Alzheimer’s disease (AD) is the most common cause of dementia. Metabolic disorders, including prediabetes (preDM) and type two diabetes (T2D) increase the risk to suffer AD, and may contribute to dysfunctional brain insulin signaling and abnormal tau phosphorylation. Thus, we measured cortical tau phosphorylation at Ser-199, Ser-202/Thr-205, Ser-396, Ser-404, Thr-217 and Thr-231 residues in animals reproducing PreDM and T2D, alone or with AD. We analyzed the relationship between tau phosphorylation and metabolic profile, Aβ levels, microglia activation, cytokines production and cognitive impairment. Prediabetes was induced by feeding APP/PS1 mice a high-fat diet for 22 weeks. AD-T2D animals were generated by crossing db/db and APP/PS1 mice. Studies were performed at 26 weeks of age, when T2D and AD are completely established in these animal models. Tau phosphorylation at residues Thr-217 and Thr-231, Thr-231 and Ser-202/Thr-205, and Ser-396 and Ser-202/Thr-205 correlated in both PreDM and AD-T2D animals, suggesting a crosstalk among these residues. Moreover, tau phosphorylation at different residues positively correlated with either hyperglycemia (Ser-202/Thr-205 in T2D) or hyperinsulinemia (Ser-199, Ser-202/Thr-205 and Thr-217 in PreDM). Also, inverse correlations were detected between tau phosphorylation and cognitive performance in PreDM, linking tau hyperphosphorylation with spatial memory impairment. Our data suggest that both hyperglycemia and hyperinsulinemia are differentially involved in the higher risk of AD that present subjects with T2D. Funding: RECOGNISED (Clinical Trials gov registration no. NCT04281186) European Commission (H2020-GA847749). Ministerio de Ciencia e Innovacion. (PID2020-115499RB-I00/AEI/10.13039/501100011033). Proyectos de I+D+i Plan Andaluz de Investigacion, Desarrollo e Innovacion (P20-00928).