Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM
Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM
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DOI：
10.1172/jci.insight.95913
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发表时间：
2017-10-19
期刊：
影响因子：
8
通讯作者：
Sherwin, Robert S.
中科院分区：
文献类型：
--
作者：
Hwang, Janice J.;Jiang, Lihong;Sherwin, Robert S.
在啮齿动物模型中，肥胖和高血糖改变脑葡萄糖代谢和葡萄糖转运到脑中，导致脑功能紊乱以及对稳态和享乐输入的不适当反应。人类大脑中是否也有类似的发现尚不清楚。在这项研究中，25名受试者（9名健康受试者; 10名肥胖非糖尿病受试者;和6名控制不佳、接受胰岛素和二甲双胍治疗的2型糖尿病（T2 DM）受试者）在枕叶进行1H磁共振波谱扫描，以测量2小时高血糖钳夹期间脑内葡萄糖水平的变化（葡萄糖类似于220 mg/dl）。在控制年龄和性别后，尽管基线和高血糖期间的血糖水平相似，但各组脑内葡萄糖的变化存在显著差异。与瘦型参与者相比，肥胖和T2 DM参与者的大脑葡萄糖增量较低。此外，脑葡萄糖的变化与血浆游离脂肪酸（FFA）水平呈负相关。这些数据表明，肥胖和控制不佳的T2 DM逐渐减少脑葡萄糖对高血糖的反应，这不仅对理解改变的进食行为，而且对理解与肥胖和T2 DM相关的不良神经认知后果具有重要意义。
In rodent models, obesity and hyperglycemia alter cerebral glucose metabolism and glucose transport into the brain, resulting in disordered cerebral function as well as inappropriate responses to homeostatic and hedonic inputs. Whether similar findings are seen in the human brain remains unclear. In this study, 25 participants (9 healthy participants; 10 obese nondiabetic participants; and 6 poorly controlled, insulin-and metformin-treated type 2 diabetes mellitus (T2DM) participants) underwent 1H magnetic resonance spectroscopy scanning in the occipital lobe to measure the change in intracerebral glucose levels during a 2-hour hyperglycemic clamp (glucose similar to 220 mg/dl). The change in intracerebral glucose was significantly different across groups after controlling for age and sex, despite similar plasma glucose levels at baseline and during hyperglycemia. Compared with lean participants, brain glucose increments were lower in participants with obesity and T2DM. Furthermore, the change in brain glucose correlated inversely with plasma free fatty acid (FFA) levels during hyperglycemia. These data suggest that obesity and poorly controlled T2DM progressively diminish brain glucose responses to hyperglycemia, which has important implications for understanding not only the altered feeding behavior, but also the adverse neurocognitive consequences associated with obesity and T2DM.