Table 3.
Mediation analysis of lifestyle and metformin interventions (effect on risk of T2DM within 5 years: overall and with/without CVD)
| T2DM ≤5 years** |
T2DM ≤5 years (with CVD during study)† |
|||||||
|---|---|---|---|---|---|---|---|---|
| Excess relative risk (95% CI)†† |
Proportion attributable to intermediate outcome (95% CI)‡ | Excess relative risk (95% CI)†† |
Proportion attributable to intermediate outcome (95% CI)‡ | |||||
| TE | TDE | PIE | TE | TDE | PIE | |||
| Lifestyle intervention mediation analysis | ||||||||
| Intermediate outcomes: 1-year effect size of | ||||||||
| MetS-Z | 0.67 | 0.26 | 0.41 | 61.6% | 1.31 | 0.44 | 0.87 | 66.5% |
| (0.39, 0.95) | (−0.04, 0.56) | (0.25, 0.57) | (29.2%, 94.0%) | (−0.13, 0.08) | (−1.28, 2.15) | (0.05, 1.69) | (0%, 100%) | |
| WC | 0.72 | 0.18 | 0.54 | 75.0% | 1.42 | 0.67 | 0.75 | 52.7% |
| (0.49, 0.95) | (−0.07, 0.43) | (0.36, 0.72) | (45.2%, 100%) | (−0.06, 2.89) | (−1.02, 2.36) | (−0.10, 1.59) | (0%, 100%) | |
| GLU | 0.67 | 0.35 | 0.32 | 48.2% | 1.19 | 0.57 | 0.62 | 52.4% |
| (0.41, 0.92) | (0.08, 0.61) | (0.20, 0.44) | (25.0%, 75.0%) | (−0.22, 2.60) | (−1.00, 2.13) | (0.15, 1.10) | (0%, 100%) | |
| HDL | 0.53 | 0.50 | 0.04 | 6.7% | 1.21 | 1.08 | 0.14 | 11.2% |
| (0.26, 0.81) | (0.22, 0.77) | (−0.00, 0.08) | (0%, 15.1%) | (−0.20, 2.62) | (−0.35, 2.50) | (−0.02, 0.29) | (0%, 29.9%) | |
| TRI | 0.54 | 0.44 | 0.10 | 18.9% | 1.27 | 1.09 | 0.18 | 14.1% |
| (0.27, 0.82) | (0.16, 0.72) | (0.04, 0.16) | (4.4%, 33.3%) | (−0.15, 2.69) | (−0.37, 2.55) | (−0.08, 0.44) | (0%, 40.7%) | |
| SBP | 0.59 | 0.58 | 0.01 | 2.2% | 1.58 | 1.51 | 0.07 | 4.6% |
| (0.31, 0.88) | (0.29, 0.87) | (−0.01, 0.04) | (0%, 6.3%) | (−0.00, 3.17) | (−0.08, 3.10) | (−0.03, 0.18) | (0%, 12.7%) | |
| Metformin mediation analysis | ||||||||
| Intermediate outcomes: 1-year effect size of | ||||||||
| MetS-Z | 0.24 | 0.18 | 0.06 | 25.1% | 0.22 | 0.07 | 0.15 | 68.8% |
| (0.10, 0.38) | (0.05, 0.31) | (0.02, 0.10) | (8.6%, 41.5%) | (−0.39, 0.83) | (−0.56, 0.69) | (0.00, 0.29) | (0%, 100%) | |
| WC | 0.16 | 0.13 | 0.03 | 20.7% | 0.35 | 0.24 | 0.11 | 31.7% |
| (−0.02, 0.34) | (−0.05, 0.31) | (−0.00, 0.07) | (0%, 51.6%) | (−0.33, 1.02) | (−0.44, 0.91) | (−0.01, 0.23) | (0%, 100%) | |
| GLU | 0.20 | 0.09 | 0.11 | 55.2% | 0.32 | 0.12 | 0.20 | 61.0% |
| (0.04, 0.36) | (−0.08, 0.26) | (0.07, 0.16) | (6.0%, 100%) | (−0.37, 1.01) | (−0.48, 0.83) | (0.04, 0.35) | (0%, 100%) | |
| HDL | 0.16 | 0.14 | 0.01 | 9.1% | 0.34 | 0.31 | 0.03 | 9.5% |
| (−0.03, 0.34) | (−0.04, 0.32) | (−0.01, 0.04) | (0%, 27.7%) | (−0.34, 1.02) | (−0.38, 1.00) | (−0.04, 0.10) | (0%, 38.3%) | |
| TRI | 0.15 | 0.15 | −0.01 | 0% | 0.25 | 0.24 | 0.00 | 1.7% |
| (−0.04, 0.33) | (−0.03, 0.33) | (−0.02, 0.01) | (0%, 5.8%) | (−0.39, 0.89) | (−0.40, 0.88) | (−0.03, 0.04) | (0%, 15.4%) | |
| SBP | 0.17 | 0.17 | −0.00 | 0% | 0.05 | 0.08 | −0.03 | 0% |
| (−0.02, 0.35) | (−0.01, 0.35) | (−0.02, 0.01) | (0%, 6.4%) | (−0.44, 0.53) | (−0.40, 0.56) | (−0.15, 0.09) | (0%, 100%) | |
Effect on the risk of T2DM within 5 years: overall and with/without CVD, adjusting for baseline value of corresponding 1-year intermediate outcome (Supplementary Fig. 2). GLU, fasting glucose; TRI, fasting triglycerides.
**Among 2,177 with no disease by 1 year, T2DM developed in 580 within 5 years.
†Among the 1,261 eligible participants, 70 of these participants developed both T2DM within 5 years and CVD in the overall study.
††Excess relative risk of placebo relative to the intervention = relative risk − 1 = [risk (placebo)/risk (intervention)] − 1.
‡Proportion attributable to intermediate outcome = PIE/TE.