Chalmers, Jane
(2021)
The role of ethnicity in the increased susceptibility to non-alcoholic fatty liver disease in people of Indian origin.
PhD thesis, University of Nottingham.
Abstract
Introduction
Non-alcoholic fatty liver disease (NAFLD) is fast becoming a global health concern. It is closely associated with obesity, diabetes and the metabolic syndrome, has a global pooled prevalence of 25% and is the leading cause of chronic liver disease in Europe and the United States.
People of Indian ethnicity are at increased risk of diabetes and metabolic complications at a lower body mass index (BMI) than Caucasians. This predisposition for NAFLD is further compounded by Westernisation of Asian culture resulting in increased intake of sugar-rich, energy-dense foods and decreased levels of physical activity.
Despite this well documented propensity to metabolic disease (including NAFLD), there is a lack of knowledge about the true disease prevalence in India. The studies that have been published are biased towards urban, tertiary centres, where access to healthcare and appropriate diagnostic tools is more readily available. In addition to this, there is conflicting data about the role of changing lifestyle habits on NAFLD risk – particularly in relation to diet. Reduced brown adipose tissue (BAT) activity has also been linked to obesity and diabetes, however there have been no prospective studies done to examine whether reduced BAT activity could also contribute to the increased NAFLD risk within this ethnic group.
Aims
The aim of this thesis is therefore to fill the above gaps in knowledge, to estimate accurately the NAFLD prevalence within a large Indian population, to identify the impact of different NAFLD risk factors within this population and compare NAFLD risk profile of native Indians with their UK migrant counterparts. It will also investigate the impact of BAT activity on NAFLD risk and understand the ethnic differences in BAT activity.
Results
Through population-level sampling of a large Southern Indian district, NAFLD prevalence (as diagnosed by ultrasound) was shown to be 49.8%.
Risk factors for NAFLD within India were the same as those seen worldwide, namely male gender (adjusted OR 2.29 1.86-2.83, p<0.001), obesity (adjusted OR 2.81 2.015-3.68, p<0.001) – in particular central obesity – and components of the metabolic syndrome (diabetes adjusted OR 1.76 1.40-2.21, p<0.001). Dietary fat intake was also independently associated with NAFLD within India (adjusted OR 1.02 1.00-1.03, p=0.019). These risk factors appear unchanged by migration to the UK. Although there were no significant differences in dietary habits following UK migration, there appeared to be an element of dietary acculturation with decreased consumption of carbohydrate within the UK-migrant Indian cohort. This may result in changes to NAFLD phenotype over time.
BAT activity was lower in native Indians (ΔTrel 0.36°C) compared to UK Caucasians (ΔTrel 0.50°C, p=0.010) and UK South Asian migrants (ΔTrel 0.57°C, p<0.001). This difference was however due to environment, as there was no difference in BAT activity between control groups of different ethnicity living in the same country. BAT activity does not directly influence risk of NAFLD (adjusted OR 0.47 0.07-3.20, p=0.444). Any differences in BAT activity were related to increasing BMI, which is itself a risk factor for NAFLD.
Conclusion
The prevalence of NAFLD in India is significantly higher than current national and global estimates. There is a commonality of risk between India and the rest of the world – namely obesity, diabetes and a diet high in fat. Within India, increased consumption of saturated fat in the form of edible oils and meat appears to impact NAFLD risk additionally. Whilst BAT activity is lower in Indians, it is not a direct cause for the increased NAFLD risk in this ethnic group. This work highlights the need for NAFLD screening for people of Indian ethnicity, both in India and in migrant populations. Further research needs to focus on education and interventional strategies to reduce prevalence of obesity and diabetes, which may be achieved through dietary manipulation.
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