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1 型糖尿病:氧化应激、细胞因子、胃肠道动力和小肠细菌过度生长的复杂相互作用。

Type 1 diabetes mellitus: Complex interplay of oxidative stress, cytokines, gastrointestinal motility and small intestinal bacterial overgrowth.

机构信息

Department of Super Specialty of Gastroenterology, Post Graduate Institute of Medical Education & Research, Chandigarh, India.

Department of Endocrinology, Post Graduate Institute of Medical Education & Research, Chandigarh, India.

出版信息

Eur J Clin Invest. 2018 Nov;48(11):e13021. doi: 10.1111/eci.13021. Epub 2018 Sep 19.

Abstract

BACKGROUND

Oxidative stress is risk factor in progression of diabetes. It can increase cytokine production via several different mechanisms. Inflammation can affect gut neural apparatus that may lead to dysmotility which may exaggerate occurrence of bacterial overgrowth in intestine. Thus, a study was planned to understand the complex interplay of oxidative stress, inflammatory cytokines, gut motility and small intestinal bacterial overgrowth in type 1 diabetes mellitus (T1DM) patients.

MATERIALS AND METHODS

Seventy-five T1DM patients and 75 healthy controls were enrolled. Small intestinal bacterial overgrowth (SIBO) and orocecal transit time (OCTT) were measured using noninvasive glucose and lactulose hydrogen breath tests, respectively. Plasma levels of interleukin-6 (IL-6), tissue necrosis factor-alfa (TNF-α) and interleukin-10 (IL-10) were measured in all subjects by ELISA. Oxidative stress and anti-oxidant parameters were measured by standard methods.

RESULTS

Out of 75 T1DM patients, 36 were males with Mean ± SD age 22.3 ± 5.2 years, IL-6, TNF-α and IL-10 were significantly higher (P < 0.05) in T1DM patients as compared to controls. Lipid peroxidation (LPO) was significantly increased (P < 0.001), while reduced glutathione (GSH) significantly decreased (P < 0.01), whereas superoxide dismutase (SOD) and catalase significantly higher (P < 0.05) in T1DM patients as compared to controls. Positive correlation was observed between glycated haemoglobin (HbA1c) levels with LPO and negative correlation with GSH. Further, there was positive correlation between LPO and inflammatory cytokines (IL-6 & IL-10). OCTT was delayed and SIBO significantly higher in patients as compared to controls. On comparison of T1DM based on duration of disease, effect of all parameters was more pronounced in disease duration ≥5 years.

CONCLUSION

This study indicates that there is association between hyperglycaemia, oxidative stress (LPO), anti-oxidants (GSH, SOD and catalase), inflammatory cytokines, gut motility (OCTT), and small intestinal overgrowth in type 1 diabetes mellitus patients. This association is intensified as duration of disease increases.

摘要

背景

氧化应激是糖尿病进展的危险因素。它可以通过几种不同的机制增加细胞因子的产生。炎症会影响肠道神经装置,可能导致运动障碍,从而加剧肠道细菌过度生长。因此,计划进行一项研究,以了解 1 型糖尿病(T1DM)患者中氧化应激、炎症细胞因子、肠道动力和小肠细菌过度生长之间的复杂相互作用。

材料和方法

纳入 75 例 T1DM 患者和 75 名健康对照者。分别采用非侵入性葡萄糖和乳果糖氢呼气试验测量小肠细菌过度生长(SIBO)和口盲通过时间(OCTT)。采用 ELISA 法测定所有受试者血浆白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)水平。采用标准方法测定氧化应激和抗氧化参数。

结果

75 例 T1DM 患者中,男性 36 例,平均年龄 22.3±5.2 岁,T1DM 患者的 IL-6、TNF-α和 IL-10 明显高于对照组(P<0.05)。脂质过氧化(LPO)明显升高(P<0.001),还原型谷胱甘肽(GSH)明显降低(P<0.01),超氧化物歧化酶(SOD)和过氧化氢酶明显升高(P<0.05)T1DM 患者与对照组相比。糖化血红蛋白(HbA1c)水平与 LPO 呈正相关,与 GSH 呈负相关。此外,LPO 与炎症细胞因子(IL-6 和 IL-10)之间存在正相关。OCTT 延迟,SIBO 明显高于对照组。根据疾病持续时间比较 T1DM,所有参数的影响在疾病持续时间≥5 年时更为明显。

结论

本研究表明,1 型糖尿病患者的高血糖、氧化应激(LPO)、抗氧化剂(GSH、SOD 和过氧化氢酶)、炎症细胞因子、肠道动力(OCTT)和小肠过度生长之间存在关联。随着疾病持续时间的增加,这种关联会加剧。

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