Elina Isokuortti1,2, You Zhou3,4, Markku Peltonen5, Elisabetta Bugianesi6, Karine Clement7,8, Dominique Bonnefont-Rousselot9,10,11, Jean-Marc Lacorte7,8,12, Amalia Gastaldelli13, Detlef Schuppan14, Jörn M Schattenberg15, Antti Hakkarainen16, Nina Lundbom16, Pekka Jousilahti5, Satu Männistö5, Sirkka Keinänen-Kiukaanniemi17, Juha Saltevo18, Quentin M Anstee19,20, Hannele Yki-Järvinen21,22. 1. Minerva Foundation Institute for Medical Research, Biomedicum Helsinki 2 U, Tukholmankatu 8, FIN - 00290, Helsinki, Finland. elina.isokuortti@helsinki.fi. 2. Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. elina.isokuortti@helsinki.fi. 3. Systems Immunity University Research Institute, Cardiff University, Cardiff, UK. 4. Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK. 5. National Institute for Health and Welfare, Helsinki, Finland. 6. Division of Gastroenterology, Department of Medical Sciences, University of Torino, Torino, Italy. 7. Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, Paris, France. 8. Sorbonne Université, UPMC University Paris 06, UMR_S 1166, Inserm, Paris, France. 9. Department of Metabolic Biochemistry, La Pitié Salpêtrière-Charles Foix University Hospital (AP-HP), Paris, France. 10. Department of Biochemistry, Faculty of Pharmacy, Paris Descartes University, Paris, France. 11. CNRS UMR8258 - Inserm U1022, Faculty of Pharmacy, Paris Descartes University, Paris, France. 12. Department of Endocrine and Oncological Biochemistry, La Pitié Salpêtrière-Charles Foix University Hospital (AP-HP), Paris, France. 13. Cardiometabolic Risk Laboratory, Institute of Clinical Physiology, CNR, Pisa, Italy. 14. Institute of Translational Immunology, Research Center of Immune Therapy, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany. 15. Department of Medicine I, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany. 16. Helsinki Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 17. Institute of Health Sciences, University of Oulu, Oulu, Finland. 18. Department of Medicine, Central Finland Central Hospital, Jyväskylä, Finland. 19. Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle upon Tyne, UK. 20. Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, UK. 21. Minerva Foundation Institute for Medical Research, Biomedicum Helsinki 2 U, Tukholmankatu 8, FIN - 00290, Helsinki, Finland. 22. Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
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.
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: M Del Ben; L Polimeni; M Brancorsini; A Di Costanzo; L D'Erasmo; F Baratta; L Loffredo; D Pastori; P Pignatelli; F Violi; M Arca; F Angelico Journal: Eur J Intern Med Date: 2014-06-16 Impact factor: 4.487
Authors: E Bonora; S Kiechl; J Willeit; F Oberhollenzer; G Egger; G Targher; M Alberiche; R C Bonadonna; M Muggeo Journal: Diabetes Date: 1998-10 Impact factor: 9.461
Authors: S Lillioja; D M Mott; M Spraul; R Ferraro; J E Foley; E Ravussin; W C Knowler; P H Bennett; C Bogardus Journal: N Engl J Med Date: 1993-12-30 Impact factor: 91.245
Authors: Susan E Manley; Stephen D Luzio; Irene M Stratton; Tara M Wallace; Penelope M S Clark Journal: Diabetes Care Date: 2008-06-05 Impact factor: 19.112
Authors: Nicolai J Wewer Albrechtsen; Kristine Færch; Troels M Jensen; Daniel R Witte; Jens Pedersen; Yuvaraj Mahendran; Anna E Jonsson; Katrine D Galsgaard; Marie Winther-Sørensen; Signe S Torekov; Torsten Lauritzen; Oluf Pedersen; Filip K Knop; Torben Hansen; Marit E Jørgensen; Dorte Vistisen; Jens J Holst Journal: Diabetologia Date: 2018-01-05 Impact factor: 10.122
Authors: José G González-González; Jorge R Violante-Cumpa; Miguel Zambrano-Lucio; Erick Burciaga-Jimenez; Patricia L Castillo-Morales; Mariano Garcia-Campa; Ricardo César Solis; Alejandro D González-Colmenero; René Rodríguez-Gutiérrez Journal: High Blood Press Cardiovasc Prev Date: 2022-10-01
Authors: Liz Simon; Diego Torres; Ari Saravia; Danielle E Levitt; Curtis Vande Stouwe; Heather McGarrah; Larry Coleman; Jason P Dufour; Angela M Amedee; Patricia E Molina Journal: Am J Physiol Regul Integr Comp Physiol Date: 2021-09-15 Impact factor: 3.210
Authors: Stefany D Primeaux; Liz Simon; Tekeda F Ferguson; Danielle E Levitt; Meghan M Brashear; Alice Yeh; Patricia E Molina Journal: Alcohol Clin Exp Res Date: 2021-08-02 Impact factor: 3.928