Relationship of Bone Turnover Markers with Serum Uric Acid-to-Creatinine Ratio in Men and Postmenopausal Women with Type 2 Diabetes

Figures & data

Table 1 Comparison of Indicators Between the Male and Postmenopausal Female Groups

	All Patients	Male Patients	Postmenopausal Female Patients	P	Adjusted P for FDR
n	1691	1028	663	–	–
Age (years)	60(52,68)	56(47,65)	65(58,72)	<0.001	0.004
BMI (kg/m^2)	25.95(23.44,28.11)	26.03(23.84,28.34)	25.71(23.14,28.00)	0.006	0.029
Course(years)	10.00(3.00,17.00)	8.00(2.00,15.00)	10.00(5.00,20.00)	<0.001	0.025
Ca2+ (mmol/L)	2.29(2.22,2.36)	2.29(2.21,2.36)	2.29(2.23,2.37)	0.103	0.004
TG (mmol/L)	1.38(0.99,2.09)	1.41(0.99,2.21)	1.33(1.00,1.92)	0.052	0.032
HDL-C(mmol/L)	1.10(0.92,1.35)	1.02(0.87,1.26)	1.20(1.02,1.48)	<0.001	0.036
HbA1c (%)	8.60(7.30,10.20)	8.6(7.2,10.2)	8.60(7.45,10.30)	0.417	0.046
FPG(mmol/L)	7.84(6.10,10.46)	7.85(6.15,10.55)	7.81(5.98,10.30)	0.425	0.050
PTH(pg/mL)	37.31(28.45,48.52)	37.08(28.56,46.81)	37.82(28.35,50.23)	0.183	0.039
25(OH)D3 (ng/mL)	17.28(13.43,22.27)	18.71(14.68,23.46)	15.72(12.42,19.92)	<0.001	0.004
SUA/Cr	4.19(3.29,5.09)	4.18(3.30,5.04)	4.24(3.31,5.17)	0.400	0.043
OC(ng/mL)	12.74(9.96,16.49)	11.84(9.45,14.80)	14.77(11.19,19.30)	<0.001	0.004
PINP(ng/mL)	38.68(29.29,51.63)	35.84(27.855,47.63)	44.10(32.59,58.71)	<0.001	0.004
β-CTX(ng/mL)	0.38(0.26,0.53)	0.35(0.24,0.49)	0.42(0.28,0.60)	<0.001	0.021

Abbreviations: BMI, body mass index; Ca2+, calcium ion; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; HbA1c, glycosylated hemoglobin A1c; FPG, fasting plasma glucose; PTH, parathyroid hormone; 25(OH)D3, 25-hydroxyvitamin D3; SUA/Cr, serum UA-to-creatinine ratio; OC, osteocalcin; PINP, type I procollagen amino-terminal peptide; β-CTX, type I collagen carboxyl terminal peptide; FDR, false discovery rate.

Figure 1 Flow chart.

Table 2 Comparison of Indicators Between the Low SUA/Cr and High SUA/Cr Groups

	All Patients				Male Patients				Postmenopausal Female Patients
	Low SUA/Cr	High SUA/Cr	P	Adjusted P	Low SUA/Cr	High SUA/Cr	P	Adjusted P	Low SUA/Cr	High SUA/Cr	P	Adjusted P
n	845	846	–	–	521	507	–	–	324	339	–
Age (years)	63.00(54.00,70.00)	57.00(49.00,66.00)	<0.001	0.011	60.00(51.00,69.00)	53.00(44.00,61.00)	<0.001	0.004	65.00(59.00,72.00)	63.00(57.00,72.00)	0.246	0.039
BMI (kg/m2)	25.65(23.19,27.68)	26.35(23.83,28.59)	<0.001	0.025	25.71(23.38,27.68)	26.56(24.22,29.01)	<0.001	0.018	25.39(23.09,27.94)	25.91(23.32,28.08)	0.312	0.043
Course(years)	10.00(5.00,19.00)	9.00(2.00,15.00)	<0.001	0.021	10.00(3.00,18.00)	7.00(2.00,12.00)	<0.001	0.021	11.00(6.00,20.00)	10.00(5.00,19.00)	0.086	0.025
Ca2+ (mmol/L)	2.28(2.2,2.35)	2.31(2.24,2.37)	<0.001	0.018	2.28(2.19,2.34)	2.30(2.23,2.37)	<0.001	0.025	2.28(2.21,2.36)	2.31(2.24,2.38)	0.011	0.018
TG (mmol/L)	1.21(0.91,1.74)	1.56(1.09,2.43)	<0.001	0.004	1.2(0.89,1.76)	1.67(1.12,2.66)	<0.001	0.004	1.23(0.94,1.76)	1.45(1.05,2.08)	<0.001	0.011
HDL-C (mmol/L)	1.16(0.95,1.48)	1.05(0.89,1.26)	<0.001	0.014	1.11(0.89,1.39)	0.98(0.86,1.17)	<0.001	0.014	1.27(1.04,1.63)	1.18(0.99,1.36)	<0.001	0.007
HbA1c (%)	8.6(7.4,10.2)	8.60(7.20,10.20)	0.263	0.046	8.60(7.30,10.10)	8.70(7.10,10.20)	0.835	0.05	8.60(7.60,10.40)	8.06(7.30,10.28)	0.112	0.032
FPG(mmol/L)	7.61(5.80,10.40)	7.99(6.44,10.66)	0.001	0.032	7.62(5.80,10.10)	8.05(6.49,11.36)	0.001	0.029	7.61(5.53,10.88)	7.89(6.33,10.09)	0.234	0.036
PTH(pg/mL)	37.42(28.03,48.66)	37.17(29.38,48.13)	0.446	0.050	36.87(27.87,46.73)	37.08(29.31,46.90)	0.265	0.043	38.08(28.03,51.91)	37.36(29.40,49.27)	0.858	0.05
25(OH)D3 (ng/mL)	16.81(13.07,22.34)	17.95(13.85,22.22)	0.0570	0.039	17.84(13.79,24.18)	19.23(15.31,23.23)	0.043	0.039	15.84(12.16,19.82)	15.39(12.48,20.00)	0.678	0.046
SUA/Cr	3.29(2.53,3.79)	5.09(4.63,5.99)	<0.001	0.004	3.31(2.65,3.78)	5.05(4.61,5.87)	<0.001	0.004	3.28(2.34,3.82)	5.14(4.64,6.13)	<0.001	0.004
OC(ng/mL)	12.99(10.01,16.72)	12.52(9.94,15.98)	0.072	0.043	11.88(9.30,15.17)	11.79(9.61,14.53)	0.442	0.046	14.95(11.46,20.38)	14.08(10.89,18.38)	0.020	0.021
PINP(ng/mL)	40.33(29.78,52.83)	37.61(28.62,50.13)	0.003	0.036	37.32(28.63,49.81)	34.35(26.75,44.90)	0.004	0.032	45.54(33.04,61.01)	42.35(31.75,56.78)	0.019	0.029
β-CTX(ng/mL)	0.40(0.27,0.58)	0.36(0.25,0.50)	<0.001	0.029	0.36(0.25,0.52)	0.33(0.23,0.47)	0.013	0.036	0.45(0.31,0.65)	0.40(0.28,0.56)	0.001	0.014

Abbreviations: BMI, body mass index; Ca2+, calcium ion; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; HbA1c, glycosylated hemoglobin A1c; FPG, fasting plasma glucose; PTH, parathyroid hormone; 25(OH)D3, 25-hydroxyvitamin D3; SUA/Cr, serum UA-to-creatinine ratio; OC, osteocalcin; PINP, type I procollagen amino-terminal peptide; β-CTX, type I collagen carboxyl terminal peptide; FDR, false discovery rate.

Figure 2 Spearman's correlation coefficient matrix illustrating the association between SUA/Cr and baseline patient characteristics in T2DM patients (A) all patients; (B) male patients; (C) postmenopausal female patients.

Figure 3 The correlation between SUA/Cr and BTMs levels in T2DM participants (A) all patients; (B) male patients; (C) postmenopausal female patients.

Table 3 Correlation of SUA/Cr with BTMs in T2DM Patients

		Model I		Model II		Model III
		β (95% CI)	P	β (95% CI)	P	β (95% CI)	P
Male patients	OC	−0.145(−0.298,0.008)	0.063	−0.164(−0.373,0.044)	0.121	−0.135(−0.339,0.069)	0.193
	PINP	−0.813(−1.368,-0.258)	0.004	−0.965(−1.692,-0.239)	0.009	−0.829(−1.564,-0.094)	0.027
	β-CTX	−0.011(−0.018,-0.003)	0.005	−0.015(−0.024,-0.006)	0.001	−0.015(−0.024,-0.006)	0.001
Female patients	OC	−0.443(−0.77,-0.116)	0.008	−0.953(−1.528,-0.378)	0.001	−0.916(−1.497,-0.334)	0.002
	PINP	−1.183(−2.254,-0.113)	0.030	−2.74(−4.656,-0.825)	0.005	−3.1(−5.095,-1.106)	0.002
	β-CTX	−0.029(−0.041,-0.016)	<0.001	−0.035(−0.052,-0.017)	<0.001	−0.036(−0.053,-0.019)	<0.001

Notes: Model I crude model; Mode II adjusted for age, BMI, course; Model III further adjusted for Ca2+, TG, HDL-C, HbA1c, FPG, 25(OH)D3, PTH.

Table 4 Subgroup Correlation Analysis of SUA/Cr and BTMs

		OC		PINP		β-CTX
		β	P	β	P	β	P
Male patients	NAFLD	−0.351	0.376	−2.872	0.016	−0.048	0.011
	Non-NAFLD	−0.324	0.481	−2.196	0.149	−0.035	0.064
	25(OH)D3<20	−0.519	0.042	−2.159	0.028	−0.036	0.002
	25(OH)D3≥20	−0.021	0.851	−0.460	0.196	−0.010	0.042
	Course≤5	−0.009	0.944	−0.352	0.439	−0.006	0.354
	Course>5	−0.267	0.146	−1.684	0.013	−0.029	<0.001
	HbA1c≤7	−0.222	0.767	−3.147	0.217	−0.065	0.032
	HbA1c>7	−0.118	0.203	−0.714	0.044	−0.013	0.002
	BMI<28	−0.175	0.362	−1.424	0.038	−0.032	<0.001
	BMI≥28	−0.046	0.568	−0.439	0.209	−0.003	0.518
	TG<1.7	−0.281	0.153	−1.348	0.055	−0.032	<0.001
	TG≥1.7	−0.002	0.984	−0.432	0.332	−0.006	0.249
Female patients	NAFLD	−0.88	0.06	−2.275	0.091	−0.039	0.012
	Non-NAFLD	−0.057	0.93	1.207	0.659	−0.038	0.103
	25(OH)D3<20	−1.109	0.002	−3.663	0.003	−0.037	<0.001
	25(OH)D3≥20	−0.378	0.386	−0.773	0.643	−0.034	0.071
	Course≤5	−0.547	0.236	−1.477	0.352	−0.017	0.356
	Course>5	−1.053	0.005	−3.705	0.004	−0.044	<0.001
	HbA1c≤7	−1.527	0.100	−6.639	0.044	−0.071	0.003
	HbA1c>7	−1.013	0.001	−2.808	0.006	−0.036	<0.001
	BMI<28	−0.745	0.019	−2.672	0.017	−0.029	0.004
	BMI≥28	−1.432	0.062	−4.121	0.087	−0.061	0.001
	TG<1.7	−1.203	0.004	−3.428	0.015	−0.037	0.002
	TG≥1.7	−0.588	0.096	−2.889	0.046	−0.04	0.001

Notes: The model was adjusted for age, BMI, course, Ca2+, TG, HDL-C, HbA1c, FPG, 25(OH)D3, PTH.

Figure 4 Mediation of TYG on the association between SUA/Cr and BTMs (A) PINP; (B) β-CTX.