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 ε4 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 ε4 participants or those with diabetic levels of HbA1c. These findings demonstrate that diabetes may potentially exacerbate cerebrovascular and white matter disease.

中文翻译：

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较高的 HbA1c 与两年内白质高信号的进展程度更大相关

脑 MRI 图像上的白质高信号 (WMH) 病变是脑小血管疾病 (CSVD) 的替代标志物。检验糖尿病与 WMH 进展之间关系的纵向研究得出了不同的结果。因此，在本研究中，我们在调整 WMH 进展的已知危险因素后，研究了 HbA1c（高血糖存在及其严重程度的生物标志物）与纵向 WMH 变化之间的关联。我们从韩国记忆诊所招募了 64 名参与者，进行基线脑 MRI 检查和两年随访。我们发现：首先，在调整已知风险因素后，较高的 HbA1c 与较大的整体 WMH 体积 (WMHV) 变化相关 (B = 7.7E-04，p = 0.025)；其次，基线 WMHV 和 WMHV 进展之间的关联仅在糖尿病 HbA1c 水平下才显着（当 HbA1c > 6.51% 时，p < 0.05），非 APOE ε4 携带者在 HbA1c 和 WMHV 进展之间表现出更强的关联（B = -2.59E-03，p = 0.004）；第三，与脑室周围 WMHV 变化和额叶 (B = 5.00E-04，p < 0.001) 相比，WMHV 进展与 HbA1c 的关联在深部 WMHV 变化 (B = 7.17E-04，p < 0.01) 中尤其明显。与枕叶和颞叶 WMHV 变化相比，顶叶 (B = 1.534-04，p < 0.05) WMHV 变化。总之，较高的 HbA1c 水平与两年 WMHV 进展较大相关，尤其是在非 APOE ε4 参与者或患有糖尿病 HbA1c 水平的参与者中。这些发现表明，糖尿病可能会加剧脑血管和白质疾病。