非胰岛素依赖型糖尿病多发家系患者胰岛素分泌率和清除率及敏感性的研究

Primary study on characteristics of insulin secretion rate,metabolic clearance rate and sensitivity in non- insulin-dependent diabetic subjects from multiplex diabetic pedigrees

目的 观察非胰岛素依赖型糖尿病多发家系 (MDP)中患者胰岛素分泌率 (ISR)、代谢清除率 (MCR I)、敏感性的特点及与肥胖的相关关系。方法 15名对照者及 6个MDP中 11例非胰岛素依赖型糖尿病患者均行多次取样的静脉糖耐量试验 (FSIVGTT) ,所有标本测定葡萄糖、胰岛素 (INS)、C肽 (C P) ,根据自编计算机程序 ,计算各时点ISR ,MCR I;用关于葡萄糖 (G)的最小模型技术计算胰岛素敏感指数 (SI)。结果 对照组ISR曲线呈双相 ,非胰岛素依赖型糖尿病组呈延迟分泌 ;非胰岛素依赖型糖尿病组 0～ 16minC P曲线下面积 (AUCC)为 7 9nmol·min-1·L-1± 2 8nmol·min-1·L-1、INS分泌量为 6 1nmol± 2 2nmol,均低于对照组 (分别为 17 7nmol·min-1·L-1± 4 9nmol·min-1·L-1和12 3nmol± 3 9nmol) (P <0 0 1) ,而 16～ 180min高于对照组 (分别为 15 5nmol·min-1·L-1± 4 4nmol·min-1·L-1和 110nmol·min-1·L-1± 3 0nmol·min-1·L-1、76nmol± 2 6nmol和 5 4nmol± 2 0nmol) (P <0 0 5 ) ,3h胰岛素分泌总量与对照组差异无显著意义 (分别为 82nmol± 2 8nmol及 68nmol± 2 1nmol,P =0 2 )。对照组AUCS与腰臀围比 (WHR)及体表面积 (BSA)明显正相关 ,MCR I、SI与两者明显负相关 ,MCR I与SI亦显著负相关 (

Objective Toinvestigatethecharacteristicsofinsulinsecretionrate (ISR) ,metabolic clearancerate (MCR I)andsensitivityandtoexploretheirrelationshipwithobesityinnon insulin dependent diabeticsubjectsfrommultiplexdiabeticpedigrees (MDP) Methods Fifteensubjectswithnormalglucose toleranceand 11non insulin dependentdiabeticpatientsfromMDPwereincludedinthestudy Frequentlysampled intravenousglucosetolerancetest (FSIVGTT)wasperformed Glucose ,insulin (INS)andconnecting peptide (C P)concentrationsweremeasured Acomputerproceduredevisedbyourlaboratorywasusedtocalculatethevalue ofISRateachtimepoint,thenMCR Iwasacquired Insulinsensitivityindex (SI)wascalculatedaccordingto minimalmodeltechniqueaboutglucoseinFSIVGTT Results TheISRcurveincontrolgroupwasbiphasic ,while innon insulin dependentdiabeticgroup ,adelayedsecretorypeakwasseen Innon insulin dependentdiabetic group ,areasunderthecurvesofC P (AUCC)andISRlevel(AUCS)measuredduring 0～ 16minwere 7 9nmol ·min-1·L-1± 2 8nmol·min-1·L-1、and 6 1nmol± 2 2nmol,respectively ,whichweresignificantlylower thanthoseincontrolgroup 17 7nmol·min-1·L-1± 4 92nmol·min-1·L-1and 12 3nmol± 3 9nmol(P < 0 0 1) .Thetwoparameterswereslightlyhigherthanthoseincontrolgroup 15 5nmol·min-1·L-1± 4 4nmol· min-1·L-1vs10 1nmol·min-1·L-1± 3 0nmol·min-1·L-1and 76nmol± 2 6nmolvs 5 4nmol± 2 0 0nmol(P < 0 0 5 )measuredduring 16～ 180min Therewasnosignificantdifference ,betweenthetwogroupsabouttheamount ofinsulinsecretionduring 3hours ( 82nmol± 2 8nmolvs 68nmol± 2 1nmol,P =0 2 ) Incontrolgroup ,there weresignificantpositivecorrelation ,betweenAUCS ,waist hipratio (WHR) ,andbodysurfacearea ,(BSA)and significantnegativecorrelationbetweenMCR I ,SIandWHR ,BSA (P <0 0 1) ,andalsobetweenMCR Iand SI Innon insulin dependentdiabeticgroup ,AUCSweresignificantlycorrelatedwithbodymassindex (BMI) (P <0 0 1) ,andMCR IhadsignificantnegativecorrelationwithAUCC (P <0 0 1) Conclusions Thereare obviousimpairedfirstphaseinsulinsecretionafterglucosechallengeinnon insulin dependentdiabeticsubjectsfromMDP DecreaseinendogenousMCR Imightbeanimportantfactortohyperinsulinemiaandinsulinresistance Increasedinsulinsecretion ,decreasedMCR Iandinsulinsensitivitycanbeobservedinabdominalobesesubjects ofcontrolgroup