Lyoo In Kyoon, Yoon Sujung J, Musen Gail, Simonson Donald C, Weinger Katie, Bolo Nicolas, Ryan Christopher M, Kim Jieun E, Renshaw Perry F, Jacobson Alan M
Department of Psychiatry and Interdisciplinary Program in Brain Science, Seoul National University, 28 Yongon-dong, Jongno-gu, Seoul 110-744, South Korea.
Arch Gen Psychiatry. 2009 Aug;66(8):878-87. doi: 10.1001/archgenpsychiatry.2009.86.
Neural substrates for low cognitive performance and depression, common long-term central nervous system-related changes in patients with type 1 diabetes mellitus, have not yet been studied.
To investigate whether prefrontal glutamate levels are higher in patients with type 1 diabetes and whether an elevation is related to lower cognitive performance and depression.
Cross-sectional study.
General clinical research center.
One hundred twenty-three patients with adult type 1 diabetes with varying degrees of lifetime glycemic control and 38 healthy participants.
With the use of proton magnetic resonance spectroscopy, prefrontal glutamate-glutamine-gamma-aminobutyric acid (Glx) levels were compared between patients and control subjects. Relationships between prefrontal Glx levels and cognitive function and between Glx levels and mild depressive symptoms were assessed in patients with type 1 diabetes.
Prefrontal Glx concentrations were 9.0% (0.742 mmol/L; P = .005) higher in adult patients with type 1 diabetes than in healthy control subjects. There were positive linear trends for the effects of lifetime glycemic control on prefrontal Glx levels (P for trend = .002). Cognitive performances in memory, executive function, and psychomotor speed were lower in patients (P = .003, .01, and <.001, respectively) than in control subjects. Higher prefrontal Glx concentrations in patients were associated with lower performance in assessment of global cognitive function (0.11 change in z score per 1-mmol/L increase in Glx) as well as with mild depression.
The high prefrontal glutamate levels documented in this study may play an important role in the genesis of the low cognitive performance and mild depression frequently observed in patients with type 1 diabetes. Therapeutic options that alter glutamatergic neurotransmission may be of benefit in treating central nervous system-related changes in patients with adult type 1 diabetes.
1型糖尿病患者常见的长期中枢神经系统相关变化，即认知功能低下和抑郁的神经基质，尚未得到研究。
探讨1型糖尿病患者前额叶谷氨酸水平是否更高，以及这种升高是否与较低的认知功能和抑郁有关。
横断面研究。
综合临床研究中心。
123例成年1型糖尿病患者，其终生血糖控制程度不同，以及38名健康参与者。
使用质子磁共振波谱，比较患者和对照受试者之间前额叶谷氨酸-谷氨酰胺-γ-氨基丁酸（Glx）水平。评估1型糖尿病患者前额叶Glx水平与认知功能之间以及Glx水平与轻度抑郁症状之间的关系。
成年1型糖尿病患者前额叶Glx浓度比健康对照受试者高9.0%（0.742 mmol/L；P = 0.005）。终生血糖控制对前额叶Glx水平的影响呈正线性趋势（趋势P = 0.002）。患者在记忆、执行功能和精神运动速度方面的认知表现低于对照受试者（分别为P = 0.003、0.01和<0.001）。患者较高的前额叶Glx浓度与整体认知功能评估中的较低表现（Glx每增加1 mmol/L，z评分变化0.11）以及轻度抑郁有关。
本研究记录的高前额叶谷氨酸水平可能在1型糖尿病患者中经常观察到的低认知表现和轻度抑郁的发生中起重要作用。改变谷氨酸能神经传递的治疗选择可能有助于治疗成年1型糖尿病患者的中枢神经系统相关变化。
