Journal of Southern Medical University ›› 2026, Vol. 46 ›› Issue (10): 2456-2470.doi: 10.12122/j.issn.1673-4254.2026.10.15
Shijie QIAO1(
), Jinshun YOU1, Chang WANG2,3, Hongping XIONG4, Shunan LI1(
)
Received:2026-03-09
Online:2026-10-20
Published:2026-10-26
Contact:
Shunan LI
E-mail:2277605219@qq.com;fjmulsn@126.com
Shijie QIAO, Jinshun YOU, Chang WANG, Hongping XIONG, Shunan LI. Construction of predictive models for type 2 diabetic retinopathy based on the principle of differentiation of syndrome elements[J]. Journal of Southern Medical University, 2026, 46(10): 2456-2470.
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URL: https://www.j-smu.com/EN/10.12122/j.issn.1673-4254.2026.10.15
| No. | Syndrome elements | T2DM(n=376) | T2DR(n=273) | χ2/Z/t | P | |
|---|---|---|---|---|---|---|
| 1 | Yin deficiency | Severe | 233 | 269 | 120.711 | <0.01 |
| Non-severe | 143 | 4 | ||||
| 2 | Phlegm | Severe | 147 | 193 | 63.32 | <0.01 |
| Non-severe | 229 | 80 | ||||
| 3 | Liver | Severe | 177 | 266 | 185.149 | <0.01 |
| Non-severe | 199 | 7 | ||||
| 4 | Heat | Severe | 111 | 179 | 83.144 | <0.01 |
| Non-severe | 265 | 94 | ||||
| 5 | Kidney | Severe | 130 | 195 | 85.929 | <0.01 |
| Non-severe | 246 | 78 | ||||
| 6 | Dampness | Severe | 156 | 175 | 32.364 | <0.01 |
| Non-severe | 220 | 98 | ||||
| 7 | Yang deficiency | Severe | 112 | 153 | 45.134 | <0.01 |
| Non-severe | 264 | 120 | ||||
| 8 | Blood deficiency | Severe | 93 | 216 | 187.562 | <0.01 |
| Non-severe | 283 | 57 | ||||
| 9 | Blood stasis | Severe | 52 | 101 | 47.133 | <0.01 |
| Non-severe | 324 | 172 | ||||
| 10 | Qi deficiency | Severe | 45 | 128 | 98.639 | <0.01 |
| Non-severe | 331 | 145 | ||||
| 11 | Qi stagnation | Severe | 42 | 90 | 46.379 | <0.01 |
| Non-severe | 334 | 183 | ||||
| 12 | Yang excess | Severe | 4 | 65 | 86.122 | <0.01 |
| Non-severe | 372 | 208 | ||||
| 13 | Heart spirit | Severe | 16 | 38 | 19.365 | <0.01 |
| Non-severe | 360 | 235 | ||||
| 14 | Spleen | Severe | 5 | 28 | 26.144 | <0.01 |
| Non-severe | 371 | 245 | ||||
| 15 | Heart | Severe | 1 | 10 | 10.954 | <0.01 |
| Non-severe | 375 | 263 | ||||
| 16 | Essence deficiency | Severe | 0 | 6 | 8.341 | <0.01 |
| Non-severe | 376 | 267 | ||||
| 17 | Tendon-bone | Severe | 11 | 43 | 34.106 | <0.01 |
| Non-severe | 365 | 230 | ||||
| 18 | Gallbladder | Severe | 0 | 0 | - | - |
| Non-severe | 376 | 273 | ||||
| 19 | Cold | Severe | 2 | 10 | 8.544 | <0.01 |
| Non-severe | 374 | 263 | ||||
| 20 | Jin deficiency | Severe | 0 | 3 | 4.151 | <0.05 |
| Non-severe | 376 | 270 | ||||
| 21 | Meridian | Severe | 1 | 4 | 2.975 | >0.05 |
| Non-severe | 375 | 269 | ||||
| 22 | Stomach | Severe | 2 | 5 | 2.504 | >0.05 |
| Non-severe | 374 | 268 | ||||
| 23 | Lung | Severe | 2 | 33 | 41.397 | <0.01 |
| Non-severe | 374 | 240 | ||||
| 24 | Dryness | Severe | 0 | 1 | 1.379 | >0.05 |
| Non-severe | 376 | 272 | ||||
Tab.1 Screening of Traditional Chinese medicine (TCM) syndrome elements (frequency≥20%, n)
| No. | Syndrome elements | T2DM(n=376) | T2DR(n=273) | χ2/Z/t | P | |
|---|---|---|---|---|---|---|
| 1 | Yin deficiency | Severe | 233 | 269 | 120.711 | <0.01 |
| Non-severe | 143 | 4 | ||||
| 2 | Phlegm | Severe | 147 | 193 | 63.32 | <0.01 |
| Non-severe | 229 | 80 | ||||
| 3 | Liver | Severe | 177 | 266 | 185.149 | <0.01 |
| Non-severe | 199 | 7 | ||||
| 4 | Heat | Severe | 111 | 179 | 83.144 | <0.01 |
| Non-severe | 265 | 94 | ||||
| 5 | Kidney | Severe | 130 | 195 | 85.929 | <0.01 |
| Non-severe | 246 | 78 | ||||
| 6 | Dampness | Severe | 156 | 175 | 32.364 | <0.01 |
| Non-severe | 220 | 98 | ||||
| 7 | Yang deficiency | Severe | 112 | 153 | 45.134 | <0.01 |
| Non-severe | 264 | 120 | ||||
| 8 | Blood deficiency | Severe | 93 | 216 | 187.562 | <0.01 |
| Non-severe | 283 | 57 | ||||
| 9 | Blood stasis | Severe | 52 | 101 | 47.133 | <0.01 |
| Non-severe | 324 | 172 | ||||
| 10 | Qi deficiency | Severe | 45 | 128 | 98.639 | <0.01 |
| Non-severe | 331 | 145 | ||||
| 11 | Qi stagnation | Severe | 42 | 90 | 46.379 | <0.01 |
| Non-severe | 334 | 183 | ||||
| 12 | Yang excess | Severe | 4 | 65 | 86.122 | <0.01 |
| Non-severe | 372 | 208 | ||||
| 13 | Heart spirit | Severe | 16 | 38 | 19.365 | <0.01 |
| Non-severe | 360 | 235 | ||||
| 14 | Spleen | Severe | 5 | 28 | 26.144 | <0.01 |
| Non-severe | 371 | 245 | ||||
| 15 | Heart | Severe | 1 | 10 | 10.954 | <0.01 |
| Non-severe | 375 | 263 | ||||
| 16 | Essence deficiency | Severe | 0 | 6 | 8.341 | <0.01 |
| Non-severe | 376 | 267 | ||||
| 17 | Tendon-bone | Severe | 11 | 43 | 34.106 | <0.01 |
| Non-severe | 365 | 230 | ||||
| 18 | Gallbladder | Severe | 0 | 0 | - | - |
| Non-severe | 376 | 273 | ||||
| 19 | Cold | Severe | 2 | 10 | 8.544 | <0.01 |
| Non-severe | 374 | 263 | ||||
| 20 | Jin deficiency | Severe | 0 | 3 | 4.151 | <0.05 |
| Non-severe | 376 | 270 | ||||
| 21 | Meridian | Severe | 1 | 4 | 2.975 | >0.05 |
| Non-severe | 375 | 269 | ||||
| 22 | Stomach | Severe | 2 | 5 | 2.504 | >0.05 |
| Non-severe | 374 | 268 | ||||
| 23 | Lung | Severe | 2 | 33 | 41.397 | <0.01 |
| Non-severe | 374 | 240 | ||||
| 24 | Dryness | Severe | 0 | 1 | 1.379 | >0.05 |
| Non-severe | 376 | 272 | ||||
| No. | Indicators | T2DM (n=376) | T2DR (n=273) | χ2/Z/t | P | |
|---|---|---|---|---|---|---|
| 1 | Gender | Male | 216 | 137 | 3.364 | >0.05 |
| Female | 160 | 136 | ||||
| 2 | Age (years) | 60.54±13.02 | 61.33±12.41 | -0.784 | >0.05 | |
| 3 | Residence | Urban | 230 | 166 | 0.009 | >0.05 |
| Rural | 146 | 107 | ||||
| 4 | Occupation | Employed | 166 | 107 | 1.593 | >0.05 |
| Unemployed | 210 | 166 | ||||
| 5 | Marital status | Married | 313 | 222 | 0.405 | >0.05 |
| Unmarried | 63 | 51 | ||||
| 6 | Education level | Illiterate | 24 | 38 | -3.682 | <0.01 |
| Primary school | 119 | 95 | ||||
| Junior high school | 107 | 78 | ||||
Senior high school/technical secondary school/vocational high school | 83 | 44 | ||||
| College/associate degree | 43 | 17 | ||||
| Master's degree or above | 0 | 1 | ||||
| 7 | Household income (CNY/month) | ≤1000 | 28 | 24 | -1.569 | >0.05 |
| 1001-2000 | 35 | 38 | ||||
| 2001-5000 | 113 | 79 | ||||
| ≥5001 | 200 | 132 | ||||
| 8 | Living arrangement | Living with others | 330 | 244 | 0.402 | >0.05 |
| Living alone | 46 | 29 | ||||
| 9 | Religious belief | None | 224 | 155 | 0.51 | >0.05 |
| Yes | 152 | 118 | ||||
| 10 | History of insulin therapy | None | 288 | 156 | 27.697 | <0.01 |
| Yes | 88 | 117 | ||||
| 11 | Smoking history | None | 280 | 211 | 0.684 | >0.05 |
| Yes | 96 | 62 | ||||
| 12 | Smoking quantity | Non-smoker | 280 | 211 | -0.746 | >0.05 |
| <1 pack/day | 48 | 27 | ||||
| 1-2 packs/day | 36 | 29 | ||||
| >2 packs/day | 12 | 6 | ||||
| 13 | Drinking history | None | 287 | 221 | 1.987 | >0.05 |
| Yes | 89 | 52 | ||||
| 14 | Diet:time | Irregular | 147 | 122 | 2.039 | >0.05 |
| Regular | 229 | 151 | ||||
| 15 | Diet:dietary intake | Overeating | 224 | 133 | 7.532 | <0.01 |
| Controlled | 152 | 140 | ||||
| 16 | Diet:category-Staple food | Rice-based | 297 | 223 | 1.129 | >0.05 |
| Wheat-based | 17 | 9 | ||||
| Mixed | 60 | 39 | ||||
| Other | 2 | 2 | ||||
| 17 | Diet:category-non-staple food | Vegetable-based | 220 | 173 | 4.599 | >0.05 |
| White meat-based | 109 | 65 | ||||
| Red meat-based | 3 | 6 | ||||
| Balanced | 44 | 29 | ||||
| 18 | Diet:Snacking status | None | 167 | 126 | 0.193 | >0.05 |
| Yes | 209 | 147 | ||||
| 19 | Dietary preference | None | 43 | 24 | 1.195 | >0.05 |
| Yes | 333 | 249 | ||||
| 20 | Physical labor | Light | 290 | 201 | -0.96 | >0.05 |
| Moderate | 77 | 67 | ||||
| Heavy | 9 | 5 | ||||
| 21 | Exercise habits and frequency | None | 117 | 82 | -0.266 | >0.05 |
| Occasional (1-2 times/week) | 16 | 9 | ||||
| Sometimes (3-4 times/week) | 7 | 12 | ||||
| Frequently (5-6 times/week) | 8 | 2 | ||||
| Daily | 228 | 168 | ||||
| 22 | Participation in T2DM education programs | None | 366 | 269 | 1.069 | >0.05 |
| Yes | 10 | 4 | ||||
| 23 | Attention to health preservation and healthcare | Mostly ignored | 300 | 230 | -1.515 | >0.05 |
| Moderate | 53 | 33 | ||||
| Highly valued | 23 | 10 | ||||
| 24 | Regular blood glucose monitoring | None | 306 | 198 | 7.149 | <0.01 |
| Yes | 70 | 75 | ||||
Tab.2 Screening of influencing factors and clinical biochemical indicators (n)[Mean±SD, M (P25, P75)]
| No. | Indicators | T2DM (n=376) | T2DR (n=273) | χ2/Z/t | P | |
|---|---|---|---|---|---|---|
| 1 | Gender | Male | 216 | 137 | 3.364 | >0.05 |
| Female | 160 | 136 | ||||
| 2 | Age (years) | 60.54±13.02 | 61.33±12.41 | -0.784 | >0.05 | |
| 3 | Residence | Urban | 230 | 166 | 0.009 | >0.05 |
| Rural | 146 | 107 | ||||
| 4 | Occupation | Employed | 166 | 107 | 1.593 | >0.05 |
| Unemployed | 210 | 166 | ||||
| 5 | Marital status | Married | 313 | 222 | 0.405 | >0.05 |
| Unmarried | 63 | 51 | ||||
| 6 | Education level | Illiterate | 24 | 38 | -3.682 | <0.01 |
| Primary school | 119 | 95 | ||||
| Junior high school | 107 | 78 | ||||
Senior high school/technical secondary school/vocational high school | 83 | 44 | ||||
| College/associate degree | 43 | 17 | ||||
| Master's degree or above | 0 | 1 | ||||
| 7 | Household income (CNY/month) | ≤1000 | 28 | 24 | -1.569 | >0.05 |
| 1001-2000 | 35 | 38 | ||||
| 2001-5000 | 113 | 79 | ||||
| ≥5001 | 200 | 132 | ||||
| 8 | Living arrangement | Living with others | 330 | 244 | 0.402 | >0.05 |
| Living alone | 46 | 29 | ||||
| 9 | Religious belief | None | 224 | 155 | 0.51 | >0.05 |
| Yes | 152 | 118 | ||||
| 10 | History of insulin therapy | None | 288 | 156 | 27.697 | <0.01 |
| Yes | 88 | 117 | ||||
| 11 | Smoking history | None | 280 | 211 | 0.684 | >0.05 |
| Yes | 96 | 62 | ||||
| 12 | Smoking quantity | Non-smoker | 280 | 211 | -0.746 | >0.05 |
| <1 pack/day | 48 | 27 | ||||
| 1-2 packs/day | 36 | 29 | ||||
| >2 packs/day | 12 | 6 | ||||
| 13 | Drinking history | None | 287 | 221 | 1.987 | >0.05 |
| Yes | 89 | 52 | ||||
| 14 | Diet:time | Irregular | 147 | 122 | 2.039 | >0.05 |
| Regular | 229 | 151 | ||||
| 15 | Diet:dietary intake | Overeating | 224 | 133 | 7.532 | <0.01 |
| Controlled | 152 | 140 | ||||
| 16 | Diet:category-Staple food | Rice-based | 297 | 223 | 1.129 | >0.05 |
| Wheat-based | 17 | 9 | ||||
| Mixed | 60 | 39 | ||||
| Other | 2 | 2 | ||||
| 17 | Diet:category-non-staple food | Vegetable-based | 220 | 173 | 4.599 | >0.05 |
| White meat-based | 109 | 65 | ||||
| Red meat-based | 3 | 6 | ||||
| Balanced | 44 | 29 | ||||
| 18 | Diet:Snacking status | None | 167 | 126 | 0.193 | >0.05 |
| Yes | 209 | 147 | ||||
| 19 | Dietary preference | None | 43 | 24 | 1.195 | >0.05 |
| Yes | 333 | 249 | ||||
| 20 | Physical labor | Light | 290 | 201 | -0.96 | >0.05 |
| Moderate | 77 | 67 | ||||
| Heavy | 9 | 5 | ||||
| 21 | Exercise habits and frequency | None | 117 | 82 | -0.266 | >0.05 |
| Occasional (1-2 times/week) | 16 | 9 | ||||
| Sometimes (3-4 times/week) | 7 | 12 | ||||
| Frequently (5-6 times/week) | 8 | 2 | ||||
| Daily | 228 | 168 | ||||
| 22 | Participation in T2DM education programs | None | 366 | 269 | 1.069 | >0.05 |
| Yes | 10 | 4 | ||||
| 23 | Attention to health preservation and healthcare | Mostly ignored | 300 | 230 | -1.515 | >0.05 |
| Moderate | 53 | 33 | ||||
| Highly valued | 23 | 10 | ||||
| 24 | Regular blood glucose monitoring | None | 306 | 198 | 7.149 | <0.01 |
| Yes | 70 | 75 | ||||
Fig.1 Coefficient path plot (A), cross-validation error plot (B), and bar chart of non-zero coefficients (C) in Lasso regression predictor selection. X40: Liver syndrome element; X59: Lung syndrome element; X50: Yang excess syndrome element; X45: blood deficiency syndrome element; X42: Heat syndrome element; X11: T2DKD; X52: Spleen syndrome element; X39: Yin deficiency syndrome element; X47: Blood stasis syndrome element; X13: T2DPN; X49: Qi stagnation syndrome element; X44: Kidney syndrome element; X14: T2DPVD; X48: Qi deficiency syndrome element; X55: Tendon-bone syndrome element; X57: Jin deficiency syndrome element; X17: HR; X15: WHR; X7: Dietary intake status; X41: Phlegm syndrome element; X26: BUN; X36: Urea; X3: T2DM duration; X33: HGB; X20: ALT; X21: AST; X16: HC.
| Diseases | Training set | Validation set | χ2 | P |
|---|---|---|---|---|
| T2DR (n=273) | 192 (42.11) | 81 (41.97) | 0.001 | >0.05 |
| T2DM (n=376) | 264 (57.89) | 112 (58.03) |
Tab.3 Comparison of the distribution of T2DR and T2DM patients in the training and validation sets [n(%)]
| Diseases | Training set | Validation set | χ2 | P |
|---|---|---|---|---|
| T2DR (n=273) | 192 (42.11) | 81 (41.97) | 0.001 | >0.05 |
| T2DM (n=376) | 264 (57.89) | 112 (58.03) |
| No. | Models | Accuracy | Precision | Recall | Specificity | False positive rate | F1 score | AUC (95% CI) |
|---|---|---|---|---|---|---|---|---|
| 1 | LR | 0.877 | 0.925 | 0.771 | 0.955 | 0.045 | 0.841 | 0.956 (0.938-0.973) |
| 2 | ANN | 0.965 | 0.978 | 0.938 | 0.985 | 0.015 | 0.957 | 0.991 (0.984-0.998) |
| 3 | XGBoost | 0.974 | 0.979 | 0.958 | 0.985 | 0.015 | 0.968 | 0.996 (0.993-0.999) |
| 4 | RF | 0.982 | 0.989 | 0.969 | 0.992 | 0.008 | 0.979 | 1.000 (0.999-1.000) |
| 5 | SVM | 0.958 | 0.968 | 0.932 | 0.977 | 0.023 | 0.950 | 0.988 (0.979-0.997) |
| 6 | KNN | 0.890 | 0.908 | 0.823 | 0.939 | 0.061 | 0.863 | 0.961 (0.945-0.977) |
Tab.4 Performance comparison of the six ML models on the training set
| No. | Models | Accuracy | Precision | Recall | Specificity | False positive rate | F1 score | AUC (95% CI) |
|---|---|---|---|---|---|---|---|---|
| 1 | LR | 0.877 | 0.925 | 0.771 | 0.955 | 0.045 | 0.841 | 0.956 (0.938-0.973) |
| 2 | ANN | 0.965 | 0.978 | 0.938 | 0.985 | 0.015 | 0.957 | 0.991 (0.984-0.998) |
| 3 | XGBoost | 0.974 | 0.979 | 0.958 | 0.985 | 0.015 | 0.968 | 0.996 (0.993-0.999) |
| 4 | RF | 0.982 | 0.989 | 0.969 | 0.992 | 0.008 | 0.979 | 1.000 (0.999-1.000) |
| 5 | SVM | 0.958 | 0.968 | 0.932 | 0.977 | 0.023 | 0.950 | 0.988 (0.979-0.997) |
| 6 | KNN | 0.890 | 0.908 | 0.823 | 0.939 | 0.061 | 0.863 | 0.961 (0.945-0.977) |
| No. | Models | Accuracy | Precision | Recall | Specificity | False positive rate | F1 score | AUC (95% CI) |
|---|---|---|---|---|---|---|---|---|
| 1 | LR | 0.881 | 0.872 | 0.840 | 0.911 | 0.089 | 0.855 | 0.952 (0.924-0.979) |
| 2 | ANN | 0.808 | 0.782 | 0.753 | 0.848 | 0.152 | 0.767 | 0.875 (0.825-0.926) |
| 3 | XGBoost | 0.870 | 0.818 | 0.889 | 0.857 | 0.143 | 0.852 | 0.961 (0.937-0.984) |
| 4 | RF | 0.886 | 0.839 | 0.901 | 0.875 | 0.125 | 0.869 | 0.957 (0.932-0.983) |
| 5 | SVM | 0.876 | 0.800 | 0.938 | 0.830 | 0.170 | 0.864 | 0.957 (0.932-0.983) |
| 6 | KNN | 0.881 | 0.863 | 0.852 | 0.902 | 0.098 | 0.857 | 0.942 (0.912-0.973) |
Tab.5 Performance comparison of the six ML models on the validation set
| No. | Models | Accuracy | Precision | Recall | Specificity | False positive rate | F1 score | AUC (95% CI) |
|---|---|---|---|---|---|---|---|---|
| 1 | LR | 0.881 | 0.872 | 0.840 | 0.911 | 0.089 | 0.855 | 0.952 (0.924-0.979) |
| 2 | ANN | 0.808 | 0.782 | 0.753 | 0.848 | 0.152 | 0.767 | 0.875 (0.825-0.926) |
| 3 | XGBoost | 0.870 | 0.818 | 0.889 | 0.857 | 0.143 | 0.852 | 0.961 (0.937-0.984) |
| 4 | RF | 0.886 | 0.839 | 0.901 | 0.875 | 0.125 | 0.869 | 0.957 (0.932-0.983) |
| 5 | SVM | 0.876 | 0.800 | 0.938 | 0.830 | 0.170 | 0.864 | 0.957 (0.932-0.983) |
| 6 | KNN | 0.881 | 0.863 | 0.852 | 0.902 | 0.098 | 0.857 | 0.942 (0.912-0.973) |
| No. | Models | Training set AUC | Validation set AUC | P |
|---|---|---|---|---|
| 1 | LR | 0.956 | 0.952 | >0.05 |
| 2 | ANN | 0.991 | 0.875 | <0.01 |
| 3 | XGBoost | 0.996 | 0.961 | <0.01 |
| 4 | RF | 1.000 | 0.957 | <0.01 |
| 5 | SVM | 0.988 | 0.957 | <0.05 |
| 6 | KNN | 0.961 | 0.942 | >0.05 |
Tab.6 DeLong test of the 6 ML models
| No. | Models | Training set AUC | Validation set AUC | P |
|---|---|---|---|---|
| 1 | LR | 0.956 | 0.952 | >0.05 |
| 2 | ANN | 0.991 | 0.875 | <0.01 |
| 3 | XGBoost | 0.996 | 0.961 | <0.01 |
| 4 | RF | 1.000 | 0.957 | <0.01 |
| 5 | SVM | 0.988 | 0.957 | <0.05 |
| 6 | KNN | 0.961 | 0.942 | >0.05 |
| No. | LR | KNN | |
|---|---|---|---|
| 1 | Training set | Validation set | |
| 2 | Training set | -1.281 | |
| 3 | Validation set | 0.873 | |
Tab.7 DeLong test between the LR and KNN models (Z value)
| No. | LR | KNN | |
|---|---|---|---|
| 1 | Training set | Validation set | |
| 2 | Training set | -1.281 | |
| 3 | Validation set | 0.873 | |
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