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Hypoglycaemia in type 2 diabetes exacerbates amyloid‐related proteins associated with dementia
Author(s) -
Moin Abu Saleh Md,
AlQaissi Ahmed,
Sathyapalan Thozhukat,
Atkin Stephen L.,
Butler Alexandra E.
Publication year - 2021
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.14220
Subject(s) - medicine , endocrinology , type 2 diabetes , amyloid (mycology) , dementia , diabetes mellitus , alzheimer's disease , biology , disease , pathology
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.