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

doi:10.4239/wjd.v17.i2.112859

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World Journal of Diabetes

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World J Diabetes. Feb 15, 2026; 17(2): 112859
Published online Feb 15, 2026. doi: 10.4239/wjd.v17.i2.112859

Table 1 Clinical characteristics of the healthy control, type 2 diabetes mellitus, and diabetic gastric autonomic neuropathy groups, n (%)

Variables	HC (n = 75)	T2DM (n = 69)	DGAN (n = 26)	P value	P1 value	P2 value	P3 value
Gender (F, %)	45, 52.30	28, 32.20	9, 34.60	0.951	1.000	0.810	0.813
Age (years)	56.00 (48.50, 65.00)	58.00 (52.00, 64.00)	46.00 (33.00, 63.00)	0.060	0.467	0.053	0.024^a
BMI (kg/m²)	22.03 (20.67, 23.28)	25.73 (24.11, 25.73)	23.45 (20.62, 26.54)	< 0.001^b	< 0.001^b	0.067	0.050^a
Duration of diabetes, in months	-	97.65 (24.00, 97.65)	102.00 (36.00, 192.00)	0.490	-	-	0.490
Duration of GI, in months	-	-	1.50 (0.29, 15.00)	-	-	-	-
SBP, mmHg	119.00 (108.00, 127.00)	130.00 (125.00, 143.00)	127.50 (110.00, 150.00)	< 0.001^b	< 0.001^b	0.003^b	0.424
DBP, mmHg	74.00 (67.50, 82.00)	82.00 (78.00, 88.00)	86.50 (76.00, 98.00)	< 0.001^b	< 0.001^b	< 0.001^b	0.224
WBC, × 10⁹/L	6.19 (5.11, 7.56)	6.81 (5.93, 7.44)	5.96 (4.77, 7.30)	0.113	0.088	0.484	0.096
Hb, g/L	134.00 (124.00, 147.00)	137.03 (126.00, 147.00)	129.00 (112.00, 137.00)	0.014^a	0.236	0.042^a	0.003^b
PLT, × 10⁹/L	224.00 (165.50, 257.50)	219.70 (201.00, 229.00)	211.50 (171.00, 262.00)	0.994	0.944	0.825	0.968
CRP, mg/L	0.00 (0.00, 1.28)	1.00 (0.00, 2.04)	2.10 (1.00, 3.60)	0.024^a	0.007^b	0.746	0.109
FBG, mmol/L	5.24 (4.90. 5.54)	8.49 (6.00, 10.00)	6.50 (5.00, 9.00)	< 0.001^b	< 0.001^b	0.001^b	0.104
HbA1c, %	-	8.93 (7.40, 10.00)	7.93 (6.60, 10.40)	< 0.001^b	-	-	< 0.001^b
FC-P, nmol/L	-	0.81 (0.55, 0.83)	0.45 (0.25, 0.65)	< 0.001^b	-	-	< 0.001^b
2hC-P, nmol/L	-	1.84 (1.15, 1.84)	0.73 (0.34, 1.17)	< 0.001^b	-	-	< 0.001^b
BUN, mmol/L	5.28 (4.32, 6.34)	5.59 (4.60, 6.45)	4.81 (4.28, 6.02)	0.296	0.297	0.435	0.149
SCr, µmol/L	66.10 (52.95, 76.40)	68.90 (58.90, 76.10)	68.45 (49.70, 76.10)	0.528	0.253	0.989	0.571
eGFR, mL/min/1.73 m²	100.10 (100.10, 100.89)	94.83 (93.49, 103.37)	102.36 (88.93, 119.02)	0.011^a	0.005^b	0.360	0.052
UACR, mg/g	-	32.51 (7.61, 87.32)	66.19 (11.53, 694.73)	0.010^a	-	-	0.010^a
TG, mmol/L	1.48 (1.05, 1.52)	2.08 (1.29, 2.51)	1.39 (1.08, 2.08)	0.001^b	< 0.001^b	0.645	0.031^a
TC, mmol/L	4.36 (4.04, 4.40)	4.25 (3.64, 4.97)	4.11 (3.59, 4.64)	0.657	0.614	0.361	0.650
LDL-C, mmol/L	2.62 (2.28, 2.70)	2.88 (2.25, 3.32)	2.64 (2.18, 3.37)	0.018^a	0.002^b	0.528	0.439
HDL-C, mmol/L	1.34 (1.24, 1.34)	1.11 (0.96, 1.20)	1.12 (0.94, 1.22)	< 0.001^b	< 0.001^b	< 0.001^b	0.986
ALB, g/L	43.10 (39.85, 46.85)	42.39 (39.90, 44.20)	38.45 (36.30, 44.10)	0.044^a	0.249	0.024^a	0.060
ALT, U/L	15.40 (10.00, 19.10)	18.70 (12.50, 24.20)	14.05 (10.00, 21.00)	0.012^a	0.004^b	0.816	0.061
AST, U/L	17.60 (14.75, 21.95)	19.20 (14.80, 23.05)	14.35 (11.70, 20.10)	0.027^a	0.264	0.027^a	0.009^b
Smoking history	17 (22.70)	17 (24.60)	4 (15.40)	0.640	0.838	0.579	0.414
Drinking history	17 (22.70)	17 (24.60)	7 (26.90)	0.914	0.838	0.791	1.000
Diabetic family history	3 (4.00)	10 (14.50)	2 (7.70)	0.079	0.040^a	0.601	0.500
Hypertension	0	25 (36.20)	13 (50.00)	< 0.001^b	< 0.001^b	< 0.001^b	0.247
Cerebral infarction	0	10 (14.50)	3 (11.50)	0.004^b	< 0.001^b	0.016^a	0.750
Coronary atherosclerotic heart disease	0	7 (10.10)	2 (7.70)	0.018^a	0.005^b	0.064	1.000
Diabetic ketosis	-	1 (1.40)	11 (42.30)	< 0.001^b	-	-	< 0.001^b
Diabetic nephropathy	-	9 (13.00)	5 (19.20)	0.515	-	-	0.515
Diabetic autonomic neuropathy	-	0 (0.00)	10 (38.50)	< 0.001^b	-	-	< 0.001^b
Diabetic peripheral neuropathy	-	18 (26.10)	16 (61.50)	0.002^b	-	-	0.002^b
Diabetic retinopathy	-	3 (4.30)	4 (15.40)	0.086	-	-	0.086
Sulfonylureas	-	4 (5.80)	2 (7.70)	1.000	-	-	1.000
Glinides	-	3 (4.30)	1 (3.80)	1.000	-	-	1.000
Metformin	-	14 (20.30)	9 (34.60)	0.181	-	-	0.181
TZDs	-	0 (0.00)	1 (3.80)	0.275	-	-	0.275
AGI	-	2 (2.90)	1 (3.80)	1.000	-	-	1.000
SGLT-2i	-	9 (13.00)	4 (15.40)	1.000	-	-	1.000
DPP-4i	-	3 (4.30)	2 (7.70)	0.604	-	-	0.604
Insulin	-	10 (14.50)	17 (65.40)	< 0.001^b	-	-	< 0.001^b
GLP-1Ra	-	6 (8.70)	2 (7.70)	1.000	-	-	1.000

^aP < 0.05.

^bP < 0.01.

Data are presented as median (interquartile range). The groups were compared using Wilcoxon rank sum test. Monte Carlo method for testing exact significance (P). P1: Healthy control vs type 2 diabetes mellitus; P2: Healthy control vs diabetic gastric autonomic neuropathy; P3: Type 2 diabetes mellitus vs diabetic gastric autonomic neuropathy. T2DM: Type 2 diabetes mellitus; HC: Healthy control; DGAN: Diabetic gastric autonomic neuropathy; BMI: Body mass index; GI: Gastrointestinal; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; Hb: Hemoglobin; PLT: Platelets; CRP: C-reactive protein; FBG: Fasting blood glucose; HbA1c: Hemoglobin A1c; FC-P: Fasting C-peptide; 2hC-P: 2-hour c-peptide; BUN: Blood urea nitrogen; SCr: Serum creatinine; eGFR: Estimated glomerular filtration rate; UACR: Urinary albumin-to-creatinine ratio; TG: Triglycerides; TC: Total cholesterol; LDL-C: Low-density lipoprotein cholesterol; HDL-C: High-density lipoprotein cholesterol; ALB: Albumin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TZDs: Thiazolidinediones; AGI: Alpha-glucosidase inhibitor; SGLT-2i: Sodium-glucose cotransporter-2 inhibitors; DPP-4i: Dipeptidyl peptidase-4 inhibitor; GLP-1Ra: Glucagon-like peptide-1 receptor agonist; F: Female.

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Table 2 Variable importance in projection scores and fold change values of bile acids in the type 2 diabetes mellitus and diabetic gastric autonomic neuropathy groups

Variables	VIP value	FC	Log₂FC	Q value
TLCA	1.364	0.248	-2.014	0.027^a

^aQ < 0.05.

Q value, P value after false discovery rate adjusted. VIP: Variable importance in projection; FC: Fold change; TLCA: Taurolithocholic acid.

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Table 3 Univariate logistic regression analysis of clinical indicators and bile acids in the type 2 diabetes mellitus and diabetic gastric autonomic neuropathy groups

Variables	Univariate logistic regression analysis
Variables	OR (95%CI)	P value
Clinical indicators
Gender, F, %	1.131 (0.436-2.935)	0.800
Age, years	0.941 (0.904-0.978)	0.002^b
BMI, kg/m²	0.759 (0.635-0.907)	0.002^b
Duration of diabetes, months	1.002 (0.997-1.008)	0.388
SBP, mmHg	0.999 (0.973-1.025)	0.929
DBP, mmHg	1.029 (0.988-1.071)	0.172
WBC, × 10⁹/L	0.855 (0.650-1.123)	0.260
Hb, g/L	0.962 (0.936-0.989)	0.006^b
PLT, × 10⁹/L	1.000 (0.992-1.008)	0.995
CRP, mg/L	1.068 (0.987-1.157)	0.103
FBG, mmol/L	0.874 (0.732-1.044)	0.137
HbA1c, %	0.895 (0.720-1.113)	0.320
FC-P, nmol/L	0.062 (0.011-0.339)	0.001^b
2hC-P, nmol/L	0.185 (0.078-0.438)	< 0.001^b
BUN, mmol/L	0.873 (0.683-1.117)	0.281
SCr, µmol/L	1.004 (0.991-1.017)	0.555
eGFR, mL/min/1.73 m²	1.013 (0.990-1.036)	0.264
UACR, mg/g	1.001 (1.000-1.003)	0.037^a
TG, mmol/L	0.551 (0.327-1.929)	0.065
TC, mmol/L	0.985 (0.677-1.433)	0.937
LDL-C, mmol/L	0.864 (0.540-1.382)	0.542
HDL-C, mmol/L	0.393 (0.052-2.972)	0.365
ALB, g/L	0.895 (0.808-0.992)	0.034^a
ALT, U/L	0.960 (0.916-1.006)	0.088
AST, U/L	0.948 (0.887-1.012)	0.111
BAs characteristics
CA, nmol/L	1.001 (1.000-1.002)	0.070
DCA, nmol/L	1.000 (0.999-1.001)	0.813
CDCA, nmol/L	1.000 (1.000-1.001)	0.386
UDCA, nmol/L	0.997 (0.993-1.001)	0.169
LCA, nmol/L	0.996 (0.979-1.014)	0.673
GCA, nmol/L	1.000 (1.000-1.001)	0.276
GLCA, nmol/L	0.948 (0.886-1.014)	0.120
GDCA, nmol/L	1.000 (0.999-1.001)	0.663
GCDCA, nmol/L	1.000 (1.000-1.000)	0.832
GUDCA, nmol/L	0.999 (0.996-1.002)	0.561
TCA, nmol/L	1.003 (0.998-1.007)	0.226
TLCA, nmol/L	0.603 (0.377-0.964)	0.035^a
TDCA, nmol/L	0.985 (0.968-1.003)	0.106
TCDCA, nmol/L	1.001 (0.999-1.003)	0.201
TUDCA, nmol/L	1.014 (0.986-1.043)	0.333

^aP < 0.05.

^bP < 0.01.

BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; Hb: Hemoglobin; PLT: Platelets; CRP: C-reactive protein; FBG: Fasting blood glucose; HbA1c: Hemoglobin a1c; FC-P: Fasting C-peptide; 2hC-P: 2-hour C-peptide; BUN: Blood urea nitrogen; SCr: Serum creatinine; eGFR: Estimated glomerular filtration rate; UACR: Urinary albumin-to-creatinine ratio; TG: Triglycerides; TC: Total cholesterol; LDL-C: Low-density lipoprotein cholesterol; HDL-C: High-density lipoprotein cholesterol; ALB: Albumin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CA: Cholic acid; DCA: Deoxycholic acid; CDCA: Chenodeoxycholic acid; UDCA: Ursodeoxycholic acid; LCA: Lithocholic acid; GCA: Glycocholic acid; GLCA: Glycolithocholic acid; GDCA: Glycodeoxycholic acid; GCDCA: Glycochenodeoxycholic acid; GUDCA: Glycoursodeoxycholic acid; TCA: Taurocholic acid; TLCA: Taurolithocholic acid; TDCA: Taurodeoxycholic acid; TCDCA: Taurochenodeoxycholic acid; TUDCA: Tauroursodeoxycholic acid; OR: Odds ratios; CI: Confidence interval; F: Female; BA: Bile acid.

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Table 4 Multivariate logistic regression analysis of clinical indicators and bile acids in the type 2 diabetes mellitus and diabetic gastric autonomic neuropathy groups

Variables	Multivariate logistic regression analysis
	Model 1		Model 2
	OR (95%CI)	P value	OR (95%CI)	P value
Age, years	0.919 (0.851-0.993)	0.033^a	0.882 (0.779-0.998)	0.047^a
BMI, kg/m²	0.961 (0.737-1.252)	0.768	1.127 (0.813-1.562)	0.471
Hb, g/L	0.987 (0.935-1.042)	0.642	0.955 (0.884-1.032)	0.243
FC-P, nmol/L	0.060 (0.001-2.406)	0.135	0.000 (0.000-0.253)	0.017^a
2hC-P, nmol/L	0.348 (0.063-1.936)	0.228	0.660 (0.107-4.072)	0.654
UACR, mg/g	1.002 (0.998-1.006)	0.302	1.003 (0.997-1.008)	0.330
ALB, g/L	0.859 (0.694-1.063)	0.163	0.824 (0.601-1.130)	0.231
TLCA, nmol/L	/	/	0.160 (0.040-0.631)	0.009^b

^aP < 0.05.

^bP < 0.01.

BMI: Body mass index; Hb: Hemoglobin; FC-P: Fasting C-peptide; 2hC-P: 2-hour C-peptide; UACR: Urinary albumin-to-creatinine ratio; ALB: Albumin; TLCA: Taurolithocholic acid; OR: Odds ratios; CI: Confidence interval.

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Table 5 Area under the curve of bile acids in the type 2 diabetes mellitus and diabetic gastric autonomic neuropathy groups

Variables	AUC (95%CI)	P value	Cutoff value	Sensitivity	Specificity
Age, years	0.651 (0.504-0.797)	0.024^a	0.450	0.462	0.942
FC-P, nmol/L	0.760 (0.648-0.872)	< 0.001^b	0.188	0.885	0.638
TLCA, nmol/L	0.678 (0.565-0.791)	< 0.001^b	0.219	0.923	0.435
Model 1	0.933 (0.878-0.989)	< 0.001^b	0.277	0.885	0.884
Model 2	0.970 (0.937-1.000)	< 0.001^b	0.392	0.923	0.957

^aP < 0.05.

^bP < 0.01.

AUC: Area under the curve; FC-P: Fasting C-peptide; TLCA: Taurolithocholic acid; CI: Confidence interval.

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Citation: Zhu KY, Wang SJ, Li J, Ma PP, Feng SS, Guo L, Lu YB, Dong L, Ding DF. Association of serum bile acid profiles with the risk of gastrointestinal autonomic neuropathy in patients with type 2 diabetes mellitus. World J Diabetes 2026; 17(2): 112859
URL: https://www.wjgnet.com/1948-9358/full/v17/i2/112859.htm
DOI: https://dx.doi.org/10.4239/wjd.v17.i2.112859