Introduction As white matter hyperintensities (WMHs) of the brain are associated with an increased risk of stroke, cognitive decline, and depression, elucidating the associated risk factors is important. In addition to age and hypertension, pre-diabetes and diabetes may play important roles in the development of WMHs. Previous studies have, however, shown conflicting results. We aimed to investigate the effect of diabetes status and quantitative markers of glucose metabolism on WMH volume in a population-based cohort without prior cardiovascular disease. Research design and methods 400 participants underwent 3 T MRI. WMHs were manually segmented on 3D fluid-attenuated inversion recovery images. An oral glucose tolerance test (OGTT) was administered to all participants not previously diagnosed with diabetes to assess 2-hour serum glucose concentrations. Fasting glucose concentrations and glycated hemoglobin (HbA1c) levels were measured. Zero-inflated negative binomial regression analyses of WMH volume and measures of glycemic status were performed while controlling for cardiovascular risk factors and multiple testing. Results The final study population comprised 388 participants (57% male; age 56.3±9.2 years; n=98 with pre-diabetes, n=51 with diabetes). Higher WMH volume was associated with pre-diabetes (p=0.001) and diabetes (p=0.026) compared with normoglycemic control participants after adjustment for cardiovascular risk factors. 2-hour serum glucose (p<0.001), but not fasting glucose (p=0.389) or HbA1c (p=0.050), showed a significant positive association with WMH volume after adjustment for cardiovascular risk factors. Conclusion Our results indicate that high 2-hour serum glucose concentration in OGTT, but not fasting glucose levels, may be an independent risk factor for the development of WMHs, with the potential to inform intensified prevention strategies in individuals at risk of WMH-associated morbidity. Data are available upon reasonable request. The informed consent given by KORA study participants does not cover data posting in public databases. However, data are available upon request from KORA/KORA-gen () by means of a project agreement. Requests should be sent to kora.passt@helmholtz-muenchen.de and are subject to approval by the KORA Board.

中文翻译：

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糖尿病前期、糖尿病和血糖正常的白质高信号体积

介绍 由于大脑的白质高信号 (WMH) 与中风、认知能力下降和抑郁的风险增加有关，因此阐明相关的风险因素很重要。除了年龄和高血压，糖尿病前期和糖尿病可能在 WMH 的发展中发挥重要作用。然而，先前的研究显示出相互矛盾的结果。我们旨在研究糖尿病状态和葡萄糖代谢定量标志物对无既往心血管疾病的人群队列中 WMH 容量的影响。研究设计和方法 400 名参与者接受了 3 T MRI。在 3D 流体衰减反转恢复图像上手动分割 WMH。对所有先前未诊断为糖尿病的参与者进行口服葡萄糖耐量试验 (OGTT)，以评估 2 小时血清葡萄糖浓度。测量空腹血糖浓度和糖化血红蛋白 (HbA1c) 水平。在控制心血管危险因素和多重测试的同时，对 WMH 体积和血糖状态测量进行了零膨胀负二项式回归分析。结果 最终研究人群包括 388 名参与者（57% 男性；年龄 56.3±9.2 岁；n=98 患有前驱糖尿病，n=51 患有糖尿病）。在调整心血管危险因素后，与血糖正常对照参与者相比，较高的 WMH 量与糖尿病前期 (p=0.001) 和糖尿病 (p=0.026) 相关。2 小时血清葡萄糖 (p<0.001)，但不是空腹血糖 (p=0.389) 或 HbA1c (p=0.050)，在调整心血管危险因素后显示与 WMH 体积显着正相关。结论 我们的结果表明 OGTT 中的高 2 小时血清葡萄糖浓度，而不是空腹血糖水平，可能是 WMH 发展的独立危险因素，有可能为有 WMH 相关发病率风险的个体提供强化预防策略. 可应合理要求提供数据。KORA 研究参与者给予的知情同意不包括公共数据库中的数据发布。但是，数据可应 KORA/KORA-gen 的要求提供（可能是 WMH 发展的独立风险因素，有可能为有 WMH 相关发病率风险的个体提供强化预防策略。可应合理要求提供数据。KORA 研究参与者给予的知情同意不包括公共数据库中的数据发布。但是，数据可应 KORA/KORA-gen 的要求提供（可能是 WMH 发展的独立风险因素，有可能为有 WMH 相关发病率风险的个体提供强化预防策略。可应合理要求提供数据。KORA 研究参与者给予的知情同意不包括公共数据库中的数据发布。但是，数据可应 KORA/KORA-gen 的要求提供（)通过项目协议。请求应发送至 kora.passt@helmholtz-muenchen.de，并须经 KORA 董事会批准。