The effect of sodium butyrate supplementation on metabolic factors, serum oxidative stress indices and gene expression rate of pyroptosis related inflammatory factors in type 2 diabetic patients: A randomized, double-blind, placebo-controlled trial

Abstract

Background: Pyroptosis, which is a type of programmed cell death associated with the inflammatory response & oxidative stress, is involved in autoimmune and inflammatory diseases. The effects of sodium butyrate (Na.But) on diabetes and pyroptosis related factors are yet to be examined in humans. This study aimed to investigate the effects of oral Na.But on metabolic factors, serum oxidative stress indices and gene expression rate of pyroptosis related inflammatory factors in type 2 diabetic patients. Methods: In the current interventional trial, 42 patients with type 2 diabetes mellitus (T2DM) were randomly allocated into either Na.But (n=21) or placebo (n=21) group for six weeks. Anthropometric indices, daily dietary intakes, blood pressure, serum concentrations of lipid profile and glucose homeostasis indices, GPx, NO as well as pyroptosis-related genes mRNA expression, were assessed before and after the intervention. Results: Na.But administration contributed to a significant decrease in energy, carbohydrate and protein intake (p<0.001, p=0.001 and p=0.005, respectively), and a significant elevation in IL-1β & IL-18 expression levels (p=0.039 and p=0.004, respectively) compared to the placebo group at the end of the study. Within-group findings demonstrated that Na.But administration significantly reduced waist circumference (p=0.013) as well as systolic and diastolic blood pressure (p=0.016 and p=0.002, respectively). Regarding lipid profile and glycemic/oxidonitrosative indices, although differences were not significant between groups after adjustment for potential confounders, butyrate supplementation appears to decrease BS2hpp and NO levels (p=0.016 and p=0.040, respectively), and increase insulin, HOMA-IR, TC and LDL-C (p=0.047, p=0.008, p=0.001 and p=0.005, respectively). No significant differences were found in other parameters. Conclusions: We observed significant decreases in energy, carbohydrate and protein intakes as well as within-group decreases in WC, BS2hpp, systolic and diastolic blood pressure following oral butyrate treatment. While, no or even adverse changes in other biochemical parameters were found. Further investigations with longer durations are warranted to more vividly elucidate the effects of Na.But supplementation on patients with T2DM. Key Words: Type 2 diabetes mellitus, Sodium butyrate, Metabolic status, Blood Pressure, Nitric oxide, IL-1β, IL-18.