Kwok-Leung Ong1,2, Rachel O'Connell2, Andrzej S Januszewski2, Alicia J Jenkins2, Aimin Xu3,4, David R Sullivan5, Philip J Barter6,7, Russell S Scott8, Marja-Riitta Taskinen9,10, Boris Waldman2, Peter G Colman11,12, James D Best12,13, John R Simes2, Kerry-Anne Rye6,7, Anthony C Keech. 1. Lipid Research Group, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia; oklws@yahoo.com.hk. 2. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia. 3. Department of Medicine, University of Hong Kong, Hong Kong. 4. State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong. 5. Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, NSW, Australia. 6. Lipid Research Group, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. 7. Sydney Medical School, University of Sydney, Sydney, NSW, Australia. 8. Lipid and Diabetes Research Group, Christchurch Hospital, Christchurch, New Zealand. 9. Heart and Lung Centre, Cardiovascular Research Unit, Helsinki University Central Hospital, Helsinki, Finland. 10. Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland. 11. Department of Diabetes & Endocrinology, Royal Melbourne Hospital, Melbourne, VIC, Australia. 12. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia. 13. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
Abstract
BACKGROUND: It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associated with glycemic progression in patients with established type 2 diabetes. This study reports this relationship in type 2 diabetes patients participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. METHODS: Plasma FGF21 was quantified in 9697 study participants. Among patients with lifestyle-only glucose control measures at baseline, glycemic progression was defined as the initiation of oral hypoglycemic agents or insulin therapy. We assessed the relationship of FGF21 concentrations with glycohemoglobin (Hb A1c), the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycemic progression. RESULTS: Among 2584 patients with lifestyle-only glycemic therapy at baseline, plasma FGF21 concentrations were positively associated with HOMA-IR (5.1% increase per 100% increase in FGF21 concentrations). Patients with higher baseline plasma FGF21 concentrations had higher risk of glycemic progression over a 5-year period (P = 0.02), but the association was not significant after further adjusting for alanine aminotransferase (ALT) enzyme activity. During the fenofibrate active run-in phase, higher tertiles of fenofibrate-induced increase in FGF21 concentrations were associated with higher risk of glycemic progression (adjusted hazards ratio = 1.09 and 1.18 for tertiles 2 and 3, respectively, P for trend = 0.01), even after adjusting for ALT enzyme activity. This association was statistically significant in the fenofibrate group only (P = 0.01). CONCLUSIONS: Higher baseline and fenofibrate-induced increase in FGF21 concentrations predict more rapid glycemic progression in type 2 diabetes patients. This association may be partly explained by hepatic function.
BACKGROUND: It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associated with glycemic progression in patients with established type 2 diabetes. This study reports this relationship in type 2 diabetespatients participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. METHODS: Plasma FGF21 was quantified in 9697 study participants. Among patients with lifestyle-only glucose control measures at baseline, glycemic progression was defined as the initiation of oral hypoglycemic agents or insulin therapy. We assessed the relationship of FGF21 concentrations with glycohemoglobin (Hb A1c), the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycemic progression. RESULTS: Among 2584 patients with lifestyle-only glycemic therapy at baseline, plasma FGF21 concentrations were positively associated with HOMA-IR (5.1% increase per 100% increase in FGF21 concentrations). Patients with higher baseline plasma FGF21 concentrations had higher risk of glycemic progression over a 5-year period (P = 0.02), but the association was not significant after further adjusting for alanine aminotransferase (ALT) enzyme activity. During the fenofibrate active run-in phase, higher tertiles of fenofibrate-induced increase in FGF21 concentrations were associated with higher risk of glycemic progression (adjusted hazards ratio = 1.09 and 1.18 for tertiles 2 and 3, respectively, P for trend = 0.01), even after adjusting for ALT enzyme activity. This association was statistically significant in the fenofibrate group only (P = 0.01). CONCLUSIONS: Higher baseline and fenofibrate-induced increase in FGF21 concentrations predict more rapid glycemic progression in type 2 diabetespatients. This association may be partly explained by hepatic function.
Authors: Jaclyn E Welles; Michael D Dennis; Leonard S Jefferson; Scot R Kimball Journal: Am J Physiol Endocrinol Metab Date: 2020-05-18 Impact factor: 4.310
Authors: Jean-Charles Fruchart; Raul D Santos; Carlos Aguilar-Salinas; Masanori Aikawa; Khalid Al Rasadi; Pierre Amarenco; Philip J Barter; Richard Ceska; Alberto Corsini; Jean-Pierre Després; Patrick Duriez; Robert H Eckel; Marat V Ezhov; Michel Farnier; Henry N Ginsberg; Michel P Hermans; Shun Ishibashi; Fredrik Karpe; Tatsuhiko Kodama; Wolfgang Koenig; Michel Krempf; Soo Lim; Alberto J Lorenzatti; Ruth McPherson; Jesus Millan Nuñez-Cortes; Børge G Nordestgaard; Hisao Ogawa; Chris J Packard; Jorge Plutzky; Carlos I Ponte-Negretti; Aruna Pradhan; Kausik K Ray; Željko Reiner; Paul M Ridker; Massimiliano Ruscica; Shaukat Sadikot; Hitoshi Shimano; Piyamitr Sritara; Jane K Stock; Ta-Chen Su; Andrey V Susekov; André Tartar; Marja-Riitta Taskinen; Alexander Tenenbaum; Lale S Tokgözoğlu; Brian Tomlinson; Anne Tybjærg-Hansen; Paul Valensi; Michal Vrablík; Walter Wahli; Gerald F Watts; Shizuya Yamashita; Koutaro Yokote; Alberto Zambon; Peter Libby Journal: Cardiovasc Diabetol Date: 2019-06-04 Impact factor: 9.951
Authors: Anand Thakarakkattil Narayanan Nair; Louise A Donnelly; Adem Y Dawed; Sushrima Gan; Ranjit M Anjana; Mohan Viswanathan; Colin N A Palmer; Ewan R Pearson Journal: Endocrinol Diabetes Metab Date: 2020-01-07