Kristiina Santalahti1, Mikael Maksimow1, Antti Airola1, Tapio Pahikkala1, Nina Hutri-Kähönen1, Sirpa Jalkanen1, Olli T Raitakari1, Marko Salmi1. 1. MediCity Research Laboratory and Department of Medical Microbiology and Immunology (K.S., M.M., S.J., M.S.), University of Turku, Turku, Finland; Department of Information Technology (A.A., T.P.), University of Turku, Turku, Finland; Department of Pediatrics (N.H.-K.), University of Tampere and Tampere University Hospital, Tampere, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine (O.T.R.), University of Turku and Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Abstract
CONTEXT: Metabolic inflammation contributes to the development of insulin resistance (IR), but the roles of different inflammatory and other cytokines in this process remain unclear. OBJECTIVE: We aimed at analyzing the value of different cytokines in predicting future IR. DESIGN, SETTING, AND PARTICIPANTS: We measured the serum concentrations of 48 cytokines from a nationwide cohort of 2200 Finns (the Cardiovascular Risk in Young Finns Study), and analyzed their role as independent risk factors for predicting the development of IR 4 years later. MAIN OUTCOME MEASURES: We used cross-sectional regression analysis adjusted for known IR risk factors (high age, body mass index, systolic blood pressure, triglycerides, smoking, physical inactivity, and low high-density lipoprotein cholesterol), C-reactive protein and 37 cytokines to find the determinants of continuous baseline IR (defined by homeostatic model assessment). A logistic regression model adjusted for the known risk factors, baseline IR, and 37 cytokines was used to predict the future IR. RESULTS: Several cytokines, often in a sex-dependent manner, remained as independent determinants of current IR. In men, none of the cytokines was an independent predictive risk marker of future IR. In women, in contrast, IL-17 (odds ratio, 1.42 for 1-SD change in ln-transformed IL-17) and IL-18 (odds ratio, 1.37) were independently associated with the future IR. IL-17 levels also independently predicted the development of incident future IR (odds ratio, 1.48). CONCLUSIONS: The systemic levels of the T helper 1 cell cytokine IL-18 and the T helper 17 cell cytokine IL-17 thus may have value in predicting future insulin sensitivity in women independently of classical IR risk factors.
CONTEXT: Metabolic inflammation contributes to the development of insulin resistance (IR), but the roles of different inflammatory and other cytokines in this process remain unclear. OBJECTIVE: We aimed at analyzing the value of different cytokines in predicting future IR. DESIGN, SETTING, AND PARTICIPANTS: We measured the serum concentrations of 48 cytokines from a nationwide cohort of 2200 Finns (the Cardiovascular Risk in Young Finns Study), and analyzed their role as independent risk factors for predicting the development of IR 4 years later. MAIN OUTCOME MEASURES: We used cross-sectional regression analysis adjusted for known IR risk factors (high age, body mass index, systolic blood pressure, triglycerides, smoking, physical inactivity, and low high-density lipoprotein cholesterol), C-reactive protein and 37 cytokines to find the determinants of continuous baseline IR (defined by homeostatic model assessment). A logistic regression model adjusted for the known risk factors, baseline IR, and 37 cytokines was used to predict the future IR. RESULTS: Several cytokines, often in a sex-dependent manner, remained as independent determinants of current IR. In men, none of the cytokines was an independent predictive risk marker of future IR. In women, in contrast, IL-17 (odds ratio, 1.42 for 1-SD change in ln-transformed IL-17) and IL-18 (odds ratio, 1.37) were independently associated with the future IR. IL-17 levels also independently predicted the development of incident future IR (odds ratio, 1.48). CONCLUSIONS: The systemic levels of the T helper 1 cell cytokine IL-18 and the T helper 17 cell cytokine IL-17 thus may have value in predicting future insulin sensitivity in women independently of classical IR risk factors.
Authors: Sylvain Sebert; Johannes Kettunen; Eeva Sliz; Marita Kalaoja; Ari Ahola-Olli; Olli Raitakari; Markus Perola; Veikko Salomaa; Terho Lehtimäki; Toni Karhu; Heimo Viinamäki; Marko Salmi; Kristiina Santalahti; Sirpa Jalkanen; Jari Jokelainen; Sirkka Keinänen-Kiukaanniemi; Minna Männikkö; Karl-Heinz Herzig; Marjo-Riitta Järvelin Journal: J Med Genet Date: 2019-06-19 Impact factor: 6.318
Authors: Anthony H Cincotta; Eugenio Cersosimo; Mariam Alatrach; Michael Ezrokhi; Christina Agyin; John Adams; Robert Chilton; Curtis Triplitt; Bindu Chamarthi; Nicholas Cominos; Ralph A DeFronzo Journal: Int J Mol Sci Date: 2022-08-09 Impact factor: 6.208