Cardiometabolic traits mediated the relationship from early life famine exposure to adulthood nonalcoholic fatty liver disease risk.

Xu Han,Dongsheng Hu,Meian He,Yaru Li,Jing Wang

doi:10.1017/s0007114521003342

Abstract

Early life exposure to famine was associated with adulthood metabolic syndrome and nonalcoholic fatty liver disease (NAFLD), and NAFLD was also affected by cardiometabolic traits. However, the role of cardiometabolic traits in the associations from famine exposure to NAFLD was largely unknown. This study aimed to investigate whether the relationship between early life famine exposure and adulthood NAFLD risk was mediated by cardiometabolic traits. Overall, 7578 subjects aged 56·0 (sd 3·7) years in the Dongfeng-Tongji cohort were included and classified into late-exposed (1952-1954), middle-exposed (1954-1956), early-childhood-exposed (1956-1958), fetal-exposed (1959-1961) and non-exposed (1962-1966, reference) group according to the birth year. NAFLD was diagnosed by experienced physicians via abdominal B-type ultrasound inspection. Mediation analysis was used to evaluate the mediating effects of cardiometabolic traits. Compared with those non-exposed, after multivariable adjustment, participants in fetal-exposed group (OR: 1·37; 95 % CI 1·08, 1·73) had 37 % higher risk to develop NAFLD, and the overall childhood-exposed group had marginally significant association with NAFLD (OR: 1·39; 95 % CI 0·99, 1·94). Stratification analysis found the famine-NAFLD associations more evident in women and those born in areas severely affected by famine. Mediation analysis showed that cardiometabolic traits such as total cholesterol, TAG glucose index, γ-glutamyl transpeptidase, alkaline phosphatase and alanine aminotransferase mediated 6·7-22·2 % of the relation from famine exposure to higher NAFLD risk. Early life exposure to famine was related to increased adulthood NAFLD risk, and this relationship was partly mediated by cardiometabolic traits.

Highlights

With rapid economic development and transitions of lifestyle, the prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing dramatically in China [1], with estimated cases from 246 million in 2016 to over 300 million cases in 2030 [2]
In the fully-adjusted model further adjusting for smoking status, drinking status, metabolic equivalent, egg intake, red meat intake, vegetable intake, and fruit intake, individuals in late, middle, early-childhood-exposed, and fetal-exposed groups had 39% (OR: 1.39; 95% confidence intervals (CIs): 1.15-1.66; P = 0.03), 52% (OR: 1.52; 95% CI: 1.26-1.83; P = 0.004), 45% (OR: 1.45; 95% CI: 1.21-1.74; P < 0.001), and 39% (OR: 1.39; 95% CI: 1.14-1.70; P = 0.004) higher risk of NAFLD, respectively (P for trend < 0.001)
When age was introduced into the model, the above famine-NAFLD association altered to null

Summary

Introduction

With rapid economic development and transitions of lifestyle, the prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing dramatically in China [1], with estimated cases from 246 million in 2016 to over 300 million cases in 2030 [2]. The Developmental Origins of Health and Disease postulates that adverse events occurring during early phases of human development increase disease risk through life, especially metabolic diseases [4]. The Great Famine, lasting for about 3 years (1959-1961), affected almost all people living in the Chinese mainland. It caused millions of excess deaths, and its detrimental effects persisted over a relatively prolonged period [5; 6]. Previous studies has related famine exposure in early life to increased NAFLD risk in adulthood [7; 8; 9; 10]. Because of the limited numbers of studies, different grouping criteria for famine exposed people, and different definitions of NAFLD, the relationship of early life exposure to famine and adulthood NAFLD needs further investigation

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Conclusion