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Journal of Diabetes 7 (2015) 729–739
O R I G I N A L A RT I C L E
Acarbose treatment affects the serum levels of inflammatory cytokines and the gut content of bifidobacteria in Chinese patients with type 2 diabetes mellitus Benli SU,1,† Haixia LIU,1,† Jing LI,1 Yongjuan SUNLI,1 Ben LIU,2 Dandan LIU,2 Ping ZHANG1 and Xiuxiang MENG3 1 Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Dalian Medical University, 2Laboratory Center for Clinical Diagnosis, and 3Department of Laboratory Hematology, School of Laboratory Medicine, Dalian Medical University, Dalian, China
Correspondence Xiuxiang Meng, Department of Laboratory Hematology, School of Laboratory Medicine, Dalian Medical University, Dalian 116044, China. Tel: + 86 411 8611 0389 Fax: + 86 411 8458 0261 Email:
[email protected] †
These authors contributed equally. Trial registration: This trial was registered at ChiCTR.org as ChiCTR-TRC-11001753. Received 7 August 2014; revised 14 September 2014; accepted 1 October 2014. doi: 10.1111/1753-0407.12232
Abstract Background: The effects of acarbose add-on therapy on gut microbiota and inflammatory cytokines were investigated in Chinese patients with type 2 diabetes mellitus (DM). Methods: Ninety-five DM patients were randomly allocated to two groups: 59 to Group A who received antidiabetic treatment that included acarbose 150 mg/day, and 36 to Group B who received similar treatment to Group A but without acarbose. Forty-five healthy volunteers were selected as a control group. Serum concentrations of inflammatory cytokines were determined by ELISA, and the contents of 16S rDNA of gut bacteria were determined by real-time quantitative polymerase chain reaction. General linear analysis for repeated measurements was used to analyze trend differences between the two diabetic groups. Results: After 4 weeks of antidiabetic treatment, the gut contents of Bifidobacterium longum and Enterococcus faecalis were significantly increased in both diabetes groups. The increase of Bifidobacterium longum (P = 0.004) and the decrease of lipopolysaccharides (LPS) (P < 0.001) and prothrombin activator inhibitor-1 (P = 0.003) were more significant in Group A. Decreases of monocyte chemoattractant protein-1 and LPS were more significant in patients whose HbA1c decrease was ≥1%, but there were no significant differences in the changes of other cytokines and gut bacteria between patients with HbA1c 2.5 times the upper limit of the normal range or creatinine clearance 0.05) (Fig. 2c–e). Correlation of the changes of gut bacteria with serum inflammatory cytokines and biochemical indexes after 4 weeks of treatment To investigate whether modulation of gut microbiota was correlated with changes of inflammatory cytokines (concentrations after 4 weeks of treatment minus the baseline concentration), a Pearson correlation analysis was performed. As shown in Table 3, changes in the content of Enterococcus faecalis were negatively correlated with changes in LPS concentrations, while changes in the content of Bifidobacterium longum were positively correlated with changes in high-density lipoprotein cholesterol (HDL-C) concentrations. Partial correlation
Figure 1 Effects of antidiabetic treatment on the content of gut microbiota in type 2 diabetes mellitus (DM) patients. The contents of 16S rDNA of fecal Bifidobacterium longum (a) and Enterococcus faecalis (b) in DM patients before and after antidiabetic treatment were quantified by real-time quantitative polymerase chain reaction (PCR), and data were expressed as means ± SD. Changes of Bifidobacterium longum in the acarbose-treated group (×) were more significant than in the non-acarbose-treated group (□). However, no statistically significant difference in the content of Enterococcus faecalis was observed between the two groups.
analysis indicated that the negative correlation between the changes of Enterococcus faecalis and the LPS concentration could be modulated by Bifidobacteria longum. When the content of Bifidobacteria longum was used as a control, partial correlation analysis showed that the correlation between changes of Enterococcus faecalis and LPS was positive rather than negative (r = 0.259; P = 0.020), suggesting that Enterococcus faecalis might
© 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
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Acarbose, inflammation, and gut microbiota
B. SU et al.
Figure 2 Effects of antidiabetic treatment on concentrations of inflammatory cytokines in type 2 diabetes mellitus (DM) patients. The estimated marginal mean concentrations of LPS (lipopolysaccharides) (a), PAI-1 (prothrombin activator inhibitor-1), (b), TNF-α (tumor necrosis factor-α) (c), MCP-1 (monocyte chemoattractant protein-1) (d), and hsCRP (e) in DM patients before and after antidiabetic treatment were quantified by ELISA, and data were expressed as means ± SD. Statistical differences between the two groups in the changes of various cytokines after 4 weeks of treatment are indicated. ×, acarbose-treated patients; □, non-acarbose-treated patients.
be an important supplier of serum LPS, and that the increase in the content of Bifidobacteria longum could modulate the influence of Enterococcus faecalis.
Effects of glycemic control on inflammatory cytokines and gut bacteria in patients with DM To investigate whether the glycemic control status can influence changes in inflammatory cytokines and gut bacteria, the patients in both diabetic groups were divided into two subgroups: those with an HbA1c decrease (i.e. the HbA1c value after 4 weeks of treatment minus the baseline value) of ≥1% and those with an HbA1c decrease of
