Halikas Alicia, Gibas Kelly J
Human Bioenergetics & Applied Health Science, Bethel University, Minnesota, USA.
Doctorate of Behavioral Health Sciences, Human Bioenergetics & Applied Health Science, Bethel University, Minnesota, USA.
Diabetes Metab Syndr. 2018 Nov;12(6):1141-1146. doi: 10.1016/j.dsx.2018.04.033. Epub 2018 Apr 27.
Diabetics in mid-life carry a 1.5 times higher risk of developing Alzheimer's disease than those diagnosed with diabetes (T2D) later in life [1]. Recent research points to accelerated cognitive decline within a range of 20%-50% for middle-aged diabetics as compared to non-diabetic populations [2,3]. Metabolic syndrome (MetS), a type 2 diabetes (T2D) precursor, is also linked to MCI and AD pathologies via hypo-metabolic brain circuitry that inhibits glucose metabolism and attenuates cognitive function [4]. Dysregulation of intracellular and extracellular signaling as mediated by the mTOR and AMPK pathways is the result. These critical nutrient sensing pathways modulate epigenetic shifts in the genome by channeling fuel substrates either towards mitochondrial fatty acid oxidation (AMPK) or cytosolic glycolysis and substrate level phosphorylation (mTOR) [5]. This case study was designed to examine the link between peripheral insulin resistance and early stage memory loss in a type 2 diabetic male. Reactivating the AMPK pathway via induced and controlled nutritional ketosis combined with high intensity interval training (HIIT) (in order to inhibit mTOR signaling) were primary features of the 10 week intervention. Post intervention results revealed statistically significant reductions in HgA1c, fasting insulin and HOMA-IR (homeostatic model assessment of insulin resistance). Restoring peripheral and hypothalamic insulin sensitivity by way of AMPK activation may restore memory function, improve neuroplasticity, and normalize MetS biomarkers (Demetrius and Driver, 2014; [4,6]).
中年糖尿病患者患阿尔茨海默病的风险比晚年被诊断为2型糖尿病（T2D）的患者高1.5倍[1]。最近的研究表明，与非糖尿病人群相比，中年糖尿病患者的认知能力下降加速了20%-50%[2,3]。代谢综合征（MetS）是2型糖尿病（T2D）的前驱疾病，它还通过抑制葡萄糖代谢并削弱认知功能的低代谢脑回路与轻度认知障碍（MCI）和阿尔茨海默病（AD）的病理状况相关联[4]。其结果是由mTOR和AMPK信号通路介导的细胞内和细胞外信号失调。这些关键的营养感应通路通过将燃料底物导向线粒体脂肪酸氧化（AMPK）或胞质糖酵解及底物水平磷酸化（mTOR）来调节基因组中的表观遗传变化[5]。本案例研究旨在探讨一名2型糖尿病男性外周胰岛素抵抗与早期记忆丧失之间的联系。通过诱导和控制营养性酮症联合高强度间歇训练（HIIT）（以抑制mTOR信号传导）来重新激活AMPK信号通路是为期10周干预的主要特点。干预后的结果显示，糖化血红蛋白（HgA1c）、空腹胰岛素和胰岛素抵抗稳态模型评估（HOMA-IR）在统计学上有显著降低。通过激活AMPK来恢复外周和下丘脑的胰岛素敏感性可能会恢复记忆功能、改善神经可塑性并使代谢综合征生物标志物正常化（德米特里厄斯和德赖弗，2014年；[4,6]）。
