Baldwin Henry J, Green Aislinn E, Spellar Kayleigh M, Arthur Philip J, Phillips Hannah G, Patel Jeetesh V
Henry J Baldwin, Aislinn E Green, Kayleigh M Spellar, Philip J Arthur, Hannah G Phillips, Jeetesh V Patel, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom.
World J Diabetes. 2016 Jan 10;7(1):8-13. doi: 10.4239/wjd.v7.i1.8.
To establish a link between the risk of diabetes with haemoglobinopathies by examining available evidence of the effects of iron and blood glucose homeostasis from molecular to epidemiological perspectives.
A systematic literature search was performed using electronic literature databases using various search terms. The International Diabetes Federation World Atlas was used to generate a list of populations with high rates of diabetes. PubMed, Scopus and Google Scholar were used to identify which of these populations also had a reported prevalence of haemoglobin abnormalities.
Abnormalities in iron homeostasis leads to increases in reactive oxygen species in the blood. This promotes oxidative stress which contributes to peripheral resistance to insulin in two ways: (1) reduced insulin/insulin receptor interaction; and (2) β-cell dysfunction. Hepcidin is crucial in terms of maintaining appropriate amounts of iron in the body and is in turn affected by haemoglobinopathies. Hepcidin also has other metabolic effects in places such as the liver but so far the extent of these is not well understood. It does however directly control the levels of serum ferritin. High serum ferritin is found in obese patients and those with diabetes and a meta-analysis of the various studies shows that high serum ferritin does indeed increase diabetes risk.
From an epidemiological standpoint, it is plausible that the well-documented protective effects of haemoglobinopathies with regard to malaria may have also offered other evolutionary advantages. By contributing to peripheral insulin resistance, haemoglobinopathies may have helped to sculpt the so-called "thrifty genotype", which hypothetically is advantageous in times of famine. The prevalence data however is not extensive enough to provide concrete associations between diabetes and haemoglobinopathies - more precise studies are required.
通过从分子到流行病学的角度审视铁与血糖稳态影响的现有证据，建立血红蛋白病与糖尿病风险之间的联系。
使用电子文献数据库，通过各种检索词进行系统的文献检索。利用国际糖尿病联盟世界地图集生成糖尿病高发人群列表。使用PubMed、Scopus和谷歌学术来确定这些人群中哪些也有血红蛋白异常的报告患病率。
铁稳态异常导致血液中活性氧增加。这会促进氧化应激，氧化应激通过两种方式导致外周胰岛素抵抗：（1）胰岛素/胰岛素受体相互作用减少；（2）β细胞功能障碍。铁调素在维持体内适当铁含量方面至关重要，反过来又受血红蛋白病影响。铁调素在肝脏等部位也有其他代谢作用，但目前其程度尚不清楚。然而，它确实直接控制血清铁蛋白水平。肥胖患者和糖尿病患者中发现血清铁蛋白水平较高，对各项研究的荟萃分析表明，高血清铁蛋白确实会增加糖尿病风险。
从流行病学角度来看，有充分记录的血红蛋白病对疟疾的保护作用可能也提供了其他进化优势，这是合理的。通过导致外周胰岛素抵抗，血红蛋白病可能有助于塑造所谓的“节俭基因型”，假设在饥荒时期这是有利的。然而，患病率数据还不够广泛，无法提供糖尿病与血红蛋白病之间的确切关联——需要更精确的研究。
