重症肌无力患者糖脂代谢异常情况及其机制探讨

Glucose and fipid metabolic disorders in myasthenia gravis patients and its mechanisms

目的探讨未使用糖皮质激素的重症肌无力（MG）患者糖脂代谢异常情况，以及胰岛素水平、胰岛素抵抗、肌力、血清骨钙素、25羟维生素D（25OHD）与糖脂代谢指标的相关性。方法纳入2013年1月至2016年12月于北京协和医院神经内科与内分泌科未使用糖皮质激素治疗的MG患者102例，年龄（40±11）岁，男43例，女59例，测量优势手握力，检测空腹血糖（FBG）、餐后2 h血糖（2 h PBG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、餐后2 h胰岛素（2 h PINS）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）及骨钙素、25OHD浓度。采用胰岛素抵抗指数（HOMA-IR）评估胰岛素抵抗状况。结果空腹血糖受损或糖耐量减低、2型糖尿病、血脂异常、高胰岛素血症比例在男性和女性MG患者分别为30.0%、10.0%、50.0%、33.3%和17.5%、3.5%、27.7%、7.1%。男性和女性血清骨钙素水平分别为2.8（1.7，4.4）μg/L和2.3（1.3，3.9）μg/L，25OHD水平分别为（93.5±34.9）nmol/L和（81.0±30.5）nmol/L，握力分别为（37.0±9.4）kg和（20.5±6.3）kg。校正年龄后，男性FINS（r＝0.619，P〈0.001）、2 h PINS（r＝0.640，P〈0.001）、HOMA-IR（r＝0.534，P〈0.001）与2 h PBG呈正相关，握力与TC（r＝－0.486，P＝0.026）、LDL-C（r＝－0.485，P＝0.026）呈负相关。女性FINS（r＝0.352，P＝0.008；r＝0.300，P＝0.026；r＝0.646，P〈0.001）和2 h PINS（r＝0.278，P＝0.040；r＝0.518，P〈0.001；r＝0.382，P＝0.006）及HOMA-IR（r＝0.695，P〈0.001；r＝0.583，P〈0.001；r＝0.818，P〈0.001）与FBG、2 h PBG、HbA1c均呈正相关，握力与FBG（r＝－0.424，P＝0.016）、2 h PINS（r＝－0.345，P＝0.034）呈负相关，与HDL-C（r＝0.389，P＝0.037）正相关。未发现骨钙素及25OHD水平与糖脂代谢有明显相关性。经多重线性回归分析亦发现握力、胰岛素水平及胰岛素抵抗水平与糖脂代谢异常间存在明显相关性。结论未使用糖皮质激素治疗的MG患者存在较高比例的糖脂代谢异常，其机制可能与肌力下降引起的胰岛素抵抗相关。

ObjectiveTo investigate the glucose and lipid metabolic disorders in patients with myasthenia gravis （MG） without glucocorticoid therapy, and the relationships between insulin, insulin resistance, muscle strength, serum levels of osteocalcin, 25-hydroxy vitamin D （25OHD） and glucose and lipid metabolism.MethodsA total of 102 MG patients [（40±11） years old, 43 males and 59 females] without glucocorticoid treatment were enrolled in this cross-sectional study. Height, weight and the handgrip of dominant hands were measured. Serum levels of fasting blood glucose （FBG）, 2-hour postprandial blood glucose （2 h PBG）, glycosylated hemoglobin （HbA1c）, fasting insulin （FINS）, 2-hour postprandial insulin （2 h PINS）, total cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C） and osteocalcin, 25OHD were detected. Insulin resistance was assessed using homeostasis model assessment of insulin resistance （HOMA-IR）.ResultsThe proportion of impaired fasting glucose or impaired glucose tolerance, type 2 diabetes, dyslipidemia, hyperinsulinemia in male and female were 30.0%, 10.0%, 50.0%, 33.3% and 17.5%, 3.5%, 27.7%, 7.1%, respectively. Serum osteocalcin levels in male and female were 2.8 （1.7, 4.4） μg/L and 2.3 （1.3, 3.9） μg/L, respectively. And 25OHD levels in male and female were （93.5±34.9） nmol/L and （81.0±30.5） nmol/L, respectively. Handgrip of male and female was （37.0±9.4） kg and （20.5±6.3） kg. After adjusted for age, FINS （r=0.619, P〈0.001）, 2 h PINS （r=0.640, P〈0.001）, HOMA-IR （r=0.534, P〈0.001） were positively correlated with 2 h PBG, and the handgrip was negatively correlated with TC （r=-0.486, P=0.026）, LDL-C （r=-0.485, P=0.026） in male. FINS （r=0.352, P=0.008; r=0.300, P=0.026; r=0.646, P〈0.001） and 2 h PINS （r=0.278, P=0.040; r=0.518, P〈0.001; r=0.382, P=0.006） and HOMA-IR （r=0.695, P〈0.001; r=0.583, P〈0.001; r=0.818, P〈0.001） were positively correlated with FBG, 2 h PBG, HbA1c, and the handgrip were negatively correlated with FBG （r=-0.424, P=0.016）, 2 h PINS （r=-0.345, P=0.034） and positively correlated with HDL-C （r=0.389, P=0.037） in female. There was no association between osteocalcin, 25OHD and glucose and lipid metabolism. Multivariate linear regression analysis also found that there were significant relationships between handgrip, insulin, insulin resistance levels and glucose and lipid metabolic disorders.ConclusionThere was a high proportion of glucose and lipid metabolic disorders in MG patients without glucocorticoid treatment, and the mechanism may be related to insulin resistance induced by muscle weakness.