMO

BACKGROUND: Youth with type 1 diabetes (T1D) are encouraged to participate in physical activity (PA). Studies have identified fear of hypoglycemia (FOH) as a barrier to participating in PA. OBJECTIVES: To examine (a) PA patterns in youth with T1D by age group and (b) the relationship between both parental and youth FOH and youth PA. METHODS: A cross-sectional analysis from the SEARCH cohort study visit of youth ages 10 to 17 years with T1D (n = 1129) was conducted. Linear regression models estimated the association between self-reported number of days of vigorous PA (VPA) and moderate PA (MPA) and both youth- and parent-reported FOH. Multivariable models were adjusted for age, sex, race, duration of T1D, HbA1c, use of continuous glucose monitoring (CGM), recent severe hypoglycemia, primary insulin regimen, and BMI. RESULTS: Participants were 52% female, had mean (sd) age 14.4 (4.2) years, diabetes duration 7.5 years (1.8), HbA1c 9.2% (1.7). Older youth were less likely to engage in VPA (P < .01), or sports teams (P < .01), but more likely to engage in MPA (P < .01). Higher youth FOH (behavior subscale) was associated with increased levels of VPA (ß (se) 0.30 (0.11), P = .01) but not significantly associated with MPA (P = .06). There was no statistically significant association between parental FOH and youth PA. CONCLUSIONS: In SEARCH participants with T1D, VPA, and team sports participation declined with age, while MPA increased. We observed that higher scores on the youth FOH behavioral subscale were associated with increased VPA levels, suggesting that FOH may be less of a barrier to PA than previously thought.

14.
Pediatr Diabetes ; 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737919

RESUMO

AIMS: Examine associations of dietary strategies used to manage diabetes over time with hemoglobin A1c in youth-onset type 1 or type 2 diabetes. METHODS: The SEARCH for Diabetes in Youth observational study assessed dietary strategies used by 1814 participants with diabetes (n = 1558 type 1, n = 256 type 2) at two to three research visits over 5.5 years (range 1.7-12.2). Participants reported often, sometimes, or never using 10 different dietary strategies, and use over time was categorized into five mutually exclusive groups: often using across visits; started using at later visits; sometimes using across visits; stopped using at later visits; or never using across visits. General multivariable linear models evaluated most recent A1c by use category for each strategy. RESULTS: In type 1 diabetes, A1c was lower among those who starting tracking calories (-0.4%, Tukey P < .05), often counted carbs (-0.8%, Tukey P < .001), or sometimes chose low glycemic index foods (-0.5%, Tukey P = .02) vs those with less use, while participants who never drank more milk had the lowest A1c (-0.5%, Tukey P = .04). In type 2 diabetes, A1c was lower among those who often limited high fat foods (-2.0%, Tukey P = .02) or started counting carbohydrates (-1.7%, Tukey P = .07) than those who did so less. CONCLUSIONS: For several dietary strategies, more frequent use over time was related to lower A1c in youth-onset type 1 and type 2 diabetes, suggesting these strategies can likely support diabetes management for this population. Investigation into factors predicting receipt of advice for specific strategies and corresponding impact on intake might be considered.

15.
Obesity (Silver Spring) ; 28(9): 1718-1725, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32772475

RESUMO

OBJECTIVE: The impact of in utero exposure to maternal overweight and obesity on offspring metabolic health is well documented. Neurodevelopmental outcomes among these children are, however, less well studied. To address this gap, the current study investigated brain function among 4- to 6-year-old children exposed to maternal overweight or obesity during gestation compared with that of children born to mothers with healthy BMI in pregnancy. METHODS: Resting-state functional magnetic resonance imaging was used to study neuronal activity and connectivity during a passive viewing task (movie) among 101 typically developing children enrolled in the Healthy Start study, a longitudinal prebirth cohort in Colorado. RESULTS: Forty-nine children (48%) were exposed to maternal overweight or obesity in utero (mean age = 5 years, SD = 0.9). Children born to mothers with overweight or obesity demonstrated hyperactivity in the left posterior cingulate cortex and hypoactivity in the dorsal anterior cingulate and the supplementary motor area (P < 0.05 for all). Children born to mothers with overweight or obesity also showed ubiquitously weaker brain connectivity (P < 0.05 for all). CONCLUSIONS: These novel results suggest altered brain function among children exposed to maternal overweight and obesity in utero.

16.
Pediatrics ; 146(3)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32796097

RESUMO

OBJECTIVES: To explore the longitudinal association of neonatal adiposity (fat mass percentage) with BMI trajectories and childhood overweight and obesity from ages 2 to 6 years. METHODS: We studied 979 children from the Healthy Start cohort. Air displacement plethysmography was used to estimate fat mass percentage. Child weight and recumbent length or standing height were abstracted from medical records. Overweight and obesity were defined as BMI levels ≥85th percentile for age and sex. Mixed-effects models were used to examine the association between neonatal fat mass percentage and BMI trajectories from age 2 to 6 years. We tested for effect modification by sex, race and/or ethnicity, and breastfeeding duration. We estimated the proportion of children classified as overweight or obese at specific levels of neonatal fat mass percentage (mean ± SD). RESULTS: The mean neonatal adiposity level was 9.1% ± 4.0%. Child BMI levels differed by neonatal adiposity. Each SD increase in neonatal adiposity resulted in a 0.12 higher overall BMI level between ages 2 to 6 years (95% confidence interval: 0.03 to 0.20; P < .01), and this association was not modified by offspring sex, race and/or ethnicity, or breastfeeding duration. Increasing neonatal adiposity was associated with an increasing proportion of childhood overweight and obesity by age 5 years (P = .02). CONCLUSIONS: We provide novel evidence that higher neonatal adiposity is significantly associated with higher overall BMI levels and an increased likelihood of overweight or obesity from ages 2 to 6 years. Because various prenatal exposures may specifically influence offspring fat accretion, neonatal adiposity may be a useful surrogate end point for prenatal interventions aimed at reducing future childhood overweight and obesity.


Assuntos
Adiposidade , Índice de Massa Corporal , Obesidade Pediátrica/etiologia , Adulto , Fatores Etários , Composição Corporal , Tamanho Corporal , Aleitamento Materno , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Sobrepeso/diagnóstico , Sobrepeso/etiologia , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/etnologia , Pletismografia/métodos , Gravidez , Prevalência , Fatores Sexuais
17.
J Diabetes Complications ; 34(10): 107676, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32713707

RESUMO

AIMS: To evaluate cardiovascular risk factors and heart rate variability (HRV) in young adults with type 2 diabetes and arterial stiffness and to explore the relationship between HRV and arterial stiffness. METHODS: We studied 185 young adults with youth-onset T2D enrolled in the SEARCH for Diabetes in Youth Study. Cardiovascular risk factors and HRV were compared between individuals with and without type 2 diabetes and arterial stiffness (defined as a pulse wave velocity greater than the 90th percentile of healthy controls, >6.767 m/s). Semiparametric regression evaluated the independent relationship between HRV and PWV. RESULTS: Participants with T2D and arterial stiffness were more likely to be older, non-Hispanic Black, have higher systolic and diastolic blood pressure, greater adiposity and obesity-related dyslipidemia (higher triglycerides and lower HDLC). Participants with T2D and arterial stiffness also had lower overall HRV (lower SDNN) with parasympathetic loss (lower RMSSD and PNN50), p < 0.05. Lower HRV tended to be but was not significantly associated with arterial stiffness after adjustment for age, race/ethnicity, sex and cardiovascular risk factors (beta coefficient = -1.11, p = 0.08). CONCLUSIONS: Youth with T2D and arterial stiffness have a worse cardiovascular risk profile, specifically risk factors related to the metabolic syndrome and lower HRV.

18.
J Clin Endocrinol Metab ; 105(9)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32687159

RESUMO

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed nations. There are currently no accurate biomarkers of NAFLD risk in youth. OBJECTIVE: Identify sex-specific metabolomics biomarkers of NAFLD in a healthy cohort of youth. DESIGN/SETTING: This prospective study included 395 participants of the EPOCH cohort in Colorado, who were recruited 2006-2009 ("T1 visit") and followed for 5 years ("T2 visit"). We entered 767 metabolites measured at T1 into a reduced rank regression model to identify the strongest determinants of hepatic fat fraction (HFF) at T2, separately for boys and girls. We compared the capacity of metabolites versus conventional risk factors (overweight/obesity, insulin, alanine transaminase, aspartate transaminase) to predict NAFLD (HFF ≥5%) and high HFF (fourth vs first quartile) using area under the receiver operating characteristic curve (AUC). RESULTS: Prevalence of NAFLD was 7.9% (8.5% of boys, 7.1% of girls). Mean ± SD HFF was 2.5 ± 3.1%. We identified 13 metabolites in girls and 10 metabolites in boys. Metabolites were in lipid, amino acid, and carbohydrate metabolism pathways. At T1, the metabolites outperformed conventional risk factors in prediction of high HFF but not NAFLD. At T2, the metabolites were superior to conventional risk factors as predictors of high HFF (AUC for metabolites vs conventional risk factors for boys: 0.9565 vs 0.8851, P = 0.02; for girls: 0.9450 vs 0.8469, P = 0.02) with similar trends for NAFLD, although the differences were not significant. CONCLUSIONS: The metabolite profiles identified herein are superior predictors of high HFF when assessed 5 years prior and concurrently in a general-risk setting.

19.
Pediatr Diabetes ; 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32562358

RESUMO

The incidence of diabetes, both type 1 and type 2, is increasing. Health outcomes in pediatric diabetes are currently poor, with trends indicating that they are worsening. Minority racial/ethnic groups are disproportionately affected by suboptimal glucose control and have a higher risk of acute and chronic complications of diabetes. Correct clinical management starts with timely and accurate classification of diabetes, but in children this is becoming increasingly challenging due to high prevalence of obesity and shifting demographic composition. The growing obesity epidemic complicates classification by obesity's effects on diabetes. Since the prevalence and clinical characteristics of diabetes vary among racial/ethnic groups, migration between countries leads to changes in the distribution of diabetes types in a certain geographical area, challenging the clinician's ability to classify diabetes. These challenges must be addressed to correctly classify diabetes and establish an appropriate treatment strategy early in the course of disease for all. This may be the first step in improving diabetes outcomes across racial/ethnic groups. This review will discuss the pitfalls in the current diabetes classification scheme that is leading to increasing overlap between diabetes types and heterogeneity within each type. It will also present proposed alternative classification schemes and approaches to understanding diabetes type that may improve the timely and accurate classification of pediatric diabetes type.

20.
Diabetologia ; 63(8): 1530-1541, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32382815

RESUMO

AIMS/HYPOTHESIS: The aim of this work was to evaluate geographical variability and trends in the prevalence of diabetic ketoacidosis (DKA), between 2006 and 2016, at the diagnosis of childhood-onset type 1 diabetes in 13 countries over three continents. METHODS: An international retrospective study on DKA at diagnosis of diabetes was conducted. Data on age, sex, date of diabetes diagnosis, ethnic minority status and presence of DKA at diabetes onset were obtained from Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA and the UK (Wales). Mean prevalence was estimated for the entire period, both overall and by country, adjusted for sex and age group. Temporal trends in annual prevalence of DKA were estimated using logistic regression analysis for each country, before and after adjustment for sex, age group and ethnic minority status. RESULTS: During the study period, new-onset type 1 diabetes was diagnosed in 59,000 children (median age [interquartile range], 9.0 years [5.5-11.7]; male sex, 52.9%). The overall adjusted DKA prevalence was 29.9%, with the lowest prevalence in Sweden and Denmark and the highest in Luxembourg and Italy. The adjusted DKA prevalence significantly increased over time in Australia, Germany and the USA while it decreased in Italy. Preschool children, adolescents and children from ethnic minority groups were at highest risk of DKA at diabetes diagnosis in most countries. A significantly higher risk was also found for females in Denmark, Germany and Slovenia. CONCLUSIONS/INTERPRETATION: DKA prevalence at type 1 diabetes diagnosis varied considerably across countries, albeit it was generally high and showed a slight increase between 2006 and 2016. Increased awareness of symptoms to prevent delay in diagnosis is warranted, especially in preschool children, adolescents and children from ethnic minority groups.

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