Association of serum bile acid profiles with the risk of gastrointestinal autonomic neuropathy in patients with type 2 diabetes mellitus

Figure 1 Flow diagram of participant inclusion in the study. T2DM: Type 2 diabetes mellitus; HC: Healthy control; DGAN: Diabetic gastric autonomic neuropathy; HbA1c: Hemoglobin A1c.

Figure 2 Differences in bile acid levels among the healthy control, type 2 diabetes mellitus, and diabetic gastric autonomic neuropathy groups. A: Cholic acid; B: Deoxycholic acid; C: Chenodeoxycholic acid; D: Ursodeoxycholic acid; E: Lithocholic acid; F: Glycocholic acid; G: Glycodeoxycholic acid; H: Glycochenodeoxycholic acid; I: Glycoursodeoxycholic acid; J: Glycolithocholic acid; K: Taurocholic acid; L: Taurodeoxycholic acid; M: Taurochenodeoxycholic acid; N: Tauroursodeoxycholic acid; O: Taurolithocholic acid. Data are presented as the median (interquartile range), and significant difference was assessed using Wilcoxon’s rank sum test. ^aP < 0.05; ^bP < 0.01. T2DM: Type 2 diabetes mellitus; HC: Healthy control; DGAN: Diabetic gastric autonomic neuropathy; CA: Cholic acid; DCA: Deoxycholic acid; CDCA: Chenodeoxycholic acid; UDCA: Ursodeoxycholic acid; LCA: Lithocholic acid; GCA: Glycocholic acid; GDCA: Glycodeoxycholic acid; GCDCA: Glycochenodeoxycholic acid; GUDCA: Glycoursodeoxycholic acid; GLCA: Glycolithocholic acid; TCA: Taurocholic acid; TDCA: Taurodeoxycholic acid; TCDCA: Taurochenodeoxycholic acid; TUDCA: Tauroursodeoxycholic acid; TLCA: Taurolithocholic acid.

Figure 3 Spearman’s correlation analysis among bile acids, clinical indicators, and Gastrointestinal Symptom Rating Scale scores in the diabetic gastric autonomic neuropathy group. A: Correlations among clinical indicators, bile acid levels, and Gastrointestinal Symptom Rating Scale scores in the type 2 diabetes mellitus and diabetic gastric autonomic neuropathy groups; B-E: Scatter plots depicting the correlations among clinical indicators, bile acids, and the scores of gastrointestinal symptoms. ^aP < 0.05; ^bP < 0.01. GSRS: Gastrointestinal Symptom Rating Scale; eGFR: Estimated glomerular filtration rate; PLT: Platelets; LDL-C: Low-density lipoprotein cholesterol; TC: Total cholesterol; TG: Triglycerides; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; UACR: Urinary albumin-to-creatinine ratio; 2hC-P: 2-hour c-peptide; C-P: C-peptide; HDL-C: High-density lipoprotein cholesterol; T2DM: Type 2 diabetes mellitus; GI: Gastrointestinal; CA: Cholic acid; UDCA: Ursodeoxycholic acid; CDCA: Chenodeoxycholic acid; DCA: Deoxycholic acid; SCr: Serum creatinine; BUN: Blood urea nitrogen; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALB: Albumin; BMI: Body mass index; CRP: C-reactive protein; Hb: Hemoglobin; GUDCA: Glycoursodeoxycholic acid; GCDCA: Glycochenodeoxycholic acid; LCA: Lithocholic acid; HbA1c: Hemoglobin a1c; FBG: Fasting blood glucose; GDCA: Glycodeoxycholic acid; GLCA: Glycolithocholic acid; TLCA: Taurolithocholic acid; TDCA: Taurodeoxycholic acid; TCDCA: Taurochenodeoxycholic acid; GCA: Glycocholic acid; TCA: Taurocholic acid; TUDCA: Tauroursodeoxycholic acid.

Figure 4 Multivariate analysis of bile acids in the orthogonal partial least squares discriminant analysis model. A: Orthogonal partial least squares discriminant analysis three-dimensional model between uncomplicated type 2 diabetes mellitus and diabetic gastric autonomic neuropathy. R2X = 0.406, R2Y = 0.183, and Q2Y = -0.274; B: The permutation test demonstrated no overfitting in the orthogonal partial least squares discriminant analysis model [Q2 = (0, -0.386), R2 = (0, 0.152)]; C: The contribution of the metabolites distinguishing uncomplicated type 2 diabetes mellitus from diabetic gastric autonomic neuropathy as indicated by variable importance in projection values. T2DM: Type 2 diabetes mellitus; DGAN: Diabetic gastric autonomic neuropathy; TLCA: Taurolithocholic acid; GUDCA: Glycoursodeoxycholic acid; GLCA: Glycolithocholic acid; LCA: Lithocholic acid; UDCA: Ursodeoxycholic acid; CDCA: Chenodeoxycholic acid; GDCA: Glycodeoxycholic acid; TDCA: Taurodeoxycholic acid; CA: Cholic acid; GCA: Glycocholic acid; TCA: Taurocholic acid; TCDCA: Taurochenodeoxycholic acid; GCDCA: Glycochenodeoxycholic acid; DCA: Deoxycholic acid; TUDCA: Tauroursodeoxycholic acid.

Figure 5 Nomogram model and results of decision curve analysis for quantifying the individual risk of diabetic gastric autonomic neuropathy in patients with type 2 diabetes mellitus. A: The nomogram includes age, fasting C-peptide, and taurolithocholic acid along with their corresponding points and total risk scores; B: Decision curve analysis was performed to evaluate the clinical net benefit across different risk thresholds. TLCA: Taurolithocholic acid; FC-P: Fasting C-peptide; DGAN: Diabetic gastric autonomic neuropathy.