Estimating risk factor progression equations for the UKPDS Outcomes Model 2 (UKPDS NN ).
Leal J., Alva M., Gregory V., Hayes A., Mihaylova B., Gray AM., Holman RR., Clarke P.
OBJECTIVES: To estimate 13 equations that predict clinically plausible risk factor time paths to inform the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model version 2 (UKPDS-OM2). METHODS: Data from 5102 UKPDS participants from the 20-year trial, and the 4031 survivors with 10 years further post-trial follow-up, were used to derive equations for the time paths of 13 clinical risk factors: HbA1c , systolic blood pressure, LDL-cholesterol, HDL-cholesterol, BMI, micro- or macro-albuminuria, creatinine, heart rate, white blood cell count, haemoglobin, eGFR, atrial fibrillation and peripheral vascular disease (PVD). The incidence of events and death predicted by the UKPDS-OM2 when informed by the new risk factor equations was compared with the observed cumulative rates up to 25 years. RESULTS: The new equations were based on 24 years of follow-up and up to 65,252 person-years of data. Females were associated with higher values of all continuous risk factors except for haemoglobin. Older age and higher BMI at diagnosis were associated with higher rates of PVD (HR 1.06 and 1.02), atrial fibrillation (HR 1.10 and 1.08) and micro- or macro-albuminuria (HR 1.01 and 1.18). Smoking was associated with higher rates of developing PVD (HR 2.38) and micro- and macro-albuminuria (HR 1.39). The UKPDS-OM2, informed by the new risk factor equations, predicted event rates for complications and death consistent with those observed. CONCLUSIONS: The new equations allow risk factor time paths beyond observed data, which should improve modelling of long-term health outcomes for people with type 2 diabetes when using the UKPDS-OM2 or other models.