Decreased Physiological Serum Total Bile Acid Concentrations in Patients with Type 2 Diabetic Peripheral Neuropathy

Figures & data

Table 1 Circulating TBA Levels and Other Characteristics Between T2DM Patients with and without DPN ($\overline{x}$±s)

Variables	Non-DPN	DPN	P
	(n =709)	(n = 147)
Male/Female	329/380	85/62	0.012
Age (years)	59.33±11.17	65.78±10.20	0.000
BMI (kg/m^2)	24.28±3.53	23.33±3.94	0.005
Diabetic duration (years)	7.56±6.22	10.46±7.47	0.000
SBP (mmHg)	132.68±20.74	137.57±21.88	0.003
DBP (mmHg)	71.63±11.84	70.31±12.94	0.224
FBG (mmol/L)	10.28±4.98	11.07±4.88	0.013
HbA1c (%)	9.24±2.42	10.20±2.68	0.000
TC (mmol/L)	4.83±1.30	4.64±1.22	0.099
TG (mmol/L)	2.27±2.60	1.76±1.31	0.003
HDL-C (mmol/L)	1.19±0.35	1.19±0.36	0.469
LDL-C (mmol/L)	2.76±0.99	2.76±0.93	0.954
TyG	9.48±0.83	9.37±0.78	0.168
AI	3.37±1.85	3.14±1.42	0.166
PLT (×10^9 /L)	198.82±63.21	214.51±82.67	0.124
PCT	0.23±0.06	0.24±0.07	0.381
MPV (fl)	11.35±1.24	11.21±1.35	0.215
PDW (%)	15.10±2.80	14.59±2.93	0.076
RDW (%)	13.12±1.21	13.14±1.13	0.817
Fibrinogen (g/L)	3.51±1.17	4.22±1.55	0.000
GGT (U/L)	23.86±11.61	22.34±12.15	0.047
TBA (μmol/L)	4.56±2.02	3.38±1.73	0.000
UACR (mg/g)	222.10±32.60	473.36±96.17	0.000
Scr (μmol/L)	70.92±44.08	85.01±43.25	0.000
UA (μmol/L)	309.00±101.76	320.31±101.18	0.220
CysC (mg/L)	0.95±0.40	1.20±0.53	0.000
eGFR (mL/min/1.73 m^2)	93.72±25.17	79.59±26.52	0.000
ABI	1.03±0.14	0.96±0.24	0.017
VPT (V)	13.46±4.84	37.06±9.22	0.000
DN, n (%)	249 (35.12)	83 (56.46)	0.000
DR, n (%)	76 (10.72)	36 (24.49)	0.000
PAD, n (%)	52 (7.33)	35 (23.81)	0.000
DFU, n (%)	43 (6.06)	26 (17.69)	0.000

Note: Data are mean ±SD.

Abbreviations: SD, standard deviation; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; HbA1c, glycated hemoglobin A1c; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TyG, triglyceride–glucose index; AI, atherogenic index; UACR, urine albumin-to-creatinine ratio; Scr, serum creatinine; UA, uric acid; CysC, cystatin C; GGT, gamma glutamyltransferase; TBA, total bile acid; PLT, platelet counting; PCT, plateletcrit; MPV, mean platelet volume; PDW, platelet distribution width; RDW, red blood cell distribution width; eGFR, estimated glomerular filtration rate; ABI, ankle-brachial index; VPT, vibration perception threshold; DN, diabetic nephropathy; DR, diabetic retinopathy; PAD, peripheral arterial disease; DFU, diabetic foot ulceration; DPN, diabetic peripheral neuropathy; T2DM, type 2 diabetes mellitus.

Table 2 Association Between Serum TBA and Risk Factors Related to DPN in Study Participants

Variable	Simple
	r	P-value	Adjusted r	Adjusted P-value
Age	0.057	0.098	–	–
Gender	0.057	0.094	–	–
BMI	0.094	0.007	–	–
Diabetic duration	−0.003	0.930	0.039	0.505
SBP	0.019	0.576	0.053	0.362
DBP	−0.022	0.527	−0.066	0.256
FBG	−0.085	0.012	−0.031	0.589
HbA1c	−0.110	0.001	−0.116	0.046
TC	0.057	0.097	0.016	0.785
TG	−0.151	0.000	−0.098	0.092
HDL-C	0.008	0.813	0.016	0.782
LDL-C	−0.017	0.627	−0.042	0.466
TyG	0.063	0.068	0.057	0.102
AI	0.042	0.224	0.060	0.100
PLT	−0.082	0.017	−0.104	0.073
PCT	−0.066	0.060	−0.119	0.040
MPV	0.093	0.008	0.035	0.545
PDW	0.094	0.007	0.039	0.497
RDW	0.059	0.085	0.039	0.288
Fibrinogen	−0.127	0.008	−0.146	0.011
GGT	0.092	0.007	0.105	0.071
UACR	−0.086	0.024	−0.078	0.045
Scr	−0.036	0.293	−0.057	0.141
UA	0.028	0.414	−0.018	0.621
CysC	−0.023	0.508	−0.055	0.131
eGFR	0.002	0.955	0.059	0.128
ABI	−0.018	0.606	0.047	0.414
VPT	−0.219	0.000	−0.234	0.000
DPN	−0.212	0.000	−0.219	0.000
DN	−0.067	0.050	−0.051	0.187
DR	−0.053	0.122	−0.031	0.431
PAD	−0.071	0.040	−0.082	0.035
DFU	−0.102	0.003	−0.127	0.001

Table 3 OR and 95% CI for the Risk of DPN According to Serum TBA Quartiles

Serum TBA (μmol/L)	DPN
Quartiles of TBA	Model 1		Model 2		Model 3
	OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P
Q1 (0.7–2.7μmol/L)	1 (reference)	–	1 (reference)	–	1 (reference)	–
Q2 (2.8–4μmol/L)	0.451 (0.284–0.717)	0.001	0.450 (0.274–0.738)	0.002	0.362 (0.184–0.715)	0.003
Q3 (4.1–5.5μmol/L)	0.425 (0.263–0.689)	0.001	0.425 (0.254–0.712)	0.001	0.729 (0.532–0.997)	0.048
Q4 (5.6–7.7μmol/L)	0.218 (0.124–0.386)	0.000	0.188 (0.100–0.351)	0.000	0.518 (0.383–0.701)	0.000
P for trend	0.000		0.000		0.000

Notes: Data are expressed as OR (95% CI) +P value, unless stated otherwise. Model 1 unadjusted; Model 2 adjusted for age, gender, and BMI; Model 3 adjusted for factors listed in Model 2 plus diabetic duration, SBP, DBP, FBG, HbA1c, TC, TG, HDL-C, LDL-C, TyG, AI, UA, CysC, GGT, PLT, PCT, MPV, PDW, RDW, prevalence of DN, DR, PAD, and DFU.

Abbreviations: OR, odds ratio; CI, confidence interval.

Figure 1 ROC analysis of serum total bile acid (TBA) to indicate DPN for T2DM patients. AUC = 0.663; 95% CI, 0.613–0.712; P<0.001; identified TBA cutoff value = 2.85 μmol/L; Youden index = 0.232; sensitivity: 77.6%; specificity: 45.6%.