Adults with intellectual and developmental disabilities (IDD) are at a greater risk of developing high cholesterol and cardiovascular disease. We examined whether physical inactivity, obesity, and diabetes were predictive of reported high cholesterol and whether there were any mediating effects of diabetes on the relationship between obesity and high cholesterol in 1,618 adults with IDD across five years. Results suggest that obesity and diabetes were significantly associated with high cholesterol after adjusting for age, sex, and residence type with a partial mediator effect of diabetes in the relationship between obesity and high cholesterol across all time points. Further research is needed to explore the causal mechanisms behind the relationships between obesity, diabetes, and high cholesterol.