Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
CiBIT, Coimbra Institute for Biomedical Imaging and Translational Research, Institute of Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal.
PLoS One. 2020 Oct 29;15(10):e0240907. doi: 10.1371/journal.pone.0240907. eCollection 2020.
Glucose metabolism is pivotal for energy and neurotransmitter synthesis and homeostasis, particularly in Glutamate and GABA systems. In turn, the stringent control of inhibitory/excitatory tonus is known to be relevant in neuropsychiatric conditions. Glutamatergic neurotransmission dominates excitatory synaptic functions and is involved in plasticity and excitotoxicity. GABAergic neurochemistry underlies inhibition and predicts impaired psychophysical function in diabetes. It has also been associated with cognitive decline in people with diabetes. Still, the relation between metabolic homeostasis and neurotransmission remains elusive. Two 3T proton MR spectroscopy studies were independently conducted in the occipital cortex to provide insight into inhibitory/excitatory homeostasis (GABA/Glutamate) and to evaluate the impact of chronic metabolic control on the levels and regulation (as assessed by regression slopes) of the two main neurotransmitters of the CNS in type 2 diabetes (T2DM) and type 1 diabetes (T1DM). Compared to controls, participants with T2DM showed significantly lower Glutamate, and also GABA. Nevertheless, higher levels of GABA/Glx (Glutamate+Glutamine), and lower levels of Glutamate were associated with poor metabolic control in participants with T2DM. Importantly, the relationship between GABA/Glx and HbA1c found in T2DM supports a relationship between inhibitory/excitatory balance and metabolic control. Interestingly, this neurometabolic profile was undetected in T1DM. In this condition we found strong evidence for alterations in MRS surrogate measures of neuroinflammation (myo-Inositol), positively related to chronic metabolic control. Our results suggest a role for Glutamate as a global marker of T2DM and a sensitive marker of glycemic status. GABA/Glx may provide a signature of cortical metabolic state in poorly controlled patients as assessed by HbA1c levels, which indicate long-term blood Glucose control. These findings are consistent with an interplay between abnormal neurotransmission and metabolic control in particular in type 2 diabetes thereby revealing dissimilar contributions to the pathophysiology of neural dysfunction in both types of diabetes.
葡萄糖代谢对于能量和神经递质的合成及平衡至关重要，特别是在谷氨酸和 GABA 系统中。反过来，抑制/兴奋张力的严格控制被认为与神经精神疾病有关。谷氨酸能神经传递主导兴奋性突触功能，并参与可塑性和兴奋性毒性。GABA 能神经化学基础是抑制，并预测糖尿病患者的心理物理功能受损。它也与糖尿病患者的认知能力下降有关。然而，代谢平衡和神经传递之间的关系仍然难以捉摸。两项独立的 3T 质子磁共振波谱研究在枕叶皮层进行，以深入了解抑制/兴奋平衡（GABA/谷氨酸），并评估慢性代谢控制对 2 型糖尿病（T2DM）和 1 型糖尿病（T1DM）中中枢神经系统两种主要神经递质水平和调节（通过回归斜率评估）的影响。与对照组相比，T2DM 患者的谷氨酸和 GABA 水平显著降低。然而，T2DM 患者中 GABA/Glx（谷氨酸+谷氨酰胺）水平较高和谷氨酸水平较低与代谢控制不良相关。重要的是，T2DM 中 GABA/Glx 与 HbA1c 之间的关系支持抑制/兴奋平衡与代谢控制之间的关系。有趣的是，这种神经代谢特征在 T1DM 中未被发现。在这种情况下，我们发现了 MRS 神经炎症替代标志物（肌醇）的改变与慢性代谢控制呈正相关的有力证据。我们的结果表明谷氨酸作为 T2DM 的全局标志物和血糖状态的敏感标志物的作用。GABA/Glx 可能为 HbA1c 水平评估的代谢控制不良患者的皮质代谢状态提供特征，这表明长期血糖控制。这些发现与异常神经传递和代谢控制之间的相互作用一致，特别是在 2 型糖尿病中，从而揭示了两种类型的糖尿病中神经功能障碍的病理生理学的不同贡献。
