Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance

Summary Recent evidence suggests that the post-prandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion ( 0–10 min insulin area ÷ 0–10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2–19.4] vs 9.1 [2.6–14.5] mU·mmol^–1; p<0.01). During the clamp, circulating insulin (93±8 [mean±SEM] and 81±10 mU·l^–1) and glucagon (54±4 and 44±6 ng·l^–1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78±0.27 vs 4.47±0.53 mg·kg^–1·min^–1; p<0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38±0.10 and 0.30±0.18 mg·kg^–1·min^–1). Therefore, the main defects in subjects with impaired glucose tolerance are decreased first phase insulin secretion and peripheral non-oxidative glucose disposal, but hepatic glucose output shows normal responsiveness to insulin.Abbreviations FPIS First phase insulin secretion - PG plasma glucose - NIDDM non-insulin-dependent diabetes mellitus - IGT impaired glucose tolerance - HGO hepatic glucose output - IVGTT intravenous glucose tolerance test - OGTT oral glucose tolerance test     

空腹血糖异常、糖耐量减低患者血清胰岛素水平的变化及其意义

目的 观察空腹血糖异常(IFG)、糖耐量减低(IGT)患者血清胰岛素水平的变化。方法 对50例空腹血糖和糖耐量正常者(NGT)、40例IFC和80例IGT患者行口服葡萄糖耐量试验(0GTT)，用氧化酶法检测血糖，用放免法测定血清空腹及餐后2小时胰岛素。结果 IFG、IGT组空腹血糖、空腹胰岛素水平及胰岛素敏感指数较NGT组明显升高(P＜0.05或P＜0．01)，IFG组胰岛素敏感指数与IGT组比较无显著性差异(P＞0．05)。结论 在IFG、IGT状态下已经存在胰岛素抵抗，而且在程度上两者间并没有显著性差异，应早期干预治疗。     

糖调节受损个体胰岛β细胞功能和胰岛素抵抗观察

评价152例人选者[正常糖耐量、空腹血糖受损和(或)糖耐量受损]胰岛β细胞功能和胰岛素抵抗.结果 显示空腹血糖受损者主要表现胰岛素早期分泌功能缺陷和基础分泌不足,胰岛素抵抗严重;糖耐量受损者则胰岛素早期和晚期分泌功能显著下降伴轻度胰岛素抵抗.     

新疆汉、维民族糖调节受损人群胰岛素分泌功能和胰岛素作用功能的研究

目的 评估新疆汉、维民族在IFG,IGT及IGR阶段的胰岛素分泌功能和胰岛素作用功能。 方法 采用多中心研究进行横断面调查,行OGTT试验。用胰岛素抵抗指数（HOMA-IR）评估IR,胰岛β细胞功能指数（HOMA-β）评估基础胰岛素分泌;ΔI30/ΔG30评价胰岛素早相分泌,ΔI30/ΔG30/HOMA-IR评估葡萄糖处置指数（DI）。 结果 WC、BMI、血脂、FIns、2 hIns在汉、维民族不同糖代谢组差异有统计学意义。IFG组与NGT、IGT组比较,汉、维族人群的HOMA-IR差异有统计学意义。在汉族中NGT组与IGT、IGR组比较,HOMA-β差异有统计学意义（P=0.030、0.044）,而在维族只有IFG组与NGT组比较差异有统计学意义（P=0.001）。ΔI30/ΔG30、DI在两民族不同糖代谢组差异均无统计学意义。 结论 汉族人群IR在IFG阶段,胰岛素分泌功能在IGT阶段起主要作用。IR和胰岛素分泌功能在维族人群IFG阶段起重要作用。胰岛素早相分泌及葡萄糖处置功能在糖调节受损阶段作用不显著。     

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。     

Uric acid,impaired fasting glucose and impaired glucose tolerance in youth with overweight and obesity

Background and aimThe relationships between uric acid (UA) and prediabetes is poorly explored in youth. We investigated the association between UA, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), insulin resistance (IR) and low insulin sensitivity (IS) in youth with overweight/obesity (OW/OB).Methods and resultsA cross-sectional study was performed in 2248 youths with OW/OB (age 5–17 years). The sample was stratified in sex-specific quintiles (Q1 to Q5) of UA and the associations with fasting (FG), 2-h post-load glucose (2H-PG), IR and low IS were investigated. IR and low IS were estimated by assessment model of insulin resistance (HOMA-IR) and whole-body IS index (WBISI), respectively. IFG was defined as FG ≥ 100 < 126 mg/dL, IGT as 2H-PG ≥140 < 200 mg/dL, IR as HOMA-IR ≥75th percentile and low IS as WBISI ≤25th percentile by sex. Age, body mass index z-score, 2H-PG, HOMA-IR and WBISI, increased across sex-quintiles of UA while FG did not. The prevalence of IFG and IR were significantly increased in Q5 vs Q1 (reference quartile, P < 0.025). The prevalence of IGT increased from Q3 to Q5 vs Q1 (P < 0.025–0.0001) and that of low IS from Q2 to Q5 vs Q1 (P < 0.005–0.0001).ConclusionsIn youth with OW/OB, rates of IGT and low IS increased progressively across quintiles of UA. On the contrary, IFG and IR were associated only with the highest quintile of UA. Our data suggest that UA is a biomarker of impaired glucose metabolism prevalently in post–challenge condition rather than in fasting state.     

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。     

遗传因素对糖耐量异常人群高血压的影响

分析６５２例糖耐量异常人群高血压发病的危险因素，结果显示伴高血压压病家族史者高血压的患病率显著高于不伴高血压病家族史。多因素Ｌｏｇｉｓｔｉｃ逐步回归分析表明，阳性高血压病家族史是本组人群最重要的致高血压病危险因素（ＯＲ１１７．２，９５％ＣＩ６８．１－２０１．６）。年体重指数和尿微量白蛋白与高血压呈显著正相关。提示在高血压防治对对伴高血压病家族史的糖耐量异常人群应予以特别的注意，而着意减肥和更严格地     

Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.

AIMS: To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT). METHODS: Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored. RESULTS: Rosiglitazone significantly improved the insulin sensitivity index by 2.26 micro g/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126). CONCLUSIONS: Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects.     

吡格列酮对伴糖耐量减低的代谢综合征患者血管内皮细胞功能的影响

目的 研究吡格列酮（PIO）对伴糖耐量减低（IGT）的代谢综合征（MS）患者血管内皮细胞功能的影响.方法 对22例伴IGT的MS患者用PIO30mg/d治疗4个月.治疗前后测定外周组织葡萄糖摄取率（GDR）、胰岛素敏感指数（ISI）、内皮依赖性血管舒张功能（EDVD）,并监测血丙二醛（MDA）、还原型谷胱甘肽（GSH）、高敏C反应蛋白（hsC-RP）、血糖、Ins、HbA1c和FFA水平的改变.结果 治疗后EDVD明显改善、GDR增加（P均＜0.01）,ISI升高（P均＜0.05）.血糖、Ins、HbA1c、FFA、MDA及hsC-RP水平降低（P均＜0.01）,GSH水平升高（P＞0.05）.结论 短期PIO治疗能使伴IGT的MS患者的内皮细胞功能明显改善,其机制可能与缓解内皮细胞胰岛素抵抗以及氧化应激和慢性炎症状态有关.     

Serum sialic acid in subjects with impaired glucose tolerance and in newly diagnosed type 2 diabetic patients

Several general population studies and those carried out in diabetic patients with complications have pointed to serum sialic acid as a marker of inflammation in atherosclerosis. In this study we examined whether total sialic acid (TSA) was changed in the sera of 28 newly diagnosed subjects with type 2 diabetes (type 2 DM), 47 subjects with impaired glucose tolerance (IGT) and 72 subjects with normal glucose tolerance (NGT). The associations between sialic acid and other atherosclerotic risk factors such as lipid profile, baseline diene conjugates in low-density lipoproteins (LDL-BDC) and fasting insulin were also investigated. We found a trend to TSA increase in subjects with impaired glucose tolerance and a significant increase in TSA in newly diagnosed patients with type 2 DM (2.2±0.3 vs. 1.9±0.3 mmol/l; p<0.03) when compared to subjects with NGT. Lipid profile and LDL-BDC, as a marker of circulating oxidized LDL, did not differ among glucose tolerance categories. Significant associations between total sialic acid and 2-h post-load glucose level, fasting insulin, insulin sensitivity, HDL-cholesterol and log of triglycerides were found in the examined subjects. Multiple regression analysis showed significant correlations between serum sialic acid and 2-h post-load glucose levels and insulin sensitivity. This study indicates that measurement of TSA as a marker of subclinical inflammation may be valuable as an independent parameter in identifying subjects at higher risk of developing type 2 diabetes and those who might benefit from anti-inflammatory treatment. Received: 10 May 2002 / Accepted in revised form: 15 April 2003 Correspondence to M. Gavella     

Fasting plasma glucose and glycated haemoglobin in the screening of diabetes and impaired glucose tolerance

Abstract. The use of fasting plasma glucose (FPG) only has been proposed for the screening and diagnosis of diabetes, but its sensitivity has been reported to be unsatisfactory. The use of HbA_1C, alone or combined with FPG, has been suggested for the screening of diabetes and impaired glucose tolerance (IGT). In a sample of 1215 adult subjects without previously known diabetes, we assessed the sensitivity and specificity of FPG and HbA_1C in diagnosing diabetes and IGT, determined by oral glucose tolerance test (OGTT). All lean diabetic patients, and 85% of overweight and obese diabetic individuals, had FPG 7 mmol/l. FPG >6.1 mmol/l had a sensitivity of 98.8% and a specificity of 32.9%; HbA_1C had a lower specificity and sensitivity for the screening of diabetes. A screening strategy for diabetes based on FPG, with OGTT in all overweight subjects with FPG >6.1 mmol/l, is suggested. Neither FPG nor HbA_1C is effective in the screening of IGT; although combined FPG and HbA_1C could be useful for case finding, screening for IGT with OGTT is advisable in all subjects at high risk.     

Early and late insulin response as predictors of NIDDM in Pima Indians with impaired glucose tolerance

Summary Risk factors predicting deterioration to diabetes mellitus were examined in 181 subjects with impaired glucose tolerance. Fifty-seven subjects had impaired glucose tolerance on one occasion followed by normal glucose tolerance at a repeat oral glucose tolerance test, and 124 subjects had impaired glucose tolerance on two successive oral glucose tolerance tests. Subjects were followed for a median period of 5.0 years (range 1.0–17.2). The age- and sex-adjusted cumulative incidence of diabetes at 10 years of follow-up was higher in subjects who had impaired glucose tolerance on both tests (70%) than in those whose glucose tolerance was normal at the repeat test (53%), [rate ratio (RR)=1.6, 95% confidence intervals (CI)=1.0–2.5]. Proportional hazards analyses were used to identify baseline risk factors (measured at the repeat oral glucose tolerance test) for subsequent diabetes, and incidence rate ratios were calculated for the 90th percentile compared with the 10th percentile of each continuous variable for the whole group. In all subjects, in separate models, higher body mass index [RR=2.0, 95% CI=2.2–9.9], high fasting serum insulin concentrations [RR=2.4, 95% CI=1.4–4.2], and low early insulin response [RR=0.5, 95% CI=0.3–0.8] 30 min after a glucose load were significant predictors for deterioration to diabetes. In a multivariate analysis which controlled for age and sex, 120-min post-load glucose, fasting insulin and late insulin response predicted diabetes. In subgroup analyses the predictors of diabetes were generally similar in subjects who had impaired glucose tolerance at only one test and those who had impaired glucose tolerance on both tests. These findings suggest that in those subjects with impaired glucose tolerance whose glucose tolerance has returned to normal, the risk of subsequent diabetes is high. Insulin resistance, impaired early insulin response, or both, are predictive of subsequent development of diabetes in Pima Indians with impaired glucose tolerance.Abbreviations IGT Impaired glucose tolerance - OGTT oral glucose tolerance test - NGT normal glucose tolerance - CV coefficient of variation     

空腹血糖受损患者糖耐量异常及影响因素分析

目的了解空腹血糖受损(IFG)患者糖耐量异常(IGT)情况及其影响因素。方法纳入空腹血糖为5.6~6.1 mmol/L的IFG患者337例,检测患者口服75克葡萄糖后2小时血糖等资料,分析患者IGT情况及其影响因素。结果纳入的337例IFG患者中46.6%(157/337)伴有IGT。口服葡萄糖耐量异常和正常组超重和肥胖率分别为75.0%和63.1%(P0.05);口服葡萄糖耐量异常组甘油三酯水平显著高于正常组,高密度脂蛋白胆固醇水平低于正常组,均有统计学差异(P0.05)。多因素Logistic回归分析结果显示,年龄、体重指数、甘油三酯水平是IFG患者葡萄糖耐量异常的影响因素,相对危险分别为:1.06(95%CI:1.03~1.08);1.11(95%CI:1.05~119);1.58(95%CI:1.23~2.09)。进一步对体重正常者发生糖耐量异常的影响因素进行分析,除年龄外,甘油三酯水平是空腹血糖受损患者糖耐量异常的影响因素,相对危险为2.10(95%CI:1.29~3.43)。结论空腹血糖受损患者约半数伴有糖耐量异常,体重指数和甘油三酯水平是空腹血糖受损患者糖耐量异常的影响因素。     

High plasma insulin and triglyceride concentrations and blood pressure in offspring of people with impaired glucose tolerance

The plasma glucose and insulin response to an oral glucose challenge, fasting plasma lipid concentration, and blood pressure were compared in 13 offspring of parents previously diagnosed as having impaired glucose tolerance (IGT) and 13 offspring of parents previously shown to have normal glucose tolerance. The parents with IGT had higher plasma glucose, insulin and triglyceride concentration, and blood pressure than parents with normal glucose tolerance. The two groups of offspring were young and non-obese, and similar in terms of age, gender distribution, and body mass index. However, the total integrated plasma insulin response during a 75 g oral glucose tolerance test was significantly higher (p less than 0.05, Student's t-test) in offspring of parents with IGT (718 +/- 71 pmol l-1 h) than in the subjects whose parents had normal glucose tolerance (524 +/- 47 pmol l-1 h). In addition, serum triglyceride concentration was somewhat higher in offspring of parents with IGT (1.17 +/- 0.11 vs 0.92 +/- 0.08 mmol l-1, 0.10 greater than p greater than 0.05), as were both systolic (132 +/- 5 vs 118 +/- 3 mmHg, p less than 0.05) and diastolic (79 +/- 3 vs 70 +/- 2 mmHg, p less than 0.05) blood pressure. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that these changes have a genetic component.     

高血压合并糖耐量减低患者血清脂联素水平的研究

非高血压(HT)者43例,其中糖耐量正常者(NGT)30例,糖耐量减低者(IGT)13例。HT者45例,其中17例伴NGT,28例伴IGT,研究显示:脂联素水平(mg/L)HT伴NGT组低于非HT的NGT组(4.3±1.7vs7.1±3.6),HT伴IGT组低于非HT的IGT组(4.0±2.1vs6.6±1.4)(P均<0.05);NGT与IGT组脂联素水平的差异无统计学意义;IGT组脂联素与DBP、TG、C肽负相关;NGT组脂联素水平与BMI、SBP负相关。     

Ingestion of an exogenous ketone monoester improves the glycemic response during oral glucose tolerance test in individuals with impaired glucose tolerance: A cross-over randomized trial

Aims/IntroductionAs a low‐carbohydrate diet and the use of sodium–glucose transporter‐2 inhibitors are both known to increase D‐beta‐hydroxybutyrate levels, the effect of these levels on glucose metabolism has attracted attention. We investigated the acute effects of ketone monoester (KM) ingestion on blood glucose levels during the 75‐g oral glucose tolerance test (OGTT) in participants with impaired glucose tolerance.Materials and MethodsNine Japanese adults aged 48–62 years (4 men, 5 women) with impaired glucose tolerance participated in this study. After participants fasted overnight, we carried out OGTT for 180 min with and without KM ingestion on two separate days in a randomized cross‐over design. We compared the area under the curve (AUC) of D‐beta‐hydroxybutyrate, glucose, insulin, C‐peptide, glucagon and free fatty acids during OGTT.ResultsThe AUC of D‐beta‐hydroxybutyrate during OGTT was significantly higher with KM than without KM (KM 5995.3 ± 1257.1 mmol/L·h; without KM 116.1 ± 33.9 mmol/L·h, P < 0.0001), and the AUC of glucose with KM was significantly lower than that without KM (KM 406.6 ± 70.6 mg/dL·h; without KM 483.2 ± 74.3 mg/dL·h, P < 0.0001). This improved glucose excursion was associated with enhanced AUC of insulin during the first half (0–90 min) of OGTT, even though the AUC of C‐peptide during this period was unchanged. In contrast, the AUC of insulin, C‐peptide, glucagon and free fatty acids during 180 min of OGTT were similar in both conditions.ConclusionThe ingestion of KM decreased the AUC of glucose during 75‐g OGTT in Japanese individuals with impaired glucose tolerance, and the mechanism might involve elevated levels of circulating early phase insulin.