Circulating short-chain fatty acids and subclinical cardiovascular disease in type 2 diabetes mellitus

Type 2 diabetes (T2D) is linked to a higher risk of cardiovascular disease (CVD). However, evidence on the impact of different short‑chain fatty acids (SCFAs) on subclinical CVD is limited in patients with T2D.

We aimed to investigate the associations between circulating SCFA levels and subclinical CVD in patients with T2D.

This cross‑sectional study enrolled 326 patients with T2D from November 2016 to June 2020. The levels of 9 SCFAs, including formate, acetate, propionate, butyrate, isobutyrate, methylbutyrate, valerate, isovalerate, and methylvalerate, were measured in fasting serum using liquid chromatography-mass spectrometry. Cardiac structure and function were evaluated on echocardiography. Ankle‑brachial index (ABI) and brachial‑ankle pulse wave velocity, as a parameter of arterial stiffness, were measured. Multivariable linear and logistic regression models were adjusted for traditional risk factors including cholesterol and glycated hemoglobin (HbA1c) levels.

Mean (SD) age of the patients was 63.5 (10.4) years and 56.4% were men. Median (interquartile range) HbA1c level was 7% (6.5%-7.9%). Adjusted odds ratios of left ventricular hypertrophy for comparison of the first and third tertile levels of formate and isobutyrate were 2.39 and 2.6, respectively. Higher butyrate / isobutyrate ratio was significantly associated with a decreased risk of diastolic dysfunction. An inverse relationship between valerate level and arterial stiffness was found. The patients with the highest tertile level of butyrate had a lower risk of abnormal ABI.

Our study demonstrates that serum SCFAs are potential biomarkers of the early stage of cardiovascular remodeling in patients with T2D.