2型糖尿病青少年的胰岛素抵抗与血清游离脂肪酸及肌肉线粒体功能障碍有关。
Insulin resistance in type 2 diabetes youth relates to serum free fatty acids and muscle mitochondrial dysfunction.
作者信息
Cree-Green Melanie, Gupta Abhinav, Coe Gregory V, Baumgartner Amy D, Pyle Laura, Reusch Jane E B, Brown Mark S, Newcomer Bradley R, Nadeau Kristen J
机构信息
Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, 80045; Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045.
Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, 80045.
出版信息
J Diabetes Complications. 2017 Jan;31(1):141-148. doi: 10.1016/j.jdiacomp.2016.10.014. Epub 2016 Oct 17.
AIMS
Insulin resistance (IR) correlates with mitochondrial dysfunction, free fatty acids (FFAs), and intramyocellular lipid (IMCL) in adults with type 2 diabetes (T2D). We hypothesized that muscle IR would relate to similar factors in T2D youth.
METHODS
Participants included 17 youth with T2D, 23 normal weight controls (LCs), and 26 obese controls (OBs) of similar pubertal stage and activity level.
RESULTS
T2D and OB groups were of similar BMI. T2D youth were significantly more IR and had higher calf IMCL and serum FFA concentrations during hyperinsulinemia. ADP time constant (ADPTC), a blood-flow dependent mitochondrial function measure, was slowed and oxidative phosphorylation rates lower in T2D. In multiple linear regression of the entire cohort, lack of FFA suppression and longer ADPTC, but not IMCL or HbA1c, were independently associated with IR.
CONCLUSION
We found that elevated FFAs and mitochondrial dysfunction are early abnormalities in relatively well-controlled youth with T2D. Further, post-exercise oxidative metabolism appears affected by reduced blood flow, and is not solely an inherent mitochondrial defect. Thus, lowering FFAs and improving mitochondrial function and blood flow may be potential treatment targets in youth with T2D.
目的
在2型糖尿病（T2D）成人患者中，胰岛素抵抗（IR）与线粒体功能障碍、游离脂肪酸（FFA）及肌细胞内脂质（IMCL）相关。我们推测，T2D青少年的肌肉IR也与类似因素有关。
方法
研究对象包括17名T2D青少年、23名体重正常的对照者（LCs）以及26名肥胖对照者（OBs），他们的青春期阶段和活动水平相似。
结果
T2D组和OB组的体重指数（BMI）相似。T2D青少年在高胰岛素血症期间的胰岛素抵抗明显更强，小腿IMCL和血清FFA浓度更高。T2D患者的ADP时间常数（ADPTC，一种依赖血流的线粒体功能指标）减慢，氧化磷酸化速率降低。在整个队列的多元线性回归分析中，FFA抑制不足和较长的ADPTC，而非IMCL或糖化血红蛋白（HbA1c），与IR独立相关。
结论
我们发现，FFA升高和线粒体功能障碍是病情相对得到良好控制的T2D青少年的早期异常表现。此外，运动后氧化代谢似乎受到血流减少的影响，而不仅仅是线粒体的固有缺陷。因此，降低FFA水平、改善线粒体功能和血流可能是T2D青少年潜在的治疗靶点。
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