二甲双胍和吡格列酮对初诊糖代谢异常伴腹型肥胖患者血清ghrelin水平的影响

Effects of metformin and pioglitazone on plasma ghrelin in patients with newly diagnosed abnormal glucose metabolism and abdominal obesity

目的观察二甲双胍与吡格列酮治疗对初诊糖代谢异常伴腹型肥胖患者血清ghrelin水平的影响。方法选择2010年4月至9月在我院内分泌科门诊就诊的初诊糖代谢异常（包括糖耐量减低和新诊断的2型糖尿病，糖化血红蛋白〈7％）伴腹型肥胖患者39例，采用随机数字表法分为二甲双胍组（n=20）和吡格列酮组（n=19）。二甲双胍组男5例，女15例，年龄（51±9）岁，予二甲双胍1500mg／d干预。吡格列酮组3例男性患者因出现浮肿、瘙痒退出，余下5例，女11例，年龄（53±7）岁，予吡格列酮30mg／d治疗。所有患者行口服葡萄糖耐量试验（OGTT），观察治疗3个月前后体重、OGTT5点血糖、胰岛素和ghrelin等变化。以t检验和秩和检验、偏相关分析、多元回归分析进行统计学分析。结果（1）吡格列酮组治疗后OGTT5点（空腹、0．5、1．0、2．0、3．0h）ghrelin水平依次为（1069±467）、（898±407）、（812±371）、（705±328）和（1059±606）ng／L，均较治疗前升高[分别为（905±449）、（688±378）、（614±358）、（572±334）和（720±403）ng／L，Z值分别为-2．354～-3．351，均P〈0．05]。（2）二甲双胍组治疗后OGTT5点ghrelin水平依次为（882±429）、（682±262）、（609±259）、（576±234）和（734±267）ng／L，比治疗前[（731±241）、（642±208）、（525±195）、（462±146）、（611±267）ng／L]升高，但仅有空腹、OGTT后2．0、3．0h差异有统计学意义（均P〈0．05）。二甲双胍组治疗后0．5、1．0和3．0hghrelin水平均低于吡格列酮组（Z=-2．012、-2．006、-2．226，均P〈0．05）。结论与吡格列酮相比，二甲双胍治疗使体重降低的同时仅有部分时点血ghrelin水平升高，这可能是二甲双胍控制体重较好的原因之一。

Objective To investigate the effects of metformin and pioglitazone on plasma ghrelin in patients with newly diagnosed abnormal glucose metabolism and abdominal obesity. Methods From April to September 2010, 39 patients with abnormal glucose metabolism （including impaired glucose tolerance and newly diagnosed type diabetes mellitus, glyeated hemoglobin A1 c （HbA1 c） 〈 7% ） and obesity were enrolled in the study. They were randomly assigned to metformin group （500 mg rid, n = 20, 15 females and 5 males, aged （51 ±9） years, MET group） or pioglitazone group （30 mg/d, n = 19, 11 females and 8 males,aged （53 ± 7 ） years, PIO group） on the basis of diet and exercise therapy for 3 months. Three males in PIO group with ＆awed because of itching and edema. At baseline and after 3 months, plasma glucose, serum insulin and ghrelin levels during oral glucose tolerance test（OGTT, 0 min, 0. 5, 1.0, 2. 0, 3.0 h） ,body weight, body mass index（BMI）, HbAlc, etc were measured. The t test or Wileoxon rank-sum test was used for statistical analysis. Partial correlation and multiple regression analysis were performed to examine the association between serum ghrelin levels and influencing factors. Results （ 1 ） In PIO group, serum ghrelin levels after treatment were OGTTO min （1069 ±467）ng/L, 0.5 h （898 ±407） ng/L, 1.0 h（812 ±371）ng/L, 2. 0 h （705 ±328） ng/L and 3.0 h （ 1059 ± 606） ng/L, respectively. All increased than those before treatment（ （905 ±449）, （688 ±378）, （614 ±358）, （572 ± 334） and（720 ±403） ng/L,Z value was from -2. 354 to - 3. 351, respectively, all P 〈 0. 05）. （2） In MET group, serum ghrelin levels at OGTT 0 min, 1. 0, 2. 0, 3.0 h after treatment were （731 ±241） , （642 ±208）, （525 ±195）, （462 ±146） and （611 ± 267）ng/L, respectively. Compared with the ghrelin levels before treatment （ （731 ± 241 ） , （642 ± 208 ）, （525 ± 195 ） , （462 ± 146 ） and （611 ± 267 ）ng/L）, only the difference at 0 min, 2. 0, 3.0 h was statistically significant （ all P 〈 0. 05 ）. Serum ghrelin levels of MET group at OGTT 0. 5, 1.0 and 3.0 h were lower than that of PIO group （Z value was - 2. 012, - 2. 006, - 2. 226, respectively, all P 〈 0.05 ） . Coneluslons Compared with those in PIO group, patients treated with mefformin lose more weight, but their serum ghrelin levels only partially increase at different point OGTT. This may be one of the reasons why metformin controls weight better.