Reduced skeletal muscle phosphocreatine concentration in type 2 diabetic patients: a quantitative image-based phosphorus-31 MR spectroscopy study.
Reduced skeletal muscle phosphocreatine concentration in type 2 diabetic patients: a quantitative image-based phosphorus-31 MR spectroscopy study.
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DOI：
10.1152/ajpendo.00426.2017
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发表时间：
2018-08
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通讯作者：
E. Ripley;G. Clarke;Vala Hamidi;Robert A. Martinez;F. Settles;C. Solis;Shengwen Deng;M. Abdul-Ghani-M.-A
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作者：
E. Ripley;G. Clarke;Vala Hamidi;Robert A. Martinez;F. Settles;C. Solis;Shengwen Deng;M. Abdul-Ghani-M.-A
包括2型糖尿病(T2 DM)在内的胰岛素抵抗(IR)状态下的线粒体功能已被检测。以前在T2 DM患者中使用磷-31磁共振波谱(31P-MRS)研究的结果是代谢物比率的相对浓度，这可能掩盖了T2 DM和正常糖耐量(NGT)个体之间的磷酸肌酸([PCR])和三磷酸腺苷([ATP])浓度的差异。我们用图像引导的31P-MRS方法对11例T2 DM和14例NGT受试者股外侧肌(VL)中的[PCR]、无机磷[PI]、磷酸二酯[PDE]和[ATP]进行了定量。受试者还接受了口服葡萄糖耐量试验、正常血糖胰岛素钳夹试验、1H-MRS检测心肌细胞内脂质[IMCL]，以及VL肌肉活检以评估线粒体密度。T2 DM组[PCR28.6±3.2vs.24.6±2.4P&t；0.002；ATP7.18±0.6vs.6.37±1.1P<；0.02]明显低于NGT组(P<0.05)，而[PDE]高于NGT组，但差异无统计学意义。用传统的比率法得到的[PCR]，组间无显著差异。[PCr]与HbA1c(r=-0.63，P<；0.01)和空腹血糖(r=-0.51，P=0.01)呈负相关。[PDE]与松田指数呈负相关(r=-0.43，P=0.03)，与M/I呈负相关(r=-0.46，P=0.04)，与[IMCL](r=0.64，P<0.005)、糖化血红蛋白、空腹血糖呈正相关(r=0.6，P=0.001)。综上所述，使用一种改良的体内定量31P-MRS方法，T2 DM患者骨骼肌[PCr]和[ATP]降低，而传统的比率法没有观察到这种差异。[Pcr]与HbA1c、空腹血糖和胰岛素敏感性之间的强烈负相关支持了较低的基线骨骼肌[Pcr]与葡萄糖稳态的关键决定因素相关的概念。
Mitochondrial function has been examined in insulin-resistant (IR) states including type 2 diabetes mellitus (T2DM). Previous studies using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in T2DM reported results as relative concentrations of metabolite ratios, which could obscure differences in phosphocreatine ([PCr]) and adenosine triphosphate concentrations ([ATP]) between T2DM and normal glucose tolerance (NGT) individuals. We used an image-guided 31P-MRS method to quantitate [PCr], inorganic phosphate [Pi], phosphodiester [PDE], and [ATP] in vastus lateralis (VL) muscle in 11 T2DM and 14 NGT subjects. Subjects also received oral glucose tolerance test, euglycemic insulin clamp, 1H-MRS to measure intramyocellular lipids [IMCL], and VL muscle biopsy to evaluate mitochondrial density. T2DM subjects had lower absolute [PCr] and [ATP] than NGT subjects (PCr 28.6 ± 3.2 vs. 24.6 ± 2.4, P < 0.002, and ATP 7.18 ± 0.6 vs. 6.37 ± 1.1, P < 0.02) while [PDE] was higher, but not significantly. [PCr], obtained using the traditional ratio method, showed no significant difference between groups. [PCr] was negatively correlated with HbA1c ( r = -0.63, P < 0.01) and fasting plasma glucose ( r = -0.51, P = 0.01). [PDE] was negatively correlated with Matsuda index ( r = -0.43, P = 0.03) and M/I ( r = -0.46, P = 0.04), but was positively correlated with [IMCL] ( r = 0.64, P < 0.005), HbA1c, and FPG ( r = 0.60, P = 0.001). To summarize, using a modified, in vivo quantitative 31P-MRS method, skeletal muscle [PCr] and [ATP] are reduced in T2DM, while this difference was not observed with the traditional ratio method. The strong inverse correlation between [PCr] vs. HbA1c, FPG, and insulin sensitivity supports the concept that lower baseline skeletal muscle [PCr] is related to key determinants of glucose homeostasis.