Background
Methods
Data sources
Study cohort, outcomes, and follow-up
Measurements and definitions
Statistical analyses
Sensitivity analyses
Results
Baseline characteristics and study population
Individuals without diabetes | Individuals with type 2 diabetes | Individuals with type 1 diabetes | |
---|---|---|---|
n = 18,500,151 | n = 1913,503 | n = 9397 | |
Age (years) | 45.92 ± 14.23 | 57.81 ± 11.91 | 56.21 ± 13.99 |
Men [n (%)] | 9,435,968 (51.00) | 1,125,851 (58.84) | 5,348 (56.91) |
Low income level (lowest 20%) [n (%)] | 3,730,295 (20.16) | 435,273 (22.75) | 2,390 (25.43) |
Current smoker [n (%)] | 4,596,861 (24.85) | 485,750 (25.39) | 2,196 (23.37) |
Heavy alcohol consumers [n (%)] | 1,176,482 (6.36) | 161,349 (8.43) | 511 (5.44) |
Regular exercise [n (%)] | 9,469,745 (51.19) | 914,636 (47.80) | 4,441 (47.26) |
Body weight (kg) | 63.60 ± 11.80 | 66.24 ± 11.76 | 63.92 ± 11.06 |
BMI (kg/m2) | 23.57 ± 3.26 | 25.08 ± 3.37 | 24.13 ± 3.39 |
Waist circumference (cm) | 79.44 ± 9.20 | 85.47 ± 8.56 | 83.63 ± 9.52 |
In men | 83.16 ± 7.93 | 86.98 ± 7.95 | 85.09 ± 8.67 |
In women | 75.57 ± 8.83 | 83.31 ± 8.92 | 81.70 ± 10.21 |
Systolic BP (mmHg) | 121.22 ± 14.80 | 128.91 ± 15.63 | 126.78 ± 16.65 |
Diastolic BP (mmHg) | 75.65 ± 9.93 | 78.84 ± 10.07 | 76.57 ± 9.96 |
Fasting plasma glucose (mg/dl) | 92.87 ± 11.01 | 145.22 ± 45.76 | 156.99 ± 69.64 |
Total cholesterol (mg/dl) | 194.22 ± 35.88 | 194.96 ± 41.47 | 187.51 ± 40.96 |
Triglyceride (mg/dl) | 106.71 (106.68–106.74) | 146.24 (146.13–146.36) | 119.02 (117.60–120.45) |
HDL-C (mg/dl) | 55.90 ± 16.82 | 51.08 ± 17.14 | 53.09 ± 19.05 |
LDL-C (mg/dl) | 114.43 ± 42.68 | 110.81 ± 43.36 | 106.26 ± 36.76 |
eGFR (ml/min/1.73 m2) | 90.46 ± 47.25 | 85.47 ± 40.16 | 82.62 ± 43.45 |
Proteinuria (urine dipstick positivity) [n (%)] | 728,964 (3.94) | 205,321 (10.73) | 1,897 (20.19) |
Statin use [n (%)]a | 2,328,415 (12.59) | 926,340 (48.41) | 4,741 (50.45) |
Baseline comorbidities [n (%)] | |||
Hypertension | 4,111,022 (22.22) | 1,097,064 (57.33) | 5,291 (56.31) |
Dyslipidemia | 3,020,052 (16.32) | 829,098 (43.33) | 3,870 (41.18) |
Metabolic syndromeb | 4,155,335 (22.46) | 1,436,073 (75.05) | 5,972 (63.55) |
Incidence of cardiovascular disease according to the presence and type of diabetes
Individuals without diabetes | Individuals with type 2 diabetes | Individuals with type 1 diabetes | |
---|---|---|---|
n = 18,500,151 | n = 1,913,503 | n = 9,397 | |
Myocardial infarction | |||
Events (n) | 83,712 | 32,666 | 271 |
Follow-up duration (person-years) | 84,157,841.27 | 9,193,771.11 | 44,306.51 |
Incidence rate (per 100,000 person-years) | 99.470 | 355.306 | 611.648 |
Model 1 | 1 (Ref.) | 1.869 (1.845–1.894) | 3.321 (2.948–3.741) |
– | 1 (Ref.) | 1.771 (1.571–1.996) | |
Model 2 | 1 (Ref.) | 1.601 (1.580–1.623) | 2.844 (2.524–3.204) |
– | 1 (Ref.) | 1.751 (1.554–1.974) | |
Model 2-1 | 1 (Ref.) | 1.279 (1.262–1.296) | 2.183 (1.938–2.459) |
– | 1 (Ref.) | 1.705 (1.513–1.922) | |
Model 3 | 1 (Ref.) | 1.562 (1.540–1.583) | 2.739 (2.430–3.086) |
– | 1 (Ref.) | 1.723 (1.529–1.942) | |
Model 4 | 1 (Ref.) | 1.418 (1.395–1.442) | 2.411 (2.138–2.718) |
– | 1 (Ref.) | 1.679 (1.490–1.893) | |
Hospitalization for HF | |||
Events (n) | 89,173 | 36,448 | 376 |
Follow-up duration (person-years) | 84,188,450.19 | 9,203,077.54 | 44,238.57 |
Incidence rate (per 100,000 person-years) | 105.921 | 396.041 | 849.937 |
Model 1 | 1 (Ref.) | 1.753 (1.731–1.774) | 3.955 (3.575–4.376) |
– | 1 (Ref.) | 2.241 (2.025–2.480) | |
Model 2 | 1 (Ref.) | 1.606 (1.586–1.626) | 3.604 (3.257–3.988) |
– | 1 (Ref.) | 2.216 (2.002–2.453) | |
Model 2-1 | 1 (Ref.) | 1.463 (1.445–1.482) | 3.233 (2.921–3.577) |
– | 1 (Ref.) | 2.195 (1.983–2.429) | |
Model 3 | 1 (Ref.) | 1.578 (1.558–1.599) | 3.390 (3.063–3.752) |
– | 1 (Ref.) | 2.120 (1.915–2.348) | |
Model 4 | 1 (Ref.) | 1.417 (1.395–1.440) | 3.024 (2.730–3.350) |
– | 1 (Ref.) | 2.105 (1.901–2.330) | |
Atrial fibrillation | |||
Events (n) | 105,562 | 29,743 | 227 |
Follow-up duration (person-years) | 84,127,796.33 | 9,204,929.38 | 44,425.71 |
Incidence rate (per 100,000 person-years) | 125.478 | 323.120 | 510.965 |
Model 1 | 1 (Ref.) | 1.268 (1.251–1.284) | 2.073 (1.820–2.361) |
– | 1 (Ref.) | 1.630 (1.430–1.857) | |
Model 2 | 1 (Ref.) | 1.147 (1.132–1.162) | 1.885 (1.655–2.147) |
– | 1 (Ref.) | 1.636 (1.436–1.864) | |
Model 2-1 | 1 (Ref.) | 1.046 (1.032–1.060) | 1.694 (1.487–1.929) |
– | 1 (Ref.) | 1.627 (1.427–1.853) | |
Model 3 | 1 (Ref.) | 1.147 (1.131–1.162) | 1.829 (1.605–2.084) |
– | 1 (Ref.) | 1.587 (1.392–1.808) | |
Model 4 | 1 (Ref.) | 1.085 (1.067–1.103) | 1.748 (1.534–1.993) |
– | 1 (Ref.) | 1.608 (1.411–1.833) | |
All-cause mortality | |||
Events (n) | 249,622 | 94,018 | 876 |
Follow-up duration (person-years) | 84,326,798.16 | 9,261,598.81 | 44,788.78 |
Incidence rate (per 100,000 person-years) | 296.020 | 1015.140 | 1955.850 |
Model 1 | 1 (Ref.) | 1.569 (1.557–1.581) | 3.145 (2.944–3.360) |
– | 1 (Ref.) | 1.990 (1.862–2.127) | |
Model 2 | 1 (Ref.) | 1.685 (1.672–1.698) | 3.345 (3.131–3.574) |
– | 1 (Ref.) | 1.961 (1.835–2.096) | |
Model 2-1 | 1 (Ref.) | 1.885 (1.870–1.899) | 3.801 (3.557–4.062) |
– | 1 (Ref.) | 2.002 (1.873–2.139) | |
Model 3 | 1 (Ref.) | 1.635 (1.622–1.648) | 3.120 (2.919–3.334) |
– | 1 (Ref.) | 1.893 (1.771–2.024) | |
Model 4 | 1 (Ref.) | 1.510 (1.495–1.525) | 2.874 (2.689–3.073) |
– | 1 (Ref.) | 1.884 (1.762–2.013) |
Individuals without diabetes | Individuals with type 2 diabetes (diabetes duration < 5 years) | Individuals with type 2 diabetes (diabetes duration ≥ 5 years) | Individuals with type 1 diabetes (diabetes duration < 5 years) | Individuals with type 1 diabetes (diabetes duration ≥ 5 years) | |
---|---|---|---|---|---|
n = 18,500,151 | n = 1,158,637 | n = 754,866 | n = 8,523 | n = 874 | |
Myocardial infarction | |||||
Events (n) | 83,712 | 14,986 | 17,680 | 257 | 14 |
Follow-up duration (person-years) | 84,157,841.27 | 5,516,027.03 | 3,677,744.08 | 41,701.72 | 2,604.79 |
Incidence rate (per 100,000 person-years) | 99.470 | 271.681 | 480.729 | 616.282 | 537.471 |
Model 1 | 1 (Ref.) | 1.635 (1.607–1.664) | 2.135 (2.100–2.171) | 3.295 (2.915–3.724) | 3.904 (2.314–6.586) |
– | 1 (Ref.) | 1.387 (1.357–1.418) | 2.072 (1.832–2.344) | 2.343 (1.387–3.956) | |
Model 2 | 1 (Ref.) | 1.394 (1.369–1.419) | 1.837 (1.807–1.868) | 2.825 (2.499–3.193) | 3.303 (1.958–5.573) |
– | 1 (Ref.) | 1.374 (1.344–1.405) | 2.044 (1.807–2.313) | 2.295 (1.359–3.875) | |
Model 3 | 1 (Ref.) | 1.361 (1.336–1.386) | 1.792 (1.761–1.823) | 2.729 (2.414–3.085) | 3.136 (1.857–5.295) |
– | 1 (Ref.) | 1.385 (1.355–1.416) | 2.025 (1.790–2.291) | 2.247 (1.331–3.796) | |
Model 4 | 1 (Ref.) | 1.250 (1.226–1.276) | 1.628 (1.596–1.661) | 2.418 (2.137–2.735) | 2.830 (1.677–4.774) |
– | 1 (Ref.) | 1.351 (1.321–1.381) | 1.955 (1.728–2.212) | 2.200 (1.303–3.715) | |
Hospitalization for HF | |||||
Events (n) | 89,173 | 15,926 | 20,522 | 358 | 18 |
Follow-up duration (person-years) | 84,188,450.19 | 5,521,605.87 | 3,681,471.67 | 41,639.93 | 2,598.64 |
Incidence rate (per 100,000 person-years) | 105.921 | 288.431 | 557.440 | 859.752 | 692.670 |
Model 1 | 1 (Ref.) | 1.515 (1.490–1.541) | 1.999 (1.969–2.030) | 3.922 (3.536–4.351) | 4.682 (2.958–7.411) |
– | 1 (Ref.) | 1.373 (1.345–1.402) | 2.624 (2.363–2.913) | 3.063 (1.934-4.851) | |
Model 2 | 1 (Ref.) | 1.381 (1.357–1.405) | 1.841 (1.813–1.870) | 3.578 (3.225–3.969) | 4.196 (2.650–6.643) |
– | 1 (Ref.) | 1.371 (1.343–1.400) | 2.596 (2.338–2.883) | 3.000 (1.894–4.750) | |
Model 3 | 1 (Ref.) | 1.364 (1.340–1.388) | 1.802 (1.774–1.831) | 3.379 (3.045–3.749) | 3.927 (2.474–6.234) |
– | 1 (Ref.) | 1.371 (1.343–1.400) | 2.495 (2.247–2.771) | 2.843 (1.791–4.514) | |
Model 4 | 1 (Ref.) | 1.236 (1.212–1.260) | 1.626 (1.596–1.656) | 3.036 (2.734–3.371) | 3.535 (2.232–5.597) |
– | 1 (Ref.) | 1.346 (1.318–1.375) | 2.452 (2.208–2.723) | 2.787 (1.756–4.426) | |
Atrial fibrillation | |||||
Events (n) | 105,562 | 15,019 | 14,724 | 213 | 14 |
Follow-up duration (person-years) | 84,127,796.33 | 5,518,697.12 | 3,686,232.26 | 41,821.14 | 2,604.57 |
Incidence rate (per 100,000 person-years) | 125.478 | 272.148 | 399.432 | 509.312 | 537.517 |
Model 1 | 1 (Ref.) | 1.242 (1.221–1.264) | 1.296 (1.273–1.318) | 2.029 (1.774–2.321) | 3.015 (1.787–5.086) |
– | 1 (Ref.) | 1.072 (1.048–1.097) | 1.654 (1.445–1.894) | 2.381 (1.412–4.014) | |
Model 2 | 1 (Ref.) | 1.117 (1.098–1.136) | 1.180 (1.159–1.201) | 1.846 (1.614–2.112) | 2.705 (1.603–4.563) |
– | 1 (Ref.) | 1.081 (1.057–1.107) | 1.669 (1.458–1.911) | 2.378 (1.411–4.008) | |
Model 3 | 1 (Ref.) | 1.124 (1.105–1.144) | 1.171 (1.150–1.192) | 1.793 (1.567–2.051) | 2.650 (1.570–4.475) |
– | 1 (Ref.) | 1.070 (1.045–1.095) | 1.610 (1.407–1.844) | 2.297 (1.360–3.880) | |
Model 4 | 1 (Ref.) | 1.060 (1.039–1.081) | 1.114 (1.091–1.137) | 1.714 (1.497–1.962) | 2.508 (1.486–4.232) |
– | 1 (Ref.) | 1.074 (1.050–1.099) | 1.637 (1.430–1.875) | 2.332 (1.384–3.930) | |
All-cause mortality | |||||
Events (n) | 249,622 | 45,145 | 48,873 | 841 | 35 |
Follow-up duration (person-years) | 84,326,798.16 | 5,547,858.83 | 3,713,739.98 | 42,168.61 | 2,620.17 |
Incidence rate (per 100,000 person-years) | 296.020 | 813.740 | 1,316.000 | 1,994.370 | 1,335.790 |
Model 1 | 1 (Ref.) | 1.483 (1.468–1.498) | 1.659 (1.643–1.675) | 3.150 (2.944–3.370) | 2.917 (2.094–4.062) |
– | 1 (Ref.) | 1.132 (1.118–1.147) | 2.124 (1.984–2.274) | 1.979 (1.422–2.755) | |
Model 2 | 1 (Ref.) | 1.588 (1.572–1.604) | 1.787 (1.770–1.805) | 3.355 (3.136–3.589) | 3.072 (2.206–4.278) |
– | 1 (Ref.) | 1.139 (1.124–1.154) | 2.101 (1.962–2.249) | 1.927 (1.384–2.684) | |
Model 3 | 1 (Ref.) | 1.533 (1.517–1.549) | 1.745 (1.727–1.763) | 3.135 (2.930–3.355) | 2.891 (2.075–4.026) |
– | 1 (Ref.) | 1.154 (1.139–1.169) | 2.044 (1.909–2.188) | 1.884 (1.353–2.625) | |
Model 4 | 1 (Ref.) | 1.434 (1.417–1.451) | 1.598 (1.579–1.617) | 2.893 (2.703–3.097) | 2.638 (1.894–3.674) |
– | 1 (Ref.) | 1.124 (1.109–1.138) | 2.009 (1.876–2.151) | 1.836 (1.319–2.557) |
All-cause mortality according to the presence and type of diabetes
Subgroup analyses
n | Age groups | Sex | |||||||
---|---|---|---|---|---|---|---|---|---|
Age < 65 years | Age ≥ 65 years | Men | |||||||
Without diabetes | T2D | T1D | Without diabetes | T2D | T1D | Without diabetes | T2D | T1D | |
16,432,505 | 1,336,352 | 6444 | 2,067,646 | 577,151 | 2953 | 9,435,968 | 1,125,851 | 5348 | |
Myocardial infarction | |||||||||
Events (n) | 45,760 | 15,003 | 127 | 37,952 | 17,663 | 144 | 49,094 | 19,398 | 161 |
Follow-up durationa | 74,096,761.66 | 6,371,484.62 | 30,193.35 | 10,061,079.61 | 2,822,286.48 | 14,113.17 | 43,604,234.55 | 5,351,613.56 | 24,915.64 |
IRb | 61.760 | 235.470 | 420.620 | 377.220 | 625.840 | 1020.320 | 112.590 | 362.470 | 646.181 |
Adjusted HR (95% CI) | 1 (Ref.) | 1.384 (1.349–1.419) | 2.549 (2.138–3.038) | 1 (Ref.) | 1.462 (1.430–1.495) | 2.418 (2.051–2.850) | 1 (Ref.) | 1.362 (1.333–1.393) | 2.307 (1.975–2.696) |
Hospitalization for HF | |||||||||
Events (n) | 33,468 | 12,533 | 158 | 55,705 | 23,915 | 218 | 45,079 | 19,112 | 207 |
Follow-up durationa | 74,137,669.23 | 6,382,665.72 | 30,199.82 | 10,050,780.96 | 2,820,411.82 | 14,038.75 | 43,638,053.44 | 5,362,891.91 | 24,894.04 |
IRb | 45.140 | 196.360 | 523.180 | 554.240 | 847.930 | 1552.840 | 103.302 | 356.375 | 831.524 |
Adjusted HR (95% CI) | 1 (Ref.) | 1.533 (1.490–1.577) | 4.015 (3.427–4.704) | 1 (Ref.) | 1.397 (1.371–1.424) | 2.722 (2.382–3.112) | 1 (Ref.) | 1.419 (1.388–1.451) | 3.079 (2.683–3.533) |
Atrial fibrillation | |||||||||
Events (n) | 50,060 | 11,523 | 89 | 55,502 | 18,220 | 138 | 59,913 | 17,762 | 133 |
Follow-up durationa | 74,095,720.84 | 6,381,466.71 | 30,291.22 | 10,032,075.49 | 2,823,462.67 | 14,134.49 | 43,594,810.10 | 5,358,747.06 | 24,969.15 |
IRb | 67.561 | 180.570 | 293.815 | 553.245 | 645.307 | 976.335 | 137.431 | 331.458 | 532.657 |
Adjusted HR (95% CI) | 1 (Ref.) | 1.109 (1.079–1.141) | 1.928 (1.565–2.374) | 1 (Ref.) | 1.072 (1.050–1.095) | 1.668 (1.410–1.973) | 1 (Ref.) | 1.087 (1.064–1.111) | 1.688 (1.423–2.003) |
All-cause mortality | |||||||||
Events (n) | 96,885 | 30,131 | 300 | 152,737 | 63,887 | 576 | 161,569 | 62,460 | 581 |
Follow-up durationa | 74,189,668.59 | 6,403,591.13 | 30,439.67 | 10,137,129.57 | 2,858,007.68 | 14,349.12 | 43,703,573.26 | 5,391,593.98 | 25,187.91 |
IRb | 130.590 | 470.530 | 985.560 | 1506.710 | 2235.370 | 4014.180 | 369.690 | 1158.470 | 2306.660 |
Adjusted HR (95% CI) | 1 (Ref.) | 1.653 (1.623–1.683) | 3.328 (2.969–3.731) | 1 (Ref.) | 1.491 (1.474–1.509) | 2.833 (2.609–3.076) | 1 (Ref.) | 1.514 (1.496–1.532) | 2.790 (2.571–3.029) |
n | Sex | Presence of chronic kidney disease | |||||||
---|---|---|---|---|---|---|---|---|---|
Women | No | Yes | |||||||
Without diabetes | T2D | T1D | Without diabetes | T2D | T1D | Without diabetes | T2D | T1D | |
9,064,183 | 787,652 | 4049 | 17,617,783 | 1,700,766 | 7652 | 882,368 | 212,737 | 1745 | |
Myocardial infarction | |||||||||
Events (n) | 34,618 | 13,268 | 110 | 73,275 | 25,485 | 175 | 10,437 | 7181 | 96 |
Follow-up durationa | 40,553,606.72 | 3,842,157.55 | 19,390.88 | 79,549,644.55 | 8,151,279.45 | 36,173.82 | 4,608,196.72 | 1,042,491.65 | 8132.69 |
IRb | 85.364 | 345.327 | 567.277 | 92.110 | 312.650 | 483.780 | 226.490 | 688.830 | 1180.420 |
Adjusted HR (95% CI) | 1 (Ref.) | 1.497 (1.458–1.536) | 2.576 (2.133–3.111) | 1 (Ref.) | 1.350 (1.325–1.376) | 2.127 (1.832–2.470) | 1 (Ref.) | 1.649 (1.590–1.711) | 2.938 (2.399–3.599) |
Hospitalization for HF | |||||||||
Events (n) | 44,094 | 17,336 | 169 | 73,630 | 26,005 | 227 | 15,543 | 10,443 | 149 |
Follow-up durationa | 40,550,396.75 | 3,840,185.63 | 19,344.54 | 79,583,758.88 | 8,163,014.47 | 36,164.03 | 4,604,691.30 | 1,040,063.07 | 8074.54 |
IRb | 108.739 | 451.437 | 873.632 | 92.520 | 318.570 | 627.700 | 337.550 | 1004.070 | 1845.310 |
Adjusted HR (95% CI) | 1 (Ref.) | 1.415 (1.383–1.447) | 2.962 (2.543–3.451) | 1 (Ref.) | 1.320 (1.296–1.345) | 2.654 (2.327–3.027) | 1 (Ref.) | 1.603 (1.555–1.651) | 3.225 (2.740–3.796) |
Atrial fibrillation | |||||||||
Events (n) | 45,649 | 11,981 | 94 | 91,616 | 23,224 | 147 | 13,946 | 6519 | 80 |
Follow-up durationa | 40,532,986.22 | 3,846,182.32 | 19,456.56 | 79,525,314.43 | 8,159,959.21 | 36,253.65 | 4,602,481.89 | 1,044,970.17 | 8172.06 |
IRb | 112.622 | 311.504 | 483.127 | 115.204 | 284.609 | 405.476 | 303.010 | 623.846 | 978.946 |
Adjusted HR (95% CI) | 1 (Ref.) | 1.080 (1.052–1.108) | 1.834 (1.496–2.247) | 1 (Ref.) | 1.053 (1.033–1.073) | 1.592 (1.353–1.873) | 1 (Ref.) | 1.168 (1.126–1.210) | 1.955 (1.566–2.440) |
All-cause mortality | |||||||||
Events (n) | 88,053 | 31,558 | 295 | 212,747 | 71,494 | 573 | 36,875 | 22,524 | 303 |
Follow-up durationa | 40,623,224.90 | 3,870,004.83 | 19,600.87 | 79,697,361.81 | 8,204,635.79 | 36,493.65 | 4,629,436.35 | 1,056,963.02 | 8295.14 |
IRb | 216.760 | 815.450 | 1505.040 | 266.940 | 871.390 | 1570.140 | 796.530 | 2131.010 | 3652.740 |
Adjusted HR (95% CI) | 1 (Ref.) | 1.505 (1.480–1.530) | 3.051 (2.718–3.424) | 1 (Ref.) | 1.463 (1.447–1.479) | 2.642 (2.433–2.870) | 1 (Ref.) | 1.588 (1.556–1.620) | 3.006 (2.681–3.369) |
Sensitivity analyses
Type 1 versus type 2 diabetes | Myocardial infarction | Hospitalization for HF | Atrial fibrillation | All-cause mortality |
---|---|---|---|---|
Observed associationa | 1.679 (1.490–1.893) | 2.105 (1.901–2.330) | 1.608 (1.411–1.833) | 1.884 (1.762–2.013) |
E-value for point estimate | 2.75 | 3.63 | 2.60 | 3.17 |
E-value for confidence interval | 2.34 | 3.21 | 2.17 | 2.92 |