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Association of exposure to diabetes in utero with adiposity and fat distribution in a multiethnic population of youth: the Exploring Perinatal Outcomes among Children (EPOCH) Study.

ABSTRACT: To evaluate whether exposure to maternal gestational diabetes (GDM) is associated with adiposity and fat distribution in a multiethnic population of children.Retrospective cohort study of 82 children exposed to maternal GDM and 379 unexposed youths 6-13 years of age with measured BMI, waist circumference, skinfold thickness, and visceral and subcutaneous abdominal fat.Exposure to maternal GDM was associated with higher BMI (p?=?0.02), larger waist circumference (p?=?0.004), more subcutaneous abdominal fat (p?=?0.01) and increased subscapular to triceps skinfold thickness ratio (p?=?0.01) in models adjusted for age, sex, race/ethnicity and Tanner stage. Adjustment for socioeconomic factors, birthweight and gestational age, maternal smoking during pregnancy and current diet and physical activity did not influence associations; however, adjustment for maternal pre-pregnancy BMI attenuated all associations.Exposure to maternal GDM is associated with increased overall and abdominal adiposity, and a more central fat distribution pattern in 6- to 13-year-old youths from a multi-ethnic population, providing further support for the fetal overnutrition hypothesis.

SUBMITTER: Crume TL

PROVIDER: S-EPMC3027214 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Association of exposure to diabetes in utero with adiposity and fat distribution in a multiethnic population of youth: the Exploring Perinatal Outcomes among Children (EPOCH) Study.

Crume T L TL Ogden L L West N A NA Vehik K S KS Scherzinger A A Daniels S S McDuffie R R Bischoff K K Hamman R F RF Norris J M JM Dabelea D D

Diabetologia 20101017 1

<h4>Aims/hypothesis</h4>To evaluate whether exposure to maternal gestational diabetes (GDM) is associated with adiposity and fat distribution in a multiethnic population of children.<h4>Methods</h4>Retrospective cohort study of 82 children exposed to maternal GDM and 379 unexposed youths 6-13 years of age with measured BMI, waist circumference, skinfold thickness, and visceral and subcutaneous abdominal fat.<h4>Results</h4>Exposure to maternal GDM was associated with higher BMI (p = 0.02), large ...[more]

PMID: 20953862

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Project description:The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population-specific genetic variants associated with liver fat. We conducted a genome-wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population-based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin-like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10-15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10-8) was also observed. Rs7724941 was associated with HOMA-IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high-density lipoprotein (beta = -0.046; P = 0.04), and sex hormone binding globulin (beta = -0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association.

Project description:This study had two main objectives: To examine the association between body fat distribution and non-alcoholic fatty liver disease (NAFLD) and liver fat content, and to determine whether the relationship between NAFLD and regional body fat distribution, with respect to liver fat content in youths with excess adiposity, is independent of cardiorespiratory fitness (CRF) and a healthy diet. Liver fat content (controlled attenuation parameter (CAP)), body fat distribution (body mass index (BMI) z-score, waist circumference, waist-to-height ratio, fat mass/height, body fat percentage, total fat mass, android-to-gynoid fat mass ratio, visceral adipose tissue (VAT), and lean mass index, determined by dual-energy X-ray absorptiometry (DXA)), CRF (20-m shuttle-run test), and healthy diet (adherence to the Mediterranean diet by KIDMED questionnaire) were measured in 126 adolescents (66% girls) aged between 11 and 17 years. Participants were assigned to two groups according to the presence or absence of hepatic steatosis (CAP values ?225 dB/m or <225 dB/m of liver fat, respectively). Considering the similar total fat values for the two groups (>30% by DXA), youths with NAFLD had higher fat distribution parameters than those without NAFLD, regardless of sex, age, puberty stage, lean mass index, CRF, and healthy diet (p < 0.01). In the non-NAFLD group, the association between hepatic fat and fat distribution parameters presented a similar pattern, although the association was statistically insignificant after adjusting for a potential confounding variable (ps > 0.05), except for the case of VAT. Body fat distribution parameters were higher in youths with NAFLD compared to those without NAFLD. Additionally, body fat distribution showed a significant association with liver fat content as assessed by CAP in youths with NAFLD independent of CRF and adherence to the Mediterranean diet, supporting the notion that upper body fat distribution might play a pivotal role in the development of NAFLD in adolescents. These results may have implications for the clinical management of youths with excess adiposity given the high prevalence of NAFLD in children and young adults.

Dataset Information

Association of exposure to diabetes in utero with adiposity and fat distribution in a multiethnic population of youth: the Exploring Perinatal Outcomes among Children (EPOCH) Study.

Publications

Association of exposure to diabetes in utero with adiposity and fat distribution in a multiethnic population of youth: the Exploring Perinatal Outcomes among Children (EPOCH) Study.

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