IntroductionNo study has comprehensively quantified the individual and collective contributions of various risk factors to the growing burden of diabetes in the United States.MethodsThis study aimed to determine the extent to which an increase in the prevalence of diabetes was related to concurrent changes in the distribution of diabetes-related risk factors among US adults (aged 20 years or above and not pregnant). Seven cycles of series of cross-sectional National Health and Nutrition Examination Survey data between 2005–2006 and 2017–2018 were included. The exposures were survey cycles and seven domains of risk factors, including genetic, demographic, social determinants of health, lifestyle, obesity, biological, and psychosocial domains. Using Poisson regressions, percent reduction in the β coefficient (the logarithm used to calculate the prevalence ratio for prevalence of diabetes in 2017–2018 vs. 2005–2006) was computed to assess the individual and collective contribution of the 31 prespecified risk factors and seven domains to the growing burden of diabetes.ResultsOf the 16,091 participants included, the unadjusted prevalence of diabetes increased from 12.2% in 2005–2006 to 17.1% in 2017–2018 [prevalence ratio: 1.40 (95% CI, 1.14–1.72)]. Individually, genetic domain [17.3% (95% CI, 5.4%−40.8%)], demographic domain [41.5% (95% CI, 24.4%−76.8%)], obesity domain [35.3% (95% CI, 15.8%−70.2%)], biological domain [46.2% (95% CI, 21.6%−79.1%)], and psychosocial domain [21.3% (95% CI, 9.5%−40.1%)] were significantly associated with a different percent reduction in β. After adjusting for all seven domains, the percent reduction in β was 97.3% (95% CI, 62.7%−164.8%).ConclusionThe concurrently changing risk factors accounted for the increasing diabetes prevalence. However, the contribution of each risk factor domain varied. Findings may inform planning cost-effective and targeted public health programs for diabetes prevention.