1、Clinical Characteristics of the Subjects stratified by sex
Considering that serum osteocalcin levels might be affected by menopause (sex hormone levels) and gender [8, 13, 22], a total of 222 postmenopausal female patients and 258 male patients with type 2 diabetes were enrolled in the research. The baseline characteristics were demonstrated in Table 1. Female participants were older than male volunteers (65.05 ± 10.42 years and 59.71 ± 13.22 years, P < 0.05). The OC level in male group was lower than that in female group (12.10 ± 5.04 and 15.92 ± 18.13 ng/mL, P < 0.05), and the 1,5-AG level in male group was lower than that in female group (3.79 ± 4.22 and 5.34 ± 6.60µg/mL, P < 0.05). There was no statistically significant difference between the two groups with respect to HbA1c, GA, FBG and FCP (Table 1).
Table 1
Clinical Characteristics of the Subjects stratified by sex
Characteristics | Postmenopausal female (n = 222) | Male (n = 258) |
---|
Age (years) | 65.05 ± 10.42 | 59.71 ± 13.22* |
Diabetes duration (years) | 10.93 ± 9.64 | 9.63 ± 7.75 |
BMI (kg/m2) | 24.86 ± 4.06 | 24.78 ± 3.84 |
SBP (mmHg) | 139.26 ± 22.39 | 137.48 ± 17.78 |
OC (ng/mL) | 15.92 ± 18.13 | 12.10 ± 5.04* |
25 (OH) VD3 (ng/mL) | 19.23 ± 8.76 | 20.23 ± 8.46 |
P1NP (ng/mL) | 46.70 ± 33.18 | 37.10 ± 16.38* |
β-CTx(ng/mL) | 0.46 ± 0.30 | 0.41 ± 0.26 |
FBG (mmol/L) | 8.98 ± 4.77 | 9.37 ± 4.06 |
1,5-AG (µg/mL) | 5.34 ± 6.60 | 3.79 ± 4.22* |
HbA1c(%) | 8.67 ± 2.04 | 8.96 ± 2.15 |
GA(%) | 22.34 ± 8.39 | 24.22 ± 9.24 |
FCP (pmol/l ) | 0.68 ± 0.40 | 0.65 ± 0.41 |
Ca (mmol/L) | 2.25 ± 0.13 | 2.24 ± 0.16 |
P (mmol/L) | 1.23 ± 0.60 | 1.13 ± 0.18* |
ALP (U/L) | 83.68 ± 45.63 | 76.61 ± 19.16* |
HDL (mmol/L) | 1.27 ± 0.29 | 1.16 ± 0.26* |
LDL (mmol/L) | 2.50 ± 0.77 | 2.44 ± 0.78 |
TC (mmol/L) | 4.55 ± 1.15 | 4.27 ± 1.10* |
TG (mmol/L) | 1.80 ± 1.33 | 1.80 ± 1.52 |
eGFR (mL/min/1.73m2) | 89.43 ± 23.04 | 93.31 ± 23.01 |
UA (umol/L) | 296.75 ± 100.22 | 343.14 ± 97.95* |
BUN(mmol/L) | 6.39 ± 3.54 | 6.64 ± 2.28 |
* p < 0.05. BMI = Body mass index; SBP = systolic blood pressure; OC = osteocalcin; 25 (OH) VD3 = 25-hydroxy vitamin D3; P1NP = procollagen type 1 N-terminal propeptide; β-CTX = β-C-terminal telopeptide of type I collagen;FBG = fasting blood glucose; HbA1C = glycated hemoglobin; GA = Glycated albumin; 1,5 AG = 1,5-anhydroglucitol; FCP = fasting C peptide; Ca = calcium; P = phosphorus; ALP = alkaline phosphatase; LDL = low-density lipoprotein; HDL = high-density lipoprotein; TC = total cholesterol; TG = triglycerides; UA = uric acid; BUN = blood urea nitrogen . |
2、 Comparison of variables according to quartiles of serum OC levels.
Dividing the male and female group into three groups on the basis of OC levels respectively, we could see that with the increase of OC serum level, blood glucose markers such as FBG、HbA1c、GA significantly decreased, 1,5-AG significantly increased whatever in male or postmenopausal female patients. What’s more, TG was in a significant increase in postmenopausal female patients, which is different from male patients (Table 2).
Table 2
Comparison of variables according to quartiles of serum OC levels
| Male | Postmenopausal female |
---|
Quartiles of OC (ng/mL) | Q1 < 9.321 | Q2 9.321–13.200 | Q3 > 13.200 | Q1 < 9.861 | Q2 9.861–15.40 | Q3 > 15.40 |
| n = 86 | n = 87 | n = 85 | n = 74 | n = 74 | n = 74 |
Age (years) | 60.47 ± 13.19 | 60.31 ± 12.54 | 58.32 ± 13.96 | 64.65 ± 11.81 | 66.18 ± 9.37 | 64.32 ± 10.42 |
Diabetes duration (years) | 9.81 ± 7.92 | 9.83 ± 7.46 | 9.26 ± 7.95 | 10.03 ± 8.89 | 11.97 ± 10.19 | 10.76 ± 9.86 |
BMI (kg/m2) | 25.12 ± 3.64 | 24.61 ± 3.88 | 24.61 ± 4.01 | 25.38 ± 4.06 | 24.97 ± 4.21 | 24.26 ± 3.89 |
SBP (mmHg) | 136.79 ± 17.72 | 136.37 ± 17.11 | 139.32 ± 18.55 | 140.74 ± 22.46 | 140.97 ± 21.49 | 137.96 ± 16.92 |
25 (OH) VD3 (ng/mL) | 20.76 ± 9.09 | 18.75 ± 7.01 | 21.21 ± 9.02 | 19.97 ± 9.98 | 19.71 ± 8.59 | 18.01 ± 7.51 |
P1NP (ng/mL) | 28.28 ± 14.44 | 33.88 ± 9.62* | 49.32 ± 16.55 | 25.52 ± 12.95 | 39.71 ± 9.10 | 70.86 ± 40.29* |
β-CTx(ng/mL) | 0.28 ± 0.18 | 0.36 ± 0.18* | 0.61 ± 0.28* | 0.26 ± 0.21 | 0.42 ± 0.16* | 0.71 ± 0.33* |
FBG (mmol/L) | 10.60 ± 5.02 | 9.04 ± 3.30* | 8.46 ± 3.37 | 9.99 ± 5.62 | 9.01 ± 4.68 | 7.92 ± 3.66* |
1,5-AG (µg/mL) | 2.94 ± 3.52 | 3.86 ± 4.37 | 4.57 ± 4.51* | 3.55 ± 4.69 | 4.59 ± 5.72 | 7.88 ± 8.17* |
HbA1c(%) | 9.46 ± 2.12 | 9.06 ± 2.02 | 8.33 ± 2.17* | 9.23 ± 2.04 | 8.95 ± 1.97 | 7.84 ± 1.85* |
GA(%) | 25.60 ± 10.14 | 24.61 ± 8.90 | 22.43 ± 8.39 | 25.34 ± 8.45 | 23.34 ± 7.80 | 21.34 ± 8.52 |
FCP (pmol/l ) | 0.60 ± 0.33 | 0.64 ± 0.39 | 0.72 ± 0.49 | 0.64 ± 0.37 | 0.64 ± 0.26 | 0.76 ± 0.52 |
Ca (mmol/L) | 2.22 ± 0.24 | 2.23 ± 0.11 | 2.26 ± 0.10 | 2.25 ± 0.17 | 2.27 ± 0.10 | 2.24 ± 0.12 |
P (mmol/L) | 1.10 ± 0.18 | 1.14 ± 0.16 | 1.15 ± 0.20 | 1.28 ± 1.01 | 1.20 ± 0.17 | 1.21 ± 0.18 |
ALP (U/L) | 74.82 ± 16.95 | 73.92 ± 17.88 | 81.17 ± 21.75* | 75.51 ± 22.99 | 76.21 ± 19.45 | 99.32 ± 70.87* |
HDL (mmol/L) | 1.17 ± 0.27 | 1.16 ± 0.26 | 1.17 ± 0.25 | 1.25 ± 0.28 | 1.32 ± 0.28 | 1.25 ± 0.31 |
LDL (mmol/L) | 2.42 ± 0.79 | 2.47 ± 0.86 | 2.44 ± 0.78 | 2.47 ± 0.83 | 2.60 ± 0.71 | 2.42 ± 0.76 |
TC (mmol/L) | 4.26 ± 1.13 | 4.32 ± 1.21 | 4.22 ± 0.96 | 4.50 ± 1.22 | 4.69 ± 1.02 | 4.46 ± 1.20 |
TG (mmol/L) | 1.75 ± 1.03 | 1.83 ± 2.01 | 1.83 ± 1.37 | 2.00 ± 1.57 | 1.76 ± 1.19 | 1.65 ± 1.19 |
eGFR (mL/min/1.73m2) | 93.12 ± 20.56 | 95.47 ± 18.00 | 90.99 ± 24.05 | 93.83 ± 22.88 | 91.84 ± 13.95 | 82.62 ± 28.57* |
UA (umol/L) | 345.63 ± 99.76 | 342.60 ± 90.12 | 341.18 ± 104.68 | 291.53 ± 101.67 | 286.11 ± 66.45 | 312.61 ± 123.43 |
BUN (mmol/L) | 6.56 ± 2.70 | 6.61 ± 1.77 | 6.75 ± 2.31 | 5.86 ± 2.57 | 5.73 ± 1.39 | 7.58 ± 5.20* |
* p < 0.05. BMI = Body mass index; SBP: systolic blood pressure; OC = osteocalcin; 25 (OH) VD3 = 25-hydroxy vitamin D3; P1NP = procollagen type 1 N-terminal propeptide; β-CTX = β-C-terminal telopeptide of type I collagen;FBG = fasting blood glucose; HbA1C = glycated hemoglobin; GA = Glycated albumin; 1,5 AG = 1,5-anhydroglucitol; FCP = fasting C peptide; Ca = calcium; P = phosphorus; ALP = alkaline phosphatase; LDL = low-density lipoprotein; HDL = high-density lipoprotein; TC = total cholesterol; TG = triglycerides; UA = uric acid ; BUN = blood urea nitrogen . |
3、 Correlation analysis of OC and variables
Spearman correlation analysis demonstrated that in the male group, the OC level was negatively correlated with HbA1c (r=-0.252, p < 0.001) and GA (r = 0.158, p = 0.011), but positively correlated with 1, 5-AG (r = 0.204, p < 0.001). Similarly, in the postmenopausal female group, the OC level was found to have a negative relation with HbA1c (r=-0.286, p < 0.001) and GA (r=-0.160, p = 0.017), and a positive relation with 1, 5-AG (r = 0.329, p < 0.001). FCP was present to be positively associated with OC in male patients (r = 0.141, p = 0.023), but no association in postmenopausal female patients. In addition, there was no significant correlation between OC and other variables such as age, diabetic duration, LDL, HDL, TC, 25 (OH) VD3, BMI, while in the postmenopausal female patients, OC was demonstrated to have an inverse correlation with TG (r=-0.142, p = 0.034). (Table 3).
Table 3
Correlation analysis of OC and variables
OC (ng/mL) | Male (n = 258) | Postmenopausal female(n = 222) |
---|
| r | p | r | p |
Age (years) | -0.090 | 0.149 | 0.005 | 0.935 |
Diabetes duration (years) | -0.021 | 0.735 | 0.031 | 0.650 |
BMI (kg/m2) | -0.063 | 0.317 | -0.131 | 0.052 |
SBP (mmHg) | 0.013 | 0.832 | -0.080 | 0.238 |
25 (OH) VD3 (ng/mL) | 0.045 | 0.475 | -0.057 | 0.395 |
P1NP (ng/mL) | 0.657 | < 0.001 | 0.769 | < 0.001 |
β-CTx(ng/mL) | 0.590 | < 0.001 | 0.720 | < 0.001 |
FBG (mmol/L) | -0.206 | 0.001 | -0.185 | 0.006 |
1,5-AG (µg/mL) | 0.204 | < 0.001 | 0.329 | < 0.001 |
HbA1c(%) | -0.252 | < 0.001 | -0.288 | < 0.001 |
GA(%) | -0.152 | 0.014 | -0.198 | 0.003 |
FCP (pmol/l ) | 0.141 | 0.023 | 0.068 | 0.315 |
Ca (mmol/L) | 0.129 | 0.038 | -0.074 | 0.274 |
P (mmol/L) | 0.108 | 0.084 | 0.118 | 0.080 |
ALP (U/L) | 0.126 | 0.043 | 0.278 | < 0.001 |
HDL (mmol/L) | -0.021 | 0.743 | 0.065 | 0.337 |
LDL (mmol/L) | 0.012 | 0.849 | -0.012 | 0.859 |
TC (mmol/L) | -0.006 | 0.918 | 0.013 | 0.842 |
TG (mmol/L) | -0.044 | 0.084 | -0.142 | 0.034 |
eGFR (mL/min/1.73m2) | -0.041 | 0.515 | -0.133 | 0.048 |
UA (umol/L) | -0.021 | 0.734 | -0.023 | 0.732 |
BUN(mmol/L) | 0.057 | 0.365 | 0.168 | 0.012 |
OC = osteocalcin; 25 (OH) VD3 = 25-hydroxy vitamin D3; P1NP = procollagen type 1 N-terminal propeptide; β-CTX = β-C-terminal telopeptide of type I collagen;FBG = fasting blood glucose; HbA1C = glycated hemoglobin; GA = Glycated albumin; 1,5 AG = 1,5-anhydroglucitol; FCP = fasting C peptide; Ca = calcium; P = phosphorus; ALP = alkaline phosphatase; LDL = low-density lipoprotein; HDL = high-density lipoprotein; TC = total cholesterol; TG = triglycerides; UA = uric acid; BUN = blood urea nitroge |
4、Multiple linear regression analysis of HbA1c, GA, 1,5-AG and variables
In order to explore the correlation between OC and glucose metabolism, we investigated blood glucose markers firstly. There were significant association among HbA1c, GA and 1,5-AG (Table S1). Then we took HbA1c, GA, 1,5-AG as dependent variables respectively. OC, age, diabetic duration, BMI, SBP, LDL, HDL, TC, TG, eGFR, UA, creatinine, BUN, ALP, Ca, P, 25 (OH) VD3, FBG and FCP were selected as independent variables. The covariates were adjusted by four models respectively (Table 4). The analysis showed that OC was the independent relevant factor affecting HbA1c and 1,5-AG levels in both groups. However, there was no association between OC and GA after adjustment. In addition, we conducted P1NP and β-CTx as dependent variables (Table S2), and the results showed that P1NP and β-CTx were not related to markers of glucose metabolism, which might demonstrate that OC is the only bone marker independently correlated with the glucose metabolism [14].
5、 Multiple regression analysis of FCP, lipid indexes and various indexes
We took FCP and TG as dependent variables to investigate the correlation between OC and insulin resistance and lipid metabolism. The adjustment models were the same as above. The analysis showed that OC was not correlated with FCP in either the male population or the postmenopausal female population (Table S3). When it comes to lipid metabolism, there was no correlation between OC and lipid markers in the male population after adjusting for covariates, while in the postmenopausal female population, OC could be regarded as an independent factor influencing TG (Table S4).
Table 4 Multiple linear regression analysis of HbA1c, GA, 1,5-AG and variables
|
Male
|
Postmenopausal female
|
|
HbA1c
|
GA
|
1,5-AG
|
HbA1c
|
GA
|
1,5-AG
|
OC
|
b
|
p
|
b
|
p
|
b
|
p
|
b
|
p
|
b
|
p
|
b
|
p
|
Model 1
|
-0.069
|
0.009
|
-0.168
|
0.138
|
0.134
|
0.009
|
-0.015
|
0.008
|
-0.003
|
0.923
|
0.030
|
0.226
|
Model 2
|
-0.081
|
0.001
|
-0.219
|
0.040
|
0.154
|
0.002
|
-0.031
|
0.004
|
-0.084
|
0.061
|
0.104
|
0.003
|
Model 3
|
-0.107
|
<0.001
|
-0.344
|
0.001
|
0.169
|
0.001
|
-0.033
|
0.002
|
-0.096
|
0.036
|
0.123
|
<0.001
|
Model 4
|
-0.064
|
0.006
|
-0.162
|
0.099
|
0.102
|
0.047
|
-0.022
|
0.037
|
-0.048
|
0.278
|
0.100
|
0.004
|
OC = osteocalcin; HbA1c = glycated hemoglobin; GA=Glycated albumin; 1,5 AG=1,5-anhydroglucitol
Model 1 is adjusted for OC, age, BMI and diabetes duration. Model 2 is additionally adjusted for HDL, LDL, TC, TG ,UA, BUN and eGFR . Model 3 is adjusted for ALP, Ca,P,25 (OH) VD3 ;Model 4 is adjusted for FBG and FCP.