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

Abstract

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.

• Authors: Elina Isokuortti, You Zhou, Markku Peltonen, Elisabetta Bugianesi, Karine Clement, Dominique Bonnefont-Rousselot, Jean-Marc Lacorte, Amalia Gastaldelli, Detlef Schuppan, Jörn M Schattenberg, Antti Hakkarainen, Nina Lundbom, Pekka Jousilahti, Satu Männistö, Sirkka Keinänen-Kiukaanniemi, Juha Saltevo, Quentin M Anstee, Hannele Yki-Järvinen
• Journal: Diabetologia (Diabetologia) Vol. 60 Issue 10 Pg. 1873-1882 (10 2017) ISSN: 1432-0428 [Electronic] Germany
• PMID: 28660493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Blood Glucose
• Insulin
• aducanumab

Topics

• Adiposity (physiology)
• Antibodies, Monoclonal, Humanized
• Blood Glucose (metabolism)
• Female
• Humans
• Insulin (blood)
• Insulin Resistance (physiology)
• Liver (pathology)
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease (diagnosis, metabolism, pathology)
• Reference Values
• Young Adult