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P3‐091: Plasma Amylin Levels Are Associated With Brain Structure Among Individuals With Type‐2 Diabetes

Year: 2014
Type: article
Abstract: Amylin is a 37-amino acid long peptide p roduced in the pancreatic β-cells in parallel with insulin. Amylin is also named islet amyloid polypeptide for its tendency to aggregate into insoluble β-amyloid (Aβ) fibrils within pancreatic β-cells in type 2 diabetes (T2DM). Recently, amylin fibrils were found to co-localize with Aβ plaques in the brains of subjects with AD and dementia with T2DM. This study examines the cross-sectional and longitudinal relationship between plasma amylin and brain structure in T2DM at baseline and at 40 months follow-up. ACCORD MIND was a clinical trial of participants aged 55 - 80 years with T2DM, high HbA1c concentrations (>7.5%) and a high risk for incident cardiovascular events. MIND participants received cognitive testing and brain MRI at baseline and 40 months. All MRI-derived brain volumes were adjusted for total intracranial volume. Fasting plasma total amylin were measured at baseline using ELISA techniques. At baseline, lower total plasma amylin levels were associated with greater diabetes duration (p<0.01), insulin use (p<0.01), higher white matter hyperintensity volume (WMH, rho=-0.14, p<0.01), lower total brain volume (rho=0.09, p=0.05) and lower total gray matter volume (rho=0.09, p=0.05) in unadjusted models. In models adjusted for age, gender, diabetes duration and study arm, the association between lower plasma amylin and higher WMH as still significant. Changes in brain structure over 40 months were not associated with baseline amylin levels in the total group. Individuals with a long duration of T2DM have lower levels of circulating soluble amylin. Low levels of plasma amylin levels correspond to greater WMH and lower gray matter volume at baseline. Low levels of amylin may represent either: 1) reduced soluble amylin production in T2DM or 2) its oligomerization to insoluble Aβ that deposits as plaques.
DOI: 10.1016/j.jalz.2014.05.1179
Authors: Timothy M. Hughes, Suzanne Craft, Michael E. Miller, Jeff Williamson, Hertzel Gerstein, Santica Markovina, Anne Murray, Nick Bryan, Lenore Launer
Institutions: Wake Forest University Health Sciences, Wake Forest University, McMaster University, University of Washington, Berman Center for Outcomes and Clinical Research, University of Pennsylvania, National Institute on Aging
Language: English
Field: Medicine
Open Access status: bronze
OpenAlex ID: W2102255300
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