Introduction and Objective: Obesity (Ob) and insulin resistance (IR) are high in T1D and gut microbial imbalance (dysbiosis) has been linked to the development of both. Studies show that metformin partially improves IR through gut microbiome changes in type 2 diabetes. Here, we examined this metformin effect on circulating gut microbial metabolites in overweight/obese (OW/OB) youth with T1D after treatment.
Methods: Using ultra-high performance liquid chromatography tandem mass spectrometry, we analyzed serum from a placebo-controlled randomized multi-center clinical trial (NCT01881828) in 140 OW/OB youth with T1D, aged 12 -< 20 yrs (mean T1D duration 7 yrs). We examined differences in metabolites after 26 weeks of treatment.
Results: Compared to placebo, we saw a significant difference in metabolites in the metformin arm, Fig 1A. Allantoic acid was lower (high levels associated with Ob and IR), while 3-indoxyl sulphate and 5-hydroxyindole were higher (low levels associated with dysbiosis and Ob), Fig 1B-D. The non-microbial metabolites carnitine, tyrosine, ornithine and citrulline were also lower in the metformin arm (high levels associated with Ob and IR).
Conclusion: In T1D, metformin therapy for 26 weeks is associated with gut microbial and non-microbial metabolite changes that have been linked to Ob and IR. This provides further insights into mechanism of metformin action.
E.R. Flammer: None. T.J. Garrett: None. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics.
NIDDK
