Introduction
Methods
Study population
Patient data
Statistical analysis
Development of a regularized and weighted random survival forests model
Results
Clinical and biochemical characteristics
Patient Percentage (%) | |
---|---|
Demographic | |
Male | 50.4 |
Type 1 Diabetes Mellitus | 7.37 |
Comorbidities | |
Hypertension | 35.6 |
Ophthalmological Complications | 32.2 |
Ischemic Heart Disease | 16.2 |
Ischemic Stroke and Transient Ischemic Attack | 11.8 |
Heart Failure | 9.8 |
Chronic Renal Disease | 8.8 |
Chronic Liver Disease | 5.8 |
Acute Myocardial Infarction | 5.1 |
Chronic Obstructive Pulmonary Disease | 3.5 |
Anti-diabetic Medication | |
Biguanide | 57.6 |
Sulphonylurea | 41.5 |
Thiazolidinedione | 3.5 |
Alpha-Glucosidase | 3.0 |
Dipeptidyl Peptidase-4 Inhibitor | 0.4 |
Glucagon-Like Peptide-1 Receptor Agonist | < 0.1 |
Cardiovascular medication | |
Angiotensinogen-Converting Enzyme Inhibitor/ Angiotensin-Receptor Blocker | 59.8 |
Calcium Channel Blocker | 43.6 |
Lipid-Lowering Agents | 42.4 |
Aspirin | 36.2 |
Diuretic | 29.2 |
Beta-Adrenergic Receptor Blocker | 28.1 |
Mean | Standard Deviation | |
---|---|---|
Urinalysis | ||
Albumin/Creatinine Ratio (mg/mmol) | 38.1 | 121 |
Creatinine Clearance (ml/min) | 54.1 | 35.9 |
Spot Protein (g/d) | 1.17 | 1.96 |
Spot Albumin (mg/L) | 170 | 545 |
Spot Glucose (mmol/L) | 12.5 | 6.68 |
24-h Total Protein (g/d) | 1.17 | 1.97 |
24-h Total Albumin (mg/d) | 271 | 695 |
Baseline Blood Test | ||
Fasting Glucose (mmol/L) | 8.96 | 3.75 |
Random Glucose (mmol/L) | 12.3 | 7.47 |
HbA1c (%) | 8.56 | 1.94 |
Total Cholesterol (mmol/L) | 4.74 | 1.12 |
High Density Lipoprotein (HDL) Cholesterol (mmol/L) | 1.24 | 0.403 |
Calculated Low Density Lipoprotein (LDL) Cholesterol (mmol/L) | 2.74 | 0.927 |
Direct LDL Cholesterol (mmol/L) | 2.80 | 0.925 |
Triglyceride (mmol/L) | 1.80 | 1.72 |
Renal Function Test | ||
Creatinine (umol/L) | 144 | 159 |
Sodium (mmol/L) | 139 | 3.33 |
Potassium (mmol/L) | 4.31 | 0.506 |
Urate (umol/L) | 0.408 | 0.129 |
Urea (mmol/L) | 8.82 | 6.04 |
Liver Function Test | ||
Albumin (g/L) | 39.2 | 5.56 |
Alanine Aminotransferase (ALT) (U/L) | 24.3 | 21.6 |
Alkaline Phosphatase (ALP) (U/L) | 85.2 | 47.0 |
Total Bilirubin (umol/L) | 11.3 | 8.98 |
Total Protein (g/L) | 74.4 | 7.13 |
Complete Blood Count | ||
Hemoglobin (g/dL) | 12.5 | 1.99 |
Mean Corpuscular Hemoglobin (MCH) (pg) | 29.7 | 2.95 |
Mean Corpuscular Hemoglobin Concentration (MCHC) (g/dL) | 34.0 | 0.952 |
Mean Corpuscular Volume (MCV) (fL) | 87.2 | 7.44 |
Hematocrit (L/L) | 0.376 | 0.539 |
Basophil (×109/L) | 0.029 | 0.042 |
Eosinophil (×109/L) | 0.223 | 0.235 |
Lymphocyte (×109/L) | 1.87 | 0.867 |
Monocyte (×109/L) | 0.538 | 0.266 |
Neutrophil (×109/L) | 5.47 | 2.79 |
Platelet (×109/L) | 256 | 83.3 |
Red Blood Cell (× 1012/L) | 4.26 | 0.740 |
White Blood Cell (×109/L) | 8.09 | 2.91 |
Anti-diabetic drug classes and outcomes
Adverse outcome and predictors
Outcome | Number of events | Incidence rate | Age of onset | Number of pre-existing comorbidities | Mean onset in follow-up (days) |
---|---|---|---|---|---|
Mortality | 12,372 | 49.12% | 69.7 ± 12.0 | 2.71 ± 1.66 | 3056 ± 1396 |
Renal | 5389 | 21.40% | 66.5 ± 12.2 | 3.51 ± 1.67 | 3500 ± 1367 |
Ophthalmological | 4705 | 18.68% | 62.8 ± 11.9 | 3.11 ± 1.81 | 3590 ± 1296 |
Ischemic Heart Disease | 4532 | 17.99% | 66.8 ± 11.6 | 3.70 ± 1.74 | 3700 ± 1119 |
Acute myocardial infarction | 3178 | 12.62% | 68.3 ± 11.1 | 4.15 ± 1.59 | 3882 ± 859 |
Neurological | 1861 | 7.39% | 64.2 ± 11.9 | 4.03 ± 1.77 | 3952 ± 835 |
Atrial Fibrillation | 1846 | 7.33% | 70.4 ± 10.3 | 3.75 ± 1.74 | 3993 ± 715 |
Heart Failure | 1810 | 7.19% | 68.9 ± 11.4 | 4.61 ± 1.45 | 3993 ± 711 |
Ischemic Stroke | 1350 | 5.36% | 69.2 ± 10.9 | 3.55 ± 1.79 | 4037 ± 634 |
Intracranial Hemorrhage | 1049 | 4.17% | 68.4 ± 11.7 | 3.45 ± 1.67 | 4075 ± 530 |
Dementia | 952 | 3.78% | 74.4 ± 8.30 | 3.37 ± 1.68 | 4077 ± 535 |
Peripheral vascular disease | 711 | 2.82% | 66.6 ± 12.4 | 4.39 ± 1.85 | 4094 ± 505 |
Osteoporosis | 275 | 1.09% | 72.1 ± 11.3 | 3.01 ± 1.68 | 4146 ± 299 |
Predictors | Mean | Standard Deviation |
---|---|---|
HbA1c | ||
Baseline (%, n = 24,064) | 8.56 | 1.94 |
Mean (%, n = 22,625) | 8.64 | 1.36 |
Standard Deviation | 1.28 | 0.851 |
Coefficient of Variation | 14.5 | 8.76 |
Total Cholesterol (TC) | ||
Baseline (mmol/L, n = 23,532) | 4.74 | 1.12 |
Mean (mmol/L, n = 20,445) | 4.82 | 0.871 |
Standard Deviation | 0.663 | 0.459 |
Coefficient of Variation | 13.5 | 7.95 |
High Density Lipoprotein-Cholesterol (HDL-C) | ||
Baseline (mmol/L, n = 23,178) | 1.24 | 0.402 |
Mean (mmol/L, n = 19,303) | 1.25 | 0.362 |
Standard Deviation | 0.161 | 0.100 |
Coefficient of Variation | 1.24 | 0.403 |
Low Density Lipoprotein-Cholesterol (LDL-C) | ||
Baseline (mmol/L, n = 32,075) | 1.24 | 0.913 |
Mean (mmol/L, n = 18,803) | 2.78 | 0.734 |
Standard Deviation | 0.553 | 0.359 |
Coefficient of Variation | 20.3 | 12.5 |
Triglyceride | ||
Baseline (mmol/L, n = 23,518) | 1.80 | 1.72 |
Mean (mmol/L, n = 20,398) | 1.86 | 1.43 |
Standard Deviation | 6.90 | 1.15 |
Coefficient of Variation | 30.8 | 17.8 |
Other Tests | ||
Baseline NLR | 3.80 | 4.16 |
Baseline Hemoglobin Count (g/dL) | 12.5 | 1.99 |
Hypoglycemia Frequency | 0.537 | 1.38 |
Predictor | Hazard Ratio (HR) | 95% Confidence Interval (CI) | P-Value |
---|---|---|---|
Age | 1.04 | [1.03, 1.04] | < 0.0001 |
Male | 1.18 | [1.11, 1.27] | < 0.0001 |
Diabetes Duration | 0.956 | [0.943, 0.970] | < 0.0001 |
HbA1c | |||
Mean | 1.09 | [1.04, 1.15] | < 0.001 |
Standard Deviation | 1.10 | [0.825, 1.47] | 0.511 |
Coefficient of Variation | 0.998 | [0.973, 1.02] | 0.869 |
Total Cholesterol (TC) | |||
Mean | 1.14 | [0.994, 1.30] | 0.061 |
Standard Deviation | 0.787 | [0.501, 1.24] | 0.299 |
Coefficient of Variation | 1.02 | [1.00, 1.05] | 0.050 |
High Density Lipoprotein-Cholesterol (HDL-C) | |||
Mean | 0.603 | [0.513, 0.708] | < 0.0001 |
Standard Deviation | 2.19 | [1.52, 3.14] | < 0.0001 |
Low Density Lipoprotein-Cholesterol | |||
Mean | 0.916 | [0.811, 1.03] | 0.157 |
Standard Deviation | 1.19 | [0.866, 1.64] | 0.281 |
Coefficient of Variation | 0.992 | [0.983, 1.00] | 0.062 |
Triglyceride (TG) | |||
Baseline | 0.996 | [0.979, 1.01] | 0.694 |
Mean | 1.06 | [0.993, 1.14] | 0.080 |
Standard Deviation | 0.932 | [0.851, 1.02] | 0.126 |
Coefficient of Variation | 0.998 | [0.995, 1.00] | 0.190 |
Other Tests | |||
Baseline Neutrophil-Lymphocyte Ratio | 1.01 | [1.01, 1.02] | < 0.001 |
Baseline Hemoglobin Count | 0.911 | [0.889, 0.934] | < 0.0001 |
Baseline Anemia | 1.08 | [0.981, 1.19] | 0.119 |
Hypoglycemia Frequency | 1.03 | [1.01, 1.05] | 0.002 |
Anti-Diabetic Agent | |||
Sulphonylurea | 1.08 | [1.02, 1.16] | 0.015 |
Biguanide | 0.616 | [0.575, 0.660] | < 0.0001 |
Dipeptidyl peptidase-4 Inhibitor | 0.706 | [0.424, 1.18] | 0.181 |
Thiazolidinedione | 0.885 | [0.761, 1.03] | 0.110 |
The relationship between NLR, frequency of hypoglycemic episodes and glycemic variability
HbA1c/ Lipid Variability | Hazard ratio [95% Confidence Interval] | P-Value |
---|---|---|
HbA1c: SD | 1.01 [1.01, 1.01] | < 0.0001 |
HbA1c: CV | 1.13 [1.10, 1.17] | < 0.0001 |
HDL-C: SD | 1.00 [1.00, 1.00] | < 0.0001 |
HDL-C: CV | 1.19 [1.15, 1.23] | < 0.0001 |
Triglyceride: CV | 1.08 [1.01, 1.16] | 0.019 |
Total Cholesterol: SD | 1.01 [1.00, 1.01] | < 0.0001 |
Total Cholesterol: CV | 1.10 [1.07, 1.13] | < 0.0001 |
Survival learning results
Our model | RSF | Cox | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Precision | Recall | AUC | C-index | Precision | Recall | AUC | C-index | Precision | Recall | AUC | C-index | |
Mortality | 0.9212 | 0.8663 | 0.8986 | 0.8804 | 0.8468 | 0.8962 | 0.8377 | 0.8178 | 0.7576 | 0.8025 | 0.7221 | 0.7676 |
Renal | 0.9237 | 0.9180 | 0.8763 | 0.8269 | 0.8855 | 0.8563 | 0.8577 | 0.8194 | 0.7625 | 0.7803 | 0.8008 | 0.7470 |
PVD | 0.8913 | 0.8565 | 0.8880 | 0.8701 | 0.8922 | 0.8617 | 0.8517 | 0.7701 | 0.7779 | 0.7289 | 0.7517 | 0.7848 |
Neurological | 0.9104 | 0.9252 | 0.9111 | 0.8318 | 0.8842 | 0.8223 | 0.8480 | 0.8511 | 0.7874 | 0.7434 | 0.7969 | 0.7706 |
Ophthalmological | 0.8902 | 0.8766 | 0.9065 | 0.8208 | 0.8557 | 0.8234 | 0.8643 | 0.8237 | 0.7671 | 0.7522 | 0.7814 | 0.7517 |
Ischemic stroke | 0.8998 | 0.9010 | 0.8885 | 0.8527 | 0.8367 | 0.8983 | 0.8634 | 0.8484 | 0.7925 | 0.7752 | 0.7884 | 0.7538 |
AF | 0.9352 | 0.8641 | 0.8998 | 0.8740 | 0.8194 | 0.8733 | 0.8523 | 0.8125 | 0.7747 | 0.7571 | 0.7742 | 0.7647 |
HF | 0.8963 | 0.9175 | 0.8947 | 0.8943 | 0.8700 | 0.8533 | 0.8330 | 0.7767 | 0.8047 | 0.7708 | 0.7585 | 0.7749 |
ICH | 0.7893 | 0.7992 | 0.7156 | 0.7154 | 0.7918 | 0.7796 | 0.7034 | 0.7070 | 0.6405 | 0.6590 | 0.6857 | 0.6414 |
IHD | 0.8829 | 0.8948 | 0.9108 | 0.8528 | 0.8775 | 0.8375 | 0.8328 | 0.87964 | 0.7720 | 0.7579 | 0.7985 | 0.7738 |
AMI | 0.9073 | 0.9077 | 0.8861 | 0.8386 | 0.8689 | 0.8455 | 0.8246 | 0.7782 | 0.7815 | 0.7640 | 0.7499 | 0.7845 |
Osteoporosis | 0.7341 | 0.7142 | 0.7014 | 0.6372 | 0.6565 | 0.7487 | 0.7372 | 0.6244 | 0.6760 | 0.6717 | 0.6890 | 0.5857 |
Dementia | 0.8837 | 0.8651 | 0.8660 | 0.8784 | 0.8354 | 0.8594 | 0.8549 | 0.8790 | 0.7566 | 0.7575 | 0.7345 | 0.7772 |