Objective: Hypoglycemia is a common complication of tighter glucose control regimens in type 2 diabetes (T2D) and may increase the risk of dementia, Alzheimer’s disease being the most common form. We measured amyloid-related proteins during induced hypoglycemia in a cohort of subjects with and without T2D, hypothesizing that these protein levels would be further elevated during hypoglycemia in T2D subjects.

Methods: A prospective, parallel study was conducted in individuals with T2D (n=23) and controls (n=22). Hypoglycaemia (<2.2mmol/l: <40mg/dl) was achieved by intravenous infusion of soluble insulin. Blood samples were collected at baseline and at 0, 30, 60, 120, 240 minutes and 24 hours following hypoglycaemia and proteomic (Somalogic) analysis of four amyloid-related proteins (Amyloid P component [APCS], Amyloid precursor protein [APP], Pappalysin [PAPPA] and Serum amyloid A1 [SAA1]) at baseline, at hypoglycemia and at 24-hours post-clamp was undertaken.

Results: No changes from baseline in serum levels of the four amyloid-related proteins were seen in subjects with or without T2D, either at the time of hypoglycemia or at 24-hours post-clamp.

Conclusions: Induced hypoglycemia is not associated with a significant increase in serum levels of amyloid-related proteins. Thus, no clear mechanistic link based on serum proteins between T2D-related hypoglycemic episodes and Alzheimer’s disease emerged from this study, although it is important to consider that protein levels in the cerebrospinal fluid may differ.


A. Moin: None. T. Sathyapalan: Research Support; Self; Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; Ipsen Biopharmaceuticals. S. Atkin: None. A.E. Butler: None.

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