Association between birth weight and visceral fat in adults

Background: Several studies reported inverse associations between birth weight and central adiposity in adults. However, few studies investigated the contributions of different abdominal fat compartments. Objective: We examined associations between birth weight and adult visceral and subcutaneous abdominal fat in the population-based Fenland study. Design: A total of 1092 adults (437 men and 655 women) aged 3055 y had available data on reported birth weight, standard anthropometric measures, and visceral and subcutaneous abdominal fat estimated by ultrasound. In a subgroup (n = 766), dual-energy X-ray absorptiometry assessment of total abdominal fat was performed. Linear regression models were used to analyze relations between birth weight and the various fat variables adjusted for sex, age, education, smoking, and body mass index (BMI). Results: After adjustment for adult BMI, there was an inverse association between birth weight and total abdominal fat [B (partial regression coefficient expressed as SD/1-kg change in birth weight) = -0.09, P = 0.002] and visceral fat (B = -0.07, P = 0.01) but not between birth weight and subcutaneous abdominal fat (B = -0.01, P = 0.3). Tests for interaction showed that adult BMI modified the association between birth weight and visceral fat (P for interaction = 0.01). In stratified analysis, the association between birth weight and visceral fat was apparent only in individuals with the highest BMI tertile (B = -0.08, P = 0.04). Conclusions: The inverse association between birth weight and adult abdominal fat appeared to be specific to visceral fat. However, associations with birth weight were apparent only after adjustment for adult BMI. Therefore, we suggest that rapid postnatal weight gain, rather than birth weight alone, leads to increased visceral fat. Am J Clin Nutr 2010; 92: 347-52

Associations of stunting in early childhood with cardiometabolic risk factors in adulthood

Abstract Early life stunting may have long-term effects on body composition, resulting in obesity-related comorbidities. We tested the hypothesis that individuals stunted in early childhood may be at higher cardiometabolic risk later in adulthood. 1753 men and 1781 women participating in the 1982 Pelotas (Brazil) birth cohort study had measurements of anthropometry, body composition, lipids, glucose, blood pressure, and other cardiometabolic traits at age 30 years. Early stunting was defined as height-for-age Z-score at age 2 years below -2 against the World Health Organization growth standards. Linear regression models were performed controlling for sex, maternal race/ethnicity, family income at birth, and birthweight. Analyses were stratified by sex when p-interaction<0.05. Stunted individuals were shorter (β=-0.71 s.d.; 95% CI: -0.78 to -0.64), had lower BMI (β=-0.14 s.d.; 95%CI: -0.25 to -0.03), fat mass (β=-0.28 s.d.; 95%CI: -0.38 to -0.17), SAFT (β=-0.16 s.d.; 95%CI: -0.26 to -0.06), systolic (β=-0.12 s.d.; 95%CI: -0.21 to -0.02) and diastolic blood pressure (β=-0.11 s.d.; 95%CI: -0.22 to -0.01), and higher VFT/SAFT ratio (β=0.15 s.d.; 95%CI: 0.06 to 0.24), in comparison with non-stunted individuals. In addition, early stunting was associated with lower fat free mass in both men (β=-0.39 s.d.; 95%CI: -0.47 to -0.31) and women (β=-0.37 s.d.; 95%CI: -0.46 to -0.29) after adjustment for potential confounders. Our results suggest that early stunting has implications on attained height, body composition and blood pressure. The apparent tendency of stunted individuals to accumulate less fat-free mass and subcutaneous fat might predispose them towards increased metabolic risks in later life.The last phase of the 1982 Pelotas (Brazil) birth cohort study was supported by the Wellcome Trust and the Fundação de Aparo à Pesquisa do Estado do Rio Grande do Sul; Brazil (Edital 04/2012 – PQG; Processo 12/2185-9). Earlier phases were funded by the International Development Research Centre (Canada), the WHO (Department of Child and Adolescent Health and Development and Human Reproduction Programme) to BLH, the Overseas Development Administration (currently the Department for International Development, United Kingdom), the European Union, the United Nations Development Fund for Women, the National Program for Centres of Excellence, the Pastorate of the Child (Brazil), the National Council for Scientific and Technological Development (CNPq; Brazil), and the Ministry of Health (Brazil). GVAF was supported by the Brazilian Coordination of Improvement of Higher Education Personnel (scholarship process BEX 5077/13-3). EDLR and KKO are supported by the Medical Research Council [Unit Programme number MC_UU_12015/2]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Validity of visceral adiposity estimates from DXA against MRI in Kuwaiti men and women

Objectives - The prevalence of obesity and diabetes in the Middle East is amongst the highest in the world. Valid measures of abdominal adiposity are essential to understanding the metabolic consequences of obesity. Dual-energy X-ray absorptiometry (DXA) is increasingly being utilised to assess body composition in population studies, and has recently been used to estimate visceral adipose tissue (VAT). The aim of this study was to determine the accuracy of DXA-derived VAT in a Middle Eastern population using magnetic resonance imaging (MRI) as the criterion measure. ${\bf Method:}$ VAT was estimated from abdominal DXA measures in 237 adult men (n=130) and women (n=107), aged 18-65 years, participating in the Kuwait Wellbeing Study. These estimates were compared to MRI measures of the corresponding anatomical region. The agreement between methods was assessed using Bland-Altman as well as correlation analysis. ${\bf Results:}$ Median MRI-VAT was 1148.5 (95% CI: 594.2-1734.6) cm$^3$ in men and 711.3 (95% CI: 395.5-1042.8) cm$^3$ in women. DXA estimates of VAT showed high correlations with corresponding MRI measures (r= 0.94 (p<0.0001) in men; r= 0.93 (p<0.0001) in women). DXA overestimated VAT with a mean bias (95% limits of agreement) of 79.7 (-767; 963) cm$^3$ in men and 46.8 (-482; 866) cm$^3$ in women. The imprecision of DXA increased with increasing VAT adiposity in both men and women. ${\bf Conclusion:}$ DXA estimates of VAT are valid for use in Middle Eastern populations, although accuracy decreases with increasing level of obesity.This research was supported by funding from His Highness Shiekh Nasser Al-Mohammad Al-Sabah, the Dasman Diabetes Institute (RA-2010-001), and the Medical Research Council (MC_UU_12015/1 and MC_UU_12015/3)

The association between adherence to the Mediterranean diet and hepatic steatosis: cross-sectional analysis of two independent studies, the UK Fenland Study and the Swiss CoLaus Study.

The risk of hepatic steatosis may be reduced through changes to dietary intakes, but evidence is sparse, especially for dietary patterns including the Mediterranean diet. We investigated the association between adherence to the Mediterranean diet and prevalence of hepatic steatosis. Cross-sectional analysis of data from two population-based adult cohorts: the Fenland Study (England, n = 9645, 2005-2015) and CoLaus Study (Switzerland, n = 3957, 2009-2013). Habitual diet was assessed using cohort-specific food frequency questionnaires. Mediterranean diet scores (MDSs) were calculated in three ways based on adherence to the Mediterranean dietary pyramid, dietary cut-points derived from a published review, and cohort-specific tertiles of dietary consumption. Hepatic steatosis was assessed by abdominal ultrasound and fatty liver index (FLI) in Fenland and by FLI and non-alcoholic fatty liver disease (NAFLD) score in CoLaus. FLI includes body mass index (BMI), waist circumference, gamma-glutamyl transferase, and triglyceride; NAFLD includes diabetes, fasting insulin level, fasting aspartate-aminotransferase (AST), and AST/alanine transaminase ratio. Associations were assessed using Poisson regression. In Fenland, the prevalence of hepatic steatosis was 23.9% and 27.1% based on ultrasound and FLI, respectively, and in CoLaus, 25.3% and 25.7% based on FLI and NAFLD score, respectively. In Fenland, higher adherence to pyramid-based MDS was associated with lower prevalence of hepatic steatosis assessed by ultrasound (prevalence ratio (95% confidence interval), 0.86 (0.81, 0.90) per one standard deviation of MDS). This association was attenuated [0.95 (0.90, 1.00)] after adjustment for body mass index (BMI). Associations of similar magnitude were found for hepatic steatosis assessed by FLI in Fenland [0.82 (0.78, 0.86)] and in CoLaus [0.85 (0.80, 0.91)], and these were also attenuated after adjustment for BMI. Findings were similar when the other two MDS definitions were used. Greater adherence to the Mediterranean diet was associated with lower prevalence of hepatic steatosis, largely explained by adiposity. These findings suggest that an intervention promoting a Mediterranean diet may reduce the risk of hepatic steatosis

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.This study was funded by the UK Medical Research Council through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1. This work was supported by the MRC Metabolic Diseases Unit (MC_UU_12012/5) and the Cambridge NIHR Biomedical Research Centre and EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant 115372). Funding for the InterAct project was provided by the EU FP6 program (grant LSHM_CT_2006_037197). This work was funded, in part, through an EFSD Rising Star award to R.A.S. supported by Novo Nordisk. D.B.S. is supported by Wellcome Trust grant 107064. M.I.M. is a Wellcome Trust Senior Investigator and is supported by the following grants from the Wellcome Trust: 090532 and 098381. M.v.d.B. is supported by a Novo Nordisk postdoctoral fellowship run in partnership with the University of Oxford. I.B. is supported by Wellcome Trust grant WT098051. S.O'R. acknowledges funding from the Wellcome Trust (Wellcome Trust Senior Investigator Award 095515/Z/11/Z and Wellcome Trust Strategic Award 100574/Z/12/Z)

Liver fat accumulation is associated with reduced hepatic insulin extraction with beta cell dysfunction in healthy older individuals

BackgroundThere is a well-established association between type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) secondary to excess accumulation of intrahepatic lipid (IHL), but the mechanistic basis for this association is unclear. Emerging evidence suggests that in addition to being associated with insulin resistance, NAFLD may be associated with relative beta-cell dysfunction. We sought to determine the influence of liver fat on hepatic insulin extraction and indices of beta-cell function in a cohort of apparently healthy older white adults.MethodsWe performed a cross-sectional analysis of 70 healthy participants in the Hertfordshire Physical Activity Trial (39 males, age 71.3?±?2.4 years) who underwent oral glucose tolerance testing with glucose, insulin and C-Peptide levels measured every 30 minutes over two hours. The areas under the concentration curve for glucose, insulin and C-Peptide were used to quantify hepatic insulin extraction (HIE), the insulinogenic index (IGI), the C-Peptide increment (CGI), the Disposition Index (DI) and Adaptation Index (AI). Visceral fat was quantified with magnetic resonance (MR) imaging and IHL with MR spectroscopy. Insulin sensitivity was measured with the Oral Glucose Insulin Sensitivity (OGIS) model.Results29 of 70 participants (41%) exceeded our arbitrary threshold for NAFLD, i.e. IHL &gt;5.5%. Compared to those with normal IHL, those with NAFLD had higher weight, BMI, waist and MR visceral fat, with lower insulin sensitivity and hepatic insulin extraction. Alcohol consumption, age, HbA1c and alanine aminotransferase (ALT) levels were similar in both groups. Insulin and C-Peptide excursions after oral glucose loading were higher in the NAFLD group, but the CGI and AI were significantly lower, indicating a relative defect in beta-cell function that is only apparent when C-Peptide is measured and when dynamic changes in glucose levels and also insulin sensitivity are taken into account. There was no difference in IGI or DI between the groups.ConclusionsAlthough increased IHL was associated with greater insulin secretion, modelled parameters suggested relative beta-cell dysfunction with NAFLD in apparently healthy older adults, which may be obscured by reduced hepatic insulin extraction. Further studies quantifying pancreatic fat content directly and its influence on beta cell function are warranted.Trial registrationISRCTN6098657

Association between birth weight and visceral fat in adults

BACKGROUND: Several studies reported inverse associations between birth weight and central adiposity in adults. However, few studied investigated the contributions of different abdominal fat compartments. OBJECTIVE: We examined associations between birth weight and adult visceral and subcutaneous abdominal fat in the population-based Fenland study. DESIGN: A total of 1092 adults (437 men and 655 women) aged 30-55 y had available data on reported birth weight, standard anthropometric measures, and visceral and subcutaneous abdominal fat estimated by ultrasound. In a subgroup (n = 766), dual-energy X-ray absorptiometry (DXA) assessment of total abdominal fat was performed. Linear regression models were used to analyze relations between birth weight and the various fat variables adjusted for sex, age, education, smoking, and body mass index (BMI). RESULTS: After adjustment for adult BMI, there was an inverse association between birth weight and total abdominal fat [B (partial regression coefficient expressed as SD/1-kg change in birth weight) = -0.09, P = 0.002] and visceral fat (B = -0.07, P = 0.01) but not between birth weight and subcutaneous abdominal fat (B = -0.01, P = 0.3). Tests for interaction showed that adult BMI modified the association between birth weight and visceral fat (P for interaction = 0.01). In stratified analysis, the association between birth weight and visceral fat was apparent only in individuals with the highest BMI tertile (B = -0.08, P = 0.04). CONCLUSIONS: The inverse association between birth weight and adult abdominal fat appeared to be specific to visceral fat. However, associations with birth weight were apparent only after adjustment for adult BMI. Therefore, we suggest that rapid postnatal weight gain, rather than birth weight alone, leads to increased visceral fat

Adolescent parenthood associated with adverse socio-economic outcomes at age 30 years in women and men of the Pelotas, Brazil: 1982 Birth Cohort Study.

OBJECTIVE: To investigate the potential long-term effects of adolescent parenthood on completed education and income. DESIGN: Population-based birth cohort study. SETTING: All live births in 1982, whose mothers lived in the urban area of Pelotas, southern Brazil. SAMPLE: A total of 3701 participants: 1914 women and 1787 men at age 30 years. METHODS: Questionnaires were completed by the mothers in the early phases of this study, and by the cohort members in adolescence and adulthood. Linear regression models and G-computation were used in the analyses. MAIN OUTCOME MEASURES: Educational attainment and income at age 30 years. RESULTS: In women, adolescent parenthood was associated with lower attained education compared with women without adolescent maternity: by -2.8 years [95% confidence interval (CI) -3.2 to -2.3] if their first birth was at age 16-19, and by -4.4 years (-5.5 to -3.3) at age 11-15. These effects were greater among women who had three or more children. Women with adolescent parenthood also had 49 or 33% lower income at age 30 if their first child was born when aged 16-19 or 11-15, respectively. In men, the adverse effect of adolescent parenthood on education appeared to be mediated by a higher number of children and there was no effect of adolescent paternity on income at age 30 years. CONCLUSION: These findings suggest lasting socio-economic disadvantages of adolescent parenthood, with larger effects being apparent in women than in men. TWEETABLE ABSTRACT: Adolescent parenthood has an adverse effect on educational attainment later in life, and on household income among women