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Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: a population-based and inter-laboratory study
Open accessAbstract
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 (1 H-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 1 H-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.
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“insulin resistance can also be measured clinically with the HOMA-IR index from fasting insulin or C-peptide and fasting glucose concentrations, including in people with T2D (unless on insulin treatment). 219 -221”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [220]
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Tanase, D. M., Gosav, E. M., Costea, C. F., Ciocoiu, M., Lacatusu, C. M., Maranduca, M. A., Ouatu, A., & Floria, M. (2020) · Journal of Diabetes Research · doi:10.1155/2020/3920196 · Cited by 627
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From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options
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Self-citationMuzurović, E. M., Mikhailidis, D. P., & Mantzoros, C. S. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154770 · Cited by 363
Metadata
- Authors
- Isokuortti, E., Zhou, Y., Peltonen, M., Bugianesi, E., Clement, K., Bonnefont-Rousselot, D., Lacorte, J.-M., Gastaldelli, A., Schuppan, D., Schattenberg, J. M., Hakkarainen, A., Lundbom, N., Jousilahti, P., Männistö, S., Keinänen-Kiukaanniemi, S., Saltevo, J., Anstee, Q. M., & Yki-Järvinen, H.
- Affiliations
- University of Helsinki (FI)
- Cardiff University (GB)
- Finnish Institute for Health and Welfare (FI)
- University of Turin (IT)
- Inserm (FR)
- Istituto di Fisiologia Clinica (IT)
- Johannes Gutenberg University Mainz (DE)
- Central Finland Health Care District (FI)
- Freeman Hospital (GB)
- Corresponding author
- Isokuortti, Elina
- ORCID
- Venue
- Diabetologia
- Published
- 2017-06-29
- Volume
- 60
- Issue
- 10
- Pages
- 1873-1882
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2728177312
- Cited by
- 120
- References
- 49
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 20 · 2023: 9 · 2022: 18 · 2021: 12 · 2020: 20 · 2019: 14 · 2018: 6 · 2017: 3
- FWCI
- 9.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- HAL (submittedVersion)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- The Novo Nordisk Foundation
- Suomen Akatemia
- Paulon Säätiö
- Horizon 2020 Framework Programme (Grant Agreement 634413)
- The Sigrid Juselius Foundation
- Suomen Lääketieteen Säätiö
- EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant no. 115372)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, HOMA-IR, insulin resistance, reference values, upper limit of normal, diagnostic thresholds, PNPLA3 rs738409, sex differences, inter-laboratory variability, liver fat, 1H NMR, type 2 diabetes prevention
- MeSH terms
- Blood Glucose, Female, Humans, Insulin, Insulin Resistance, Liver, Male, Middle Aged, Reference Values, Adiposity, Young Adult, Antibodies, Monoclonal, Humanized, Non-alcoholic Fatty Liver Disease
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