Langdahl Jakob Høgild, Frederiksen Anja Lisbeth, Vissing John, Frost Morten, Yderstræde Knud Bonnet, Andersen Per Heden
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Endocr Connect. 2019 Jul;8(7):829-837. doi: 10.1530/EC-19-0118.
This case-control study aimed to examine impairments in glucose metabolism in non-diabetic carriers of the mitochondrial mutation m.3243A>G by evaluating insulin secretion capacity and sensitivity.
Glucose metabolism was investigated in 23 non-diabetic m.3243A>G carriers and age-, sex- and BMI-matched healthy controls with an extended 4-h oral glucose tolerance test (OGTT). Insulin sensitivity index and acute insulin response were estimated on the basis of the OGTT. This was accompanied by examination of body composition by dual-energy X-ray absorptiometry (DXA), maximum aerobic capacity and a Recent Physical Activity Questionnaire (RPAQ).
Fasting p-glucose, s-insulin and s-c-peptide levels did not differ between m.3243A>G carriers and controls. Insulin sensitivity index (BIGTT-S1) was significantly lower in the m.3243A>G carriers, but there was no difference in the acute insulin response between groups. P-lactate levels were higher in carriers throughout the OGTT. VO2max, but not BMI, waist and hip circumferences, lean and fat body mass%, MET or grip strength, was lower in mutation carriers. BIGTT-S1 remained lower in mutation carriers after adjustment for multiple confounding factors including VO2max in regression analyses.
Glucose metabolism in m.3243A>G carriers was characterized by reduced insulin sensitivity, which could represent the earliest phase in the pathogenesis of m.3243A>G-associated diabetes.
本病例对照研究旨在通过评估胰岛素分泌能力和敏感性，检测线粒体突变m.3243A>G的非糖尿病携带者的葡萄糖代谢障碍。
采用延长的4小时口服葡萄糖耐量试验（OGTT），对23名非糖尿病m.3243A>G携带者以及年龄、性别和体重指数相匹配的健康对照者的葡萄糖代谢进行研究。根据OGTT评估胰岛素敏感性指数和急性胰岛素反应。同时，通过双能X线吸收法（DXA）检测身体成分、最大有氧能力以及近期体力活动问卷（RPAQ）。
m.3243A>G携带者与对照组之间的空腹血糖、空腹胰岛素和空腹C肽水平无差异。m.3243A>G携带者的胰岛素敏感性指数（BIGTT-S1）显著降低，但两组之间的急性胰岛素反应无差异。在整个OGTT过程中，携带者的血乳酸水平较高。突变携带者的最大摄氧量较低，但体重指数、腰围和臀围、瘦体重和脂肪量百分比、代谢当量或握力无差异。在回归分析中，对包括最大摄氧量在内的多个混杂因素进行调整后，突变携带者的BIGTT-S1仍然较低。
m.3243A>G携带者的葡萄糖代谢特征为胰岛素敏感性降低，这可能代表m.3243A>G相关糖尿病发病机制的最早阶段。
