Hypoglycaemia in type 2 diabetes exacerbates amyloid-related proteins associated with dementia

Aims Hypoglycaemia in diabetes (T2D) may increase the risk of Alzheimer's disease (AD). We hypothesized that hypoglycaemia-induced amyloid-related protein changes would be exacerbated in T2D. Materials and methods A prospective, parallel study in T2D (n = 23) and controls (n = 23). Subjects underwent insulin-induced hypoglycaemia with blood sampling at baseline, hypoglycaemia and post-hypoglycaemia; proteomic analysis of amyloid-related proteins was undertaken. Results At baseline, amyloid-precursor protein (APP) (P < .01) was elevated and alpha-synuclein (SNCA) (P < .01) reduced in T2D. At hypoglycaemia, amyloid P-component (P < .01) was elevated and SNCA (P < .05) reduced in T2D; APP (P < .01) and noggin (P < .05) were elevated and SNCA (P < .01) reduced in controls. In the post-hypoglycaemia follow-up period, APP and microtubule-associated protein tau normalized in controls but showed a below-baseline decrease in T2D; noggin normalized in both; SNCA normalized in T2D, with a below-baseline decrease in controls. Conclusion The AD-associated protein pattern found in T2D, with basal elevated APP and reduced SNCA, was exaggerated by hypoglycaemia with increased APP and decreased SNCA. Additional AD-associated protein levels that changed in response to hypoglycaemia, particularly in T2D, included amyloid P-component, microtubule-associated protein tau, apolipoproteins A1 and E3, pappalysin and noggin. These results are in accordance with the reported detrimental effects of hypoglycaemia.