Time-dependent covariate(s) | Further ≥3-step progression | PDR | ||||||||
---|---|---|---|---|---|---|---|---|---|---|

Risk associated with the covariate | Effect of DCCT intensive diabetes therapy | Risk associated with the covariate | Effect of DCCT intensive diabetes therapy | |||||||

Hazard ratio (95% CI)^{†} | P value | Risk reduction (%) (95% CI) | P value | % explained by covariate | Hazard ratio (95% CI)^{†} | P value | Risk reduction (%) (95% CI)^{‡} | P value | % explained by covariate | |

Baseline adjusted model^{*} | 46 (36, 54) | <0.0001 | — | 46 (29, 59) | <0.0001 | — | ||||

HbA_{1c} (per 10% increase)^{‡} | 0 (−28, 22) | 0.9821 | 100% | −1 (−51, 32) | 0.9555 | 100% | ||||

DCCT mean | 1.17 (1.07, 1.29) | 0.0006 | 1.22 (1.06, 1.42) | 0.0063 | ||||||

Updated EDIC mean | 1.57 (1.46, 1.68) | <0.0001 | 1.66 (1.49, 1.85) | <0.0001 | ||||||

Hyperlipidemia vs. not^{§} | 1.39 (1.16, 1.67) | 0.0003 | 42 (31, 52) | <0.0001 | 37% | 1.39 (1.06, 1.82) | 0.018 | 44 (24, 58) | 0.0001 | 24% |

Sustained AER >30 mg/24 h vs. not | 1.79 (1.42, 2.25) | <0.0001 | 44 (34, 53) | <0.0001 | 10% | 2.54 (1.93, 3.34) | <0.0001 | 39 (19, 53) | 0.0006 | 40% |

Currently smoking vs. not | 1.34 (1.10, 1.61) | 0.0028 | 46 (36, 54) | <0.0001 | 0% | 1.27 (0.94, 1.71) | 0.12 | 46 (29, 59) | <0.0001 | 1.6% |

Mean arterial blood pressure | 1.02 (1.01, 1.03) | <0.0001 | 47 (37, 55) | <0.0001 | 0% | 1.04 (1.02, 1.05) | <0.0001 | 46 (30, 59) | <0.0001 | 0% |

RAAS inhibitor use | 0.96 (0.76, 1.21) | 0.70 | 46 (36, 54) | <0.0001 | 0.1% | 1.34 (1.00, 1.81) | 0.052 | 45 (28, 59) | <0.0001 | 2.8% |

* Basic Weibull proportional hazards models evaluated the associations of DCCT treatment group with risk of further three or more–step progression or new PDR in EDIC, respectively, after adjustment for diabetes duration, HbA

_{1c}at DCCT entry, and retinopathy level at DCCT closeout. Risk reduction associated with intensive diabetes therapy is calculated as (1 − hazard ratio of intensive vs. conventional diabetes therapy with or without adjustment for covariate) × 100%.† Separate Weibull models evaluated associations of each time-dependent covariate with risk of retinopathy progression or new PDR to generate each covariate hazard ratio. Hazard ratio for covariates is evaluated per 10% increase in DCCT or EDIC HbA

_{1c}(e.g., from 8 to 8.8%), unit change in other quantitative covariates, or status change in binary covariates. DCCT mean HbA_{1c}(a fixed covariate) and EDIC mean HbA_{1c}(a time-dependent covariate) modeled together.Additional models assessed the interaction between the covariate and the DCCT/EDIC weighted mean HbA

_{1c}. None was significant at the 0.05 level.‡ Separate Weibull models then evaluated the risk reduction with DCCT intensive vs. conventional diabetes therapy on risk of retinopathy progression or new PDR in EDIC, adjusting for each time-dependent covariate one at a time in addition to the covariates adjusted in the basic model (and modeling DCCT HbA

_{1c}along with the EDIC HbA_{1c}). The percent of the DCCT treatment effect explained by group differences in each covariate is computed as the percentage change in the DCCT treatment group χ^{2}test value from the basic treatment effect model to the model adjusted for the time-dependent covariate. Since each covariate is evaluated in a separate model, the proportions do not sum to 100%.§ Hyperlipidemia was defined by an LDL cholesterol level ≥130 mg/dL (3.4 mmol/L) or the use of lipid-lowering agents.