Raimund Pechlaner1, Günter Weiss2, Sukhvinder Bansal3, Manuel Mayr4, Peter Santer5, Barbara Pallhuber6, Marlene Notdurfter6, Enzo Bonora7, Johann Willeit1, Stefan Kiechl1. 1. Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. 2. Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria. 3. Institute of Pharmaceutical Science, King's College London, London, UK. 4. King's British Heart Foundation Centre, King's College London, London, UK. 5. Department of Laboratory Medicine, Hospital of Bruneck, Bruneck, Italy. 6. Department of Internal Medicine, Hospital of Bruneck, Bruneck, Italy. 7. Division of Endocrinology, Diabetes and Metabolic Diseases, University and Hospital Trust of Verona, Verona, Italy.
Abstract
BACKGROUND: Type 2 diabetes mellitus (T2DM) is closely associated with elevated body iron stores. The hormone hepcidin is the key regulator of iron homeostasis. Inadequately low hepcidin levels were recently reported in subjects with manifest T2DM. We investigated whether alterations of hepcidin levels precede the manifestation of T2DM and predict T2DM development independently of established risk conditions. METHODS: This prospective population-based study included 675 subjects aged 50-89 years, 51.9% of whom were female. Hepcidin levels were measured by gold standard tandem mass spectrometry. Diabetes was diagnosed according to American Diabetes Association criteria, and incident diabetes was recorded between baseline in 2000 and 2010. RESULTS: The baseline hepcidin-to-ferritin ratio in subjects that subsequently developed diabetes during follow-up was reduced on average by 29.8% as compared with subjects with normal glucose tolerance (95% confidence interval, -50.7% to -0.2%; p = 0.049). After adjustment for age, sex, and serum ferritin, higher hepcidin levels were associated with reduced risk of incident diabetes (hazard ratio per 1-unit higher log2 hepcidin, 0.80; 95% confidence interval, 0.64-0.98; p = 0.035; 33 events). Additional adjustment for established diabetes risk factors and determinants of hepcidin concentration did not appreciably change these results (HR, 0.81; 95% CI, 0.66-0.99). Likewise, inadequately low hepcidin levels were also detected in subjects with prevalent T2DM (n = 76). CONCLUSIONS: Hepcidin levels that are inadequately low in relation to body iron stores are an independent predictor for incident T2DM and may contribute to diabetes-related tissue iron overload.
BACKGROUND:Type 2 diabetes mellitus (T2DM) is closely associated with elevated body iron stores. The hormone hepcidin is the key regulator of iron homeostasis. Inadequately low hepcidin levels were recently reported in subjects with manifest T2DM. We investigated whether alterations of hepcidin levels precede the manifestation of T2DM and predict T2DM development independently of established risk conditions. METHODS: This prospective population-based study included 675 subjects aged 50-89 years, 51.9% of whom were female. Hepcidin levels were measured by gold standard tandem mass spectrometry. Diabetes was diagnosed according to American Diabetes Association criteria, and incident diabetes was recorded between baseline in 2000 and 2010. RESULTS: The baseline hepcidin-to-ferritin ratio in subjects that subsequently developed diabetes during follow-up was reduced on average by 29.8% as compared with subjects with normal glucose tolerance (95% confidence interval, -50.7% to -0.2%; p = 0.049). After adjustment for age, sex, and serum ferritin, higher hepcidin levels were associated with reduced risk of incident diabetes (hazard ratio per 1-unit higher log2 hepcidin, 0.80; 95% confidence interval, 0.64-0.98; p = 0.035; 33 events). Additional adjustment for established diabetes risk factors and determinants of hepcidin concentration did not appreciably change these results (HR, 0.81; 95% CI, 0.66-0.99). Likewise, inadequately low hepcidin levels were also detected in subjects with prevalent T2DM (n = 76). CONCLUSIONS:Hepcidin levels that are inadequately low in relation to body iron stores are an independent predictor for incident T2DM and may contribute to diabetes-related tissue iron overload.
Authors: Driton Vela; Jovica Leshoski; Elizabeta S Gjorgievska; Nikola Hadzi-Petrushev; Muharrem Jakupaj; Ramadan B Sopi; Mitko Mladenov Journal: Oman Med J Date: 2017-05
Authors: Jordi Mayneris-Perxachs; José María Moreno-Navarrete; José Manuel Fernández-Real Journal: Nat Rev Endocrinol Date: 2022-08-19 Impact factor: 47.564