Lifestyle Patterns and Incidence of Cardiovascular Diseases, Cancer, Respiratory Diseases, and Type 2 Diabetes: A Large-Scale Prospective Cohort Study

<b>Background</b>: Lifestyle factors often interact in complex ways when influencing chronic disease risk. We aimed to examine the prospective associations between empirically derived real-life lifestyle patterns (LPs) and the incidence of major chronic diseases, and to explore the linearity of the relationships between lifestyle summation scores and disease risk. <b>Methods</b>: We included adults free of cardiovascular diseases (CVDs), cancer, chronic respiratory diseases (CRDs), or type 2 diabetes (T2D) at baseline (2006-2013) from the Dutch Lifelines cohort. LPs and lifestyle summation scores were derived from baseline self-reported data on diet, physical activity, substance use, sleep, stress, and social connectedness, each categorised as healthy, moderately healthy, or unhealthy. Fine-Gray sub-hazard regression models assessed associations between LPs and disease incidence, with natural spline functions used to evaluate linearity in summation scores. <b>Results</b>: Among 114,919 T2D-free, 131,248 cancer-free, 91,777 CRD-free, and 77,645 CVD-free participants, we observed 3114 T2D, 4685 cancer, 4133 CRDs, and 2850 CVD incident cases (median follow-up time: 8 years). Compared to the "Unhealthy" pattern, both the "Healthy-in-a-balanced-way" and "Healthy-but-physically-inactive" patterns were broadly significantly protective. The "Unhealthy-but-no-substance-use" pattern was associated with increased T2D risk (Sub-Hazard Ratio (SHR) = 1.27, 95% Confidence Interval (CI): 1.11-1.47) but reduced cancer risk (SHR = 0.85, 95%CI: 0.74-0.97). The "Unhealthy-but-light-drinking-and-never-smoked" pattern was protective for T2D (SHR = 0.89, 95%CI: 0.79-0.99). Linear associations were observed between lifestyle summation scores and disease risk, except for "healthy lifestyle" scores with T2D and "unhealthy lifestyle" scores with CRDs (non-linear <i>p</i>-value < 0.05). <b>Conclusions</b>: There are potential protective effects of healthy lifestyles on T2D, cancer, CRDs, and CVDs. However, the "Unhealthy but no substance use" demonstrated increased risk on T2D, protective effect on cancer and no significant effect on CRDs or CVDs. The relationship between combined lifestyle factors and NCD risk is complex and partly non-linear, showing diminishing benefits beyond certain thresholds, especially T2D and CRDs.