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Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: a population-based and inter-laboratory study

Isokuortti, Elina, Zhou, You ORCID:, Peltonen, Markku, Bugianesi, Elisabetta, Clement, Karine, Bonnefont-Rousselot, Dominique, Lacorte, Jean-Marc, Gastaldelli, Amalia, Schuppan, Detlef, Schattenberg, Jörn M., Hakkarainen, Antti, Lundbom, Nina, Jousilahti, Pekka, Männistö, Satu, Keinänen-Kiukaanniemi, Sirkka, Saltevo, Juha, Anstee, Quentin M. and Yki-Järvinen, Hannele 2017. Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: a population-based and inter-laboratory study. Diabetologia 60 (10) , pp. 1873-1882. 10.1007/s00125-017-4340-1

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Aims/hypothesis Recent European guidelines for non-alcoholic fatty liver disease (NAFLD) call for reference values for HOMA-IR. In this study, we aimed to determine: (1) the upper limit of normal HOMA-IR in two population-based cohorts; (2) the HOMA-IR corresponding to NAFLD; (3) the effect of sex and PNPLA3 genotype at rs738409 on HOMA-IR; and (4) inter-laboratory variations in HOMA-IR. Methods We identified healthy individuals in two population-based cohorts (FINRISK 2007 [n = 5024] and the Programme for Prevention of Type 2 Diabetes in Finland [FIN-D2D; n = 2849]) to define the upper 95th percentile of HOMA-IR. Non-obese individuals with normal fasting glucose levels, no excessive alcohol use, no known diseases and no use of any drugs were considered healthy. The optimal HOMA-IR cut-off for NAFLD (liver fat ≥5.56%, based on the Dallas Heart Study) was determined in 368 non-diabetic individuals (35% with NAFLD), whose liver fat was measured using proton magnetic resonance spectroscopy (1H-MRS). Samples from ten individuals were simultaneously analysed for HOMA-IR in seven European laboratories. Results The upper 95th percentiles of HOMA-IR were 1.9 and 2.0 in healthy individuals in the FINRISK (n = 1167) and FIN-D2D (n = 459) cohorts. Sex or PNPLA3 genotype did not influence these values. The optimal HOMA-IR cut-off for NAFLD was 1.9 (sensitivity 87%, specificity 79%). A HOMA-IR of 2.0 corresponded to normal liver fat (<5.56% on 1H-MRS) in linear regression analysis. The 2.0 HOMA-IR measured in Helsinki corresponded to 1.3, 1.6, 1.8, 1.8, 2.0 and 2.1 in six other laboratories. The inter-laboratory CV% of HOMA-IR was 25% due to inter-assay variation in insulin (25%) rather than glucose (5%) measurements. Conclusions/interpretation The upper limit of HOMA-IR in population-based cohorts closely corresponds to that of normal liver fat. Standardisation of insulin assays would be the first step towards definition of normal values for HOMA-IR.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: Springer
ISSN: 0012-186X
Date of First Compliant Deposit: 5 July 2017
Date of Acceptance: 15 May 2017
Last Modified: 16 Nov 2023 20:35

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