Clinical study on the intervention of Tangdi prescription on spleen deficiency and phlegm-dampness syndrome of prediabetes and its mechanism of targeted regulation of intestinal flora–BCAA

Background: The treatment of pre-diabetes mellitus (pre-DM) currently includes lifestyle intervention, modern medicine treatment, and traditional Chinese medicine(TCM) synthetic therapy. TCM has shown curative effects in pre-DM treatment, including Chinese herbal compounds, Chinese patent medicine, acupuncture, massage, exercise, and other therapies. However, the existing studies seldom treat patients with pre-DM based on syndrome differentiation, and the essence of TCM is treatment based on syndrome differentiation. Therefore, a unique survey of patients with pre-DM of a particular TCM syndrome type is necessary, and this study will focus on patients with spleen deficiency and phlegm turbidity in pre-DM. Methods and design: A single-center, randomized, double-masked, and placebo-controlled trial is planned. A total of 186 patients will be enrolled in the study. Participants will be randomly assigned to the experimental or control group in a 1:1 ratio. The experimental group will be treated with Tangdi prescription (TDP) granule combined with healthy lifestyle intervention, and the control group will be treated with TDP placebo combined with healthy lifestyle intervention. This study will take 3 weeks as a course of treatment for 4 classes, and will be followed up at 3rd, 6th, 9th, and 12th weeks during the treatment period. The primary outcome indicators are the improvement rate of TCM syndrome, the incidence of diabetes, and the reversal rate of pre-DM. The secondary outcome indicators include fasting blood glucose, 2-hour postprandial blood glucose, glycosylated albumin, glycosylated hemoglobin, and lipid metabolism indicators. Exploratory indicators are fecal intestinal flora and branched chain amino acid (BCAA). Discussion: In this study, we will observe the clinical efficacy of TDP in the treatment of prediabetic spleen deficiency and phlegm-dampness syndrome. We will evaluate its clinical value and safety, collect the plasma of the 2 groups for BCAA targeted metabolites detection, analyze differences in the gut flora-derived metabolite BCAA between the 2 groups, and explore the therapeutic mechanism of TDP in the treatment of prediabetic spleen deficiency and phlegm-dampness syndrome from the point of view of intestinal flora.