Davis Timothy M E, Beilby John, Davis Wendy A, Olynyk John K, Jeffrey Gary P, Rossi Enrico, Boyder Conchita, Bruce David G
School of Medicine and Pharmacology, Fremantle Hospital, University of Western Australia, Fremantle, Australia.
Diabetes Care. 2008 Sep;31(9):1795-801. doi: 10.2337/dc08-0248. Epub 2008 Jun 19.
To examine the relationship between iron status, hereditary hemochromatosis (HFE) gene mutations, and clinical features and outcomes of type 2 diabetes in a well-characterized representative sample of community-based patients.
HFE genotype data were available for 1,245 type 2 diabetic patients from the longitudinal observational Fremantle Diabetes Study (FDS), representing 96.2% of the total FDS type 2 diabetes cohort. Data were collected at recruitment between 1993 and 1996 and annually until the end of June 2001. Hospitalization and mortality data were available until the end of June 2006. The presence of the C282Y HFE mutation was determined in all subjects and H63D in C282Y heterozygotes. Fasting serum iron, transferrin, and ferritin were measured in all C282Y homozygotes and C282Y/H63D heterozygotes and in 286 randomly selected wild-type subjects. Multiple logistic regression analysis was performed to determine independent baseline associates of prevalent complications (myocardial infarction, cerebrovascular disease, retinopathy, neuropathy, and nephropathy), as was Cox proportional hazards modeling to determine predictors of incident complications and mortality.
Although there were expected positive associations between HFE gene mutations and serum iron and transferrin saturation, there were no independent positive associations between HFE gene status and either microvascular or macrovascular complications in cross-sectional and longitudinal analyses. HFE gene status did not independently predict cardiac or all-cause mortality. Measures of iron metabolism including serum ferritin were not associated with combined microvascular or macrovascular end points.
Directed screening for iron overload and/or HFE mutations appears unwarranted in patients with type 2 diabetes.
在一个特征明确的社区患者代表性样本中，研究铁状态、遗传性血色素沉着症（HFE）基因突变与2型糖尿病的临床特征及转归之间的关系。
来自纵向观察性弗里曼特尔糖尿病研究（FDS）的1245例2型糖尿病患者有HFE基因型数据，占FDS 2型糖尿病队列总数的96.2%。数据于1993年至1996年招募时收集，并每年收集直至2001年6月底。住院和死亡率数据可获取至2006年6月底。在所有受试者中检测C282Y HFE突变的存在，在C282Y杂合子中检测H63D突变。对所有C282Y纯合子和C282Y/H63D杂合子以及286例随机选择的野生型受试者测量空腹血清铁、转铁蛋白和铁蛋白。进行多因素logistic回归分析以确定常见并发症（心肌梗死、脑血管疾病、视网膜病变、神经病变和肾病）的独立基线关联因素，同时进行Cox比例风险模型分析以确定新发并发症和死亡率的预测因素。
尽管HFE基因突变与血清铁和转铁蛋白饱和度之间存在预期的正相关，但在横断面和纵向分析中，HFE基因状态与微血管或大血管并发症之间均无独立的正相关。HFE基因状态不能独立预测心脏或全因死亡率。包括血清铁蛋白在内的铁代谢指标与微血管或大血管联合终点无关。
对2型糖尿病患者进行铁过载和/或HFE突变的定向筛查似乎没有必要。
