Oluwatomisono I. Akinrimisi1, Jean L.J.M. Scheijen2, Coco M. Fuhri Snethlage1, Pleun de Groen1, Pascalle Lucassen 1, Mark Davids1, Max Nieuwdorp1,3, Casper G. Schalkwijk2, Nordin M.J. Hanssen1,3
1Department of Experimental Vascular and Internal Medicine, Amsterdam University Medical Centre, The Netherlands
2CARIM, School for Cardiovascular Diseases, Department of Internal Medicine, Maastricht University Medical Centre, The Netherlands
3Diabeter Centre Amsterdam, The Netherlands
Background:
Methylglyoxal (MGO), a glycolysis byproduct, promotes protein glycation and inflammation and has been linked to various diseases. This study examined the associations between plasma and faecal MGO levels, the gut microbiome, and clinical parameters.
Methods:
Data from 457 individuals with type 1 diabetes from the GUTDM1 cohort were analysed (64% female; median age: 40 years [IQR: 28-53]; median BMI: 24.7 kg/m² [IQR: 22.6-27.4]; HbA1c 54 mmol/mol [IQR 48-62]. MGO levels were quantified by UPLC-MS/MS.
Results:
Plasma and faecal MGO levels were negatively correlated with time in range (Spearman ρ = -0.22, p<0.01) and (Spearman ρ = -0.14, p<0.01), respectively. Using urinary C-peptide creatinine ratio (UCPCR) as a marker of residual beta cell function, individuals in the low/undetectable UCPCR group exhibited higher plasma MGO levels (median 253 nmol/L [IQR 216-305]) compared with those in the intermediate/high UCPCR group (median 237 nmol/L [IQR 207-279], p < 0.05). Faecal MGO levels were partially predicted by gut microbiome composition using an XGBoost model (Spearman ρ = 0.26, p < 0.05). Faecal short chain fatty acids (SCFAs) showed weak negative correlations with MGO: acetate was negatively correlated with both plasma (ρ = -0.10, p < 0.05) and faecal MGO (ρ = -0.10, p < 0.05). Plasma metabolomics analysis identified several metabolites negatively correlated with plasma MGO levels, including palmitoylcholine (ρ = -0.30, p < 0.01), 6- bromotryptophan (ρ = -0.20, p < 0.01), and 1,5-anhydroglucitol (ρ = -0.20, p < 0.01).
Conclusion:
MGO may impair β-cell function, with faecal MGO linked to specific microbes and plasma metabolomics identifying potential MGO quenchers.
Funding
O.I.A. and N.M.J.H. are supported by a ZONMW-VIDI grant 2023 (09150172210019). NMJH is supported by a Senior Clinical Dekker grant by the Dutch Heart Foundation (grant number 2021T055). The study was supported by a DFN-DON grant 2020.10.002, on which CMS was appointed. M.N. is supported by a personal NWO VICI grant 2020 (09150182010020) and an ERC Advanced Grant (101141346).