铁蛋白、氧化低密度脂蛋白与2型糖尿病内皮依赖性血管舒张功能的关系

目的探索血清铁蛋白（SF）、氧化低密度脂蛋白（ox-LDL）与2型糖尿病（T2DM）早期血管内皮舒张功能的关系。方法选择50例无大血管并发症的T2DM患者（DM组）,34例年龄、性别相匹配健康个体作为对照（Nc）组。高分辨血管外超声法检测肱动脉血流介导的内皮依赖性血管舒张功能（FMD）和硝酸甘油介导的内皮非依赖性血管舒张功能（NMD）,检测ox-LDL、SF。结果与NC组比较,DM组SF、ox-LDL明显升高（P〈O．01）,而FMD、NMD明显下降（P〈0．01）。分别以FMD、NMD为因变量进行多元线性回归分析,提示SF、ox-LDL与FMD明显相关（P〈0．05）,而与NMD无明显相关（P〉0．05）。结论SF、ox-LDL在2型糖尿病早期可能参与了血管内皮依赖性舒张功能受损。     

2型糖尿病患者血浆护骨素浓度与内皮依赖性血管舒张功能关系的研究

目的探讨T2DM患者血浆护骨素(OPG)浓度与内皮依赖性血管舒张功能的关系。方法选取T2DM患者(T2DM组)154例和健康对照(NC)者46名,分别测定其血浆OPG浓度,并采用高分辨血管外超声法检测肱动脉血流介导的内皮依赖性血管舒张功能和硝酸甘油介导的非内皮依赖性血管舒张功能。结果 T2DM组血流介导的内皮依赖性血管舒张功能为(3.56±0.64)%,低于NC组(5.32±0.55)%(P<0.01)。多元回归分析显示,内皮依赖性血管舒张功能、24hUAlb均与血浆OPG水平相关。Pearson相关分析显示,OPG浓度与内皮依赖性血管舒张功能呈负相关(r=-0.284,P=0.000)。结论血浆OPG水平在T2DM患者中升高,其水平与内皮依赖性血管舒张功能呈负相关。     

彩色多普勒超声对糖尿病血管内皮功能的评价

用高分辨率彩色多普勒超声检测33例2型糖尿病（T2DM）患者肱动脉反应性充血后，以及含服硝酸甘油后的血管内径和血流量变化。结果：T2DM组反应性充血时肱动脉内径变化比正常对照组明显减弱（P〈0．01），硝酸甘油介导的肱动脉内径扩张与正常对照组比较有显著性差异（P〈0．05）。结论：T2DM患者不仅存在血管内皮依赖性舒张功能障碍，而且还存在非血管内皮依赖性舒张功能障碍。     

罗格列酮对2型糖尿病大鼠主动脉内皮依赖性血管舒张功能的影响

目的观察2型糖尿病（T2DM）大鼠胸主动脉内皮依赖性血管舒张功能和一氧化氮（NO）、一氧化氮合酶（eNOS）的变化及罗格列酮（RSG）治疗对其内皮功能的影响。方法SD大鼠经高糖高脂喂养6周后予小剂量链脲佐菌素腹腔注射建立T2DM大鼠模型，糖尿病大鼠又分为对照（DM）组和RSG治疗组，RSG组用RSG干预8周，另选正常大鼠为正常对照（NC）组。实验终止时用正常葡萄糖高胰岛素钳夹技术的葡萄糖输注率（GIR）评价胰岛素抵抗，观察大鼠离体主动脉内皮依赖性血管舒张反应和主动脉NO、eNOS的变化。结果T2DM大鼠GIR、胸主动脉内皮依赖性血管舒张反应、主动脉NO含量及eNOS阳性表达较NC组显著降低（P〈0、01），RSG治疗后上述指标均显著升高（P〈0．05）。结论T2DM大鼠存在内皮依赖性血管舒张功能紊乱，RSG治疗可改善内皮功能，增强NO水平和eNOS的活性。     

2型糖尿病患者血管内皮功能与动脉弹性的关系

目的分析2型糖尿病（T2DM）患者血管内皮功能与血管弹性的关系。方法应用超声血管回声跟踪技术检测T2DM患者（T2DM组）及正常对照组的颈动脉各血管弹性参数,测量其肱动脉血流介导的内皮依赖的舒张功能（FMEDD）和硝酸甘油介导的非内皮依赖的舒张功能（NIEID）,并进行相关分析。结果T2DM组NIEID及FMEDD明显低于对照组;颈动脉的血管弹性系数（Ep）、硬化值（β）明显高于对照组（P均〈0．05）。FMEDD、NIEID与Ep、β均呈明显负相关（P均〈0．05）。结论T2DM患者血管内皮功能受损直接影响其动脉血管弹性。     

2型糖尿病早期内皮依赖性血管舒张功能的临床研究

目的探讨2型糖尿病（T2DM）早期患者血管内皮功能的变化及其临床意义。方法选择44例新诊断无并发症的T2DM早期患者和40名年龄、性别等匹配的正常对照者。采集空腹静脉血测定FPG、Fins、HbA,c、TC、TG、HDL—C、LDL-C、UA、NO、内皮素1（ET～1）等,并行75g葡萄糖耐量试验测定2hPG。采用高分辨率血管外彩超测定肱动脉、颈动脉的血管内径及颈动脉内膜中层厚度（IMT）,以反应性充血前后血管内径变化百分比反映血管舒张功能。对IMT与各项指标的变化进行相关性分析。结果T2DM组与对照组之间FPG、Fins、2hPG、HbA1C、TG、TC、HDL—C、LDL-C、H（）MAIR、NO、ET-1差异均有统计学意义（P〈0．05或P〈0．01）,而性别、年龄、BMI、收缩压、舒张压、UA差异无统计学意义（P〉0．05）。T2DM组基础血管内径、血流介导的内皮依赖性舒张功能和硝酸甘油介导的非内皮依赖性舒张功能与对照组之间差异有统计学意义（P〈0．01）。基础血流在两组问差异无统计学意义（P〉0．05）。不同部位IMT在不同人群中的密切相关因素是不同的。结论T2DM早期患者就有血管内皮功能损伤,不仅存在内皮依赖性血管舒张功能障碍,而且存在非内皮依赖性血管舒张功能障碍。     

IGT患者肱动脉内皮舒张功能的超声研究

采用高分辨率超声测定68例IGT患者和50例正常人血流介导的肱动脉内皮依赖性舒张功能。结果：IGT组较正常对照组低（P〈0．001）。结论：IGT对人内皮依赖性血管舒张功能造成损伤。     

超声检查评价老年糖尿病患者肱动脉内皮功能的价值与局限性

目的探讨超声测定肱动脉舒张功能评价老年糖尿病患者血管内皮功能的价值与局限性。方法用高分辨率二维超声测定反应性充血时血流介导肱动脉舒张功能（FMD）技术对67例老年T2DM患者（DM组）血管内皮功能进行评价。结果DM组肱动脉基础内径及基础流速与正常对照（NC）组无统计学差异,加压反应性充血后均可见血管扩张,血液流速增加,DM组加压后肱动脉内径增加及流速增加显著低于NC组;单因素线性相关性分析FMD与病程、TG、ISI和年龄呈负相关（P〈0．05或P〈0．01）,而与BMI、TC、FPG、HbA1c、Fins不相关。结论FMD对评价老年T2DM患者血流介导的血管内皮舒张功能障碍有一定的价值,但要综合考虑病人的年龄、性别、种族、病程、血脂等因素。     

糖代谢紊乱患者的血管内皮细胞功能变化

目的 观察糖耐量受损（IGT）、2型糖尿病（DM）患者的内皮依赖性血管舒张功能（EDF）、血清超氧化歧化酶（SOD）、丙二醛（MDA）、超敏C反应蛋白（hsCRP）、可溶性血管细胞黏附分子1（sVCAM-1）的变化。方法 30例IGT患者、30例2型DM患者及33名正常对照者（NGT）纳入本研究。采集空腹静脉血测定葡萄糖（FPG）、胰岛素（FINS）、SOD、MDA、hsCRP、sVCAM-1，并行75g口服葡萄糖耐量试验。采用高分辨率血管外彩超测定肱动脉的血管内径，以肱动脉反应性充血前后血管内径变化百分比反映EDF。结果 （1）IGT组、DM组的EDF较NGT组显著下降（均P〈0．01），DM组较IGT组更低（P〈0．01）。（2）IGT组、DM组的SOD较NGT组显著下降（均P〈0．01），而MDA显著上升（均P〈0．01）。DM组与IGT组比较SOD显著下降（P〈0．01），MDA显著上升（P〈0．01）。（3）hsCRP、sVCAM-1在NGT、IGT、DM组逐渐上升，两两比较差异均有统计学意义（均P〈0．01）。（4）多因素逐步回归分析显示：EDF与HOMA—IR、hsCRP明显负相关（r分别为-0．059、-0．447，均P〈0．01，n=93）。结论 EDF的损害在IGT阶段即可出现，而在DM患者中损害更为严重。胰岛素抵抗、hsCRP与EDF的损害密切相关。SOD、MDA、hsCRP、sVCAM-1可能参与上述患者的血管内皮功能损伤。     

糖耐量受损患者维生素C对葡萄糖负荷后内皮依赖性血管舒张功能的保护作用

在口服糖耐量试验中，糖耐量受损（IGT）组各时点内皮依赖性血管舒张功能（EDD）低于健康对照组；IGT＋维生素C组60、120minEDD高于IGT组；IGT患者血糖与EDD负相关（均P〈0.05）。     

Acute hyperglycemia rapidly suppresses endothelium-dependent arterial dilation in first-degree relatives of type 2 diabetic patients.

OBJECTIVE: Previous studies showed that endothelium-dependent arterial dilation is impaired in first-degree relatives of type 2 diabetes in the fasting state. In the present study, we examined whether endothelial dysfunction occurs when acute hyperglycemia is induced by oral glucose loading in this cohort. PATIENTS AND METHODS: This study included 32 normal glucose tolerant subjects. Of them, 17 with a family history (FH) of type 2 diabetic parents (FH+) and 15 with no first-degree relative with diabetes or coronary artery disease (FH-). The examination of vascular function was performed in fasting state and repeated 1 and 2 hours after a 75-g oral glucose loading by high resolution ultrasound. RESULTS: Endothelium- dependent arterial dilation in FH+ group were significantly lower than those in FH- before and after oral glucose loading (5.12+/-0.61% vs 6.03+/-0.56%, fasting; 4.0+/-0.65% vs 5.70+/-0.42%, 1 h; 4.43+/-0.61% vs 5.82+/-0.67% 2 h, p<0.05 each). In FH+ group, endothelium-dependent arterial dilation decreased significantly at 60 min (4.0+/-0.65% vs 5.12+/-0.61%, p<0.01) and increased markedly from 60 min at 120 min (4.43+/-0.61% vs 4.0+/-0.65%, p<0.05), which was still significantly lower than baseline (4.43+/-0.61% vs 5.12+/-0.61%, p<0.01) . In FH- group, however, the arterial dilation did not differ significantly among the three time points (p 0.05). In multiple regression analysis, endothelium-dependent arterial dilation was significantly correlated to FH+(r=-0.302, p<0.01). In addition, endothelium-dependent arterial dilation showed a correlation with plasma glucose (r=-0.460, p<0.01) and TBARS (r=-0.382, p<0.01) during OGTT in FH+ subjects. CONCLUSION: Significant endothelial dysfunction is present in the fasting state, hyperglycemia in response to oral glucose loading rapidly suppresses endothelium-dependent arterial dilation in FH+ subjects, probably through increased production of oxygen-derived free radicals.     

糖耐量受损患者肱动脉内皮依赖性血管舒张功能变化的研究

采用高分辨血管外超声检测糖耐量受损(IGT)患者肱动脉血流介导的内皮依赖性血管舒张功能(EDD)和硝酸甘油介导的内皮非依赖性血管舒张功能(EID)。IGT组EDD明显低于对照组(P<0.05)。EID在两组间无明显差异(P>0.05)。     

The antioxidant alpha-lipoic acid improves endothelial dysfunction induced by acute hyperglycaemia during OGTT in impaired glucose tolerance

Objective Impaired glucose tolerance (IGT) is considered a transitional phase in the development of type 2 diabetes, and is also independently associated with the occurrence of cardiovascular disease. Endothelial dysfunction (ED) represents a very early step in the development of atherosclerosis. The aim of the present study was to examine ED in the fasting state and after a glucose challenge as well as after administration of an antioxidant agent. Patients and methods The study subjects included 42 IGT patients and 26 healthy individuals (control group). The IGT patients were randomly divided into two groups, 21 in each group (the alpha‐lipoic acid group and the placebo group). In the alpha‐lipoic acid group, 300 mg of alpha‐lipoic acid was administrated before an oral glucose tolerance test (OGTT); in the placebo group, 250 ml of 0·9% sodium chloride was administrated before the OGTT. In addition, 250 ml of 0·9% sodium chloride was also administrated to the control subjects before the OGTT (control group), and then vascular function was examined in the fasting state and repeated 1 and 2 h after the glucose load. High‐resolution ultrasound was used to measure flow‐mediated endothelium‐dependent arterial dilation (FMD) and glyceryltrinitrate (GTN)‐induced endothelium‐independent arterial dilation. Results In the fasting state, and at 60 and 120 min, FMD in both the placebo and alpha‐lipoic acid groups was significantly lower than in the controls (P < 0·01). In the control group, FMD tended to decrease at 60 min after glucose loading and returned to the baseline levels at 120 min (P > 0·05). In the placebo group, FMD decreased significantly at 60 min after glucose loading (P < 0·01) and increased markedly from 60 to 120 min (P < 0·01). The alpha‐lipoic acid‐treated patients showed FMD values intermediate between the control subjects and the IGT patients treated with placebo, at both 60 and 120 min, and the differences were significant (P < 0·01). In multiple regression analysis, FMD was significantly correlated to fasting blood glucose (FBG), low density lipoprotein cholesterol (LDL‐C), lipoprotein (a) [Lp(a)], C‐reactive protein (CRP), thiobarbituric acid reactive substances (TBARS) and age in IGT patients at baseline (P < 0·01). Spearman's analysis showed a significant negative correlation between FMD and plasma glucose levels, and between FMD and TBARS during the OGTT in IGT patients (placebo group) (P < 0·01). There was also a significant correlation between FMD and plasma glucose levels, and between FMD and TBARS during the OGTT in IGT patients treated with alpha‐lipoic acid (P < 0·05), although the power of association decreased. Conclusion In subjects with IGT, FMD was impaired both in the fasting state and after a glucose challenge, probably through increased production of oxygen‐derived free radicals. The ED observed after a glucose challenge is related to the extent of hyperglycaemia and TBARS, and an antioxidant agent can improve the impairment of endothelial function induced by acute hyperglycaemia.     

不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗

目的　研究不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗 (IR)之间的关系。方法　将受试者根据口服葡萄糖耐量试验 (OGTT)结果分为正常糖耐量组 (NGT) ,糖耐量受损组 (IGT )及 2型糖尿病组(DM )。采用毛细血管气相色谱法测定血浆脂肪酸谱 ,用胰岛素敏感指数 (IAI)评估IR。结果　DM组及IGT组血浆软脂酸 (C16:0 )、硬脂酸 (C18:0 )、二十二烷酸 (C2 2 :0 )、二十四烷酸 (C2 4:0 )和饱和脂肪酸浓度较NGT组明显升高 (P <0 .0 5～P <0 .0 1) ;花生四烯酸 (C2 0 :4)分别从NGT、IGT和DM组依次升高 ,差异有显著性 (P <0 .0 5～P <0 .0 1) ;血浆饱和脂肪酸 (SFA)从NGT、IGT、DM亚组依次升高 (P <0 .0 5～P <0 .0 1) ;NGT组的多不饱和脂肪酸 (PUFA)与饱和脂肪酸 (SFA)的比率高于IGT组和DM组 (均P <0 .0 5 ) ;血浆C16:0、C2 0 :4、C2 2 :0、SFA与IAI呈负相关 (P均 <0 .0 1)、PUFA/SFA与IAI呈正相关 (P <0 .0 1)。结论　不同糖耐量者血浆脂肪酸谱不同 ,糖耐量减低与 2型糖尿病患者SFA浓度升高 ,PUFA/SFA下降 ,且与胰岛素抵抗密切相关     

The ROC analysis for different time points during oral glucose tolerance test

This purpose was to discuss optimal reference value for normal glucose tolerance (NGT) at different time points during an oral glucose tolerance test (OGTT) by receiver operating characteristic (ROC) analysis. One thousand seven hundred and forty-six subjects from March 2004 to March 2005 were given 75 g OGTT and the blood samples were collected at 0, 30, 60, 120 and 180 min for glucose measurement. Other demographic data (e.g. age, sex, body mass index, BMI) were also recorded. The status of NGT, impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and DM was determined according to American Diabetes Association (ADA) criteria. IGT and IFG were merged as impaired glucose regulation (IGR). Using IGR as the assumed test, the cutoff values at 0, 30, 60, 120 and 180 min during OGTT for normal reference range were calculated by ROC analysis. The cutoff values were 5.6, 9.5, 10.1, 7.8 and 6.1 mmol/l at 0, 30, 60, 120 and 180 min, respectively, in whole subjects. In addition, we provided the ROC information in age-stratified groups since there are differences among different age groups. When the results of OGTT were considered, the present study provided a reference range value to evaluate the status of glucose tolerance. Because of the heterogeneity of diabetes, further studies are necessity. And the sample collection is continuing.     

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.     

Insulin‐secretion capacity in normal glucose tolerance,impaired glucose tolerance,and diabetes in obese and non‐obese Japanese patients

Aims/Introduction: Pronounced reduction of insulin secretion in response to a rise in glucose level has been reported in Japanese patients compared with Caucasian patients, but the mean body mass index (BMI) is also lower in Japanese patients. As BMI is a determinant of insulin secretion, we examined insulin‐secretion capacity in obese and non‐obese Japanese patients. Materials and Methods: Using the oral glucose tolerance test (OGTT), we estimated the insulin‐secreting capacity in obese (BMI ≥ 25) and non‐obese (BMI < 25) Japanese patients, including 1848 patients with normal glucose tolerance (NGT), 321 patients with impaired glucose tolerance (IGT) and 69 diabetes (DM) patients. Results: The insulinogenic index (I.I.), calculated by dividing the increment in serum insulin by the increment in plasma glucose from 0 to 30 min during OGTT, decreased from NGT to IGT and to DM in patients with and without obesity. In patients with NGT, IGT and DM, the I.I. values of obese patients were higher than those of the non‐obese patients. The peak of insulin concentration in OGTT appeared at 60 min in NGT and at 120 min in IGT in both obese and non‐obese patients, but in DM it was observed at 120 min in obese patients and at 60 min in non‐obese patients. Conclusions: These results show that early‐phase insulin secretion in obese Japanese patients is higher than in non‐obese patients in all stages of glucose tolerance, and delayed insulin‐secretion capacity is also conserved in obese Japanese patients, even in IGT and DM, which is similar to Caucasian patients. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00180.x , 2011)     

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.     

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.     

In middle-aged siblings of patients with type 2 diabetes mellitus normal glucose tolerance is associated with insulin resistance and with increased insulin secretion. The SPIDER study

OBJECTIVES: To evaluate the frequency of impaired glucose tolerance (IGT) and of Type 2 diabetes mellitus (Type 2 DM) in siblings of patients with Type 2 DM, and to assess insulin release and insulin sensitivity in siblings with normal glucose tolerance (NGT), compared with NGT spouses of probands without family history of Type 2 DM. DESIGN AND METHODS: We evaluated 87 families including 103 Type 2 DM patients (87 probands), and we carried out an oral glucose tolerance test (OGTT) in 130 siblings and in 60 spouses. Among NGT subjects, 12 siblings and 16 spouses underwent a low-dose insulin-glucose infusion test (LDIGIT) to evaluate C-peptide release and insulin sensitivity. RESULTS: After the OGTT, 24 siblings were classified as having Type 2 DM, 31 as IGT, and only 14 spouses as IGT (P=0.0012 vs siblings). NGT siblings (n=75) showed higher insulin levels at 120 min than NGT spouses (n=46) at OGTT, in spite of identical blood glucose levels; at LDIGIT, NGT siblings secreted more C-peptide and showed a lower insulin sensitivity than NGT spouses. CONCLUSIONS: These data indicate that middle-aged siblings of probands with Type 2 DM have a high frequency of IGT and Type 2 DM, and that NGT siblings have increased insulin resistance and increased insulin secretion when compared with adequate controls.