Background
Materials and methods
Participants
Definition of microvascular and macrovascular disease at baseline
Definition of outcomes
Statistical analyses
Results
Clinical characteristics at baseline
Overall (n = 11,140) | History of microvascular or macrovascular disease at baseline | |||||
---|---|---|---|---|---|---|
Dual absence (n = 6789) | Microvascular alone (n = 761) | Macrovascular alone (n = 3196) | Both (n = 394) | p | ||
Male sex, n (%) | 6407 (57.5) | 3628 (53.4) | 404 (53.1) | 2107 (65.9) | 268 (68.0) | <0.0001 |
Region of origin: Asia, n (%) | 4136 (37.1) | 2525 (37.2) | 350 (46.0) | 1115 (34.9) | 146 (37.1) | <0.0001 |
Region of origin: established market economies, n (%) | 4862 (43.7) | 3012 (44.4) | 292 (38.4) | 1389 (43.5) | 169 (42.9) | |
Region of origin: Eastern Europe, n (%) | 2142 (19.2) | 1252 (18.4) | 119 (15.6) | 692 (21.6) | 79 (20.0) | |
Age (years): mean (SD) | 65.8 (6.4) | 65.9 (6.3) | 65.3 (6.4) | 65.6 (6.6) | 67.0 (6.6) | <0.0001 |
Duration of diabetes (years): mean (SD) | 7.9 (6.4) | 7.6 (6.1) | 10.3 (7.3) | 7.7 (6.3) | 10.2 (7.2) | <0.0001 |
Body mass index (kg/m2): mean (SD) | 28.3 (5.2) | 28.4 (5.3) | 27.7 (5.2) | 28.4 (4.9) | 28.2 (5.4) | 0.002 |
Systolic blood pressure (mmHg): mean (SD) | 145 (22) | 145 (21) | 149 (24) | 144 (22) | 148 (23) | <0.0001 |
Diastolic blood pressure (mmHg): mean (SD) | 81 (11) | 81 (11) | 81 (12) | 80 (11) | 81 (11) | 0.41 |
Use of antihypertensive treatment, n (%) | 7655 (68.7) | 4357 (64.2) | 521 (68.5) | 2466 (77.2) | 311 (78.9) | <0.0001 |
HbA1c (%): mean (SD) | 7.5 (1.6) | 7.5 (1.6) | 7.9 (1.7) | 7.4 (1.5) | 7.9 (1.6) | <0.0001 |
HbA1c (mmol/mol): mean (SD) | 59 (17) | 58 (17) | 63 (19) | 57 (16) | 62 (18) | |
eGFR (ml/min/1.73 m2) | 74 (18) | 76 (17) | 73 (20) | 73 (18) | 69 (20) | <0.0001 |
Urinary ACR (mg/g): median (Q1, Q3) | 15 (7, 40) | 13 (7, 31) | 49 (12, 390) | 15 (7, 36) | 86 (13, 461) | <0.0001 |
Serum total cholesterol (mmol/l): mean (SD) | 5.2 (1.2) | 5.3 (1.2) | 5.3 (1.2) | 5.0 (1.2) | 4.9 (1.2) | <0.0001 |
Serum HDL cholesterol (mmol/l): mean (SD) | 1.3 (0.4) | 1.3 (0.4) | 1.3 (0.4) | 1.2 (0.3) | 1.2 (0.3) | <0.0001 |
Serum LDL cholesterol (mmol/l): mean (SD) | 3.1 (1.0) | 3.2 (1.0) | 3.2 (1.0) | 3.0 (1.1) | 2.9 (1.0) | <0.0001 |
Serum triglycerides (mmol/l): median (Q1, Q3) | 1.6 (1.2, 2.3) | 1.6 (1.2, 2.3) | 1.6 (1.2, 2.3) | 1.7 (1.2, 2.3) | 1.6 (1.1, 2.2) | 0.05 |
History of ever smoking, n (%) | 4674 (42.0) | 2702 (39.8) | 271 (35.6) | 1529 (47.8) | 172 (43.7) | <0.0001 |
Incidence of major outcomes during follow-up according to status of microvascular and macrovascular disease at baseline
History of microvascular or macrovascular disease Number of events (event rate) | Microvascular disease alone vs. dual absence | Macrovascular disease alone vs. dual absence | Both micro- and macrovascular disease vs. dual absence | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Dual absence (n = 6789) | Microvascular alone (n = 761) | Macrovascular alone (n = 3196) | Both (n = 394) | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | |
All-cause mortality | 1136 (1.9) | 201 (3.3) | 773 (2.9) | 155 (5.3) | 1.43 (1.20 to 1.71) | <0.0001 | 1.43 (1.30 to 1.57) | <0.0001 | 2.01 (1.65 to 2.45) | <0.0001 |
Major macrovascular events | 970 (1.7) | 177 (3.1) | 872 (3.6) | 147 (5.6) | 1.64 (1.37 to 1.97) | <0.0001 | 2.04 (1.86 to 2.25) | <0.0001 | 2.92 (2.40 to 3.55) | <0.0001 |
Cardiovascular death | 396 (0.7) | 98 (1.6) | 406 (1.5) | 88 (3.0) | 1.96 (1.52 to 2.52) | <0.0001 | 2.13 (1.84 to 2.46) | <0.0001 | 3.19 (2.44 to 4.17) | <0.0001 |
Myocardial infarction | 310 (0.5) | 57 (1.0) | 295 (1.1) | 60 (2.2) | 1.68 (1.22 to 2.30) | 0.001 | 1.94 (1.65 to 2.29) | <0.0001 | 3.60 (2.63 to 4.92) | <0.0001 |
Stroke | 446 (0.8) | 67 (1.1) | 402 (1.6) | 53 (1.9) | 1.32 (0.99 to 1.76) | 0.06 | 2.15 (1.87 to 2.47) | <0.0001 | 2.36 (1.71 to 3.25) | <0.0001 |
Major clinical microvascular events | 342 (0.6) | 170 (3.2) | 198 (0.8) | 97 (3.9) | 4.74 (3.86 to 5.82) | <0.0001 | 1.26 (1.06 to 1.51) | 0.01 | 6.30 (4.93 to 8.06) | <0.0001 |
Retinal photocoagulation or blindness | 284 (0.5) | 143 (2.7) | 166 (0.6) | 76 (3.1) | 5.28 (4.25 to 6.56) | <0.0001 | 1.34 (1.10 to 1.63) | 0.003 | 6.98 (5.33 to 9.14) | <0.0001 |
ESRD or renal death | 70 (0.1) | 36 (0.6) | 36 (0.1) | 26 (0.9) | 1.95 (1.12 to 3.37) | 0.02 | 0.91 (0.60 to 1.38) | 0.66 | 2.71 (1.53 to 4.81) | 0.0006 |
Additive values of microvascular or macrovascular disease at baseline in discrimination and classification of outcomes during follow-up
Risk of all-cause mortality | P | |
---|---|---|
C-statistic (95% CI) for basic model | 0.704 (0.693 to 0.716) | |
Change in C-statistic (95% CI) for basic model + microvascular disease | 0.005 (0.002 to 0.008) | 0.02 |
Change in C-statistic (95% CI) for basic model + macrovascular disease | 0.005 (0.002 to 0.007) | <0.0001 |
Change in C-statistic (95% CI) for basic model + microvascular disease + macrovascular disease | 0.011 (0.007 to 0.014) | <0.0001 |
IDI (95% CI) | 0.013 (0.010 to 0.016) | <0.001 |
Continuous NRI (95% CI) | 0.275 (0.227 to 0.325) | <0.001 |
Categorical NRI (95% CI) | 0.021 (0.011 to 0.032) | <0.001 |
Risk of major macrovascular events (MACE)
| ||
C-statistic (95% CI) for basic model | 0.648 (0.631 to 0.665) | |
Change in C-statistic (95% CI) for basic model + microvascular disease | 0.009 (0.003 to 0.014) | 0.002 |
IDI (95% CI) | 0.008 (0.006 to 0.010) | <0.001 |
Continuous NRI (95% CI) | 0.120 (0.073 to 0.167) | <0.001 |
Categorical NRI (95% CI) | 0.011 (0.001 to 0.020) | 0.02 |
Risk of major clinical microvascular events
| ||
C-statistic (95% CI) for basic model | 0.664 (0.639 to 0.689) | |
Change in C-statistic (95% CI) for basic model + macrovascular disease | 0.004 (−0.003 to 0.011) | 0.25 |
IDI (95% CI) | 0.002 (0.001 to 0.002) | <0.001 |
Continuous NRI (95% CI) | 0.211 (0.112 to 0.305) | <0.001 |
Categorical NRI (95% CI) | 0.041 (0.002 to 0.087) | 0.03 |