Department of Pediatrics, School of Medicine, University of California, Davis, Sacramento, California, USA.
Diabetes. 2012 Jul;61(7):1831-7. doi: 10.2337/db11-1286. Epub 2012 Apr 12.
Diabetic ketoacidosis (DKA) may cause brain injuries in children. The mechanisms responsible are difficult to elucidate because DKA involves multiple metabolic derangements. We aimed to determine the independent effects of hyperglycemia and ketosis on cerebral metabolism, blood flow, and water distribution. We used magnetic resonance spectroscopy to measure ratios of cerebral metabolites (ATP to inorganic phosphate [Pi], phosphocreatine [PCr] to Pi, N-acetyl aspartate [NAA] to creatine [Cr], and lactate to Cr) and diffusion-weighted imaging and perfusion-weighted imaging to assess cerebral water distribution (apparent diffusion coefficient [ADC] values) and cerebral blood flow (CBF) in three groups of juvenile rats (hyperglycemic, ketotic, and normal control). ATP-to-Pi ratio was reduced in both hyperglycemic and ketotic rats in comparison with controls. PCr-to-Pi ratio was reduced in the ketotic group, and there was a trend toward reduction in the hyperglycemic group. No significant differences were observed in NAA-to-Cr or lactate-to-Cr ratio. Cortical ADC was reduced in both groups (indicating brain cell swelling). Cortical CBF was also reduced in both groups. We conclude that both hyperglycemia and ketosis independently cause reductions in cerebral high-energy phosphates, CBF, and cortical ADC values. These effects may play a role in the pathophysiology of DKA-related brain injury.
糖尿病酮症酸中毒 (DKA) 可能导致儿童脑损伤。由于 DKA 涉及多种代谢紊乱,因此难以阐明其发病机制。我们旨在确定高血糖和酮症对大脑代谢、血流和水分布的独立影响。我们使用磁共振波谱测量脑代谢物(三磷酸腺苷与无机磷 [Pi]、磷酸肌酸 [PCr] 与 Pi、N-乙酰天门冬氨酸 [NAA] 与肌酸 [Cr]、乳酸与 Cr)的比值,以及扩散加权成像和灌注加权成像来评估三组幼年大鼠(高血糖组、酮症组和正常对照组)的脑水分布(表观扩散系数 [ADC] 值)和脑血流(CBF)。与对照组相比,高血糖和酮症组的 ATP 与 Pi 的比值均降低。酮症组的 PCr 与 Pi 的比值降低,而高血糖组有降低的趋势。NAA 与 Cr 或乳酸与 Cr 的比值无明显差异。两组的皮质 ADC 均降低(表明脑细胞肿胀)。两组的皮质 CBF 也均降低。我们的结论是,高血糖和酮症均独立导致大脑高能磷酸化合物、CBF 和皮质 ADC 值降低。这些影响可能在 DKA 相关脑损伤的病理生理学中起作用。