Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population

Gastaldelli, A.; Kozakova, M.; Hojlund, K.; Flyvbjerg, A.; Favuzzi, A.; Mitrakou, A.; Balkau, B.; Heine, R. J.; Dekker, J.; Nijpels, G.; Boorsma, W.; Tournis, S.; Kyriakopoulou, K.; Thomakos, P.; Lalic, N.; Lalic, K.; Jotic, A.; Lukic, L.; Civcic, M.; Nolan, J.; Yeow, T. P.; Murphy, M.; Delong, C.; Neary, G.; Colgan, M. P.; Hatunic, M.; Konrad, T.; Bohles, H.; Fuellert, S.; Baer, F.; Zuchhold, H.; Golay, A.; Harsch Bobbioni, E.; Barthassat, V.; Makoundou, V.; Lehmann, T. N. O.; Merminod, T.; Petrie, J. R.; Perry, C.; Neary, F.; Macdougall, C.; Shields, K.; Malcolm, L.; Laakso, M.; Salmenniemi, U.; Aura, A.; Raisanen, R.; Ruotsalainen, U.; Sistonen, T.; Laitinen, M.; Saloranta, H.; Coppack, S. W.; Mcintosh, N.; Khadobaksh, P.; Laville, M.; Bonnet, F.; Brac de la Perriere, A.; Louche-Pelissier, C.; Maitrepierre, C.; Peyrat, J.; Serusclat, A.; Gabriel, R.; Sanchez, E. M.; Carraro, R.; Friera, A.; Novella, B.; Nilsson, P.; Persson, M.; Oostling, G.; Melander, O.; Burri, P.; Piatti, P. M.; Monti, L. D.; Setola, E.; Galluccio, E.; Minicucci, F.; Colleluori, A.; Walker, M.; Ibrahim, I. M.; Jayapaul, M.; Carman, D.; Short, K.; Mcgrady, Y.; Richardson, D.; Beck-Nielsen, H.; Staehr, P.; Hojlund, K.; Vestergaard, V.; Olsen, C.; Hansen, L.; Bolli, G. B.; Porcellati, F.; Fanelli, C.; Lucidi, P.; Calcinaro, F.; Saturni, A.; Ferrannini, E.; Natali, A.; Muscelli, E.; Pinnola, S.; Kozakova, M.; Mingrone, G.; Guidone, C.; Favuzzi, A.; Di Rocco, P.; Anderwald, C.; Bischof, M.; Promintzer, M.; Krebs, M.; Mandl, M.; Hofer, A.; Luger, A.; Waldhaausl, W.; Roden, M.; Coppack, S. W.; Dekker, J. M.; Mari, A.; Walker, M.; Gaffney, P.; Boran, G.; Kok, A.; Dekker, J.; Patel, S.; Ciociaro, D.; Guillanneuf, M. T.; Mhamdi, L.; Pacini, G.; Cavaggion, C.; Hills, S. A.; Landucci, L.; Mota, L.

doi:10.1002/hep.22845

Patients with fatty liver (FL) disease have a high risk of developing diabetes and cardiovascular diseases. The aim was to evaluate the association between FL, insulin resistance (IR), coronary heart disease (CHD) risk, and early atherosclerosis in a large European population (RISC Study). In 1,307 nondiabetic subjects (age 30-60 years) recruited at 19 centers, we evaluated liver enzymes, lipids, insulin sensitivity (by euglycemic-hyperinsulinemic clamp), glucose tolerance (by 75 g oral glucose tolerance test), carotid atherosclerosis as intima media thickness (IMT), CHD risk by the Framingham Heart study prediction score, and physical activity (by accelerometer). The presence of FL was estimated using the fatty liver index (FLI;>60, likelihood>78% presence FL; FLI<20 likelihood >91«sence of FL). Subjects were divided into three groups: G1: FLI<20 (n=608); G3: FLI>60 (n=234), G2: intermediate group (n=465). Compared to G1,G3 included more men (70% versus 24%) and people with impaired glucose tolerance (23% versus 5%). IMT increased with FLI (G3= 0.64±0.08 versusG1=0.58±0.08mm,P<0.0001). FLI was associated with increased CHD risk (r = 0.48), low-density lipoprotein cholesterol (r = 0.33), alanine aminotransferase (r = 0.48), aspartate aminotransferase (r = 0.25), systolic blood pressure (r = 0.39) and IMT (r = 0.30), and reduced insulin sensitivity (r=-0.43), high-density lipoprotein cholesterol (r=-0.50), adiponectin (r=-0.42), and physical activity (r=-0.16, all P < 0.0001). The correlations hold also in multivariate analysis after adjusting for age, gender, and recruiting center. Conclusion: In middle-age nondiabetic subjects, increased IMT, CHD risk, and reduced insulin sensitivity are associated with high values of FLI. Copyright © 2009 by the American Association for the Study of Liver Diseases.