Ellervik C, Mandrup-Poulsen T, Nordestgaard B G, Larsen L E, Appleyard M, Frandsen M, Petersen P, Schlichting P, Saermark T, Tybjaerg-Hansen A, Birgens H
Departments of Haematology L, Herlev Hospital, University of Copenhagen, DK-2730, Herlev, Denmark.
Lancet. 2001 Oct 27;358(9291):1405-9. doi: 10.1016/S0140-6736(01)06526-6.
Although genotyping studies suggest that hereditary haemochromatosis is one of the most common genetic disorders in white people, it is still thought of as an uncommon disease. Our aim was to test the hypothesis that hereditary haemochromatosis is a disease often overlooked in patients with late-onset type 1 diabetes mellitus, a late manifestation of untreated iron overload.
We did a retrospective study in which we genotyped for the C282Y and H63D mutations in the haemochromatosis gene in 716 unselected Danish patients who developed type 1 diabetes mellitus after age 30 years and 9174 controls from the general Danish population. We also screened for hereditary haemochromatosis by assessment of transferrin saturation.
More patients with diabetes (n=9, relative frequency 1.26%, 95% CI 0.58-2.37) than controls (23, 0.25%, 0.16-0.38) were homozygous for C282Y (odds ratio 4.6, 2.0-10.1, p=0.0001). These patients had unrecognised signs of haemochromatosis. Transferrin saturation and ferritin concentrations ranged from 57% to 102% and 17 microg/L to 8125 microg/L, respectively. Frequency of compound heterozygosity (C282Y/H63D) did not differ between patients with diabetes (eight) and controls (131) (odds ratio 0.8, 95% CI 0.4-1.7). Positive and negative predictive values of transferrin saturation greater than 50%, in identification of C282Y homozygosity, were 0.26 and 1.00, respectively. A saturation of less than 50% therefore excluded C282Y homozygosity, whereas a saturation of more than 50% suggested C282Y homozygosity.
Measurement of transferrin saturation followed by genetic testing could prevent liver and heart problems and improve life expectancy in patients with diabetes. Population screening before the onset of diabetes might improve the outlook of patients even further, but will be less cost effective.
尽管基因分型研究表明遗传性血色素沉着症是白人中最常见的遗传性疾病之一，但它仍被认为是一种罕见病。我们的目的是检验这样一个假设，即遗传性血色素沉着症是一种在迟发性1型糖尿病患者中常被忽视的疾病，是未经治疗的铁过载的晚期表现。
我们进行了一项回顾性研究，对716名30岁后患1型糖尿病的未经过选择的丹麦患者以及9174名丹麦普通人群对照进行血色素沉着症基因C282Y和H63D突变的基因分型。我们还通过评估转铁蛋白饱和度来筛查遗传性血色素沉着症。
糖尿病患者中C282Y纯合子（n = 9，相对频率1.26%，95%CI 0.58 - 2.37）比对照组（23，0.25%，0.16 - 0.38）更多（优势比4.6，2.0 - 10.1，p = 0.0001）。这些患者有未被识别的血色素沉着症体征。转铁蛋白饱和度和铁蛋白浓度分别在57%至102%和17μg/L至8125μg/L之间。糖尿病患者（8例）和对照组（131例）的复合杂合子（C282Y/H63D）频率无差异（优势比0.8，95%CI 0.4 - 1.7）。转铁蛋白饱和度大于50%在识别C282Y纯合子时的阳性预测值和阴性预测值分别为0.26和1.00。因此，饱和度小于50%可排除C282Y纯合子，而饱和度大于50%提示C282Y纯合子。
测量转铁蛋白饱和度后进行基因检测可预防糖尿病患者的肝脏和心脏问题并提高预期寿命。在糖尿病发病前进行人群筛查可能会进一步改善患者的前景，但成本效益较低。
