摘要
【目的】观察微粒化非诺贝特对伴高甘油三酯(TG)糖代谢异常患者急性胰岛素分泌反应和胰岛素抵抗的改善作用。【方法】53例入选者为按2:1随机分为非诺贝特组[36例,其中空腹血糖调节受损(IFG)3例,糖耐量减低(IGT)19例,IFG合并IGT6例,2型糖尿病T2DM8例]和对照组(17例,其中IFG1例,IGT9例,IFG合并IGT4例,T2DM3例),为期3月。治疗前后测血糖、血脂、游离脂肪酸(FFA),行静脉葡萄糖耐量试验(IVGTT)。计算IVGTT中急性胰岛素分泌反应(AIR)和胰岛素分泌峰值(CINS,MAX)与空腹胰岛素(FINS)比值、差值(CINS,MAX/FINS、ΔCINS)。计算HOMAIR。【结果】非诺贝特组治疗后血TG、低密度脂蛋白胆固醇、FFA明显下降,高密度脂蛋白胆固醇显著升高,腰围明显减小;对照组上述指标无改变。非诺贝特组ΔCINS、CINS,MAX/FINS治疗后均增加(分别是808±473pmol/L比660±472pmol/L和中位数8.4比5.3,P<0.0001);AIR显著改善(5585±3441比4444±3642pmol·L-1·min-1,P<0.0001);FINS、HOMAIR显著下降(108±65pmol/L比166±115pmol/L,P=0.002;3.8±2.3比6.0±4.2,P=0.001)。对照组3月后复查CINS,MAX/FINS、ΔCINS、AIR降低(4.6比7.0,P=0.01;641±286pmol/L比720±321pmol/L,P=0.039;4313±1943pmol·L-1·min-1比5362±2861pmol·L-1·min-1,P=0.024),HOMAIR增加(7.8±4.2比5.6±3.2,P<0.0001)。AIR改善与TG、FFA下降显著相关(r=0.41,0.36,P=0.002,0.014)。【结论】非诺贝特短期调脂治疗可显著改善糖代谢异常的高TG血症患者血脂谱,降低FFA水平,减小腰围,改善急性胰岛素分泌反应,减轻胰岛素抵抗;非诺贝特对胰岛素分泌功能的改善作用和减轻脂毒性相关。
【Objective】 The study was conducted to investigate the effect of micronized fenofibrate on acute insulin response in the subjects with impaired glucose metabolism and hypertriglyceridemia.【Methods】 Fifty-three subjects were randomly （2： 1 ratio） allocated to fenofibrate group （n = 36,including IFG 3 cases,IGT 19 cases,IFG / IGT 6 cases,T2DM 8 cases） or control group （n = 17,including IFG 1 case,IGT 9 cases,IFG / IGT 4 cases,T2DM 3 cases） without any intervention for 3 months.Fasting blood samples were collected for measuring fasting plasma glucose （FPG）,free fatty acids （FFA）,and lipid profile.IVGTTs were carried out with measurement of plasma insulin before and after treatment.Acute insulin response （AIR）,the maximum insulin concentrations （CINS,MAX） to fasting insulin （FINS） ratio （CINS,MAX/ FINS） and values of the maximum insulin concentrations increment （ΔCINS） during IVGTT were calculated as indexes of first-phase insulin secretion.HOMA insulin resistance index （HOMA IR） was used for assessing insulin resistance.【Results】 After 3-month treatment,the lipid profile was evidently improved in fenofibrate group.Levels of triglyceridemia （TG）,low-density lipoprotein cholesterol and FFA were significantly reduced and high-density lipoprotein cholesterol increased significantly.Waist circumference was also significantly declined.No change of above indicators was found in control group.In fenofibrate group,CINS,MAX/ FINS and ΔCINS were significantly increased （median 8.4 pmol / L vs.5.3 pmol / L,808 ± 473 pmol / L vs.660 ± 472 pmol / L,both P 0.0001）,along with great improvement of AIR （5 585 ± 3 441 pmol·L-1·min-1 vs.4 444 ± 3 642 pmol·L-1·min-1,P 0.000 1）.The level of FINS and HOMA IR was also markedly reduced （108 ± 65 pmol / L vs.166 ± 115 pmol / L,P = 0.002;3.8 ± 2.3 vs.6.0 ± 4.2,P = 0.001）.In contrast,there were modest declining in acute insulin response （AIR： 4 313 ± 1 943 pmol·L-1·min-1 vs.5 362 ± 2 861 pmol·L-1·min-1;CINS,MAX/ FINS： median 4.6 vs.7.0,P = 0.01;ΔCINS： 641 ± 286 pmol / L,vs.720 ± 321 pmol / L,P = 0.003 9） and increasing HOMA IR （7.8 ± 4.2 vs.5.6 ± 3.2,P 0.000 1） in control group after 3-month follow-up.The improvement of AIR was correlated with the decreasing of plasma FFA and TG （r = 0.41,0.36,P = 0.002,0.014）,but no correlation with the changing of FPG and HOMA IR.【Conclusions】 These results indicated that short-term lipid-lowering treatment with fenofibrate evidently improved acute insulin response and alleviated insulin resistance in subjects with impaired glucose metabolism and hypertriglyceridemia.Moreover,the improvement of insulin secretion capacity may be mainly due to the relieving of lipotoxity resulting from finofibrate.
出处
《中山大学学报（医学科学版）》
CAS
CSCD
北大核心
2010年第1期100-105,共6页
Journal of Sun Yat-Sen University:Medical Sciences
基金
广东省自然科学基金重点项目(9251008901000030)
"863"计划子课题(2006AA02A409)
