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

Introduction:  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.

Objectives:  This study was aimed to investigate the associations between circulating SCFA levels and subclinical CVD in patients with T2D.

Patients and methods:  This cross-sectional study enrolled 326 patients with T2D from November 2016 to June 2020. The levels of nine SCFAs including formate, acetate, propionate, butyrate, isobutyrate, methylbutyrate, valerate, isovalerate and methylvalerate in fasting serum were measured using liquid chromatography mass spectrometry. Cardiac structure and function were evaluated by echocardiography. Ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV), as a parameter of arterial stiffness, were measured. Multivariable linear and logistic model were adjusted for traditional risk factors including cholesterol and glycated hemoglobin (HbA1C).

Results:  The mean age of the patients was 63.5 (10.4) years and 56.4% were male. The median HbA1C level was 7.0%. The adjusted odd ratios of left ventricular hypertrophy were 2.39 and 2.60 for tertiles 3 of formate and isobutyrate compared with tertiles 1 of formate and isobutyrate, respectively. Higher circulating butyrate / isobutyrate ratio was significantly associated with decreased risk of diastolic dysfunction. An inverse relationship between circulating valerate level and arterial stiffness was found. Patients with the highest tertile of circulating butyrate level had lower risk of abnormal ABI.

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