Associations of Combined Healthy Lifestyle Factors with Risks of Diabetes, Cardiovascular Disease, Cancer, and Mortality Among Adults with Prediabetes: Four Prospective Cohort Studies in China, the United Kingdom, and the United States

Lifestyle modification is an effective measure for diabetes prevention in people with prediabetes, but its associations with the long-term risks of cardiovascular disease (CVD), cancer, and mortality remain largely uncertain. We aimed to investigate the associations of combined healthy lifestyle factors with these health outcomes among participants with prediabetes. The study included 121 254 people with prediabetes from four prospective cohorts: the Dongfeng-Tongji (DFTJ) cohort and Kailuan study, both from China; the UK Biobank; and the US National Health and Nutrition Examination Survey (NHANES; for mortality analysis only). We documented a total of 18 333 incident diabetes, 10 829 incident CVD, 6926 incident cancer, and 9877 deaths during follow-up. Combined healthy lifestyle scores (scored from 0 to 5) were constructed based on never smoking or quitting smoking for ≥ 10 years, low-to-moderate alcohol drinking, optimal physical activity, healthy diet, and optimal waist circumference. First, Cox proportional-hazards regression models were used to quantify the associations of combined lifestyle score with health outcomes in each cohort; then, multivariable-adjusted hazard ratios (HRs) were pooled via a random-effects model of meta-analysis. Compared with participants with the least healthy lifestyle (a score of 0–1), participants with the healthiest lifestyle (a score of 4–5) had significantly reduced risks of all outcomes. The HRs (95% confidence interval (CI)) were 0.57 (0.48–0.69) for diabetes, 0.67 (0.62–0.73) for CVD, 0.80 (0.73–0.88) for cancer, and 0.54 (0.42–0.70) for mortality. Significant associations were consistently found across subgroups of baseline demographic characteristics and metabolic health status. In conclusion, our pooled analyses of four cohorts from three countries reveal that greater adherence to a healthy lifestyle is associated with considerably lower risks of diabetes and its major complications among adults with prediabetes. These findings provide informative and compelling evidence for establishing clinical guidelines and public health policies.