Association between serum retinol-binding protein and lower limb atherosclerosis risk in type 2 diabetes mellitus

Table 1 Baseline characteristics in the study participants

Characteristic	Overall (n = 4428)	Non-lower limb atherosclerosis (n = 1913)	Lower limb atherosclerosis (n = 2515)	P value
RBP, mg/L	31.90 [26.15, 38.90]	30.96 [25.50, 36.95]	32.76 [26.80, 40.50]	< 0.001
Age, years	56.00 [48.00, 65.00]	50.00 [40.00, 58.00]	59.00 [52.00, 68.00]	< 0.001
Male, n (%)	2691 (60.77)	1051 (54.94)	1640 (65.21)	< 0.001
Cigarette smoking history, n (%)	1786 (40.33)	649 (33.93)	1137 (45.21)	< 0.001
Alcohol consumption history, n (%)	1722 (38.89)	671 (35.08)	1051 (41.79)	< 0.001
Hypertension, n (%)	2765 (62.44)	995 (52.01)	1770 (70.38)	< 0.001
Hyperlipidemia, n (%)	2521 (56.93)	1102 (57.61)	1419 (56.42)	0.449
CHD, n (%)	838 (18.93)	227 (11.87)	611 (24.29)	< 0.001
SBP, mmHg	129.00 [116.00, 143.00]	126.00 [114.00, 139.00]	132.00 [119.00, 145.00]	< 0.001
DBP, mmHg	80.50 [73.00, 89.00]	81.00 [73.00, 90.00]	80.00 [73.00, 89.00]	0.196
BMI, kg/m2	24.20 [21.80, 26.60]	24.20 [21.70, 26.90]	24.10 [21.90, 26.40]	0.132
HbA1c, %	8.40 [7.00, 10.30]	8.30 [6.80, 10.45]	8.50 [7.10, 10.20]	0.020
FBG, mmol/L	8.49 [6.56, 11.40]	8.29 [6.38, 11.59]	8.62 [6.70, 11.29]	0.054
TC, mmol/L	4.59 [3.87, 5.39]	4.62 [3.92, 5.34]	4.58 [3.82, 5.42]	0.67
LDL, mmol/L	2.86 [2.35, 3.41]	2.86 [2.37, 3.35]	2.87 [2.33, 3.46]	0.383
TG, mmol/L	1.56 [1.11, 2.35]	1.57 [1.10, 2.43]	1.56 [1.13, 2.27]	0.351
HDL, mmol/L	1.10 [0.92, 1.30]	1.11 [0.94, 1.32]	1.09 [0.92, 1.29]	0.004
WBC count, 109/L	6.30 [5.24, 7.64]	6.10 [5.10, 7.41]	6.46 [5.35, 7.86]	< 0.001
CRP, mg/L	2.93 [1.19, 11.58]	2.62 [1.08, 9.14]	3.20 [1.26, 14.24]	< 0.001
AST, IU/L	20.67 [17.00, 26.10]	21.10 [17.20, 27.40]	20.40 [16.85, 25.10]	< 0.001
ALT, IU/L	19.45 [14.10, 28.80]	20.90 [15.00, 32.75]	18.65 [13.70, 26.62]	< 0.001
UA, μmol/L	326.20 [265.00, 398.00]	326.00 [265.10, 396.00]	327.00 [264.00, 399.50]	0.850
eGFR, mL/minute/1.73 m2	97.66 [77.73, 113.18]	104.67 [88.91, 120.20]	91.16 [69.40, 107.07]	< 0.001

Data are presented as median and interquartile range [25%, 75%]. RBP: Retinol-binding protein; CHD: Coronary heart disease; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BMI: Body mass index; HbA1c: Glycated hemoglobin; FBG: Fasting blood glucose; TC: Total cholesterol; LDL: Low-density lipoprotein; TG: Triglycerides; HDL: High-density lipoprotein; WBC: White blood cell; CRP: C-reactive protein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; UA: Uric acid; eGFR: Estimated glomerular filtration rate.

Table 2 Baseline characteristics in the study participants based on serum retinol-binding protein tertiles

Characteristic	Q1 (n = 1474)	Q2 (n = 1478)	Q3 (n = 1476)	P value
lower limb atherosclerosis, n (%)	759 (51.49)	794 (53.73)	962 (66.18)	< 0.001
Age, years	56.00 [47.00, 64.00]	55.00 [47.25, 64.75]	56.00 [49.00, 65.00]	0.130
Male, n (%)	775 (52.58)	893 (60.42)	1023 (69.31)	< 0.001
Cigarette smoking history, n (%)	501 (33.99)	595 (40.26)	690 (46.75)	< 0.001
Alcohol consumption history, n (%)	469 (31.82)	578 (39.11)	675 (45.73)	< 0.001
Hypertension, n (%)	727 (49.32)	912 (61.71)	1126 (76.29)	< 0.001
CHD, n (%)	207 (14.04)	279 (18.88)	352 (23.85)	< 0.001
Hyperlipidemia, n (%)	598 (40.57)	905 (61.23)	1018 (68.97)	< 0.001
SBP, mmHg	126.00 [113.00, 139.00]	129.00 [117.00, 142.00]	132.00 [119.00, 148.00]	< 0.001
DBP, mmHg	79.00 [71.00, 87.00]	81.00 [73.00, 89.75]	83.00 [75.00, 92.00]	< 0.001
BMI, kg/m2	23.20 [20.70, 26.00]	24.20 [22.10, 26.40]	24.90 [22.60, 27.20]	< 0.001
RBP, mg/L	23.80 [20.40, 26.15]	31.90 [30.07, 33.90]	42.61 [38.90, 48.16]	< 0.001
HbA1c, %	9.00 [7.20, 10.90]	8.30 [7.00, 10.20]	8.05 [6.80, 9.70]	< 0.001
FBG, mmol/L	8.93 [6.52, 12.57]	8.37 [6.52, 11.19]	8.23 [6.59, 10.78]	< 0.001
TC, mmol/L	4.38 [3.68, 5.12]	4.66 [3.92, 5.42]	4.80 [4.00, 5.63]	< 0.001
LDL, mmol/L	2.74 [2.23, 3.25]	2.88 [2.41, 3.46]	2.96 [2.39, 3.52]	< 0.001
TG, mmol/L	1.27 [0.94, 1.80]	1.57 [1.15, 2.32]	1.95 [1.37, 2.91]	< 0.001
HDL, mmol/L	1.10 [0.90, 1.34]	1.11 [0.94, 1.30]	1.08 [0.94, 1.28]	0.440
WBC count, 109/L	6.17 [4.99, 7.56]	6.18 [5.22, 7.44]	6.58 [5.46, 7.89]	< 0.001
CRP, mg/L	3.87 [1.32, 21.64]	2.37 [1.08, 7.73]	2.74 [1.19, 9.30]	< 0.001
AST, IU/L	20.60 [16.36, 27.80]	20.50 [17.21, 25.30]	20.98 [17.30, 25.75]	0.466
ALT, IU/L	18.65 [13.11, 30.30]	19.73 [14.61, 27.90]	19.90 [14.75, 29.10]	0.027
UA, μmol/L	277.00 [227.00, 333.00]	325.00 [270.89, 384.00]	380.00 [321.00, 441.12]	< 0.001
eGFR, mL/minute/1.73 m2	105.85 [90.95, 120.70]	100.24 [85.50, 114.03]	81.76 [53.80, 101.49]	< 0.001

Data are presented as median and interquartile range [25%, 75%]. CHD: Coronary heart disease; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BMI: Body mass index; RBP: Retinol-binding protein; HbA1c: Glycated hemoglobin; FBG: Fasting blood glucose; TC: Total cholesterol; LDL: Low-density lipoprotein; TG: Triglycerides; HDL: High-density lipoprotein; WBC: White blood cell; CRP: C-reactive protein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; UA: Uric acid; eGFR: Estimated glomerular filtration rate.

Table 3 Association between serum retinol-binding protein levels and lower limb atherosclerosis risk in type 2 diabetes mellitus patients

Serum RBP levels	Model 1, OR (95%CI)	Model 1, P value	Model 2, OR (95%CI)	Model 2, P value	Model 3, OR (95%CI)	Model 3, P value
Continuous	1.02 (1.02, 1.03)	< 0.001	1.01 (1.01, 1.02)	< 0.001	1.01 (1.00, 1.02)	0.004
Tertiles
Q1	Reference		Reference		Reference
Q2	1.09 (0.95, 1.26)	0.200	1.00 (0.84, 1.18)	0.900	1.00 (0.84, 1.19)	0.900
Q3	1.76 (1.52, 2.04)	< 0.001	1.44 (1.21, 1.71)	< 0.001	1.36 (1.12, 1.67)	0.002
P for trend	< 0.001		< 0.001		0.005

Model 1 unadjusted. Model 2 adjusted for age, gender, body mass index, cigarette smoking history, alcohol consumption history, hypertension, hyperlipidemia, and CHD. Model 3 adjusted for age, gender, body mass index, cigarette smoking history, alcohol consumption history, hypertension, hyperlipidemia, coronary heart disease, systolic blood pressure, diastolic blood pressure fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, uric acid, C-reactive protein, white blood cell count, and estimated glomerular filtration rate. RBP: Retinol-binding protein; OR: Odds ratio; CI: Confidence interval.

Table 4 Subgroup analysis of relationship between serum retinol-binding protein level and lower limb atherosclerosis risk in type 2 diabetes mellitus patients

Subgroups	OR (95%CI)	P value	P for interaction
Age			0.019
< 60 years	1.01 (1.00, 1.02)	0.016
≥ 60 years	1.01 (0.99, 1.02)	0.400
Sex			0.700
Male	1.02 (1.01, 1.03)	0.003
Female	1.01 (0.99, 1.02)	0.500
BMI			0.900
< 25 kg/m2	1.01 (1.00, 1.02)	0.110
≥ 25 kg/m2	1.02 (1.00, 1.03)	0.011
Hypertension			0.800
Yes	1.01 (1.00, 1.02)	0.037
No	1.02 (1.00, 1.03)	0.036
Hyperlipidemia			0.700
Yes	1.01 (1.00, 1.02)	0.022
No	1.01 (1.00, 1.02)	0.091
CHD			0.200
Yes	1.03 (1.01, 1.06)	0.003
No	1.01 (1.00, 1.02)	0.069
eGFR			0.800
≤ 60 mL/minute/1.73 m2	1.02 (1.00, 1.03)	0.046
> 60 mL/minute/1.73 m2	1.01 (1.00, 1.02)	0.027

OR: Odds ratio; CI: Confidence interval; BMI: Body mass index; CHD: Coronary heart disease; eGFR: Estimated glomerular filtration rate. Adjusted for age, gender, body mass index, systolic blood pressure, diastolic blood pressure, cigarette smoking and alcohol consumption histories, hypertension, hyperlipidemia, coronary heart disease, fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, uric acid, C-reactive protein, white blood cell count, and estimated glomerular filtration rate; except the corresponding stratification variable.