Table 1.
Clinical characteristics of cases and matched controls
| Characteristics | At Baseline, No. (%)a | During Follow-up, No. (%)c | ||||
|---|---|---|---|---|---|---|
| Cases (n = 2700) | Controls (n = 9272) | SDb | Cases (n = 2700) | Controls (n = 9272) | SDb | |
| Age, mean ± s.d | 73.2 ± 10.3 | 71.3 ± 10.1 | 0.193 | 72.8 ± 10.1 | 71.9 ± 9.9 | 0.193 |
| Sex, male No. (%) | 1800 (66.7) | 6210 (67.0) | 0.007 | 1912 (69.3) | 7364 (70.1) | 0.007 |
| Periods from the first COPD visit to the initial use of antidiabetic agents, days (mean ± s.d.) | 519 ± 922 | 435 ± 826 | 0.052 | NA | NA | NA |
| DM severity indicators, No. (%) | ||||||
| aDCSI | ||||||
| 0 | 742 (27.5) | 2930 (31.6) | 0.090 | 764 (28.3) | 3074 (33.2) | 0.105 |
| 1–2 | 1061 (39.3) | 3778 (40.8) | 0.030 | 1024 (37.9) | 3622 (39.1) | 0.023 |
| 3–4 | 626 (23.2) | 1846 (19.9) | 0.080 | 633 (23.4) | 1845 (19.9) | 0.086 |
| ≥ 5 | 271 (10.0) | 718 (7.7) | 0.090 | 279 (10.3) | 731 (7.9) | 0.085 |
| Insulin | ||||||
| Nonusers | 1786 (66.2) | 6634 (71.6) | 0.117 | 1801 (66.7) | 6864 (74.0) | 0.161 |
| Short acting only | 831 (30.8) | 2366 (25.5) | 0.117 | 754 (27.9) | 1899 (20.5) | 0.174 |
| Long acting | 83 (3.1) | 272 (2.9) | 0.008 | 145 (5.4) | 509 (5.5) | 0.005 |
| Regimens of oral hypoglycemic agentsd | ||||||
| Nonusers | 0 | 0 | 333 (12.3) | 919 (9.9) | 0.077 | |
| Monotherapy | 1376 (51.0) | 4958 (53.5) | 0.050 | 940 (34.8) | 2939 (31.7) | 0.066 |
| Dual therapy | 944 (35.0) | 3286 (35.4) | 0.010 | 900 (33.3) | 3508 (37.8) | 0.094 |
| Triple therapy or more | 380 (14.1) | 028 (11.1) | 0.090 | 527 (19.5) | 1906 (20.6) | 0.026 |
| Metabolic acidosis | 9 (0.3) | 21 (0.2) | 0.020 | 21 (0.8) | 22 0.2) | 0.076 |
| New users of oral hypoglycemic agents | 1589 (58.9) | 5744 (62.0) | 0.063 | NA | NA | NA |
| COPD severity indicators, No. (%) | ||||||
| No. of inpatient visit for COPD exacerbationse | ||||||
| 0 | 2589 (95.9) | 9032 (97.4) | 0.085 | NA | NA | NA |
| 1 | 85 (3.2) | 201 (2.2) | 0.061 | NA | NA | NA |
| ≥ 2 | 26 (1.0) | 39 (0.4) | 0.065 | NA | NA | NA |
| No. of ER visit for COPD exacerbations | ||||||
| 0 | 2590 (95.9) | 9017 (97.3) | 0.073 | 2488 (92.2) | 8940 (96.4) | 0.185 |
| 1 | 85 (3.2) | 221 (2.4) | 0.047 | 149 (5.5) | 304 (3.3) | 0.109 |
| ≥ 2 | 25 (0.9) | 34 (0.4) | 0.070 | 63 (2.3) | 28 (0.3) | 0.179 |
| No. of OPD visit for COPD exacerbationsf | ||||||
| 0 | 2284 (84.6) | 7876 (84.6) | 0.010 | 2252 (83.4) | 8129 (87.7) | 0.121 |
| 1 | 296 (11.0) | 1013 (11.0) | 0.001 | 289 (10.7) | 768 (8.3) | 0.083 |
| ≥ 2 | 120 (4.4) | 383 (4.4) | 0.015 | 159 (5.9) | 375 (4.0) | 0.085 |
| Types of COPD regimens | ||||||
| Nonusers | 894 (33.1) | 3,040 (32.8) | 0.007 | 360 (13.3) | 1,306 (14.0) | 0.022 |
| Triple therapy | 15 (0.6) | 33 (0.4) | 0.030 | 15 (0.6) | 15 (0.2) | 0.066 |
| Dual therapy | 224 (8.3) | 722 (7.8) | 0.019 | 305 (11.3) | 719 (7.8) | 0.121 |
| Others | 1567 (58.0) | 5477 (59.1) | 0.021 | 2020 (74.8) | 7,232 (78.0) | 0.075 |
| Comorbidities, No. (%) | ||||||
| CV diseases | ||||||
| Hypertension | 1951 (72.4) | 6572 (70.9) | 0.033 | 1906 (70.6) | 6720 (72.5) | 0.042 |
| Coronary artery disease | 895 (33.2) | 3009 (32.5) | 0.015 | 853 (31.6) | 2873 (31.0) | 0.013 |
| Stroke | 826 (30.6) | 2122 (22.9) | 0.175 | 911 (33.7) | 2416 (26.1) | 0.168 |
| Hyperlipidemia | 636 (23.6) | 2390 (25.8) | 0.052 | 581 (21.5) | 2695 (29.1) | 0.174 |
| Heart failure | 488 (18.1) | 1387 (15.0) | 0.084 | 625 (23.2) | 1518 (16.4) | 0.171 |
| Arrhythmia | 387 (14.3) | 1193 (12.9) | 0.043 | 427 (15.8) | 1166 (12.6) | 0.093 |
| Peripheral vascular disease | 171 (6.3) | 551 (5.9) | 0.016 | 168 (6.2) | 540 (5.8) | 0.017 |
| Rheumatic heart disease | 46 (1.7) | 122 (1.3) | 0.032 | 51 (1.9) | 151 (1.6) | 0.020 |
| Pulmonary embolism | 7 (0.3) | 15 (0.2) | 0.021 | 10 (0.4) | 21 (0.2) | 0.026 |
| Pulmonary disease | ||||||
| Acute bronchitis | 1090 (40.4) | 4107 (44.3) | 0.079 | 905 (33.5) | 3188 (34.4) | 0.018 |
| Asthma | 819 (30.3) | 3092 (33.4) | 0.065 | 897 (33.2) | 2729 (29.4) | 0.082 |
| Pneumonia | 804 (29.8) | 2386 (25.7) | 0.090 | 972 (36.0) | 2598 (28.0) | 0.172 |
| Influenza | 193 (7.2) | 780 (8.4) | 0.047 | 109 (4.0) | 500 (5.4) | 0.064 |
| Mental disease | ||||||
| Dementia | 264 (9.8) | 523 (5.6) | 0.156 | 342 (12.7) | 709 (7.7) | 0.167 |
| Depression | 153 (5.7) | 476 (5.1) | 0.024 | 148 (5.5) | 433 (4.7) | 0.037 |
| Schizophrenia | 15 (0.6) | 49 (0.5) | 0.004 | 15 (0.6) | 43 (0.5) | 0.013 |
| Chronic liver disease | 322 (11.9) | 1214 (13.1) | 0.035 | 257 (9.5) | 1004 (10.8) | 0.043 |
| Cancer | 311 (11.5) | 1011 (10.9) | 0.019 | 345 (12.8) | 1279 (13.8) | 0.030 |
| Sepsis | 227 (8.4) | 424 (4.6) | 0.156 | 390 (14.4) | 769 (8.3) | 0.195 |
| Chronic renal disease | 216 (8.0) | 538 (5.8) | 0.087 | 347 (12.9) | 917 (9.9) | 0.093 |
| GERD | 144 (5.3) | 397 (4.3) | 0.049 | 212 (7.9) | 617 (6.7) | 0.046 |
| Parkinsonism | 132 (4.9) | 303 (3.3) | 0.082 | 148 (5.5) | 365 (3.9) | 0.073 |
| Co-medication, No. (%) | ||||||
| CV medication | ||||||
| Diuretics | 1771 (65.6) | 5709 (61.6) | 0.084 | 1755 (65.0) | 5425 (58.5) | 0.134 |
| Calcium channel blockers | 1724 (63.9) | 5766 (62.2) | 0.034 | 1616 (59.9) | 5275 (56.9) | 0.060 |
| Antiplatelets | 1688 (61.8) | 5508 (59.4) | 0.049 | 1465 (54.3) | 4722 (50.9) | 0.067 |
| Angiotensin-converting enzyme inhibitors | 874 (32.4) | 3113 (33.6) | 0.026 | 579 (21.4) | 2014 (21.7) | 0.007 |
| Angiotensin receptor blockers | 849 (31.4) | 2754 (29.7) | 0.038 | 938 (34.7) | 3479 (37.5) | 0.058 |
| Nitrates | 665 (24.6) | 2011 (21.6) | 0.072 | 617 (22.9) | 1773 (19.1) | 0.092 |
| β-blockers | ||||||
| Non-CV selective | 641 (23.7) | 2088 (22.5) | 0.029 | 418 (15.5) | 1402 (15.1) | 0.010 |
| CV selective | 567 (21.0) | 1983 (21.4) | 0.009 | 348 (12.9) | 1404 (15.1) | 0.065 |
| Digoxin | 334 (12.4) | 979 (10.6) | 0.057 | 334 (12.4) | 979 (10.6) | 0.057 |
| Anticoagulants | 221 (8.2) | 555 (6.0) | 0.086 | 174 (6.4) | 519 (5.6) | 0.036 |
| Antiarrhythmic agents | 132 (4.9) | 310 (3.3) | 0.078 | 193 (7.2) | 390 (4.2) | 0.127 |
| Lipid-lowering agents | ||||||
| Statins | 469 (17.4) | 1567 (16.9) | 0.012 | 458 (17.0) | 2,135 (23.0) | 0.152 |
| Others | 218 (8.1) | 853 (9.2) | 0.040 | 133 (4.9) | 635 (6.9) | 0.082 |
| COPD medications | ||||||
| Inhaled corticosteroids | 392 (14.5) | 1411 (15.2) | 0.020 | 432 (16.0) | 1230 (13.3) | 0.077 |
| LABA | 250 (9.3) | 801 (8.6) | 0.022 | 341 (126) | 1002 (10.8) | 0.057 |
| LAMA | 58 (2.2) | 202 (2.2) | 0.002 | 103 (3.8) | 206 (2.2) | 0.093 |
| Short-acting β2 agonists | ||||||
| Nebulized | 810 (30.0) | 2174 (23.5) | 0.148 | 1067 (39.5) | 2583 (27.9) | 0.249 |
| Inhaled | ||||||
| 0 canister | 2254 (83.5) | 7768 (83.8) | 0.008 | 2174 (80.5) | 8051 (86.8) | 0.171 |
| ≤ 6 canisters | 381 (14.1) | 1291 (13.9) | 0.005 | 493 (18.3) | 1158 (12.5) | 0.160 |
| > 6 canisters | 65 (2.4) | 213 (2.3) | 0.007 | 33 (1.2) | 63 (0.7) | 0.056 |
| Short-acting muscarinic antagonists | ||||||
| Nebulized | 674 (25.0) | 1717 (18.5) | 0.157 | 970 (35.9) | 2365 (25.5) | 0.227 |
| Inhaled | ||||||
| 0 canister | 2465 (91.3) | 8567 (92.4) | 0.040 | 2442 (90.4) | 8814 (95.1) | 0.179 |
| ≤ 6 canisters | 205 (7.6) | 610 (6.6) | 0.040 | 246 (9.1) | 433 (4.7) | 0.176 |
| > 6 canisters | 30 (1.1) | 95 (1.0) | 0.008 | 12 (0.4) | 25 (0.3) | 0.029 |
| Oral β2 agonists | 1511 (56.0) | 5586 (60.3) | 0.087 | 1329 (49.2) | 4279 (46.2) | 0.062 |
| Methylxanthines | 1223 (45.3) | 4600 (49.6) | 0.086 | 1208 (44.7) | 3783 (40.8) | 0.080 |
| Gastric acid suppressants | ||||||
| H-blockers | 1054 (39.0) | 3338 (36.0) | 0.063 | 851 (31.5) | 2599 (28.0) | 0.076 |
| PPI | 414 (15.3) | 1006 (10.9) | 0.133 | 454 (16.8) | 976 (10.5) | 0.184 |
| Anti-inflammatory agents | ||||||
| NSAID | 1953 (72.3) | 6998 (75.5) | 0.072 | 1309 (48.5) | 5117 (55.2) | 0.135 |
| Systemic corticosteroid | 1593 (59.0) | 5449 (58.8) | 0.005 | 1570 (58.2) | 4213 (45.4) | 0.256 |
| Aspirin (≥ 325 mg) | 521 (19.3) | 1722 (18.6) | 0.018 | 387 (14.3) | 1103 (11.9) | 0.072 |
| Psychotropic drugs | ||||||
| Benzodiazepines and Z-drugs | 1785 (66.1) | 6134 (66.2) | 0.001 | 1478 (54.7) | 4807 (51.8) | 0.058 |
| Antipsychotics | 611 (22.6) | 1771 (19.1) | 0.087 | 518 (19.2) | 1529 (16.5) | 0.070 |
| Opioids | 1443 (53.4) | 5132 (55.4) | 0.038 | 1092 (40.4) | 3535 (38.1) | 0.047 |
| Vaccines (influenza and pneumonia) | 1061 (39.3) | 3682 (39.7) | 0.008 | 798 (29.6) | 3195 (34.5) | 0.105 |
SD, standardized difference; s.d., standard deviation; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; aDCSI, adapted diabetes complications severity index; NA, not applicable; No., number; ER, emergency room; OPD, outpatient department; CV, cardiovascular; GERD, gastroesophageal reflux disease; LABA, inhaled long-acting β2 agonists; LAMA, inhaled long-acting antimuscarinic antagonists; PPI, proton pump inhibitor; NSAID, nonsteroidal anti-inflammatory drug
a All comorbidities, DM severity indicators, COPD severity indicators, and co-medications were measured in the year before the cohort entry date
b SD with > 0.1 represents meaningful differences between two groups
c All comorbidities, COPD severity indicators, aDSCI metabolic acidosis, and pneumonia and influenza vaccinations were measured in the year preceding the index date; co-medications and other DM severity indicators were measured in the 6 months before the index date
d Regimens of oral hypoglycemic agents were measured at the cohort entry date, and the measurements during follow-up were similar to those of co-medications
e Number of inpatient visit for COPD exacerbations was measured during 31–365 days before the cohort entry date
f OPD visits for COPD exacerbations were defined as patients with a primary diagnosis of COPD refilling oral corticosteroids or antibiotics for use 3–14 days after an outpatient visit