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

被引:102
作者
Isokuortti, Elina [1 ,2 ,3 ]
Zhou, You [4 ,5 ]
Peltonen, Markku [6 ]
Bugianesi, Elisabetta [7 ]
Clement, Karine [8 ,9 ]
Bonnefont-Rousselot, Dominique [10 ,11 ,12 ]
Lacorte, Jean-Marc [8 ,9 ,13 ]
Gastaldelli, Amalia [14 ]
Schuppan, Detlef [15 ]
Schattenberg, Joern M. [16 ]
Hakkarainen, Antti [3 ,17 ]
Lundbom, Nina [3 ,17 ]
Jousilahti, Pekka [6 ]
Mannisto, Satu [6 ]
Keinanen-Kiukaanniemi, Sirkka [18 ]
Saltevo, Juha [19 ]
Anstee, Quentin M. [20 ,21 ]
Yki-Jarvinen, Hannele [1 ,2 ,3 ]
机构
[1] Helsinki 2 U, Minerva Fdn, Inst Med Res, Biomedicum, Tukholmankatu 8, FIN-00290 Helsinki, Finland
[2] Univ Helsinki, Dept Med, Helsinki, Finland
[3] Helsinki Univ Hosp, Helsinki, Finland
[4] Cardiff Univ, Syst Immun Univ Res Inst, Cardiff, S Glam, Wales
[5] Cardiff Univ, Sch Med, Div Infect & Immun, Cardiff, S Glam, Wales
[6] Natl Inst Hlth & Welf, Helsinki, Finland
[7] Univ Turin, Div Gastroenterol, Dept Med Sci, Turin, Italy
[8] Hop La Pitie Salpetriere, Inst Cardiometab & Nutr ICAN, Paris, France
[9] UPMC Univ Paris 06, Sorbonne Univ, INSERM, UMR S 1166, Paris, France
[10] La Pitie Salpetriere Charles Foix Univ Hosp, AP HP, Dept Metab Biochem, Paris, France
[11] Paris Descartes Univ, Dept Biochem, Fac Pharm, Paris, France
[12] Paris Descartes Univ, CNRS, INSERM, Fac Pharm,UMR8258,U1022, Paris, France
[13] La Pitie Salpetriere Charles Foix Univ Hosp, AP HP, Dept Endocrine & Oncol Biochem, Paris, France
[14] CNR, Inst Clin Physiol, Cardiometab Risk Lab, Pisa, Italy
[15] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Translat Immunol, Res Ctr Immune Therapy, Mainz, Germany
[16] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 1, Mainz, Germany
[17] Univ Helsinki, Helsinki Med Imaging Ctr, Helsinki, Finland
[18] Univ Oulu, Inst Hlth Sci, Oulu, Finland
[19] Cent Finland Cent Hosp, Dept Med, Jyvaskyla, Finland
[20] Newcastle Univ, Inst Cellular Med, Med Sch, Newcastle Upon Tyne, Tyne & Wear, England
[21] Freeman Rd Hosp, Newcastle Tyne Hosp NHS Trust, Liver Unit, Newcastle Upon Tyne, Tyne & Wear, England
基金
芬兰科学院;
关键词
Insulin; Liver fat; NAFLD; PNPLA3; Reference values; HOMEOSTASIS MODEL ASSESSMENT; INSULIN-RESISTANCE; METABOLIC SYNDROME; GLUCOSE-TOLERANCE; HEPATIC STEATOSIS; THRESHOLD VALUE; GENE VARIANT; PNPLA3; PREVALENCE; PATHOGENESIS;
D O I
10.1007/s00125-017-4340-1
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Aims/hypothesis Recent European guidelines for nonalcoholic 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 cutoff for NAFLD was 1.9 (sensitivity 87%, specificity 79%). A HOMA-IR of 2.0 corresponded to normal liver fat (<5.56% on H-1-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.
引用
收藏
页码:1873 / 1882
页数:10
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