Acute Hyperglycemia Induced by Hyperglycemic Clamp Affects Plasma Amyloid-β in Type 2 Diabetes.

• Individuals with type 2 diabetes (T2D) have an increased risk of cognitive symptoms and Alzheimer's disease (AD). Mis-metabolism with aggregation of amyloid-β peptides (Aβ) play a key role in AD pathophysiology. Therefore, human studies on Aβ metabolism and T2D are warranted.The objective of this study was to examine whether acute hyperglycemia affects plasma Aβ 1-40 and Aβ 1-42 concentrations in individuals with T2D and matched controls.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. Aβ 1-40, Aβ 1-42, and insulin-degrading enzyme (IDE) plasma concentrations were measured in blood samples taken at 0 and 4hours of each clamp. Linear mixed-effect regression models were used to evaluate the 4-hour changes in Aβ 1-40 and Aβ 1-42 concentrations, adjusting for body mass index, estimated glomerular filtration rate, and 4-hour change in insulin concentration.At baseline, Aβ 1-40 and Aβ 1-42 concentrations did not differ between the two groups. During the hyperglycemic clamp, Aβ decreased in the control group, compared to the placebo clamp (Aβ 1-40: p=0.034, Aβ 1-42: p=0.020), IDE increased (p=0.016) during the hyperglycemic clamp, whereas no significant changes in either Aβ or IDE was noted in the T2D group.Clamp-induced hyperglycemia was associated with increased IDE levels and enhanced Aβ 40 and Aβ 42 clearance in controls, but not in individuals with T2D. We hypothesize that insulin-degrading enzyme was inhibited during hyperglycemic conditions in people with T2D.

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

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