Table 3.
Results of mediation analysis: total, direct and indirect effects of type 2 diabetes on all‐cause mortality; 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 | 1.35 (1.21‐1.51) | 100% | 1.37 (1.50‐2.07) | 100% | 1.37 (1.22‐1.54) | 100% | 1.37 (1.52‐2.13) | 100% |
| Direct effecta | 1.24 (1.11‐1.41) | 71.0% (48.7‐86.5) | 1.28 (1.22‐1.52) | 78.6% (59.7‐93.2) | 1.25 (1.11‐1.41) | 70.8% (46.8‐89.5) | 1.21 (1.56‐1.62) | 57.8% (27.4‐81.7) |
| Indirect effect, combinedb | 1.09 (1.04‐1.14) | 29.0% (13.5‐51.3) | 1.07 (1.02‐1.12) | 21.4% (6.8‐40.3) | 1.09 (1.03‐1.16) | 29.2% (10.5‐53.2) | 1.13 (1.00‐1.30) | 42.2% (18.3‐72.6) |
| Indirect effect through:b | ||||||||
| Insulin resistance | 1.05 (1.02‐1.10) | 17,8% (5.2‐35.0) | 1.06 (1.02‐1.10) | 18,5% (5.0‐34.4) | 1.06 (1.02‐1.10) | 18,3% (5.9‐35.1) | 1.05 (1.02‐1.06) | 15,4% (0.8‐32.7) |
| Systolic blood pressure | 1.01 (1.00‐1.02) | 3.7% (0.8‐7.9) | 1.01 (1.00‐1.02) | 3.3% (0.6‐7.0) | 1.01 (1.00‐1.02) | 3.4% (0.4‐7.1) | 1.01 (0.98‐1.02) | 2.7% (−0.1‐6.9%) |
| Kidney function | 1.02 (1.01‐1.04) | 7.5% (3.1‐14.4) | 1.02 (1.01‐1.04) | 7.3% (3.1‐13.5) | 1.02 (1.01‐1.04) | 7.3% (2.9‐13.1) | 1.02 (1.02‐1.05) | 6.7% (2.5‐13.0) |
| LDL‐c | ‐ | ‐ | 0.98 (0.96‐0.99) | −7.6% (−14.5 to −3.0) | 0.98 (0.97‐0.99) | −7.1% (−13.6 to −2.3) | 0.98 (0.98‐1.01) | −7.3% (−15.0 to −2.3) |
| Triglycerides | ‐ | ‐ | ‐ | ‐ | 1.02 (1.01‐1.04) | 7.3% (2.4‐14.0%) | 1.02 (0.99‐1.03) | 7.0% (1.9‐13.9) |
| Micro‐albuminuria | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | 1.05 (1.03‐1.07) | 17.6% (9.9‐29.0) |
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).