2型糖尿病患者糖耐量正常一级亲属降脂治疗对胰岛B细胞功能的影响

目的观察2型糖尿病患者糖耐量正常一级亲属血清游离脂肪酸(FFA)浓度降低后,胰岛B细胞分泌功能的变化。方法2004年4月至2005年7月,对安徽医科大学第一附属医院内分泌科38例2型糖尿病(T2DM)患者糖耐量正常的一级亲属,给予阿昔莫司0.25g,每日3次,口服,连用5d。服药前后均进行75g口服葡萄糖耐量试验(OGTT)。结果服用阿昔莫司后,空腹FFA、胰岛素抵抗指数(HOMA-IR)、OGTT葡萄糖曲线下面积(AUCg)、游离脂肪酸曲线下面积(AUCf)均明显降低(P<0.05或P<0.01),胰岛B细胞功能指数(ΔI30/ΔG30)、胰岛B细胞功能调整指数(ΔI30.ΔG30-1.HOMA-IR-1)均明显增加(P<0.05或P<0.01),而体重指数(BMI)、腰臀围比(WHR)、空腹血糖、空腹胰岛素、胰岛素曲线下面积(AUCi)均无显著改变(P>0.05)。服药前后ΔI30/ΔG30、ΔI30.ΔG30-1.HOMA-IR-1的改变值与空腹FFA改变值(ΔFFA)、AUCf改变值(ΔAUCf)呈显著负相关(r=-0.39~-0.49,P<0.05或P<0.01),HOMA-IR改变值(ΔHOMA-IR)与ΔFFA、ΔAUCf均呈显著正相关(r=0.31,0.35,P<0.05);服药前后AUCg改变值(ΔAUCg)与ΔI30/ΔG30、ΔI30.ΔG30-1.HOMA-IR-1的改变值呈显著负相关(r=-0.52,-0.56,P<0.01),与ΔHOMA-IR无显著相关性(r=0.28,P=0.07);ΔAUCg与ΔAUCf之间呈显著正相关(r=0.44,P<0.05)。结论阿昔莫司在降低T2DM患者糖耐量正常的一级亲属FFA的同时,可明显改善胰岛素敏感性、口服葡萄糖耐量以及胰岛B细胞的分泌功能,提示脂毒性可能参与早期胰岛B细胞功能缺陷的发生。     

胰岛素抵抗综合征患者血清脂联素和胰岛素敏感性的相关性研究

目的 检测正常人和胰岛素抵抗综合征患者血清脂联素,进一步探讨脂联素与胰岛素敏感性、血糖、血胰岛素、血脂等的相关性。方法 用减少样本数的Bergman微小模型技术结合静脉葡萄糖耐量试验检测正常、肥胖、糖耐量低减(IGT)和2型糖尿病(DM)患者的胰岛素敏感性指数(SI),同时测定受试者的体重指数(BMI)和腰臀比(WHR),检测空腹状态下脂联素和血脂、空腹和餐后2h血糖及胰岛素水平。结果 与正常组相比,肥胖、IGT和2型DM组的SI均显著降低,差异有显著性(P<0.001),而非正常组之间此指标差异无显著性。正常组的血清脂联素[(12.84±3.64)mg/L]显著大于肥胖、IGT和2型DM组[(7.65±2.45、7.55±2.64、5.19±2.36)mg/L,均P<0.001],后3组中2型DM组的脂联素显著低于肥胖和IGT组,差异有显著性(P<0.01,P<0.05),而肥胖组和IGT组间此值差异无显著性。脂联素与SI呈正相关,而与腰围、BMI、WHR和空腹、餐后2h血糖及血甘油三酯呈显著负相关。多元逐步回归分析提示血清脂联素与SI(r~2=0.29)、空腹血糖(r~2=0.26)、WHR(r~2=0.17)具有高度的相关性(均P<0.05)。结论 胰岛素抵抗综合征患者血清脂联素水平显著降低,并以2型DM患者降低更为明显;血清脂联素与SI呈正相关,而与空腹血糖和WHR呈显著负相关。     

不同糖耐量人群及糖尿病患者血浆内脂素与血糖及胰岛功能的关系研究

目的探讨不同糖耐量人群血浆内脂素的变化及其与体重指数(BMI)、腰围、血糖、胰岛素抵抗指数、胰岛B细胞功能、血脂等的关系。方法2006年4月至2006年10月在南京医科大学第一附属医院门诊常规健康体检及糖尿病初次就诊者95名,按WHO1999糖尿病诊断标准分为初诊2型糖尿病组(53例)、糖耐量减退组(7例)、正常糖耐量组(35名);以WHO1998肥胖诊断标准分为超重或肥胖组(50名)、正常体重组(45名)。检测受试者BMI、腰围、血压,测定空腹血浆内脂素、血糖、血脂、胰岛素等。结果初诊2型糖尿病患者空腹血浆内脂素明显高于正常糖耐量组(P<0.01)。超重或肥胖组与正常体重组间血浆内脂素差异无显著性意义。人群中血浆内脂素与空腹血糖(r=0.338,P<0.01)、餐后2h血糖(r=0.340,P<0.01)、胰岛素抵抗指数(r=0.227,P<0.05)呈正相关,与胰岛素分泌指数(HOMA-B)呈负相关(r=-0.296,P<0.05)。在2型糖尿病组,血浆内脂素与糖化血红蛋白(HbA1c)呈正相关(r=0.356,P<0.01)。多元线性逐步回归分析表明,餐后2h血糖是影响血浆内脂素的独立相关因素。结论初诊2型糖尿病患者血浆内脂素显著升高,可能是机体针对体内血糖增高、胰岛功能受损所发生的一种代偿效应。     

肥胖者胰岛素分泌功能对糖耐量低减及糖尿病发生的影响

目的　探讨肥胖者胰岛素分泌变化对糖耐量低减 (IGT)及糖尿病 (DM)发生的影响。　方法　对 30例单纯性肥胖 [体重指数 (BMI) >2 7]患者进行血糖和胰岛素测定 ,并观察胰岛细胞分泌指数 (HOMA- IS)及胰岛素敏感性指数 (IAI) ,并对这些患者进行 15年随访。　结果　肥胖者空腹胰岛素 (FINS)水平明显高于正常人 (P <0 .0 1) ,与 HOMA - IS明显的正相关 (P <0 .0 1) ;空腹血糖(FPG)与 HOMA- IS及 IAI呈明显的负相关 (P<0 .0 1)。15年内 6 3.3%的肥胖者发展成 IGT,5 0 .0 %的肥胖者及发展成 IGT者发展为 2型 DM。　结论　肥胖对 IGT及糖尿病的发生、发展有着明显的影响 ,控制体重是减少 IGT发生的重要环节。     

2型糖尿病患者血浆脂联素和抵抗素水平的测定及意义

为探讨2型糖尿病患者血浆脂联素和抵抗素水平的变化及意义。将60例2型糖尿病患者分为非肥胖糖尿病组30例(体质指数<25kg/m2)和肥胖糖尿病组30例(体质指数>25kg/m2);并选择28例健康者作对照。用酶联免疫吸附检测法测空腹血浆脂联素和抵抗素浓度;并测定各组的空腹血糖、胰岛素和血脂的水平;根据HOMA稳态模型提出的公式,计算胰岛素抵抗指数和胰岛素敏感指数,分析各指标间的相关性。结果发现,①糖尿病各组血浆脂联素的水平明显低于对照组,且肥胖糖尿病组低于非肥胖组,差异有显著性(P<0.01)。②糖尿病各组血浆抵抗素的水平明显高于对照组,而且肥胖糖尿病组明显高于非肥胖组,差异有显著性(P<0.01)。③相关分析发现,血浆脂联素浓度与体质指数、空腹血糖、胰岛素抵抗指数和甘油三酯呈显著负相关(分别为r=-0.55,P<0.01;r=-0.51,P<0.01;r=-0.52,P<0.01;r=-0.39,P<0.05),而与胰岛素敏感指数呈显著正相关(r=0.45,P<0.01);抵抗素则与体质指数、空腹血糖、胰岛素抵抗指数和甘油三酯呈显著正相关(r=0.40,P<0.01;r=0.52,P<0.01;r=0.46,P<0.01;r=0.27,P<0.05);与胰岛素敏感指数)呈显著负相关(r=-0.32,P<0.01)。此结果提示,脂联素和抵抗素都参与了胰岛素抵抗的发生过程,可能与2型糖尿病的糖脂代谢紊乱有关。     

上海地区肥胖糖调节受损者的胰岛素敏感性和1相胰岛素分泌功能研究

目的研究上海地区肥胖的糖调节受损(IGR)者胰岛素敏感性和胰岛β细胞1相胰岛素分泌功能。方法共有129例受试者[非肥胖正常对照38名,IGR包括单独糖耐量受损(IGT)64例,单独空腹血糖受损(IFG)8例,IFG+IGT 19例]接受了口服75g葡萄糖耐量试验和胰岛素改良的减少样本数(n =12)的Bergman微小模型技术结合频繁采血的静脉葡萄糖耐量试验(FSIGTT)。胰岛素抵抗由FSIGTT中胰岛素敏感性指数(S1)加以评估,而FSIGTT中对葡萄糖急性胰岛素分泌反应(AIRg)则用以评价胰岛β细胞分泌功能。处理指数(DI=AIRg×S1)用于评价AIRg是否代偿机体的胰岛素抵抗。结果(1)与正常对照组相比,3组IGR患者之S1明显降低(均P<0．01),3组差异无统计学意义;(2)AIRg在正常组和IGT组之间差异无统计学意义,但均大于IFG和IFG+IGT组,差异有统计学意义(P<0．05或JP<0．01)。IFG +IGT组的AIRg值显著低于IGT组(P<0．01);(3)与正常组相比,DI指数在3组IGR显著降低(P< 0．01),但在IGR组间差异无统计学意义;(4)S1与空腹胰岛素、体重指数、血清尿酸呈显著负相关(校正r2 =0．568,P<0．01);而AIRg与2h胰岛素显著正相关,与空腹血糖、2h血糖和年龄负相关(校正r2=0．402, P<0．01)。结论上海地区肥胖的初诊IGR患者(包括单独IGT、单独IFG和IFG+IGT患者)存在着程度近似的胰岛素抵抗;急性相胰岛素分泌功能在校正胰岛素抵抗影响因素后IGT患者尚属正常,在IFG和IFG+IGT患者已明显降低,且3组的β细胞代偿功能均为一致性失代偿。     

不同方法评估不同糖代谢人群胰岛素抵抗结果的分析

目的探讨临床工作中不同糖代谢状态下不同胰岛素抵抗评估方法的可靠性。方法对25~73岁的正常糖耐量(NGT)者448例;空腹血糖受损(IFG)者56例;糖耐量受损(IGT)者197例;IFG合并IGT(IFG+IGT)者63例;糖尿病(DM)患者225例,采用以下6种方法评估不同糖代谢状态下胰岛素抵抗程度:(1)OGTT计算胰岛素敏感指数;(2)HOMA-IR;(3)李光伟胰岛素敏感指数[1/(FINS×FPG)];(4)胰岛素曲线下面积(AUCinsulin);(5)葡萄糖曲线下面积/胰岛素曲线下面积比值(AUCglucose/AUCinsulin);(6)空腹血糖/空腹胰岛素比值(FPG/FINS)。结果OGTT计算胰岛素敏感指数、HOMA-IR以及1/(FINS×FPG)显示,IFG、IFG+IGT、IGT、DM组胰岛素抵抗显著高于NGT(P<0.05),而DM组显著高于NGT、IFG、IFG+IGT、IGT组(P<0.05);AUCinsulin显示,IGT组胰岛素抵抗显著高于NGT、IFG、IFG+IGT、DM组(P<0.05),而DM组显著低于NGT、IFG、IFG+IGT、IGT组(P<0.05);AUCglucose/AUCinsulin、FPG/FINS显示,NGT、IFG、IFG+IGT、IGT四组患者之间胰岛素抵抗差异无显著性(P>0.05),而DM组显著高于NGT、IFG、IFG+IGT、IGT组(P<0.05)。结论OGTT计算胰岛素敏感指数、1/(FINS×FPG)与HOMA-IR得出结果基本一致,并且OGTT计算胰岛素敏感指数可以分辨不同糖调节异常状态下胰岛素抵抗程度;AUCinsulin、AUCglucose/AUCinsulin、FPG/FINS不能准确分辨不同糖代谢人群胰岛素抵抗程度。     

依折麦布对糖尿病前期不稳定性心绞痛患者胰岛素释放的影响

目的观察依折麦布对糖尿病前期不稳定性心绞痛患者胰岛素释放的影响。方法选取糖尿病前期不稳定性心绞痛患者222例,随机分为对照组和依折麦布组,对照组给予阿托伐他汀治疗;依折麦布组给予阿托伐他汀联合依折麦布治疗,分别治疗7天、1月、3月,比较两组葡萄糖耐量试验(OGTT)和胰岛素释放试验(IRT)结果。结果与对照组比较,依折麦布组7天、1月、3月OGTT 0.5 h、1 h、2 h血糖显著降低(P0.05、0.01),0.5 h、1 h、2 h、3 h血糖曲线下面积显著减少(P0.05、0.01、0.001);IRT 0.5 h、1 h胰岛素明显升高(P0.05、0.01),2 h胰岛素降低(P0.05),0.5 h、1 h、2 h胰岛素曲线下面积增加(P0.01、0.001、0.05)。不同时间点血糖曲线下面积和胰岛素曲线下面积存在负相关(r=-0.387,P0.01);不同时间段血糖减低量与胰岛素增加量存在正相关(r=0.473,P0.001)。与对照组比较,依折麦布组稳态模型胰岛素抵抗指数于1月、3月明显降低(P0.05、0.01);胰岛素作用指数于7天、1月、3月明显升高(P0.05、0.01);稳态模型-β于3月明显升高(P0.05)。结论依折麦布改善糖尿病前期不稳定性心绞痛患者胰岛素分泌,提高胰岛素敏感性,改善糖耐量。     

肥胖和非肥胖糖耐量受损患者胰岛素敏感性和1相胰岛素分泌研究

目的研究肥胖和非肥胖糖耐量受损(IGT)患者的胰岛素敏感性和β细胞1相胰岛素分泌功能,以探讨在IGT患者中肥胖对胰岛素抵抗和1相胰岛素分泌的影响。方法共有99位受试者(包括正常对照者32名,肥胖IGT44例,非肥胖IGT23例)接受了口服75 g葡萄糖耐量试验(OGTT)和胰岛素改良的减少样本数(采血样12次)的Bergman微小模型技术结合静脉葡萄糖耐量试验(FSIGTT)。胰岛素抵抗由FSIGTT中胰岛素敏感性指数(SI)加以评估,而OGTT中糖负荷后30 min胰岛素增值与血糖增值之比值[ΔI30/ΔG30=(I30 min-I0 min) /(G30 min-G0 min)]和FSIGTT中急性胰岛素分泌反应(AIRg)则用以评价胰岛β细胞分泌功能。处理指数(DI =AIRg×SI)用于评价AIRg是否代偿机体的胰岛素抵抗。结果与正常对照组[(7.52±10.89)×10-4]相比,二组IGT患者之SI明显降低,而肥胖IGT组的SI[(1.72±1.11)×10-4]较非肥胖组[(3.15±1.49)×10-4]更低(均P<0.01); AIRg和ΔI30/ΔG30在正常组(412±191,14.45±8.47)和肥胖IGT组(378±235,17.02±11.30)之间差异无统计学意义,但均大于非肥胖组(196±160,8.93±6.69,均P<0.01);与正常组(2 851±1 180)相比,DI指数在二组IGT显著降低(595±485,584±517),但后二组间此值差异无统计学意义。SI与2 h胰岛素、体重指数、尿酸和胆固醇呈显著的负相关性(校正r2=0.603,P<0.01);而AIRg与ΔI30/ΔG30显著正相关,与空腹血糖负相关(校正r2=0.479,P<0.01)。结论IGT患者存在胰岛素抵抗和β细胞功能异常。与非肥胖IGT患者相比,肥胖IGT患者胰岛素抵抗程度更为严重,但胰岛β细胞胰岛素1相分泌相对充分。     

不同糖耐量个体血浆内脂素水平的变化

目的探讨不同糖耐量人群血浆内脂素(visfatin)水平变化及其与体重指数(BMI)、腰臀比(WHR)、血糖、血浆胰岛素水平等的关系。方法采用酶联免疫法测定了2型糖尿病(DM)、糖耐量受损(IGT)患者和正常健康人空腹和糖负荷后2h血浆内脂素水平,并分析血浆内脂素与BMI、WHR、胰岛素抵抗指数(HOMA-IR)、血脂、血糖、血浆胰岛素和游离脂肪酸(FFA)水平等的关系。结果(1)2型DM患者空腹和糖负荷后2h血浆内脂素水平明显低于正常对照组[(11.63±7.48)μg/L vs(16.82±6.06)μg/L和(12.02±6.86)μg/L vs(16.26±7.78)μg/L,均P＜0.05],IGT组内脂素水平介于2型DM和对照组之间；肥胖组血浆内脂素水平较非肥胖组有升高趋势；(2)相关性研究显示,血浆内脂素水平与WHR呈正相关(r=0.42,P＜0.01),与糖负荷后2h血糖(2hPG)和HbA_(IC)呈明显负相关(r=-0.33,P＜0.01和r=～0.25,JP＜0.05)；(3)多元线性逐步回归分析表明WHR、HbA_(IC)空腹血糖、2hPG、高密度脂蛋白胆固醇分别是影响血浆内脂素水平的独立相关因素。结论血浆内脂素水平与糖代谢状态有关,并可能在肥胖和2型糖尿病的发生和发展中具有一定的作用。     

Adipocytes in subjects with impaired fasting glucose and impaired glucose tolerance are resistant to the anti-lipolytic effect of insulin

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two intermediate states in the transition from normal glucose metabolism to type 2 diabetes. Insulin clamp studies have shown that subjects with IGT have increased insulin resistance in skeletal muscle, while subjects with IFG have near normal muscle insulin sensitivity. Because of the central role of altered free fatty acid (FFA) metabolism in the pathogenesis of insulin resistance, we have examined plasma free fatty acid concentration under fasting conditions, and during OGTT in subjects with IGT and IFG. Seventy-one NGT, 70 IGT and 46 IFG subjects were studied. Fasting plasma FFA in IGT subjects was significantly greater than NGT, while subjects with IFG had similar fasting plasma FFA concentration to NGT. However, fasting plasma insulin concentration was significantly increased in IFG subjects compared to NGT while subjects with IGT had near normal fasting plasma insulin levels. The adipocyte insulin resistance index (product of fasting plasma FFA and FPI) was significantly increased in both IFG and IGT subjects compared to NGT. During the OGTT both IFG and IGT subjects suppressed their plasma FFA concentration similarly to NGT subjects, but the post-glucose loads were significantly increased in both IFG and IGT subjects. These data suggest that both subjects with IFG and IGT have increased resistance to the antilipolytic action of insulin. However, under basal conditions, fasting hyperinsulinemia in IFG subjects is sufficient to offset the adipocyte insulin resistance and maintain normal fasting plasma FFA concentration while the lack of increase in FPI in IGT subjects results in an elevated fasting plasma FFA.     

Evaluation of insulin release and insulin sensitivity through oral glucose tolerance test: differences between NGT,IFG, IGT,and type 2 diabetes mellitus. A cross-sectional and follow-up study

Abstract. We evaluated both insulin release (IR) and insulin sensitivity (IS) through a single oral glucose tolerance test (OGTT) (blood samples at 0, 60, 120 min, as routinely performed in Europe) in subjects with normal and abnormal glucose tolerance. The value 1/HOMA was used as an index of IS and I/G at 60 min was used as an index of IR. In preliminary experiments, 1/HOMA correlated with glucose infusion rate (GIR) at euglycaemic insulin clamp (r=0.495) and with insulin sensitivity index (ISI) at LDIGIT (r=0.714). At OGTT with blood samples at 0, 30, 60 and 120 min, insulin levels at 30 min correlated with insulin levels at 60 min (I30 vs. I60, r=0.584) and I/G at 30 and at 60 min correlated (r=0.365). Values of 1/HOMA from 345 subjects with normal glucose tolerance (NGT), 32 with impaired fasting glucose (IFG), 186 with impaired glucose tolerance (IGT) and 72 with type 2 diabetic mellitus were divided into quartiles. For each quartile, mean (± SE) and 95% confidence intervals (CI) of I/G at 60 min were calculated, and subjects were represented by plotting IS vs. IR. Plots of NGT, IGT, and type-2 diabetes mellitus described different curves. Values of subjects with IFG, IGT and type 2 diabetes mellitus fell outside the 95% CI of NGT subjects in all quartiles of IS. To validate this finding, 113 morbidly obese subjects (basal OGTT: 55 NGT, 40 IGT, 18 T2DM) who underwent a major reduction of body weight through bariatric surgery received a second OGTT one year after surgery. Glucose tolerance improved in 40 patients, deteriorated in 8, did not change in 65; the new plots were concordant with the new class of glucose tolerance. OGTT can be used to evaluate both IR and IS in subjects with NGT, IFG, IGT, and type 2 diabetes mellitus in population studies and in follow-up studies. IFG, IGT and type 2 diabetes mellitus are characterized by reduced IR compared to IS.     

Assessment of insulin sensitivity from plasma insulin and glucose in the fasting or post oral glucose-load state.

OBJECTIVE: To compare insulin sensitivity indexes derived from plasma insulin (I) and glucose (G) in the basal state (Sib) and at the second hour (I2h and G2h) of an oral glucose tolerance test (OGTT, Si2h) (i) with measurements of insulin sensitivity using the insulin modified frequently sampled intravenous glucose tolerance test (FSIVGTT) [Si(IVGTT)] and (ii) with modelling of fasting glucose and insulin by the homeostasis model assessment (HOMA). SUBJECTS: 47 subjects entered the study. 31 subjects were classified as having normal glucose tolerance (NGT), 10 as having impaired tolerance to glucose (IGT) and six as type 2 diabetes mellitus according to the World Health Organisation (WHO) criteria. MEASUREMENTS: Sib and Si2h were calculated as follows. Sib = 10(8)/(I x G x VD), Si2h = 10(8)/(I2hr x G2hr x VD) where VD is an estimate of the apparent glucose distribution volume. A third insulin sensitivity index (SiM) was calculated by averaging Sib and Si2h. HOMA was calculated as follows: I/(22.5 x e(-lnG)) RESULTS: Si(IVGTT), Sib, SI2h and SiM were all significantly higher in subjects with NGT than in those with IGT or type 2 diabetes. Si(IVGTT) was highly correlated (P < or = 0.0001) with the three insulin sensitivity indexes found in the total population, in subjects with NGT and in those with IGT. In type 2 diabetic patients, a significant correlation was only noted when SiM was tested against Si(IVGTT) (P < or = 0.05). In most circumstances, the associations of Si(IVGTT) with Sib, SI2h and SiM were stronger than the corresponding associations with Ib, I2h or HOMA. SiM was the index that correlated best with Si(IVGTT) in the whole group (r = 0.92, P < 0.0001) as well as in NGT (r = 0.86, P < 0.0001), IGT (r = 0.96; P < 0.0001) and type 2 diabetes (r = 0.83, P < or = 0.05) subgroups. CONCLUSIONS: Calculations of sensitivity indexes from G and I concentrations in the basal state and during a conventional 2 h OGTT appear to be useful for coupling in the same simple and single test both a determination of glucose tolerance and an estimate of insulin sensitivity.     

新诊断2型糖尿病患者葡萄糖耐量试验与糖化血红蛋白水平的相关分析

目的 对比分析新诊断2型糖尿病及糖尿病前期患者口服葡萄糖耐量试验(OGTT)与糖化血红蛋白(HbAIc)水平变化的特点及影响因素. 方法 按照OGTT结果将受检者分为糖耐量正常组(正常组):31例,年龄29～75岁,平均(48.4±15.3)岁;空腹血糖受损组(血糖受损组):33例.年龄38～72岁,平均(50.8±9.8)岁;糖耐量受损组:34例,年龄33～74岁,平均(54.5±11.4)岁;2型糖尿病组(T2DM组):117例,年龄29～75岁,平均(54.3±14.1)岁.采用OGTT试验、HbAlc结果评价糖代谢状态,胰岛β细胞功能指数(HOMA-E)、OGTT 30 min胰岛素分泌增值与血糖增值比值(△I30/△G330)、胰岛素分泌曲线下面积(AUCINS)及胰岛素抵抗指数(HOMA-IR)分别反映胰岛β细胞分泌功能和胰岛素抵抗情况. 结果 (1)T2DM、糖耐量受损组和正常组HbAlc分别为7.41%、5.85%和5.21%,差异有统计学意义(P<0.01),T2DM、糖耐量受损组和血糖受损组HOMA-β指数与正常组比较,分别下降了53.1%(P<0.01)、29.3%(P<0.01)和23.4%(P<0.05),T2DM组HOMA-IR分别是正常组的1.66倍(P<0.01)、血糖受损组的1.29倍(P<0.001)和糖耐量受损组的1.44倍(P<0.05);(2)HbAIc与糖负荷后3 h血糖水平相关性最高(r=0.71,P<0.01),且独立相关;△I30/△G330与糖负荷后1 h和2 h血糖水平独立负相关(P<0.01);AUCINS只与糖负荷后3 h血糖水平独立负相关(P<0.01);HOMA-β与2 h以外的其他各点血糖独立负相关(P<0.01);HOMA-IR与OGTT各点血糖水平均呈正相关(P<0.01或P<0.05);三酰甘油与空腹血糖独立正相关(P<0.05),腰围与1/2 h血糖独立正相关(P<0.01).OGTT试验血糖水平变化的独立相关因素依次为△I30/△G330、AUCINS、HOMA-β、HOMA-IR和腰围.HbAlc水平的独立相关因素是OGTT 3 h血糖变化. 结论 在2型糖尿病、糖耐量低减及正常等不同糖代谢状态人群中,HbAlc水平存在差异,当HbAlc>8.0%时,OGTT试验、血糖、胰岛素水平或曲线下面积均不能反映出病情差别和变化的显著性.     

不同状态的糖调节受损患者胰岛素分泌和胰岛素敏感性的差异

目的评估初发的单纯空腹血糖受损（IFG）和单纯糖耐量受损（IGT）患者的胰岛素分泌以及胰岛素敏感性（IS）特征。方法北京市东城区既往无糖尿病史的2388名受试者行葡萄糖耐量试验,同时行胰岛素释放试验,本文纳入2244例,其中糖耐量正常（NGT）1608例,IFG240例,IGT243例,IFG＋IGT 153例。比较各组胰岛素抵抗指数（HOMA-IR）、IS指数（Matsudaindex）、B细胞功能指数（1相Stumvoll index、△I30／△G30）。结果与NGT组比较,其余三组HOMA-IR显著升高,Matsuda指数及B细胞功能指数均显著降低（P均〈0．01）;IFG组HOMA-IR及Matsuda指数均高于IGT组;IFG组△I30／△G30高于IGT组,而Stumvoll指数低于IGT组（P〈0．01）;与IFG组、IGT组比较,IFG＋IGT组HOMA-IR显著升高,Matsuda指数、1相Stumvoll指数显著降低（P均〈0．01）。结论糖尿病前期人群存在不同程度的胰岛素分泌缺陷和IR,IFG组肝IR较重,而IGT组肌肉IR较重。     

Pancreatic beta-cell function and insulin sensitivity in japanese subjects with impaired glucose tolerance and newly diagnosed type 2 diabetes mellitus

To clarify whether pancreatic beta-cell function and/or insulin resistance contributes to development of glucose intolerance in Japanese subjects, we investigated 551 subjects who underwent a 75-g oral glucose tolerance test (OGTT). Subjects were divided into 3 groups: normal glucose tolerance (NGT, n = 238), impaired glucose tolerance (IGT, n = 211), and newly diagnosed type 2 diabetes mellitus (n = 102). The diabetics were subdivided into 3 subgroups as follows: diabetes with normal fasting glucose (fasting plasma glucose [FPG] < 110 mg/dL), diabetes with impaired fasting glucose (FPG 110 to 125 mg/dL), and diabetes with diabetic fasting glucose (FPG >or= 126 mg/dL). Insulinogenic index as early-phase insulin secretion, homeostasis model assessment (HOMA-beta and HOMA-resistance), and 4 different formulas of insulin sensitivity index were assessed by plasma glucose and insulin concentrations obtained at fasting or during a 75-g OGTT. Both early-phase insulin secretion and insulin sensitivity were low even in the IGT stage compared with NGT. The transition from IGT to diabetes was accompanied by a progressive deterioration of insulin reserve as well as insulin resistance. During the further progression in diabetes, insulinogenic index decreased additionally, whereas declines in insulin sensitivity were relatively small. In conclusion, both impaired insulin secretion and insulin resistance may contribute to the underlying mechanisms of glucose intolerance in Japanese subjects.     

Thiazolidinediones increase hepatic insulin extraction in African Americans with impaired glucose tolerance and type 2 diabetes mellitus. A pilot study of rosiglitazone

Peripheral insulin levels are determined by beta-cell secretion, insulin sensitivity, and hepatic insulin extraction (HIE). We have previously shown that whereas sulfonylureas reduce insulin extraction, metformin enhances HIE. However, the effects of thiazolidinediones (TZDs) on HIE remain uncertain. Thus, we investigated the potential contribution of hepatic insulin clearance to peripheral insulin levels during rosiglitazone therapy in African Americans with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM). The study was composed of 12 first-degree relatives with IGT and 17 patients with newly diagnosed type 2 DM. Nineteen healthy relatives with normal glucose tolerance served as controls. Serum glucose, insulin, and C-peptide, and HIE (C-peptide-insulin molar ratios) were measured at t = 0 and 120 minutes during oral glucose tolerance test (OGTT) in all the subjects. The OGTT was performed before and after 3 months of rosiglitazone therapy (4 mg/d x 4 weeks and >8 mg/d x 8 weeks) in patients with IGT and type 2 DM. Insulin resistance index and beta-cell function were calculated in each subject using homeostasis model assessment (HOMA). Rosiglitazone therapy improved but did not normalize the overall glycemic control in the IGT and type 2 DM groups. After rosiglitazone therapy, the mean serum insulin and C-peptide levels at fasting remained unchanged. However, the 2-hour serum glucose and insulin were lower, whereas serum C-peptide was unchanged during 3 months of rosiglitazone treatment. Mean insulin resistance index of HOMA was reduced by 30% (4.12 +/- 1.95 vs 6.33 +/- 3.54, P < .05) in the type 2 DM group and by 21% (3.78 +/- 2.45 vs 4.81 +/- 3.49, P = NS) in the IGT group. Mean HIE values were significantly lower (70%) in the type 2 DM and IGT groups when compared with the normal glucose tolerance group. At 3 months, basal HIE was not significantly changed by rosiglitazone therapy in IGT and type 2 DM groups when compared with the baseline (0 month). However, rosiglitazone therapy was associated with increased HIE at 2 hours during OGTT by 40% and 30% in the IGT and type 2 DM groups, respectively, from the baseline (0 month) values. Furthermore, HIE inversely correlated with the insulin resistance index of HOMA (r = -.46, P < .05). We conclude that rosiglitazone therapy improved overall glucose tolerance and enhanced insulin sensitivity in patients with IGT and type 2 DM. Although basal HIE remained unchanged, rosiglitazone therapy increased postglucose challenge HIE in African Americans with IGT and type 2 DM. We speculate that TZDs increase insulin clearance or HIE after oral glucose challenge. This study suggests that in addition to insulin sensitization, rosiglitazone may be involved in insulin metabolism. The significance of the increased insulin clearance by TZD therapy remains uncertain and deserves further investigation in patients with insulin resistance and glucose intolerance.     

2型糖尿病高危人群的血管内皮功能与血浆游离脂肪酸水平

目的研究2型糖尿病（T2DM）患者、糖耐量正常的2型糖尿病一级亲属（FDRs）、糖耐量减低（IGT）人群的血管内皮功能、血浆游离脂肪酸（FFA）水平并与健康对照组进行比较。方法测定36例健康人（男16例,女20例）、57例FDRs（男27例,女30例）、59例IGT（男25例,女34例）,35例T2DM（男15例,女20例）的FFA水平、内皮依赖性血管舒张功能（EDV）以及空腹胰岛素、TC、TG、BMI、腰臀围比、空腹血糖及糖化血红蛋白,同时计算胰岛素敏感性指数（IAI）。结果FDRs、IGT及T2DM组的EDV显著低于健康对照组[FDRs组（5．03±0．34）％,IGT组（3．09±0．28）％,T2DM组（2．62±0．29）％,对照组（12．45±3．37）％];FFA水平高于对照组[FDRs组（0．52±0．08）mmol／L,IGT组（0．52±0．12）mmol／L,T2DM组（0．59±0．23）mmol／L,对照组（0．46±0．18）mmol／L];IAI低于对照组（FDRs组-4．20±0．38,IGT组-4．41±0．72,T2DM组-4．65±0．64,对照组-3．79±0．57）,差异均有统计学意义（P值均〈0．05）。结论T2DM、糖耐量正常的FDRs及IGT人群存在IAI降低、血管内皮功能受损、FFA升高。     

Loss of the First Phase Insulin Response to Intravenous Glucose in Subjects with Persistent Impaired Glucose Tolerance

Loss of the first phase insulin response to intravenous glucose is one of the earliest detectable defects of beta cell dysfunction in Type 2 diabetes mellitus. Impaired glucose tolerance (IGT) is considered a prediabetic condition, therefore loss of first phase insulin secretion in subjects with IGT would suggest beta cell dysfunction as an early lesion in the development of Type 2 diabetes. Three groups of subjects were studied, 7 subjects with persistent IGT (classified as having IGT at two 75 g oral glucose tolerance tests (OGTT) done 6 months apart), 6 subjects with transient IGT (IGT at the first OGTT, but normal glucose tolerance at a repeat OGTT 6 months later), and 7 normal controls. First phase insulin secretion was studied using an intravenous glucose tolerance test with arterialized blood sampling. Fasting, 3, 4 and 5 min samples were assayed for glucose and insulin (specific two-site immunoradiometric assay). The fasting insulin was similar in all three groups, however the 3 min insulin response was significantly lower in those with persistent impaired glucose tolerance (p < 0.02). Thus subjects with persistent impaired glucose tolerance demonstrated loss of the first phase insulin response as an early indicator of beta cell dysfunction while subjects with transient IGT had a normal insulin response to intravenous glucose. During the OGTT, the 30 min glucose was not significantly different (p = 0.1) but the 30 min insulin to glucose ratio was significantly lower in subjects with persistent IGT (p < 0.03). In the whole group the 30 min insulin to glucose ratio during the OGTT showed a significant correlation with the peak insulin response during the IVGTT (r = 0.76, p < 0.001). This study suggests that beta cell dysfunction with impaired early insulin release is present before the development of Type 2 diabetes.     

Higher fasting plasma free Fatty Acid levels are associated with lower insulin secretion in children and adults and a higher incidence of type 2 diabetes

Context: There are limited data in humans on the association between fasting free fatty acid (FFA) levels and pancreatic β-cell function. Objective: Our objective was to examine this association in children and adults with normal glucose tolerance and to explore fasting FFA levels in relation to subsequent risk of impaired glucose tolerance (IGT) and type 2 diabetes (T2D). Design: We measured FFA, glucose, and insulin levels after an overnight fast and 30 min after an oral glucose load in 797 children aged 8 yr in the Avon Longitudinal Study of Parents and Children and 770 adults aged 44-71 yr in the Medical Research Council Ely Study. We calculated the homeostasis model assessment to estimate fasting insulin sensitivity, the insulinogenic index to estimate insulin secretion, and the disposition index to assess insulin secretion corrected for insulin sensitivity. Results: Higher fasting FFA levels were associated with lower insulin secretion in children (boys, P = 0.03; girls, P = 0.001) and adults (men, P = 0.03, women, P = 0.04). Associations with insulin sensitivity were more variable, but after adjustment for insulin sensitivity, higher fasting FFA levels remained associated with lower insulin secretion (disposition index). Compared with adults in the lowest tertile of fasting FFA levels, those in the middle and highest tertiles had a 3-fold higher incidence of IGT or T2D over the following 5-8 yr. Conclusions: Higher fasting FFA levels were consistently associated with lower insulin secretion in children and adults with normal glucose tolerance. Furthermore, higher fasting FFA levels were prospectively associated with a greater risk of subsequent IGT and T2D.