Deuterium metabolic imaging reveals greater liver fat contribution from lipogenesis in South Asian men than European men: a potential mechanism underlying elevated type 2 diabetes risk.

Authors

Mueed Azhar, Jieniean Worsley, Kaitlyn M J H Dennis, Emanuella De Lucia Rolfe, Amy Barrett, Mandour O Mandour, Enes Demir, Katherine Carr, Michele Ferraro, Ranalie De Jesus, Samuel King, Sherly Jose, Simon R White, Peter Barker, Graham J Kemp, Kevin M Brindle, Krishna K Chatterjee, Nita G Forouhi, Michelle Venables, Laura Watson, Leanne Hodson, David B Savage, Alison Sleigh

Published in

Diabetologia. Oct 06, 2026. Epub Oct 06, 2026.

Abstract

South Asian individuals are up to six times more likely to develop type 2 diabetes than individuals from other ethnic groups, often at a younger age and lower BMI. It has been shown that liver fat accumulates more readily in South Asian individuals, and this is thought to be a key driving factor contributing to the insulin resistance and diabetes in this population. However, the mechanisms underlying this phenomenon remain unclear. Understanding the role of de novo lipogenesis (DNL) in liver fat accumulation has been hampered by a lack of non-invasive techniques to quantify DNL-derived liver fat. We developed a method to quantify DNL-derived liver fat and used it in a proof-of-concept case-control study, hypothesising that there would be greater liver fat contribution from DNL in South Asian individuals than in European individuals.
A total of seven South Asian and six European participants, matched for age and BMI, underwent deuterium magnetic resonance scans at baseline and after 5 days of ²H water enrichment, from which the fractional and absolute amounts of liver fat from DNL (DNL_MR) were calculated. Proton magnetic resonance spectroscopy (¹H-MRS) and MRI were used to determine lipid quantity and composition.
Our method allowed precise quantification of ²H-labelled liver lipids (intraclass correlation coefficient [ICC]>0.956), which enabled us to accurately detect changes in liver fat due to DNL. Both fractional and absolute DNL_MR were higher in South Asian participants than in European participants (both p=0.041). DNL_MR correlated with liver fat content (fractional r_s=0.874, absolute r_s=0.888; both p=0.001), as well as the saturation ratio of both liver fat (fractional r_s=0.692, absolute r_s=0.748; both p<0.05) and visceral adipose tissue (fractional r_s=0.648, absolute r_s=0.708; both p<0.01). Liver fat content correlated with insulin resistance (HOMA-IR) (r_s=0.659, p=0.014).
DNL or related factors may play a pivotal role in driving the increased liver fat and risk of diabetes in South Asian individuals. The novel methodology used to quantify DNL provides a powerful tool for studying DNL-derived liver fat in human metabolic disorders including diabetes.

PMID:
42836860
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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