铁代谢多种生物标志物与2型糖尿病的关联：欧洲癌症与营养前瞻性调查-INTERACT研究
Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study.
作者信息
Podmore Clara, Meidtner Karina, Schulze Matthias B, Scott Robert A, Ramond Anna, Butterworth Adam S, Di Angelantonio Emanuele, Danesh John, Arriola Larraitz, Barricarte Aurelio, Boeing Heiner, Clavel-Chapelon Françoise, Cross Amanda J, Dahm Christina C, Fagherazzi Guy, Franks Paul W, Gavrila Diana, Grioni Sara, Gunter Marc J, Gusto Gaelle, Jakszyn Paula, Katzke Verena, Key Timothy J, Kühn Tilman, Mattiello Amalia, Nilsson Peter M, Olsen Anja, Overvad Kim, Palli Domenico, Quirós J Ramón, Rolandsson Olov, Sacerdote Carlotta, Sánchez-Cantalejo Emilio, Slimani Nadia, Sluijs Ivonne, Spijkerman Annemieke M W, Tjonneland Anne, Tumino Rosario, van der A Daphne L, van der Schouw Yvonne T, Feskens Edith J M, Forouhi Nita G, Sharp Stephen J, Riboli Elio, Langenberg Claudia, Wareham Nicholas J
机构信息
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K.
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
出版信息
Diabetes Care. 2016 Apr;39(4):572-81. doi: 10.2337/dc15-0257. Epub 2016 Feb 9.
OBJECTIVE
Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores in T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigated associations of ferritin, transferrin saturation (TSAT), serum iron, and transferrin with T2D incidence to clarify the role of iron in the pathogenesis of T2D.
RESEARCH DESIGN AND METHODS
The European Prospective Investigation into Cancer and Nutrition-InterAct study includes 12,403 incident T2D cases and a representative subcohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron, and transferrin with incident T2D in 11,052 cases and a random subcohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population.
RESULTS
Higher levels of ferritin and transferrin were associated with a higher risk of T2D (hazard ratio [HR] [95% CI] in men and women, respectively: 1.07 [1.01-1.12] and 1.12 [1.05-1.19] per 100 μg/L higher ferritin level; 1.11 [1.00-1.24] and 1.22 [1.12-1.33] per 0.5 g/L higher transferrin level) after adjustment for age, center, BMI, physical activity, smoking status, education, hs-CRP, alanine aminotransferase, and γ-glutamyl transferase. Elevated TSAT (≥45% vs. <45%) was associated with a lower risk of T2D in women (0.68 [0.54-0.86]) but was not statistically significantly associated in men (0.90 [0.75-1.08]). Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (Pinteraction < 0.01).
CONCLUSIONS
The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D.
目的
观察性研究表明铁蛋白与2型糖尿病（T2D）之间存在关联，提示高铁储存量在T2D发生发展中起作用。然而，铁蛋白受铁储存量以外的因素影响，而铁代谢的其他生物标志物受此类因素影响较小。我们研究了铁蛋白、转铁蛋白饱和度（TSAT）、血清铁和转铁蛋白与T2D发病率之间的关联，以阐明铁在T2D发病机制中的作用。
研究设计与方法
欧洲癌症与营养前瞻性调查-交互作用研究纳入了12403例T2D新发病例以及来自欧洲队列的16154名个体的代表性亚队列，随访时间达399万人年。我们在11052例病例和15182名个体的随机亚队列中研究了铁蛋白、TSAT、血清铁和转铁蛋白与T2D发病的前瞻性关联，并评估了这些关联在不同人群亚组中是否存在差异。
结果
在调整年龄、中心、体重指数、体力活动、吸烟状况、教育程度、高敏C反应蛋白、丙氨酸氨基转移酶和γ-谷氨酰转移酶后，较高水平的铁蛋白和转铁蛋白与T2D风险较高相关（男性和女性的风险比[HR][95%置信区间]分别为：铁蛋白水平每升高100μg/L，HR为1.07[1.01 - 1.12]和1.12[1.05 - 1.19]；转铁蛋白水平每升高0.5g/L，HR为1.11[1.00 - 1.24]和1.22[1.12 - 1.33]）。TSAT升高（≥45%对比<45%）与女性T2D风险较低相关（0.68[0.54 - 0.86]），但在男性中无统计学显著关联（0.90[0.75 - 1.08]）。血清铁与T2D无关。铁蛋白与T2D的关联在较瘦个体中更强（交互作用P<0.01）。
结论
TSAT和转铁蛋白与T2D的关联模式表明，铁储存量与T2D之间的潜在关系比铁蛋白与T2D的关联所提示的简单联系更为复杂。
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