Background
Methods
Subjects
Clinical examination
Metabolite measurements
Circulating Hp detection
Statistical analyses
Results
Basic clinical features
Variable | Low Hp | Middle Hp | High Hp | P value |
---|---|---|---|---|
T2DM (n = 120) | ||||
Number | 39 | 40 | 41 | – |
Age (years) | 56.85 ± 11.18 | 56.88 ± 12.16 | 58.25 ± 11.46 | 0.8245 |
Male/female | 30/9 | 22/18 | 32/9 |
0.0410
|
BMI (kg/m2) | 24.69 ± 4.24 | 24.63 ± 3.25 | 24.62 ± 2.89 | 0.9959 |
SBP (mmHg) | 130 (120, 150) | 127 (110, 134) | 130 (120, 150) | 0.0852 |
DBP (mmHg) | 80 (74, 90) | 75 (70, 82) | 80 (72, 90) | 0.1756 |
Duration of diabetes (years) | 10 (4, 15) | 10 (7, 10) | 10 (4, 15) | 0.8267 |
HbA1c (%) | 8.00 (7.20, 10.20) | 8.40 (7.20, 10.30) | 8.30 (7.20, 9.70) | 0.9903 |
Total cholesterol (mmol/L) | 4.64 (4.28, 5.59) | 4.61 (3.78, 5.37) | 4.40 (3.87, 4.87) | 0.3833 |
Triglycerides (mmol/L) | 1.50 (1.20, 2.20) | 1.29 (0.79, 1.93) | 1.39 (1.03, 1.65) | 0.2756 |
HDL-C (mmol/L) | 1.09 (0.95, 1.20) | 0.99 (0.88, 1.24) | 1.00 (0.81, 1.10) | 0.2181 |
LDL-C (mmol/L) | 2.76 ± 0.85 | 2.74 ± 0.76 | 2.65 ± 0.84 | 0.7488 |
Carotid IMT (mm) | 0.80 (0.70, 0.90) | 0.75 (0.65, 0.90) | 0.80 (0.70, 0.90) | 0.3466 |
Carotid IAD (mm) | 6.17 ± 0.70 | 6.28 ± 0.78 | 6.65 ± 0.67 |
0.0088
|
Serum Hp levels (mg/dL) | 54.82 (3.60, 71.58) | 103.20 (95.30, 107.27) | 151.64 (131.12, 175.55) | < 0.0001 |
Non-DM (n = 120) | ||||
Number | 39 | 40 | 41 | – |
Age (years) | 64.06 ± 4.31 | 64.10 ± 4.27 | 64.58 ± 4.15 | 0.8720 |
Male/female | 17/22 | 20/20 | 23/18 | 0.5378 |
BMI (kg/m2) | 24.11 ± 3.27 | 25.09 ± 3.18 | 25.64 ± 4.06 | 0.1522 |
SBP (mmHg) | 125 (120, 139) | 129 (122, 138) | 129 (123, 138) | 0.5074 |
DBP (mmHg) | 81 (78, 87) | 81 (78, 83) | 82 (80, 87) | 0.4709 |
HbA1c (%) | 5.64 ± 0.59 | 5.61 ± 0.65 | 5.82 ± 0.51 | 0.1398 |
Total cholesterol (mmol/L) | 4.36 (4.00, 4.89) | 4.49 (3.98, 4.97) | 4.40 (4.07, 4.79) | 0.8007 |
Triglycerides (mmol/L) | 1.03 (0.80, 1.43) | 1.10 (0.89, 1.41) | 0.99 (0.80, 1.26) | 0.7676 |
HDL-C (mmol/L) | 1.31 (1.09, 1.58) | 1.29 (1.17, 1.52) | 1.22 (1.14, 1.41) | 0.6175 |
LDL-C (mmol/L) | 2.53 (2.25, 2.89) | 2.56 (2.15, 2.97) | 2.61 (2.28, 2.91) | 0.7962 |
Carotid IMT (mm) | 0.64 ± 0.10 | 0.65 ± 0.09 | 0.66 ± 0.08 | 0.4667 |
Serum Hp levels (mg/dL) | 39.48 (17.23, 51.45) | 99.41 (92.96, 113.38) | 167.67 (140.35, 209.73) | < 0.0001 |
Association between blood metabolites and serum Hp levels
Metabolites | Low Hp | Middle Hp | High Hp | P value |
---|---|---|---|---|
T2DM (n = 120) | ||||
Acylcarnitines (μM) | ||||
C12:1 | 0.142 ± 0.042 | 0.148 ± 0.044 | 0.116 ± 0.032 | 0.0017 |
C14:1 | 0.241 ± 0.064 | 0.229 ± 0.067 | 0.201 ± 0.048 | 0.0119 |
Lyso-phosphatidylcholines (μM) | ||||
Lyso-PC a C20:3 | 1.284 ± 0.423 | 1.050 ± 0.319 | 1.064 ± 0.332 | 0.0158 |
Phosphatidylcholines (μM) | ||||
PC aa C32:1 | 5.437 ± 2.670 | 4.678 ± 1.994 | 4.128 ± 1.775 | 0.0398 |
PC aa C34:1 | 109.683 ± 37.529 | 99.877 ± 34.435 | 89.110 ± 23.902 | 0.0117 |
PC aa C34:2 | 323.235 ± 80.457 | 308.206 ± 90.611 | 283.969 ± 72.902 | 0.0456 |
PC aa C36:1 | 22.898 ± 6.344 | 21.283 ± 4.553 | 19.615 ± 6.216 | 0.0041 |
PC aa C40:4 | 2.093 ± 0.646 | 1.881 ± 0.541 | 1.809 ± 0.594 | 0.0458 |
PC ae C32:1 | 1.329 ± 0.294 | 1.281 ± 0.268 | 1.171 ± 0.245 | 0.0364 |
PC ae C32:2 | 0.335 ± 0.088 | 0.301 ± 0.062 | 0.281 ± 0.058 | 0.0094 |
PC ae C34:1 | 3.305 ± 0.712 | 3.254 ± 0.733 | 2.902 ± 0.559 | 0.0270 |
PC ae C36:0 | 0.577 ± 0.180 | 0.546 ± 0.128 | 0.470 ± 0.098 | 0.0055 |
PC ae C36:1 | 4.953 ± 0.948 | 4.642 ± 0.925 | 4.417 ± 0.814 | 0.0327 |
PC ae C40:5 | 2.140 ± 0.418 | 2.034 ± 0.527 | 1.871 ± 0.374 | 0.0329 |
PC ae C42:2 | 0.333 ± 0.080 | 0.307 ± 0.082 | 0.287 ± 0.060 | 0.0443 |
Amino acids (μM) | ||||
His | 115.000 ± 15.508 | 111.528 ± 15.191 | 105.444 ± 14.510 | 0.0183 |
Lys | 330.411 ± 57.377 | 306.053 ± 61.629 | 300.033 ± 54.178 | 0.0255 |
Trp | 65.594 ± 14.239 | 59.247 ± 13.020 | 58.258 ± 10.826 | 0.0238 |
Tyr | 89.152 ± 19.114 | 84.488 ± 17.566 | 79.436 ± 16.558 | 0.0494 |
Non-DM (n = 120) | ||||
Acylcarnitines (μM) | ||||
C16:1-OH | 0.018 ± 0.004 | 0.010 ± 0.002 | 0.013 ± 0.002 | 0.0440 |
C2 | 6.327 ± 2.720 | 5.684 ± 1.558 | 6.773 ± 2.023 | 0.0385 |
C3 | 0.334 ± 0.109 | 0.299 ± 0.124 | 0.386 ± 0.191 | 0.0294 |
C4 | 0.211 ± 0.075 | 0.184 ± 0.082 | 0.225 ± 0.090 | 0.0209 |
C6/C4:1-DC | 0.085 ± 0.038 | 0.083 ± 0.058 | 0.113 ± 0.074 | 0.0240 |
Lyso-phosphatidylcholines (μM) | ||||
LysoPC a C17:0 | 1.302 ± 0.361 | 1.208 ± 0.318 | 1.115 ± 0.326 | 0.0463 |
LysoPC a C24:0 | 0.371 ± 0.121 | 0.312 ± 0.112 | 0.307 ± 0.120 | 0.0450 |
Phosphatidylcholines (μM) | ||||
PC aa C32:3 | 0.260 ± 0.047 | 0.239 ± 0.061 | 0.225 ± 0.059 | 0.0087 |
PC aa C42:2 | 0.276 ± 0.062 | 0.289 ± 0.116 | 0.243 ± 0.070 | 0.0326 |
PC ae C32:2 | 0.475 ± 0.098 | 0.453 ± 0.131 | 0.424 ± 0.089 | 0.0602 |
PC ae C36:2 | 7.123 ± 1.446 | 6.882 ± 2.063 | 6.309 ± 1.124 | 0.0304 |
PC ae C38:0 | 1.141 ± 0.298 | 1.062 ± 0.377 | 0.969 ± 0.252 | 0.0471 |
PC ae C40:1 | 1.286 ± 0.246 | 1.164 ± 0.263 | 1.101 ± 0.189 | 0.0071 |
PC ae C42:1 | 0.372 ± 0.093 | 0.347 ± 0.091 | 0.321 ± 0.071 | 0.0197 |
Amino acids (μM) | ||||
Asp | 32.646 ± 5.990 | 31.854 ± 4.664 | 36.137 ± 6.343 | 0.0034 |
Trp | 75.043 ± 8.173 | 71.877 ± 9.742 | 68.875 ± 11.423 | 0.0244 |
Ac-Orn | 2.189 ± 0.159 | 2.239 ± 0.001 | 1.596 ± 0.941 | 0.0185 |
Selected metabolites associated with blood lipid traits
Metabolites | Total cholesterol | Triglycerides | HDL-C | LDL-C | Serum Hp | Carotid IMT | Carotid IAD |
---|---|---|---|---|---|---|---|
Acylcarnitines (μM) | |||||||
C16-OH | 0.017 ± 0.011 | − 0.002 ± 0.002 | − 0.011 ± 0.005 | − 0.008 ± 0.006 | − 0.001 ± 0.001 | 0.012 ± 0.004 | − 0.002 ± 0.007 |
0.1099 | 0.4393 |
0.0270
| 0.1690 |
0.0452
|
0.0074
| 0.7911 | |
Lyso-phosphatidylcholines (μM) | |||||||
Lyso-PC a C20:3 | − 0.316 ± 1.027 | 0.834 ± 0.233 | 1.073 ± 0.485 | − 0.202 ± 0.580 | − 0.092 ± 0.041 | − 0.173 ± 0.404 | 0.511 ± 0.693 |
0.7588 |
0.0005
|
0.0290
| 0.7286 |
0.0272
| 0.6698 | 0.4621 | |
Phosphatidylcholines (μM) | |||||||
PC aa C32:0 | 10.436 ± 4.062 | 1.295 ± 0.921 | 1.681 ± 1.918 | − 2.026 ± 2.294 | − 0.356 ± 0.163 | 2.011 ± 1.597 | 3.939 ± 2.741 |
0.0116
| 0.1626 | 0.3828 | 0.3791 |
0.0308
| 0.2106 | 0.1536 | |
PC aa C32:1 | − 4.69 ± 5.368 | 5.805 ± 1.217 | 6.355 ± 2.534 | 5.062 ± 3.032 | − 0.458 ± 0.215 | − 0.323 ± 2.11 | 2.788 ± 3.622 |
0.3843 | < 0.0001 |
0.0137
| 0.0979 |
0.0356
| 0.8787 | 0.4432 | |
PC aa C34:1 | − 11.594 ± 75.657 | 92.794 ± 17.157 | 89.522 ± 35.716 | 57.696 ± 42.730 | − 7.002 ± 3.033 | − 2.744 ± 29.739 | 34.784 ± 51.050 |
0.8785 | < 0.0001 |
0.0137
| 0.1798 |
0.0229
| 0.9267 | 0.4971 | |
PC aa C34:4 | 0.095 ± 0.634 | 0.617 ± 0.144 | 0.824 ± 0.299 | 0.145 ± 0.358 | − 0.054 ± 0.025 | − 0.193 ± 0.249 | − 0.092 ± 0.428 |
0.8806 | < 0.0001 |
0.0070
| 0.6861 |
0.0370
| 0.4397 | 0.8303 | |
PC aa C36:3 | 14.350 ± 36.596 | 49.046 ± 8.299 | 69.044 ± 17.276 | − 5.324 ± 20.669 | − 3.283 ± 1.467 | − 9.846 ± 14.385 | 10.639 ± 24.693 |
0.6957 | < 0.0001 |
0.0001
| 0.7972 |
0.0273
| 0.4951 | 0.6674 | |
PC ae C32:1 | 0.972 ± 0.740 | − 0.094 ± 0.168 | 0.437 ± 0.349 | 0.072 ± 0.418 | − 0.078 ± 0.030 | − 0.054 ± 0.291 | 0.964 ± 0.499 |
0.1918 | 0.5766 | 0.2136 | 0.8629 |
0.0095
| 0.8543 | 0.0561 | |
PC ae C32:2 | 0.411 ± 0.196 | − 0.033 ± 0.045 | 0.081 ± 0.093 | − 0.136 ± 0.111 | − 0.028 ± 0.008 | − 0.073 ± 0.077 | 0.318 ± 0.133 |
0.0390
| 0.4613 | 0.3837 | 0.2241 |
0.0005
| 0.3475 |
0.0182
| |
PC ae C34:1 | 2.502 ± 1.734 | 0.505 ± 0.393 | 1.905 ± 0.819 | − 0.554 ± 0.979 | − 0.171 ± 0.070 | 0.759 ± 0.682 | 1.971 ± 1.170 |
0.1519 | 0.2021 |
0.0218
| 0.5728 |
0.0155
| 0.2678 | 0.0950 | |
PC ae C36:5 | 10.917 ± 4.572 | − 1.698 ± 1.037 | 2.473 ± 2.158 | − 2.333 ± 2.582 | − 0.389 ± 0.183 | − 2.415 ± 1.797 | 0.752 ± 3.085 |
0.0187
| 0.1044 | 0.2544 | 0.3683 |
0.0360
| 0.1818 | 0.8079 | |
PC ae C38:6 | 5.671 ± 3.030 | − 0.272 ± 0.687 | 2.976 ± 1.431 | − 0.609 ± 1.711 | − 0.252 ± 0.121 | − 1.226 ± 1.191 | 0.707 ± 2.045 |
0.0640 | 0.6927 |
0.0399
| 0.7227 |
0.0407
| 0.3058 | 0.7303 | |
PC ae C40:5 | 2.559 ± 1.247 | − 0.166 ± 0.283 | 0.694 ± 0.589 | − 0.934 ± 0.704 | − 0.111 ± 0.050 | − 0.314 ± 0.490 | 0.182 ± 0.841 |
0.0426
| 0.5596 | 0.2413 | 0.1877 |
0.0286
| 0.5231 | 0.8287 | |
Amino acids (μM) | |||||||
His | − 150.758 ± 41.991 | 37.965 ± 9.523 | 39.971 ± 19.823 | 65.304 ± 23.716 | − 4.080 ± 1.683 | 6.756 ± 16.506 | − 17.531 ± 28.334 |
0.0005
|
0.0001
|
0.0463
|
0.0069
|
0.0170
| 0.6831 | 0.5374 | |
Phe | − 36.314 ± 54.241 | 13.975 ± 12.301 | − 7.065 ± 25.606 | 33.892 ± 30.634 | − 4.385 ± 2.175 | 57.330 ± 21.321 | 41.455 ± 36.600 |
0.5046 | 0.2584 | 0.7831 | 0.2711 |
0.0462
|
0.0083
| 0.2599 |
Metabolites | Total cholesterol | Triglycerides | HDL-C | LDL-C | Serum Hp | Carotid IMT |
---|---|---|---|---|---|---|
Lyso-phosphatidylcholines (μM) | ||||||
LysoPC a C16:0 | − 494.124 ± 89.651 | 39.362 ± 16.748 | 133.887 ± 36.720 | 310.854 ± 52.472 | − 5.264 ± 2.417 | 25.137 ± 34.301 |
< 0.0001 |
0.0207
|
0.0004
| <0.0001 |
0.0317
| 0.4653 | |
LysoPC a C17:0 | − 3.953 ± 1.356 | 0.401 ± 0.253 | 1.140 ± 0.555 | 2.706 ± 0.793 | − 0.088 ± 0.037 | − 0.303 ± 0.519 |
0.0043
| 0.1160 |
0.0425
|
0.0009
|
0.0183
| 0.5606 | |
LysoPC a C18:2 | 52.100 ± 26.226 | − 2.782 ± 4.899 | − 0.547 ± 10.742 | − 28.897 ± 15.350 | − 1.675 ± 0.707 | − 5.400 ± 10.034 |
0.0496
| 0.5714 | 0.9595 | 0.0626 |
0.0197
| 0.5916 | |
LysoPC a C24:0 | − 1.237 ± 0.515 | 0.239 ± 0.096 | 0.724 ± 0.211 | 0.648 ± 0.301 | − 0.031 ± 0.014 | 0.191 ± 0.197 |
0.0181
|
0.0145
|
0.0009
|
0.0339
|
0.0302
| 0.3344 | |
Phosphatidylcholines (μM) | ||||||
PC ae C32:2 | 0.007 ± 0.463 | 0.029 ± 0.087 | 0.478 ± 0.190 | 0.114 ± 0.271 | − 0.026 ± 0.012 | − 0.229 ± 0.177 |
0.9886 | 0.7380 |
0.0133
| 0.6752 |
0.0390
| 0.2000 | |
PC ae C34:0 | − 0.158 ± 0.737 | 0.284 ± 0.138 | 0.666 ± 0.302 | 0.075 ± 0.431 | − 0.041 ± 0.020 | − 0.080 ± 0.282 |
0.8312 |
0.0418
|
0.0295
| 0.8621 |
0.0441
| 0.7761 | |
PC ae C34:3 | 15.585 ± 3.858 | − 1.788 ± 0.721 | 1.492 ± 1.580 | − 6.850 ± 2.258 | − 0.230 ± 0.104 | − 2.803 ± 1.476 |
0.0001
|
0.0148
| 0.3473 |
0.0031
|
0.0292
| 0.0605 | |
PC ae C36:2 | 29.048 ± 6.159 | − 0.149 ± 1.151 | − 2.674 ± 2.523 | − 15.795 ± 3.605 | − 0.338 ± 0.166 | − 2.884 ± 2.356 |
< 0.0001 | 0.8969 | 0.2915 | < 0.0001 |
0.0446
| 0.2238 | |
PC ae C40:1 | 2.153 ± 0.872 | 0.357 ± 0.163 | 0.862 ± 0.357 | − 0.748 ± 0.510 | − 0.074 ± 0.024 | − 0.253 ± 0.334 |
0.0152
|
0.0306
|
0.0176
| 0.1456 |
0.0020
| 0.4491 | |
Amino acids (μM) | ||||||
Gln | 865.339 ± 430.321 | − 124.218 ± 80.390 | − 303.854 ± 176.254 | − 428.871 ± 251.864 | − 32.233 ± 11.602 | − 127.624 ± 164.646 |
0.0469
| 0.1254 | 0.0877 | 0.0916 |
0.0065
| 0.4400 |
Metabolite ratios associated with clinical traits
Metabolite ratios | Total cholesterol | Triglycerides | HDL-C | LDL-C | Serum Hp | Carotid IMT | Carotid IAD |
---|---|---|---|---|---|---|---|
Asn/PC ae C32:2 | − 0.949 ± 0.290 | 0.061 ± 0.066 | − 0.006 ± 0.137 | 0.277 ± 0.164 | 0.033 ± 0.012 | 0.344 ± 0.114 | − 0.230 ± 0.196 |
0.0015
| 0.3555 | 0.9626 | 0.0942 |
0.0059
|
0.0032
| 0.2433 | |
Asp/PC ae C32:2 | − 0.723 ± 0.367 | 0.047 ± 0.083 | − 0.153 ± 0.173 | 0.290 ± 0.207 | 0.041 ± 0.015 | 0.361 ± 0.144 | − 0.516 ± 0.248 |
0.0513
| 0.5726 | 0.3789 | 0.1651 |
0.0059
|
0.0138
|
0.0396
| |
Glu/PC ae C32:2 | − 1.121 ± 0.400 | 0.218 ± 0.091 | − 0.113 ± 0.189 | 0.554 ± 0.226 | 0.039 ± 0.016 | 0.252 ± 0.157 | − 0.817 ± 0.270 |
0.0061
|
0.0183
| 0.5520 |
0.0160
|
0.0160
| 0.1125 |
0.0031
| |
Ile/PC ae C32:2 | − 1.084 ± 0.329 | 0.241 ± 0.075 | − 0.037 ± 0.156 | 0.473 ± 0.186 | 0.031 ± 0.013 | 0.170 ± 0.129 | − 0.534 ± 0.222 |
0.0014
|
0.0017
| 0.8101 |
0.0124
|
0.0222
| 0.1933 |
0.0180
| |
Val/PC ae C32:2 | − 1.011 ± 0.300 | 0.189 ± 0.068 | − 0.071 ± 0.142 | 0.499 ± 0.169 | 0.031 ± 0.012 | 0.183 ± 0.118 | − 0.569 ± 0.202 |
0.0010
|
0.0064
| 0.6197 |
0.0039
|
0.0116
| 0.1241 |
0.0059
|
Metabolite ratios | Total cholesterol | Triglycerides | HDL-C | LDL-C | Serum Hp | Carotid IMT |
---|---|---|---|---|---|---|
Asp/PC ae C32:2 | 0.028 ± 0.538 | − 0.072 ± 0.101 | − 0.605 ± 0.220 | − 0.254 ± 0.315 | 0.048 ± 0.015 | 0.362 ± 0.206 |
0.9592 | 0.4748 |
0.0071
| 0.4212 |
0.0012
|
0.0820
| |
Glu/PC ae C32:2 | − 0.830 ± 0.584 | 0.020 ± 0.109 | − 0.442 ± 0.239 | 0.317 ± 0.342 | 0.043 ± 0.016 | 0.386 ± 0.223 |
0.1585 | 0.8514 |
0.0673
| 0.3559 |
0.0071
|
0.0870
| |
Phe/PC ae C32:2 | − 0.311 ± 0.407 | − 0.052 ± 0.076 | − 0.493 ± 0.167 | 0.062 ± 0.238 | 0.029 ± 0.011 | 0.351 ± 0.156 |
0.4470 | 0.4945 |
0.0039
| 0.7948 |
0.0094
|
0.0267
|