Circulating short chain fatty acid levels and body composition in type 2 diabetes mellitus

Background: Short-chain fatty acids (SCFAs) may play key functional roles in the pathophysiology of type 2 diabetes (T2D) through regulating energy intake and substrate metabolism. Body composition, including fat tissue, muscle tissue and the pattern of their distribution in the body, can represent health status and be the cause or consequence of T2D complications. The aim of this study was to explore the relationship between serum SCFA levels and body composition distribution in patients with T2D. Methods: This observational cross-sectional study enrolled 430 patients with T2D from October 2016 to June 2020. The levels of nine kinds of SCFAs in serum were measured using liquid chromatography mass spectrometry. Body composition, including lean tissue and fat tissue, was measured once using bioimpedance spectroscopy at enrollment. Results: The mean age of the patients was 61.7 ± 12.3 years and 54.0% were male. Multivariate linear analysis revealed that the patients with the highest tertile of serum methylbutyrate level (β = -0.81, 95% CI = -1.56, -0.06, p = 0.03) and valerate/isovalerate ratio (β = -1.15, 95% CI = -1.86, -0.44, p = 0.002) had a lower fat tissue index (FTI). In subgroup analysis, the negative association of FTI with serum methylbutyrate level and valerate/isovalerate ratio was only found in the patients who were older, female, and had glycated hemoglobin ≤ 7%, urinary albumin-creatinine ratio < 30 mg/g, homeostatic model assessment for insulin resistance ≤ median value, and body mass index < 30 kg/m². Conversely, none of the nine SCFAs were associated with lean tissue index. Conclusions: This study found that T2D patients with a higher circulating methylbutyrate level and serum valerate/isovalerate ratio had lower FTI. The relationship was consistent in older, female patients with well-controlled glucose. Further research is needed to analyze the interactions between SCFAs and body composition with clinical metabolic outcomes in T2D patients.