Acute Hyperglycemia Induced by Hyperglycemic Clamp Affects Plasma Amyloid-ß in Type 2 Diabetes.
J Alzheimers Dis
; 99(3): 1033-1046, 2024.
Article
in En
| MEDLINE
| ID: mdl-38728183
ABSTRACT
Background:
Individuals with type 2 diabetes (T2D) have an increased risk of cognitive symptoms and Alzheimer's disease (AD). Mis-metabolism with aggregation of amyloid-ß peptides (Aß) play a key role in AD pathophysiology. Therefore, human studies on Aß metabolism and T2D are warranted.Objective:
The objective of this study was to examine whether acute hyperglycemia affects plasma Aß1-40 and Aß1-42 concentrations in individuals with T2D and matched controls.Methods:
Ten participants with T2D and 11 controls (median age, 69 years; range, 66-72 years) underwent hyperglycemic clamp and placebo clamp (saline infusion) in a randomized order, each lasting 4 hours. Aß1-40, Aß1-42, and insulin-degrading enzyme (IDE) plasma concentrations were measured in blood samples taken at 0 and 4âhours of each clamp. Linear mixed-effect regression models were used to evaluate the 4-hour changes in Aß1-40 and Aß1-42 concentrations, adjusting for body mass index, estimated glomerular filtration rate, and 4-hour change in insulin concentration.Results:
At baseline, Aß1-40 and Aß1-42 concentrations did not differ between the two groups. During the hyperglycemic clamp, Aß decreased in the control group, compared to the placebo clamp (Aß1-40 pâ=â0.034, Aß1-42 pâ=â0.020), IDE increased (pâ=â0.016) during the hyperglycemic clamp, whereas no significant changes in either Aß or IDE was noted in the T2D group.Conclusions:
Clamp-induced hyperglycemia was associated with increased IDE levels and enhanced Aß40 and Aß42 clearance in controls, but not in individuals with T2D. We hypothesize that insulin-degrading enzyme was inhibited during hyperglycemic conditions in people with T2D.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Fragments
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Amyloid beta-Peptides
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Glucose Clamp Technique
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Diabetes Mellitus, Type 2
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Hyperglycemia
Limits:
Aged
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Alzheimers Dis
Year:
2024
Document type:
Article