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

Abstract

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.

• Authors: Abu Saleh Md Moin, Ahmed Al-Qaissi, Thozhukat Sathyapalan, Stephen L Atkin, Alexandra E Butler
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 23 Issue 2 Pg. 338-349 (02 2021) ISSN: 1463-1326 [Electronic] England
• PMID: 33026133 (Publication Type: Journal Article)
• Copyright: © 2020 John Wiley & Sons Ltd.

Chemical References

• Amyloidogenic Proteins

Topics

• Alzheimer Disease
• Amyloidogenic Proteins
• Diabetes Mellitus, Type 2 (complications)
• Humans
• Hypoglycemia
• Prospective Studies
• Proteomics