Background <p>Growing evidence suggests that diabetes mellitus (DM) is associated with higher incidence and faster progression of Parkinson’s disease (PD), but the association between DM and prodromal PD has yet to be explored.</p> Methods <p>To evaluate the effect of DM in prodromal PD, we classified 63 prodromal PD into two groups according to a prior diagnosis of DM: prodromal PD without DM (<i>n</i> = 51) and prodromal PD with DM (<i>n</i> = 12). At baseline, between-group comparisons of clinical symptoms, brain structure, and cerebral spinal fluid (CSF) pathology were performed. We then compared longitudinal changes in motor and cognitive symptoms between the two groups. Finally, the incidence of disease conversion in the two groups was compared using Cox proportional hazard regression analysis.</p> Results <p>Compared to prodromal PD without DM, prodromal PD with DM had significantly lower global cognitive scores (<i>p</i> &lt; 0.001), higher CSF p-tau (<i>p</i> = 0.005), decreased grey matter volume in the frontal lobe (FWE corrected, <i>p</i> &lt; 0.05), and contracted shape in the bilateral putamina (TFCE FWE corrected <i>p</i> &lt; 0.05). The linear mixed models demonstrated that prodromal PD with DM had significantly faster motor progression (<i>p</i> = 0.009) and cognitive decline (<i>p</i> = 0.012) than those without. Additionally, DM was associated with increased risk of disease conversion in prodromal PD (HR = 6.526, <i>p</i> = 0.003).</p> Conclusion <p>Theses findings indicate that pre-existing DM may confer a detrimental effect on disease phenotype and conversion in prodromal PD.</p>