American Diabetes Association
Supplementary_Material_BriefReports_10242023_clean.pdf (237.28 kB)

Higher HbA1c is Associated with Greater Two-Year Progression of White Matter Hyperintensities

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posted on 2024-01-11, 23:23 authored by Noah Schweitzer, Sang Joon Son, Howard Aizenstein, Shaolin Yang, Bistra Iordanova, Chang Hyung Hong, Hyun Woong Rho, Yong Hyuk Cho, Bumhee Park, Na-Rae Kim, Jin Wook Choi, Jae Youn Cheong, Sang Woon Seo, Young-Sil An, So Young Moon, Seung Jin Han, Minjie Wu

White matter hyperintensity (WMH) lesions on brain MRI images are surrogate markers of cerebral small vessel disease (CSVD). Longitudinal studies examining the association between diabetes and WMH progression have yielded mixed results. Thus, in this study we investigated the association between HbA1c, a biomarker for the presence and severity of hyperglycemia, and longitudinal WMH change after adjusting for known risk factors for WMH progression. We recruited 64 participants from South Korean memory clinics to undergo brain MRI at the baseline and a two-year follow-up. We found: First, higher HbA1c was associated with greater global WMH volume (WMHV) changes after adjusting for known risk factors (B = 7.7E-04, p = 0.025); Second, the association between baseline WMHV and WMHV progression was only significant at diabetic levels of HbA1c (p < 0.05, when HbA1c > 6.51%), and non-APOE ɛ4 carriers showed a stronger association between HbA1c and WMHV progression (B = -2.59E-03, p = 0.004); Third, associations of WMHV progression with HbA1c were particularly apparent for deep WMHV change (B = 7.17E-04, p < 0.01) compared to periventricular WMHV change, and for frontal (B = 5.00E-04, p < 0.001) and parietal (B = 1.534-04, p < 0.05) WMHV change compared to occipital and temporal WMHV change. In conclusion, higher HbA1c levels were associated with greater two-year WMHV progression, especially in non-APOE ɛ4 participants or those with diabetic levels of HbA1c. These findings demonstrate that diabetes may potentially exacerbate cerebrovascular and white matter disease.


This study was conducted using biospecimens and data from the consortium of the Biobank Innovations for Chronic Cerebrovascular Disease with ALZheimer’s Disease Study (BICWALZS), which was funded by the Korea Disease Control and Prevention Agency for the Korea Biobank Project (#6637-303). This work was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (NRF-2019R1A5A2026045). This research was also supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HR22C1734). Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.