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

Abstract

Background: Fecal calprotectin, a marker of inflammation, is increased in persons with type 1 diabetes (T1D) and kidney disease. This may be explained by a reduction of butyrate-producing bacterial species in the gut. Butyrate supplementation has beneficial effects on intestinal inflammation in inflammatory bowel disease but has never been tested in persons with T1D. Objective: To assess the effect of sodium butyrate on fecal calprotectin and other inflammatory markers, kidney parameters, hba1c and gastrointestinal symptoms in persons with T1D and intestinal inflammation. Methods: Randomized placebo-controlled, double-blind, parallel clinical study including 53 participants with T1D, albuminuria and intestinal inflammation (elevated fecal calprotectin) . Participants were assigned to receive 3.6 g sodium butyrate daily (n=28) or placebo (n=25) for 12 weeks. Primary endpoint was fecal calprotectin changes, and additional outcomes were fecal short chain fatty acids, intestinal alkaline phosphatase activity and immunoglobulins; serum lipopolysaccharide, serum C-reactive protein, albuminuria, kidney function, hba1c and gastrointestinal symptoms. Results: Mean age of the participants was 54±13 years, 43% were women, diabetes duration was 30±15 years and median [Q1:Q3] urinary albumin excretion was 46 [14:121] mg/g. Median fecal calprotectin in the butyrate group was 48 [26:100] μg/g at baseline and change was -1.0 [-20:10] μg/g, the median in the placebo group was 61 [25:139] μg/g at baseline and change was -12 [-95:1] μg/g. Difference in change between groups was not significant (p=0.24) . Neither did we find an effect of butyrate compared to placebo on the other fecal and circulating inflammatory markers, kidney parameters, hba1c or gastrointestinal symptoms. Conclusion: Oral butyrate supplementation for 12 weeks did not reduce fecal calprotectin in persons with T1D and intestinal inflammation. Disclosure N.H.Tougaard: None. P.Groop: Advisory Panel; Novo Nordisk, Sanofi, Other Relationship; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Mundipharma, Speaker's Bureau; Medscape. M.Lehto: None. P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. M.Frimodt-moeller: None. H.Salmenkari: None. E.Buur stougaard: Other Relationship; Novo Nordisk. I.Mattila: None. T.W.Hansen: Stock/Shareholder; Novo Nordisk A/S. C.Legido-quigley: None. S.Hörkkö: None. C.Forsblom: None.