Potential Detrimental Interactions Between Metformin and Supplemental Dietary Fiber in Type 2 Diabetes

IF 3.7 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Rosemary M. Hall, Amber Parry-Strong, David O'Sullivan, Jeremy D. Krebs, Olivier Gasser
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引用次数: 0

Abstract

Higher intakes of dietary fiber have been associated with a reduced risk of developing Type 2 Diabetes (T2DM) and cardiovascular disease [1, 2]. Fiber supplementation improves overall glycaemia, with reductions in Hba1c and better insulin sensitivity [3]. However, there is significant reported heterogeneity on the effects of supplemental fiber on glycaemic outcomes for people with T2DM, potentially due to variations in absorption and metabolism. These differences, we believe, are worth examining more closely, especially considering the complexities of the gut microbiome, medications used in T2DM, and the role of the background diet [3].

In our recent study, we investigated the impact of supplemental fiber on glucose metabolism and glycemic control in people with pre-diabetes and T2DM who had a low habitual fiber intake. We recruited 30 participants with HbA1c levels ranging from 45 to 70 mmol/mol, and provided them with psyllium fiber supplements for 12 weeks.

Although we observed reductions in body mass index (BMI) and improvements in lipid profiles, HbA1c levels did not significantly improve overall. Surprisingly, participants taking metformin alone experienced an increase in HbA1c, while those not taking metformin experienced a slight reduction (Figure 1).

This discrepancy points to a critical issue: the potential interaction between metformin and fiber supplementation. Metformin, the most common medication for T2DM works by reducing hepatic glucose production and improving insulin sensitivity [4]. However, metformin primarily acts within the gastrointestinal tract, commonly producing gastrointestinal side-effects and may alter gut microbiome, with the potential to directly affect fiber absorption [5]. Our findings suggest that when combined with fiber supplementation, metformin may impair the metabolic benefits typically associated with fiber, alongside a potential detrimental effect on the glycaemic benefits of metformin.

This phenomenon is consistent with previous research. For example, a study by Tramontana et al. found that a high-fiber diet did not improve HbA1c in 78 patients with T2DM on metformin monotherapy [6], while other studies observed more promising results when fiber was combined with different medications [7]. These findings highlight the need for a more nuanced understanding of how dietary fiber interacts with both the gut microbiome and medications like metformin.

Moreover, the gut microbiota's role in metabolism is integral to the overall metabolic benefits. Dietary fiber, especially in the form of psyllium, is fermented by gut bacteria into short-chain fatty acids (SCFAs), which have been shown to improve immune function and reduce inflammation—factors that are crucial in managing T2DM [7, 8]. However, both metformin and fiber alter the gut microbiome in different ways, and this complex interaction may undermine the potential benefits of both fiber supplementation and metformin for some individuals [8, 9].

Given these unexpected findings, which may have clinically important implications, we urge caution when recommending fiber supplementation for people with T2DM on metformin. While a high habitual intake of dietary fiber may provide metabolic benefits, it is essential to better understand how supplemental fiber interacts with metformin. Until this interaction is clarified, healthcare providers should carefully consider the use of fiber supplements in this population.

The protocol for this study was developed by all the authors. Amber Parry-Strong (A.P.S.) recruited participants and performed study visits. Rosemary Hall (R.H.) and Jeremy Krebs (J.K.) provided clinical expertise for diabetes care. David O'Sullivan (D.O'S.) performed laboratory analysis of the samples and statistical analysis of the data. All authors contributed to data interpretation. RH wrote the manuscript and all authors contributed to the manuscript review.

The authors declare no conflicts of interest.

Abstract Image

二甲双胍和补充膳食纤维对2型糖尿病的潜在有害相互作用
较高的膳食纤维摄入量与患2型糖尿病(T2DM)和心血管疾病的风险降低有关[1,2]。补充纤维可改善总血糖,降低糖化血红蛋白,改善胰岛素敏感性。然而,据报道,补充纤维对2型糖尿病患者血糖结局的影响存在显著的异质性,可能是由于吸收和代谢的差异。我们认为,这些差异值得更仔细地研究,特别是考虑到肠道微生物群的复杂性、2型糖尿病患者使用的药物以及背景饮食的作用。在我们最近的研究中,我们调查了补充纤维对糖尿病前期和2型糖尿病患者葡萄糖代谢和血糖控制的影响,这些患者通常纤维摄入量低。我们招募了30名HbA1c水平在45至70 mmol/mol之间的参与者,并为他们提供车前草纤维补充剂12周。虽然我们观察到身体质量指数(BMI)的降低和脂质谱的改善,但HbA1c水平总体上没有显著改善。令人惊讶的是,单独服用二甲双胍的参与者HbA1c升高,而不服用二甲双胍的参与者HbA1c略有下降(图1)。这种差异指出了一个关键问题:二甲双胍和纤维补充剂之间潜在的相互作用。二甲双胍是治疗2型糖尿病最常用的药物,其作用是降低肝脏葡萄糖生成并改善胰岛素敏感性。然而,二甲双胍主要在胃肠道内起作用,通常会产生胃肠道副作用,并可能改变肠道微生物群,有可能直接影响纤维吸收。我们的研究结果表明,当与纤维补充剂结合使用时,二甲双胍可能会损害通常与纤维相关的代谢益处,同时对二甲双胍的降血糖益处产生潜在的有害影响。这一现象与之前的研究一致。例如,Tramontana等人的一项研究发现,高纤维饮食并没有改善78例二甲双胍单药治疗[6]的T2DM患者的HbA1c,而其他研究发现,当纤维与不同药物[7]联合使用时,结果更有希望。这些发现强调,需要更细致地了解膳食纤维如何与肠道微生物群和二甲双胍等药物相互作用。此外,肠道菌群在新陈代谢中的作用是整体代谢益处的组成部分。膳食纤维,尤其是车前草形式的膳食纤维,可被肠道细菌发酵成短链脂肪酸(SCFAs),已被证明可以改善免疫功能并减少炎症因子,这对控制T2DM至关重要[7,8]。然而,二甲双胍和纤维都以不同的方式改变肠道微生物群,这种复杂的相互作用可能会破坏纤维补充和二甲双胍对某些个体的潜在益处[8,9]。鉴于这些意想不到的发现,可能具有重要的临床意义,我们敦促在推荐给服用二甲双胍的2型糖尿病患者补充纤维时要谨慎。虽然高膳食纤维的习惯性摄入可能提供代谢益处,但有必要更好地了解补充纤维如何与二甲双胍相互作用。在这种相互作用被澄清之前,医疗保健提供者应该仔细考虑在这一人群中使用纤维补充剂。这项研究的方案是由所有作者共同制定的。Amber Parry-Strong (A.P.S.)招募参与者并进行研究访问。罗斯玛丽·霍尔(R.H.)和杰里米·克雷布斯(J.K.)提供了糖尿病护理的临床专业知识。David O'Sullivan (D.O'S)对样品进行了实验室分析,并对数据进行了统计分析。所有作者都对数据解释做出了贡献。RH撰写了手稿,所有作者都参与了手稿审查。作者声明无利益冲突。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Diabetes
Journal of Diabetes ENDOCRINOLOGY & METABOLISM-
CiteScore
6.50
自引率
2.20%
发文量
94
审稿时长
>12 weeks
期刊介绍: Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The Editorial team is international with a unique mix of Asian and Western participation. The Editors welcome submissions in form of original research articles, images, novel case reports and correspondence, and will solicit reviews, point-counterpoint, commentaries, editorials, news highlights, and educational content.
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