Short chain fatty acids for the risk of diabetic nephropathy in type 2 diabetes patients

Aims: This study aimed to explore relationships short chain fatty acids with diabetic nephropathy (DN) in type 2 diabetes (T2D) patients. Methods: We extracted the clinical and omics data of 100 T2D patients and 100 DN patients from April 2018 to April 2019 from a tertiary hospital. Restricted cubic splines were used to examine full-range associations of short chain fatty acids with DN in T2D.Query Logistic regression was used to obtain odds ratio (OR) and confidence interval (CI). Results: Acetate, butyrate and isovalerate were negatively correlated with DN. Isobutyrate was positively correlated with DN. Propionate ≥ 4.4 μg/mL and isobutyrate ≥ 1.4 μg/mL had threshold effects and their increasing levels above the cutoff points were associated with rapid rises in the risk of DN. The additive interaction between high propionate and high isobutyrate in serum significantly increased the risk of DN (OR34.35; 95%CI 7.11 to 166.08). Presence of hypertension further increased the OR of high propionate for DN to 8.27(95%CI 1.82 to 37.57) with a significant additive interaction. The additive interaction of the high isobutyrate and hypertension was not significant. Conclusions: Acetate, butyrate and isovalerate were negatively associated with DN. Isobutyrate was positively associated with DN. Serum high propionate and high isobutyrate worked independently and synergistically to increase the risk of DN in T2D. Presence of hypertension further amplified the effect of copresence of high propionate on DN risk.