Increased insulin secretory capacity but decreased insulin sensitivity after correction of iron overload by phlebotomy in hereditary haemochromatosis
Increased insulin secretory capacity but decreased insulin sensitivity after correction of iron overload by phlebotomy in hereditary haemochromatosis
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DOI：
10.1007/s00125-006-0445-7
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发表时间：
2006-11-01
期刊：
影响因子：
8.2
通讯作者：
McClain, D. A.
中科院分区：
文献类型：
--
作者：
Abraham, D.;Rogers, J.;McClain, D. A.
目的/假设我们最近证明，遗传性血色病的人胰岛素分泌能力下降，胰岛素敏感性代偿性增加。因此，我们确定了这些措施的变化后，纠正组织铁overload.Subjects和方法5非糖尿病受试者进行了研究，以前在最初的诊断时，通过OGTT和频繁采样的静脉葡萄糖耐量试验（FSIVGTT）进行放血，使他们的血清铁蛋白正常化。铁蛋白正常化后，他们再次进行了研究（33 +/- 4个月后，初步研究）OGTT和FSIVGTT.Results正常化的组织铁储备导致平均1.8倍的增加，在胰岛素曲线下的积分面积在OGTT（p < 0.0001），但在葡萄糖曲线下的面积没有显着变化（10%下降，p=0.32）。静脉切开术后，FSIVGTT测定的胰岛素分泌能力增加了2.2倍（对葡萄糖的急性胰岛素反应[AIRg]，p < 0.02），但同时胰岛素敏感性下降了70%（Si，p < 0.05）。处置指数（AIRgxSi）不变（增加5%，p=0.90）。BMI和空腹血糖无变化。在诊断血色病时，4名受试者患有IGT。铁蛋白正常化后，两个实现NGT和两个仍然与IGT，尽管2.5-和3.7倍增加胰岛素分泌capability.Conclusions/interpretation胰岛素分泌能力提高后，正常化的铁存储在遗传性血色病的受试者。葡萄糖耐量状态改善不完全是因为静脉切开术后胰岛素敏感性降低。我们得出结论，组织铁水平是胰岛素分泌和胰岛素作用的重要决定因素。
Aims/hypothesis We recently demonstrated that humans with hereditary haemochromatosis have decreased insulin secretory capacity with a compensatory increase in insulin sensitivity. We therefore determined how these measures change after correction of tissue iron overload.Subjects and methods Five non-diabetic subjects who had been studied previously at the time of initial diagnosis by means of the OGTT and frequently sampled intravenous glucose tolerance tests (FSIVGTT) underwent phlebotomy to normalise their serum ferritin. After normalisation of ferritin they were studied again (33 +/- 4 months after the initial studies) by OGTT and FSIVGTT.Results Normalisation of tissue iron stores resulted in an average 1.8-fold increase in the integrated area under the insulin curve during OGTT (p < 0.0001), but no significant change in the area under the glucose curve (10% decrease, p=0.32). After phlebotomy, there was a 2.2-fold increase in insulin secretory capacity as determined by FSIVGTT (acute insulin response to glucose [AIRg], p < 0.02) but a concomitant 70% fall in insulin sensitivity (Si, p < 0.05). The disposition index (AIRgxSi) was unchanged (5% increase, p=0.90). BMI and fasting glucose were unchanged. At the time of diagnosis of haemochromatosis, four of the subjects had IGT. After normalisation of ferritin, two achieved NGT and two remained with IGT, despite 2.5- and 3.7-fold increases in insulin secretory capacity.Conclusions/interpretation Insulin secretory capacity improves after normalisation of iron stores in subjects with hereditary haemochromatosis. Glucose tolerance status improves incompletely because of decreased insulin sensitivity after phlebotomy. We conclude that tissue iron levels are an important determinant of insulin secretion and insulin action.