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Glucose ingestion in cystic fibrosis induces severe redox imbalance: A potential role in diabetes
Journal of Cystic Fibrosis ( IF 5.4 ) Pub Date : 2020-05-01 , DOI: 10.1016/j.jcf.2020.02.010
William R Hunt 1 , Jason M Hansen 2 , Arlene A Stecenko 3
Affiliation  

BACKGROUND Cystic fibrosis related diabetes (CFRD) is the most common co-morbidity associated with cystic fibrosis (CF). Individuals with CF demonstrate airway and systemic oxidation compared to people without CF. Furthermore, systemic oxidation precipitated by hyperglycemia in non-CF diabetes has been shown to lead to enhanced inflammation. We hypothesized that the presence of both CF and diabetes in an individual would result in hyperglycemia-induced redox imbalance to an oxidative state. This in turn would result in enhanced production of pro-inflammatory cytokines. METHODS Systemic redox balance and pro-inflammatory cytokines were measured before and following a standard oral glucose tolerance test in healthy controls (HC) and in CF individuals with a spectrum of glucose homeostasis (i.e. normal glucose tolerant - NGT, prediabetes or frank CFRD). RESULTS There were no significant differences between groups in terms of basal or glucose-induced levels of inflammatory markers. However, baseline systemic redox potential was significantly more oxidized in CF subjects with prediabetes and CFRD compared to both CF with NGT and HC. Systemic oxidation was significantly worsened, and to a profound degree, two hours following ingestion of glucose in all CF groups (NGT, prediabetes, and CFRD). The level of redox imbalance at the two hour point was the same in all three CF groups and was not associated with the degree of hyperglycemia. There was a significant correlation between worse systemic oxidation and reduced insulin secretion. CONCLUSIONS This supports a newly identified abnormality of metabolism in CF - glucose induced redox imbalance to the oxidative state.

中文翻译:

囊性纤维化中的葡萄糖摄入会导致严重的氧化还原失衡:在糖尿病中的潜在作用

背景囊性纤维化相关糖尿病(CFRD)是与囊性纤维化(CF)相关的最常见的共病。与没有 CF 的人相比,患有 CF 的人表现出气道和全身氧化。此外,非 CF 糖尿病中高血糖引起的全身氧化已被证明会导致炎症增强。我们假设个体同时存在 CF 和糖尿病会导致高血糖引起的氧化还原失衡到氧化状态。这反过来会导致促炎细胞因子的产生增加。方法 在健康对照 (HC) 和具有一系列葡萄糖稳态(即正常葡萄糖耐受 - NGT,糖尿病前期或坦率的 CFRD)。结果 在基础或葡萄糖诱导的炎症标志物水平方面,各组之间没有显着差异。然而,与具有 NGT 和 HC 的 CF 相比,患有糖尿病前期和 CFRD 的 CF 受试者的基线全身氧化还原电位明显更多地被氧化。在所有 CF 组(NGT、前驱糖尿病和 CFRD)中,在摄入葡萄糖后两小时,全身氧化显着恶化,并在很大程度上恶化。在所有三个 CF 组中,两个小时点的氧化还原失衡水平相同,并且与高血糖程度无关。全身氧化恶化与胰岛素分泌减少之间存在显着相关性。结论 这支持了新发现的 CF 代谢异常 - 葡萄糖诱导的氧化还原失衡到氧化状态。结果 在基础或葡萄糖诱导的炎症标志物水平方面,各组之间没有显着差异。然而,与具有 NGT 和 HC 的 CF 相比,患有前驱糖尿病和 CFRD 的 CF 受试者的基线全身氧化还原电位明显更多地被氧化。在所有 CF 组(NGT、前驱糖尿病和 CFRD)中,在摄入葡萄糖后两小时,全身氧化显着恶化,并在很大程度上恶化。在所有三个 CF 组中,两个小时点的氧化还原失衡水平相同,并且与高血糖程度无关。全身氧化恶化与胰岛素分泌减少之间存在显着相关性。结论 这支持了新发现的 CF 代谢异常 - 葡萄糖诱导的氧化还原失衡到氧化状态。结果 在基础或葡萄糖诱导的炎症标志物水平方面,各组之间没有显着差异。然而,与具有 NGT 和 HC 的 CF 相比,患有糖尿病前期和 CFRD 的 CF 受试者的基线全身氧化还原电位明显更多地被氧化。在所有 CF 组(NGT、前驱糖尿病和 CFRD)中,在摄入葡萄糖后两小时,全身氧化显着恶化,并在很大程度上恶化。在所有三个 CF 组中,两个小时点的氧化还原失衡水平相同,并且与高血糖程度无关。全身氧化恶化与胰岛素分泌减少之间存在显着相关性。结论 这支持了新发现的 CF 代谢异常 - 葡萄糖诱导的氧化还原失衡到氧化状态。
更新日期:2020-05-01
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