Higher fecal butyrate is associated with lower time in euglycemic range in a cohort of 398 individuals with type 1 diabetes

Higher fecal butyrate is associated with lower time in euglycemic range in a cohort of 398 individuals with type 1 diabetes

Douwe F. de Wit1, Lente C.H.M. Blok1, Coco M. Fuhri Snethlage1, Johannes H.M. Levels1, Erik H. Serné1,2, Elena Rampanelli1-3, Stijn A. Meijnikman1, Max Nieuwdorp1,2, Nordin M.J. Hanssen1,2

  1. Department of Vascular Medicine, Amsterdam UMC
  2. Diabeter Centrum Amsterdam. Amsterdam
  3. Amsterdam institute for immunology and infectious diseases, Amsterdam

Introduction: Short chain fatty acids (SCFAs) are fermentation products of dietary fibres, usually regarded as beneficial microbial metabolites due to their anti-inflammatory properties and metabolic benefits. However, the relationship between faecal SCFAs and glycaemic control in individuals with type 1 diabetes is unknown.

Methods: In a cross-sectional cohort of 398 individuals with type 1 diabetes from the GUTDM1 cohort (64% female, mean age 42 ± 15 years, mean BMI 25±4 kg/m2, median diabetes duration 15 years [IQR 6-29]), we measured faecal short chain fatty acids (butyrate, acetate, propionate) and continuous glucose monitoring (CGM) metrics. Using a logistic regression model, adjusted for BMI, we associated SCFA concentrations with time in range (TIR), expressed as in (≥70%) or below (<70%) the guideline target.

Results: The median concentrations (µmol/g dryweight feces) of faecal SCFA [IQR] were 24.3 for butyrate [9.3-50.8], 72.2 for acetate [39.6-133.9] and 23.5 for propionate [13.1-43.5]. The median time in range in our cohort was 66[52-80]%. Lower butyrate levels were associated with a higher TIR (OR for TIR ≥70%: 0.77[0.61-0.95] and a lower TAR (OR 0.75 [0.59-0.93] per 177 µmol/g (1 SD) butyrate. The other SCFAs did not show an association with CGM-parameters. Adjusting for BMI as a potential confounder did not alter the effect of butyrate (OR 0,79 [0.62-0.98] for TIR). A higher faecal butyrate level was weakly correlated to a higher CRP (Spearman ρ = 0.10, p=0.09), but we found no associations between SCFAs and fibre intake, systolic blood pressure, leucocytes, insulin units per kg bodyweight and triglycerides.

Conclusion: Our findings indicate that higher faecal butyrate levels are associated with lower time in euglycemic range. Further mechanistic studies are needed to disentangle this relationship and ascertain whether enhanced butyrate production in the gut alone contributes to worsening glycemic control or is the result of an overall perturbation of the gut microbial ecosystem.