Longitudinal analysis of risk of (NAFLD) in adulthood.

Non-Alcoholic Fatty Liver Disease Abstract Background & Aims We aimed to determine how childhood body mass index (BMI) and metabolic health, along with change in BMI between childhood and adulthood, determine the risk of adult non-alcoholic fatty liver disease (NAFLD). Methods Data from 2,020 participants aged 3-18 years at baseline, followed up 31 years later, examined to assess the utility of four childhood metabolic phenotypes (metabolic groups I: normal BMI, no metabolic disturbances; II: normal BMI, one or more metabolic disturbances; III: overweight/obese, no metabolic disturbances; IV: overweight/obese, one or more metabolic disturbances) and four life-course adiposity phenotypes (adiposity group 1: normal child and adult BMI; 2, high child, normal adult BMI; 3, normal child BMI, high adult BMI; 4, high child and adult BMI) in predicting adult NAFLD. Results The risk for adult NAFLD was similar across all four groups after adjustment for age, sex, lifestyle factors and adult BMI. Risk of adult NAFLD was not increased among individuals overweight/obese in childhood but non-obese in adulthood. In contrast, overweight or obese adults, irrespective of their youth BMI status, had ~8-10 fold increased risk (P<0.001). Conclusion Childhood overweight/obesity, not metabolic health, is associated with increased risk for adult non-alcoholic fatty liver disease. However, the increased risk associated with childhood overweight/obesity can be largely removed by obtaining a normal body mass index by adulthood. The findings of the present study provide important novel information concerning the combined effects of childhood obesity and metabolic risk factors on adult NAFLD. We evaluated the effects of metabolically healthy vs. unhealthy obesity and explored whether the effects of childhood obesity and metabolic factors are mediated by adult obesity. These data strongly support the premise that it is obesity rather than metabolic health as the main driver for NAFLD. Initial assessments of the relative risk of NAFLD according to the four different metabolic groups, suggested metabolic phenotype was relevant, with the greatest odds ratio in the metabolically unhealthy obese, even after adjustment for age, sex, alcohol, smoking and physical activity. However, after adjustment for adulthood BMI any differences in relative risk were no longer evident. Consistent with these data, the presence or absence of childhood metabolic syndrome did not influence the relative risk of NAFLD when adulthood BMI status was considered. In contrast, those who were overweight/obese (whether a BMI cut-off of 25 or 30 kg/m 2 was adopted) in adulthood had a significantly greater increased risk of NAFLD, compared to the normal BMI population, regardless of childhood adiposity status. The relative risk was greater in overweight/obese individuals who had been overweight/obese as children than in those individuals who had been of normal BMI in childhood. Significantly, the risk of NAFLD among overweight or obese children, who became non-obese by adulthood, was similar to those who were never obese, and this finding is consistent with our previous findings for the risks of other cardio-metabolic conditions. 24 We have previously shown similar risks of type 2 diabetes, hypertension, dyslipidaemia and carotid-artery atherosclerosis in overweight or obese children who became non-obese by adulthood. relationship between BMI and hazard ratios/incidence rates of the complications overlooking the impact of the duration of obesity. Duration of obesity is an independent risk factor for obesity-related complications 26 and data from the Framingham Heart Study reveal duration of obesity to also be a relevant risk factor for NAFLD with an incremental risk for every additional year of obesity. In this study, although we were unable to examine the duration of obesity in years for any given individual, we were able to demonstrate that children who were overweight or obese in childhood and who were of normal BMI when re-examined in adulthood were not more likely to have NAFLD.