Association of bone turnover biomarkers with severe intracranial and extracranial artery stenosis in type 2 diabetes mellitus patients

Table 1 Basic and clinical characteristics of all participants and those in the no severe intracranial and extracranial artery stenosis and artery stenosis groups

Characteristics	All patients (n = 257)	NOCS group (n = 224)	AS group (n = 33)	P value
Age (yr)	66.0 (11.0)	66.0 (11.0)	68.0 (12.0)	0.236
Male, n (%)	121 (47.1)	103 (46.0)	18 (54.5)	0.358
Duration of T2DM (yr)	12.0 (13.0)	12.0 (14.0)	13.0 (11.0)	0.438
Risk factors, n (%)
Hypertension	189 (73.5)	165 (73.7)	24 (72.7)	0.910
Hyperlipidemia	124 (48.2)	112 (50.0)	12 (36.4)	0.143
CAD	74 (28.8)	63 (28.3)	11 (33.3)	0.548
Previous stroke	31 (12.1)	22 (9.8)	9 (27.3)	0.004
Current smoker	74 (28.8)	67 (29.9)	7 (21.2)	0.303
Current drinker	64 (24.9)	59 (26.3)	5 (15.2)	0.165
BMI (kg/m2)	25.76 (3.57)	25.78 (3.59)	25.76 (3.45)	0.597
Glucose (mmol/L)	7.48 (3.58)	7.49 (3.53)	6.72 (4.25)	0.563
HbA1c (%)	7.60 (2.50)	7.60 (2.60)	8.40 (2.90)	0.037
INS (µIU/mL)	12.21 (12.71)	12.00 (10.71)	16.82 (18.93)	0.159
CP (ng/mL)	2.33 (1.52)	2.33 (1.53)	2.40 (1.89)	0.754
TC (mmol/L)	4.26 (1.50)	4.27 (1.41)	4.23 (2.25)	0.721
TG (mmol/L)	1.48 (1.38)	1.50 (1.39)	1.41 (1.36)	0.433
LDL-C (mmol/L)	2.38 (1.27)	2.39 (1.20)	2.27 (1.79)	0.781
HDL-C (mmol/L)	1.12 (0.47)	1.13 (0.47)	1.04 (0.38)	0.320
Scr (µmol/L)	62.0 (24.0)	62.0 (22.8)	60.0 (43.0)	0.144
Bun (mmol/L)	5.98 (2.30)	5.92 (2.12)	6.82 (3.60)	0.137
UA (µmol/L)	341.0 (126.5)	342.0 (127.3)	339.0 (1520)	0.823
OC (ng/mL)	10.60 (5.87)	10.27 (5.87)	12.63 (7.07)	0.001
CTX (pg/mL)	0.31 (0.21)	0.29 (0.19)	0.39 (0.30)	0.007
PINP (pg/mL)	34.40 (20.96)	33.39 (20.37)	43.92 (25.50)	0.010

Data are presented as the mean ± SD unless otherwise indicated. NOCS: No severe intracranial and extracranial artery stenosis; AS: Artery stenosis; CAD: Coronary artery disease; BMI: Body mass index; HbA1c: Hemoglobin; INS: Insulin; CP: C-peptide; TC: Total cholesterol; TG: Triglyceride; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; Scr: Serum creatinine; Bun: Blood urea nitrogen; UA: Uric acid; OC: Osteocalcin; CTX: C-terminal cross-linked telopeptide of type I collagen; PINP: Procollagen type I N-peptide.

Table 2 Basic and clinical characteristics of patients in the no severe intracranial and extracranial artery stenosis, intracranial artery stenosis, severe extracranial artery stenosis and combined severe intracranial and extracranial artery stenosis groups

Characteristics	NOCS group (n = 224)	ICAS group (n = 19)	ECAS group (n = 8)	COAS group (n = 6)	P value
Age (yr)	66.0 (11.0)	65.0 (16.0)	67.5 (13.0)	71.0 (10.0)	0.373
Male, n (%)	103 (46.0)	10 (52.6)	5 (62.5)	3 (50)	0.780
Duration of T2DM (yr)	12.0 (14.0)	15.0 (11.0)	18.0 (20.8)	11.5 (7.0)	0.635
Risk factors, n (%)
Hypertension	165 (73.7)	13 (68.4)	5 (62.5)	6 (100)	0.527
Hyperlipidemia	112 (50.0)	4 (21.1)	7 (75.0)	2 (33.3)	0.029
CAD	63 (28.3)	7 (36.8)	2 (25.0)	2 (33.3)	0.826
Previous stroke	22 (9.8)	4 (21.1)	2 (25.0)	3 (50.0)	0.009
Current smoker	67 (29.9)	4 (21.1)	1 (12.5)	2 (33.3)	0.682
Current drinker	59 (26.3)	4 (21.1)	1 (12.5)	0 (0)	0.554
BMI (kg/m2)	25.78 (3.59)	26.06 (3.90)	25.32 (2.33)	23.96 (12.48)	0.821
FPG (mmol/L)	7.49 (3.53)	7.83 (4.13)	7.13 (6.89)	5.76 (2.48)	0.446
HbA1c (%)	7.60 (2.60)	7.90 (3.10)	9.15 (1.70)	7.90 (1.80)	0.067
INS (µIU/mL)	12.00 (10.71)	16.99 (19.11)	12.78 (19.72)	15.90 (25.32)	0.334
CP (ng/mL)	2.33 (1.53)	2.52 (1.45)	1.56 (2.95)	2.03 (2.31)	0.599
TC (mmol/L)	4.27 (1.41)	3.85 (1.98)	4.92 (2.35)	4.35 (2.25)	0.535
TG (mmol/L)	1.50 (1.39)	1.59 (1.31)	1.29 (1.31)	1.16 (1.85)	0.585
LDL-C (mmol/L)	2.39 (1.20)	2.27 (1.76)	2.62 (1.88)	2.01 (2.27)	0.943
HDL-C (mmol/L)	1.13 (0.47)	0.98 (0.29)	1.25 (1.21)	1.04 (0.43)	0.170
Scr (µmol/L)	62.0 (22.8)	59.0 (48.0)	78.5 (44.8)	60.0 (40.3)	0.499
Bun (mmol/L)	5.92 (2.12)	6.36 (2.74)	7.92 (6.76)	6.57 (5.00)	0.419
UA (µmol/L)	342.0 (127.3)	358.0 (174.0)	322.5 (153.3)	303.0 (136.3)	0.746
OC (ng/mL)	10.27 (5.87)	12.76 (8.14)	11.89 (4.02)	15.15 (11.43)	0.012
CTX (pg/mL)	0.29 (0.19)	0.41 (0.29)	0.35 (0.23)	0.65 (0.51)	0.027
PINP (pg/mL)	33.39 (20.37)	41.25 (24.71)	47.22 (39.85)	51.28 (37.96)	0.059

Data are presented as the mean ± SD unless otherwise indicated. NOCS: No severe intracranial and extracranial artery stenosis; ICAS: Severe intracranial artery stenosis; ECAS: Severe extracranial artery stenosis; COAS: Combined severe intracranial and extracranial artery stenosis; CAD: Coronary artery disease; BMI: Body mass index; HbA1c: Hemoglobin; INS: Insulin; FPG: Fasting plasma glucose; CP: C-peptide; TC: Total cholesterol; TG: Triglyceride; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; Scr: Serum creatinine; Bun: Blood urea nitrogen; UA: Uric acid; OC: Osteocalcin; CTX: C-terminal cross-linked telopeptide of type I collagen; PINP: Procollagen type I N-peptide.

Table 3 Association of bone turnover biomarker levels with artery stenosis

Variable	Model	OR (95%CI)	P value
OC	Model 1	1.123 (1.049-1.203)	0.001
	Model 2	1.117 (1.041-1.199)	0.002
	Model 3	1.117 (1.039-1.201)	0.003
	Model 4	1.109 (1.029-1.196)	0.007
CTX	Model 1	9.750 (1.759-54.059)	0.009
	Model 2	8.674 (1.529-49.211)	0.015
	Model 3	10.833 (1.725-68.037)	0.011
	Model 4	8.526 (1.189-61.119)	0.033
PINP	Model 1	1.024 (1.006-1.042)	0.010
	Model 2	1.022 (1.003-1.041)	0.025
	Model 3	1.022 (1.003-1.042)	0.021
	Model 4	1.020 (1.001-1.040)	0.044

Model 1: Unadjusted, crude model; Model 2: Adjusted for age and gender; Model 3: Further adjusted for hypertension, hyperlipidemia, coronary artery disease, duration of type 2 diabetes mellitus, current smoker, current drinker; Model 4: Further adjusted for body mass index, serum creatinine, blood urea nitrogen, uric acid, and hemoglobin. OC: Osteocalcin; CTX: C-terminal cross-linked telopeptide of type I collagen; PINP: Procollagen type I N-peptide.

Table 4 Spearman correlation coefficients for the associations between bone turnover biomarker levels and indicators of glucose and lipid metabolism

Variable	OC		CTX		PINP
	r	P value	r	P value	r	P value
FPG	-0.102	0.103	-0.134	0.031	-0.141	0.024
HbA1c	-0.012	0.846	-0.022	0.724	-0.012	0.845
INS	-0.050	0.425	-0.086	0.172	-0.031	0.628
CP	0.021	0.741	0.045	0.473	0.067	0.286
TC	0.185	0.003	0.147	0.018	0.112	0.074
TG	0.020	0.753	-0.058	0.351	-0.041	0.514
LDL-C	0.213	0.001	0.187	0.003	0.129	0.039
HDL-C	0.020	0.745	0.062	0.319	0.015	0.811

OC: Osteocalcin; CTX: C-terminal cross-linked telopeptide of type I collagen; PINP: Procollagen type I N-peptide; FPG: Fasting plasma glucose; HbA1c: Hemoglobin; INS: Insulin; CP: C-peptide; TC: Total cholesterol; TG: Triglyceride; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol.