Section of Endocrinology, Yale School of Medicine, New Haven, CT
Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT.
Diabetes. 2019 Jan;68(1):163-171. doi: 10.2337/db18-0722. Epub 2018 Oct 16.
The impact of glycemic variability on brain glucose transport kinetics among individuals with type 1 diabetes mellitus (T1DM) remains unclear. Fourteen individuals with T1DM (age 35 ± 4 years; BMI 26.0 ± 1.4 kg/m; HbA 7.6 ± 0.3) and nine healthy control participants (age 32 ± 4; BMI 23.1 ± 0.8; HbA 5.0 ± 0.1) wore a continuous glucose monitor (Dexcom) to measure hypoglycemia, hyperglycemia, and glycemic variability for 5 days followed by H MRS scanning in the occipital lobe to measure the change in intracerebral glucose levels during a 2-h glucose clamp (target glucose concentration 220 mg/dL). Hyperglycemic clamps were also performed in a rat model of T1DM to assess regional differences in brain glucose transport and metabolism. Despite a similar change in plasma glucose levels during the hyperglycemic clamp, individuals with T1DM had significantly smaller increments in intracerebral glucose levels ( = 0.0002). Moreover, among individuals with T1DM, the change in brain glucose correlated positively with the lability index ( = 0.67, = 0.006). Consistent with findings in humans, streptozotocin-treated rats had lower brain glucose levels in the cortex, hippocampus, and striatum compared with control rats. These findings that glycemic variability is associated with brain glucose levels highlight the need for future studies to investigate the impact of glycemic variability on brain glucose kinetics.
血糖变异性对 1 型糖尿病(T1DM)个体脑葡萄糖转运动力学的影响尚不清楚。14 名 T1DM 患者(年龄 35 ± 4 岁;BMI 26.0 ± 1.4 kg/m;HbA1c 7.6 ± 0.3)和 9 名健康对照参与者(年龄 32 ± 4 岁;BMI 23.1 ± 0.8;HbA1c 5.0 ± 0.1)佩戴连续血糖监测仪(Dexcom)测量 5 天的低血糖、高血糖和血糖变异性,然后在枕叶进行 H MRS 扫描,以测量 2 小时葡萄糖钳夹期间脑内葡萄糖水平的变化(目标血糖浓度 220 mg/dL)。还在 T1DM 大鼠模型中进行高血糖钳夹,以评估大脑葡萄糖转运和代谢的区域差异。尽管在高血糖钳夹期间血浆葡萄糖水平的变化相似,但 T1DM 患者脑内葡萄糖水平的增加明显较小(= 0.0002)。此外,在 T1DM 患者中,脑葡萄糖的变化与不稳定性指数呈正相关(= 0.67,= 0.006)。与人类的发现一致,链脲佐菌素处理的大鼠大脑皮质、海马和纹状体的葡萄糖水平明显低于对照组大鼠。这些血糖变异性与脑葡萄糖水平相关的发现强调了未来研究需要调查血糖变异性对脑葡萄糖动力学的影响。