Non-diabetic hyperglycemia exacerbates disease severity in Mycobacterium tuberculosis infected guinea pigs.
Non-diabetic hyperglycemia exacerbates disease severity in Mycobacterium tuberculosis infected guinea pigs.
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DOI：
10.1371/journal.pone.0046824
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Basaraba RJ
中科院分区：
文献类型：
--
作者：
Podell BK;Ackart DF;Kirk NM;Eck SP;Bell C;Basaraba RJ
高血糖，糖尿病的诊断特征，也发生在与慢性炎症和全身胰岛素抵抗相关的非糖尿病患者。由于糖尿病患者活动性结核病的风险增加与高血糖的严重程度和持续时间有关，我们研究了饮食诱导的高血糖对非糖尿病豚鼠结核分枝杆菌感染严重程度的影响。在正常饮食的豚鼠中，通过每天喂食40%蔗糖溶液或水作为载体对照，诱导餐后高血糖。在Mtb H37Rv毒株气溶胶暴露当天开始饲喂蔗糖，并持续感染30或60天。尽管蔗糖喂养的动物在第30天出现更严重的高血糖，但直到第60天，肺部细菌或病变负担没有显著差异。然而，在第30天，较高的脾脏和淋巴结细菌和病变负荷表明蔗糖喂养动物更早和更严重的肺外结核。在蔗糖喂养和水喂养的动物中，血清游离脂肪酸（胰岛素抵抗的重要介质）在感染后第30天升高，并一直升高到感染后第60天。结核分枝杆菌感染介导的高血糖导致肺肉芽肿中晚期糖基化终产物（AGEs）的积累，蔗糖喂养加剧了这种积累。然而，在第60天，蔗糖和水喂养的豚鼠的组织和血清AGEs均升高。这些数据表明，结核分枝杆菌感染单独诱导胰岛素抵抗和慢性高血糖，并通过蔗糖喂养加剧。此外，结核分枝杆菌感染单独导致组织和血清AGEs的积累，这也是糖尿病和糖尿病并发症发病的核心。单是结核分枝杆菌感染加剧了胰岛素抵抗和高血糖，就可以解释为什么与非糖尿病患者和血糖水平控制良好的患者相比，高血糖控制不佳的糖尿病患者的结核病更为严重。
Hyperglycemia, the diagnostic feature of diabetes also occurs in non-diabetics associated with chronic inflammation and systemic insulin resistance. Since the increased risk of active TB in diabetics has been linked to the severity and duration of hyperglycemia, we investigated what effect diet-induced hyperglycemia had on the severity of Mycobacterium tuberculosis (Mtb) infection in non-diabetic guinea pigs. Post-prandial hyperglycemia was induced in guinea pigs on normal chow by feeding a 40% sucrose solution daily or water as a carrier control. Sucrose feeding was initiated on the day of aerosol exposure to the H37Rv strain of Mtb and continued for 30 or 60 days of infection. Despite more severe hyperglycemia in sucrose-fed animals on day 30, there was no significant difference in lung bacterial or lesion burden until day 60. However the higher spleen and lymph node bacterial and lesion burden at day 30 indicated earlier and more severe extrapulmonary TB in sucrose-fed animals. In both sucrose- and water-fed animals, serum free fatty acids, important mediators of insulin resistance, were increased by day 30 and remained elevated until day 60 of infection. Hyperglycemia mediated by Mtb infection resulted in accumulation of advanced glycation end products (AGEs) in lung granulomas, which was exacerbated by sucrose feeding. However, tissue and serum AGEs were elevated in both sucrose and water-fed guinea pigs by day 60. These data indicate that Mtb infection alone induces insulin resistance and chronic hyperglycemia, which is exacerbated by sucrose feeding. Moreover, Mtb infection alone resulted in the accumulation tissue and serum AGEs, which are also central to the pathogenesis of diabetes and diabetic complications. The exacerbation of insulin resistance and hyperglycemia by Mtb infection alone may explain why TB is more severe in diabetics with poorly controlled hyperglycemia compared to non-diabetics and patients with properly controlled blood glucose levels.
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