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. 2022 Jun 21;11(13):3573.
doi: 10.3390/jcm11133573.

Effects of Butyrate Supplementation on Inflammation and Kidney Parameters in Type 1 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

Ninna H Tougaard  1 , Marie Frimodt-Møller  1   2 , Hanne Salmenkari  3   4   5 , Elisabeth B Stougaard  1 , Andressa D Zawadzki  1 , Ismo M Mattila  1 , Tine W Hansen  1 , Cristina Legido-Quigley  1 , Sohvi Hörkkö  6   7 , Carol Forsblom  3   4   5 , Per-Henrik Groop  3   4   5   8 , Markku Lehto  3   4   5 , Peter Rossing  1   9
Affiliations

Effects of Butyrate Supplementation on Inflammation and Kidney Parameters in Type 1 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

Ninna H Tougaard et al. J Clin Med. .

Abstract

Type 1 diabetes is associated with increased intestinal inflammation and decreased abundance of butyrate-producing bacteria. We investigated the effect of butyrate on inflammation, kidney parameters, HbA1c, serum metabolites and gastrointestinal symptoms in persons with type 1 diabetes, albuminuria and intestinal inflammation. We conducted a randomized placebo-controlled, double-blind, parallel clinical study involving 53 participants randomized to 3.6 g sodium butyrate daily or placebo for 12 weeks. The primary endpoint was the change in fecal calprotectin. Additional endpoints were the change in fecal short chain fatty acids, intestinal alkaline phosphatase activity and immunoglobulins, serum lipopolysaccharide, CRP, albuminuria, kidney function, HbA1c, metabolites and gastrointestinal symptoms. The mean age was 54 ± 13 years, and the median [Q1:Q3] urinary albumin excretion was 46 [14:121] mg/g. The median fecal calprotectin in the butyrate group was 48 [26:100] μg/g at baseline, and the change was -1.0 [-20:10] μg/g; the median in the placebo group was 61 [25:139] μg/g at baseline, and the change was -12 [-95:1] μg/g. The difference between the groups was not significant (p = 0.24); neither did we find an effect of butyrate compared to placebo on the other inflammatory markers, kidney parameters, HbA1c, metabolites nor gastrointestinal symptoms. Twelve weeks of butyrate supplementation did not reduce intestinal inflammation in persons with type 1 diabetes, albuminuria and intestinal inflammation.

Keywords: albuminuria; butyrate; intestinal alkaline phosphatase; intestinal inflammation; type 1 diabetes.

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Conflict of interest statement

M.F.-M. reports having received research grants from Novo Nordisk and speaking fees from Boehringer Ingelheim, Novartis, Baxter and Sanofi. T.W.H. has shares in Novo Nordisk A/S. P.H.G. is an advisory board member of AbbVie, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Medscape, MSD, Mundipharma, Nestlé, Novartis, Novo Nordisk and Sanofi, and has received lecture honoraria from Astellas, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Elo Water, Genzyme, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, Sanofi and SCIARC. P.R. has received research support and personal fees from AstraZeneca and Novo Nordisk, and personal fees from Astellas, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, Sanofi, and Vifor; all fees are given to the Steno Diabetes Center Copenhagen. N.H.T., H.S., E.B.S., A.D.Z., I.M.M., C.L.Q., S.H., C.F. and M.L. have no conflicts of interest.

Figures

Figure 1
Figure 1
Flow diagram.
Figure 2
Figure 2
Effects of 12 weeks of treatment with sodium butyrate or placebo on fecal calprotectin. Each colored line represents one participant.
See this image and copyright information in PMC

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