Background: Overweight and obesity are major risk factors for non-communicable diseases (NCDs). This study aimed to explore the pattern of multimorbidity development and disease trajectories in individuals with overweight and obesity.
Methods: We followed a cohort of 392 541 individuals retrospectively from the UK Biobank. This cohort included 131 075 with normal weight (BMI 18.5-24.9 kg/m2), 169 075 with overweight (BMI 25-29.9 kg/m2), and 92 391 with obesity (BMI ≥30.0 kg/m2). Participants were followed for the diagnoses of 49 NCDs. We used Cox proportional hazards models to assess the risk of common diseases. Disease trajectory analyses were conducted to map the progression patterns of multimorbidity among individuals with overweight or obesity.
Results: During a median follow-up of 12.74 years, compared with individuals with normal weight, individuals with overweight had a higher risk of diagnosis of 17 NCDs, while those with obesity had 27. We identified 35 and 103 disease trajectories in individuals with overweight and obesity, among which, hypertension and cardiovascular diseases were key hub diseases. In particular, the age of disease diagnosis in individuals with obesity was younger than those with overweight, and the disease trajectory network in individuals with obesity was also 1.93 times more complex than overweight. Among identified disease trajectories, cardiometabolic diseases, including hypertension, coronary heart disease (CHD) and dyslipidemia, often appeared early, while heart failure and chronic kidney disease (CKD) appeared in a later stage of disease development. In women with obesity, depression diagnosis preceded most other multimorbidities and progressed to anxiety, painful conditions and CKD.
Conclusion: Obesity can significantly contribute to a higher risk of multimorbidities at younger ages and with a more complex disease development trajectory than both normal weight and overweight populations. Early interventions for cardiometabolic diseases in individuals with overweight or obesity and depression in women with obesity are essential for multimorbidity management.
Keywords: cardiometabolic diseases; disease trajectories; multimorbidity; obesity; overweight.
© 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.