Table 2.
Results of mediation analysis: total, direct and indirect effects of type 2 diabetes on cardiovascular events; adjusted for age, sex and mediators
| Effects T2D vs. no T2D | Three mediators | Four mediators | Five mediators | Six mediators | ||||
|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | PME (95% CI) | HR (95% CI) | PME (95% CI) | HR (95% CI) | PME (95% CI) | HR (95% CI) | PME (95% CI) | |
| Total effect | 1.41 (1.25‐1.58) | 100 | 1.44 (1.29‐1.61) | 100% | 1.44 (1.29‐1.62) | 100% | 1.46 (1.29‐1.70) | 100% |
| Direct effecta | 1.26 (1.11‐1.43) | 66.7% (45.4‐82.6) | 1.31 (1.16‐1.48) | 73.2% (54.5‐87.8) | 1.25 (1.09‐1.42) | 59.7% (32.8‐78.4) | 1.28 (1.08‐1.52) | 64.5% (29.3‐85.0) |
| Indirect effect, combinedb | 1.12 (1.06‐1.17) | 33.3% (17.4‐54.6) | 1.10 (1.05‐1.16) | 26.8% (12.2‐45.5) | 1.16 (1.09‐1.23) | 40.3% (21.6‐67.2) | 1.14 (1.06‐1.23) | 35.5% (15.0‐70.7) |
| Indirect effect through:b | ||||||||
| Insulin resistance | 1.08 (1.04‐1.13) | 23.9% (9.6‐41.5) | 1.08 (1.04‐1.14) | 23.5% (11.039.0) | 1.10 (1.05‐1.15) | 26,1% (13.5‐43.0) | 1.07 (1.01‐1.12) | 17.9% (3.0‐37.2) |
| Systolic blood pressure | 1.01 (1.00‐1.02) | 1.9% (−0.7‐5.2) | 1.01 (1.00‐1.02) | 2.0% (−0.4‐4.8) | 1.01 (1.00‐1.02) | 2.0% (−0.3‐5.2) | 1.00 (0.99‐1.01) | 0.8% (−1.4‐4.2) |
| Kidney function | 1.03 (1.01‐1.04) | 7.5% (3.2‐13.5) | 1.02 (1.01‐1.04) | 6.8% (3.0‐12.1) | 1.03 (1.01‐1.04) | 6.9% (2.8‐12.9) | 1.02 (1.01‐1.05) | 6.0% (2.4‐12.2) |
| LDL‐c | ‐ | ‐ | 0.98 (0.96‐0.99) | −5.6% (−11.0‐1.7) | 0.98 (0.97‐1.00) | −4.4% (−9.8 to −0.4) | 0.98 (0.97‐1.00) | −5.3% (−10.1‐0.3) |
| Triglycerides | ‐ | ‐ | ‐ | ‐ | 1.04 (1.02‐1.05) | 9.8% (5.1‐16.3) | 1.03 (1.01‐1.05) | 8.0% (3.6‐14.0) |
| Micro‐albuminuria | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | 1.03 (1.01‐1.05) | 7.3% (2.6‐16.7) |
Abbreviations: CI, confidence interval; HR, hazard ratio; PME, proportion mediated effect; T2D, type 2 diabetes.
a
Effect of type 2 diabetes not explained by mediators.
b
Effect of type 2 diabetes through mediator(s).