Wisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA.
Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Obesity (Silver Spring). 2019 Sep;27(9):1464-1471. doi: 10.1002/oby.22558. Epub 2019 Jul 17.
Insulin regulates metabolism and influences neural health. Insulin resistance (IR) and type II diabetes have been identified as risk factors for Alzheimer disease (AD). Evidence has also suggested that myelinated white matter alterations may be involved in the pathophysiology of AD; however, it is unknown whether insulin or IR affect the underlying myelin microstructure. The relationships between insulin, IR, and myelin were examined, with the hypothesis that IR would be associated with reduced myelin.
Cognitively unimpaired adults enriched for risk factors for AD underwent multicomponent driven equilibrium single pulse observation of T1 and T2 imaging, a myelin-sensitive neuroimaging technique. Linear regressions were used to test the relationship between homeostatic model assessment of IR, insulin, and myelin water fraction (MWF) as well as interactions with APOE ε4.
Both IR and insulin level were associated with altered myelin content, wherein a significant negative association with MWF was observed in white matter regions and a positive association with MWF was observed in gray matter.
The results suggest that insulin and IR influence white matter myelination in a cognitively unimpaired population. Additional studies are needed to determine the extent to which this may contribute to cognitive decline or vulnerability to neurodegenerative disease.
胰岛素调节代谢并影响神经健康。胰岛素抵抗（IR）和 2 型糖尿病已被确定为阿尔茨海默病（AD）的危险因素。有证据表明，有髓鞘的白质改变可能与 AD 的病理生理学有关；然而，尚不清楚胰岛素或 IR 是否会影响潜在的髓鞘微观结构。本研究旨在探讨胰岛素、IR 和髓鞘之间的关系，并提出假设，即 IR 与髓鞘减少有关。
本研究纳入了认知功能正常但具有 AD 风险因素的成年人，进行了多成分驱动平衡单脉冲观察 T1 和 T2 成像，这是一种敏感的髓鞘神经影像学技术。采用线性回归检验胰岛素抵抗稳态模型评估（HOMA-IR）、胰岛素和髓鞘水分数（MWF）之间的关系，以及与 APOE ε4 的相互作用。
IR 和胰岛素水平均与髓鞘含量的改变有关，其中在白质区域观察到 MWF 与 HOMA-IR 和胰岛素呈显著负相关，而在灰质区域观察到 MWF 与 HOMA-IR 和胰岛素呈显著正相关。
这些结果表明，胰岛素和 IR 会影响认知正常人群的白质髓鞘化。需要进一步的研究来确定这在多大程度上可能导致认知能力下降或易患神经退行性疾病。
