Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06520, USA.
J Clin Endocrinol Metab. 2013 Sep;98(9):3811-20. doi: 10.1210/jc.2013-1701. Epub 2013 Jun 24.
Intensive insulin therapy reduces the risk for long-term complications in patients with type 1 diabetes mellitus (T1DM) but increases the risk for hypoglycemia-associated autonomic failure (HAAF), a syndrome that includes hypoglycemia unawareness and defective glucose counterregulation (reduced epinephrine and glucagon responses to hypoglycemia).
The objective of the study was to address mechanisms underlying HAAF, we investigated whether nonglucose fuels such as acetate, a monocarboxylic acid (MCA), can support cerebral energetics during hypoglycemia in T1DM individuals with hypoglycemia unawareness.
Magnetic resonance spectroscopy was used to measure brain transport and metabolism of [2-(13)C]acetate under hypoglycemic conditions.
The study was conducted at the Yale Center for Clinical Investigation Hospital Research Unit, Yale Magnetic Resonance Research Center.
T1DM participants with moderate to severe hypoglycemia unawareness (n = 7), T1DM controls without hypoglycemia unawareness (n = 5), and healthy nondiabetic controls (n = 10) participated in the study.
MAIN OUTCOME MEASURE(S): Brain acetate concentrations, (13)C percent enrichment of glutamine and glutamate, and absolute rates of acetate metabolism were measured.
Absolute rates of acetate metabolism in the cerebral cortex were 1.5-fold higher among T1DM/unaware participants compared with both control groups during hypoglycemia (P = .001). Epinephrine levels of T1DM/unaware subjects were significantly lower than both control groups (P < .05). Epinephrine levels were inversely correlated with levels of cerebral acetate use across the entire study population (P < .01), suggesting a relationship between up-regulated brain MCA use and HAAF.
Increased MCA transport and metabolism among T1DM individuals with hypoglycemia unawareness may be a mechanism to supply the brain with nonglucose fuels during episodes of acute hypoglycemia and may contribute to the syndrome of hypoglycemia unawareness, independent of diabetes.
强化胰岛素治疗可降低 1 型糖尿病（T1DM）患者发生长期并发症的风险，但会增加低血糖相关自主神经衰竭（HAAF）的风险，这种综合征包括低血糖意识障碍和葡萄糖代偿调节缺陷（低血糖时肾上腺素和胰高血糖素反应减弱）。
本研究旨在探讨 HAAF 的发病机制，研究人员调查了非葡萄糖燃料（如单羧酸乙酸盐，MCA）是否可在 T1DM 伴低血糖意识障碍患者发生低血糖时为大脑提供能量。
磁共振波谱用于测量低血糖条件下大脑对[2-（13）C]乙酸的转运和代谢。
该研究在耶鲁临床研究所医院研究单位和耶鲁磁共振研究中心进行。
7 名 T1DM 患者伴有中度至重度低血糖意识障碍、5 名 T1DM 对照者无低血糖意识障碍和 10 名健康非糖尿病对照者参与了该研究。
脑乙酸盐浓度、谷氨酰胺和谷氨酸的（13）C 百分含量和乙酸盐代谢的绝对速率。
与两组对照者相比，T1DM/无意识组在低血糖期间大脑皮质的乙酸盐代谢绝对速率高 1.5 倍（P=0.001）。T1DM/无意识组的肾上腺素水平明显低于两组对照者（P<0.05）。整个研究人群中，肾上腺素水平与大脑乙酸盐利用水平呈负相关（P<0.01），表明上调的大脑 MCA 利用与 HAAF 之间存在关系。
在低血糖期间，T1DM 伴低血糖意识障碍患者中 MCA 转运和代谢增加可能是大脑利用非葡萄糖燃料的一种机制，可能与低血糖意识障碍综合征有关，与糖尿病无关。
