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1.
Aims/hypothesis We compared five surrogate insulin sensitivity (IS) methods against the euglycaemic–hyperinsulinaemic clamp. These methods were the homeostasis model assessment (HOMA) and four methods based on the OGTT (OGIS, MCRest, ISIcomp, SIORAL).Methods We compared these IS methods against the clamp (0.28 nmol·min–1·m–2 insulin infusion) M value in 147 women (58–61 years; BMI 19–38 kg/m2; 116 NGT, 25 IFG/IGT, six type 2 diabetic), by evaluating the correlation coefficient with M. We also tested the ability to reproduce the relationships between IS and typical IS correlates (BMI, fasting insulin, insulin to glucose OGTT area ratio and fasting, 2 h and mean glucose) by means of the discrepancy index D, in which (1) D=0 if the correlation between IS and the variable of interest is as with the clamp, (2) D is smaller than 0 if the correlation is overestimated, and (3) D is greater than 0 if underestimated.Results All IS methods correlated with M (r=0.57–0.83, p<0.0001); for MCRest the relationship was markedly curvilinear. All IS measures correlated with the considered variables (r=0.29–0.94, p<0.0005); however, no method had D0 for all variables. The best surrogates of M were OGIS (one D0) and MCRest (two D0); the other methods either under- or overestimated the degree of correlation (three or more D0), in particular with fasting insulin (HOMA: D=–57%; ISIcomp: D=–36%) and BMI (HOMA: D=–14%; ISIcomp: D=–14%; SiORAL: D=–11%).Conclusions/interpretation All IS methods were correlated with M. OGIS and MCRest were preferable to the other methods and in particular to HOMA for reproducing relationships with the independent variables.  相似文献   

2.
Given the extreme increase in prediabetes, type 2 diabetes, and the potential for metabolic syndrome in obese youth, identifying simplified indexes for assessing stimulated insulin sensitivity is critical. The purpose of this study was validation of two surrogate indexes of insulin sensitivity determined from the oral glucose tolerance test (OGTT): the composite whole body insulin sensitivity index (WBISI) and the insulin sensitivity index (ISI). An obese population (aged 8-18 yr) of normal and impaired glucose tolerance individuals was studied. One group (n = 38) performed both the euglycemic-hyperinsulinemic clamp and OGTT for comparison of insulin sensitivity measurements as well as (1)H-magnetic resonance spectroscopy estimates of intramyocellular lipid content. Another larger (n = 368) cohort participated only in an OGTT. Both the WBISI and ISI represented good estimates (r = 0.78 and 0.74; P < 0.0005) for clamp-derived insulin sensitivity (glucose disposed, M-value), respectively. In the large cohort, the surrogate indexes demonstrated the shift toward poorer function and increased risk profile as a function of insulin resistance. Additionally, the WBISI and ISI correlated with intramyocellular lipid content (r = -0.74 and -0.71; P < 0.0001), a tissue marker for insulin resistance. Insulin sensitivity can be estimated using plasma glucose and insulin responses derived from the OGTT in obese youth with normal and impaired glucose tolerance.  相似文献   

3.
近十年来,青少年肥胖人群迅速扩大,随之而来的是2型糖尿病发病的年轻化,那些处于糖调节受损状态的肥胖青少年往往患有严重的胰岛素抵抗(IR) ,导致成年后较早出现高血压、血脂异常以及代谢综合征。判断胰岛素敏感性或胰岛素抵抗程度的指标包括( 1)正常血糖高胰岛素钳夹试验和( 2 )需要多次采血的静脉葡萄糖耐量试验(微小模型法) ,这两种方法比较经典,但费用高,操作复杂,取血量大。( 3 )基于空腹血糖和空腹胰岛素的稳态模型分析法(HOMA)也是一种评估胰岛素敏感性的方法。然而,肥胖所致的胰岛素抵抗主要是由于餐后升高的胰岛素不能够有效地…  相似文献   

4.
AimSimple estimates of insulin secretion feasible for large epidemiological studies have been proposed in adults, but have been little evaluated in young people. For this reason, this study examined the correlation between OGTT-derived and fasting-based indices of insulin secretion against the acute insulin response to glucose (AIRg) in children.MethodsTwenty subjects (nine boys and 11 girls; mean [SD] age: 9 [2] years) were studied. Their mean (SD) BMI Z score was 1.5 (0.8). All participants had normal fasting and 2-h post-load glucose. Each subject underwent an insulin-modified minimal model frequently sampled intravenous glucose tolerance test (FSIVGTT) as the reference method, and a 3-h OGTT. AIRg was computed from the FSIVGTT. A total of ten indices were calculated using OGTT data, while HOMA%beta (original formula) and HOMA2%beta (computer-based) were computed from fasting samples. Correlations were established using Spearman's rank correlations.ResultsOf the ten indices derived from the OGTT, those most closely correlated with the AIRg (using FSIVGTT) included the insulinogenic indext30 min (r = 0.80), insulin/glucose ratiot30 min (r = 0.71) and ratio of the area under the curve for insulin to glucoset0-30 min (r = 0.74). Both the HOMA%beta and HOMA2%beta correlated modestly with AIRg (r = 0.62 and r = 0.65, respectively).ConclusionOur results suggest that OGTT-derived measures of insulin secretion provide adequate estimates of first-phase insulin secretion in youth. HOMA2%beta and HOMA%beta represent acceptable compromises, although HOMA2%beta may be preferable in younger individuals, as it allows for a wider spectrum of insulin and glucose values that are physiological in this age group.  相似文献   

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6.
A new insulin sensitivity index was devised on the basis of an autoregressive model and its validity was investigated. Using data from the 75-g oral glucose tolerance test (OGTT), 115 subjects were divided into 3 groups: 40 with normal glucose tolerance, 34 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus. The new insulin sensitivity index: oral glucose insulin sensitivity index (GSI) was calculated from five sets of plasma glucose and insulin levels obtained at 0, 30, 60, 90 and 120 min during OGTT using a formula based on an autoregressive model. Forty-three of the 115 subjects were examined for insulin sensitivity index (ISI) by euglycemic hyperinsulinemic clamp. GSI decreased in the order of normal glucose tolerance group>impaired glucose tolerance group>diabetic group. There was a significant correlation between GSI and the ISI derived from euglycemic hyperinsulinemic clamp study data in all 43 subjects who underwent both tests (r=0.72; P<0.0001). The ISI calculated by previous methods poorly correlated with the ISIs obtained by euglycemic hyperinsulinemic clamp study. In conclusion, this new insulin sensitivity index based on the data obtained from OGTT using an autoregressive model is comparable to an insulin sensitivity index by euglycemic hyperinsulinemic clamp technique and may be superior to previous indexes that have been devised to determine insulin sensitivity from OGTT data.  相似文献   

7.
The aim of this study was to assess the changes in insulin secretion and insulin sensitivity in relation to fasting and 2-hour plasma glucose (PG) levels and to assess the independent contributions of their impairments to non-diabetic hyperglycemia. A total of 2157 Japanese workers (mean age 52.6±7.3 years and mean BMI 23.9±3.2 kg/m(2)) underwent an oral glucose tolerance test (OGTT). Of these subjects, 1125 had normal glucose tolerance (NGT), 525 subjects had isolated impaired fasting glucose (IFG), 159 subjects had isolated impaired glucose tolerance (IGT), 263 subjects had combined IFG and IGT, and 85 subjects had newly diagnosed type 2 diabetes. Insulinogenic index and Matsuda insulin sensitivity index (ISI) were significantly attenuated in subjects with normal but slightly elevated fasting PG, or in subjects with normal but slightly elevated 2-hour PG. Whereas, InsAUC(120)/GluAUC(120) was not significantly decreased in those subjects, and significant decrease of it was observed exclusively in subjects with abnormal fasting PG (≥ 106 mg/dL) or abnormal 2-hour PG (≥ 221 mg/dL). Using multiple regression analyses, both Matsuda ISI and insulinogenic index were independently correlated with PG concentrations in subjects with IFG and/or IGT, while Matsuda ISI alone was independently correlated with fasting PG concentrations in normoglycemic subjects. In conclusion, both insulinogenic index and Matsuda ISI were significantly attenuated in subjects with normal but slightly elevated PG. Lowering of Matsuda ISI was likely to be a strong contributor to 'elevation of fasting PG within the normal range' in this population.  相似文献   

8.
Novel insulin sensitivity index derived from oral glucose tolerance test   总被引:9,自引:0,他引:9  
The euglycemic hyperglycemic clamp is generally regarded as a reference method for assessing insulin sensitivity. However, this method is laborious and expensive. The oral glucose tolerance test (OGTT), the most commonly used method for evaluating whole body glucose tolerance, has often been used to assess insulin sensitivity. In the previous studies the correlation between the insulin sensitivity index (ISI) obtained from the OGTT (ISI(OGTT)) and those obtained from the glucose clamp (ISI(Clamp)) may not be satisfactory. This is because the glucose clamp study is designed for measuring peripheral glucose utilization, whereas plasma glucose responses during the OGTT are the results of peripheral glucose utilization and hepatic glucose production. Based on this problem, we developed a new equation, ISI(OGTT), [1.9/6 x body weight (kg) x fasting plasma glucose (mmol/liter) + 520 - 1.9/18 x body weight x area under the glucose curve (mmol/h.liter) - urinary glucose (mmol)/1.8] / [area under the insulin curve (pmol/h.liter) x body weight], which would represent peripheral glucose utilization only. We tested our equation with ISI(Clamp) and also compared with others. Thirty-three healthy volunteers (16 males) with normal glucose tolerance underwent a 75-g, 3-h OGTT on the morning of d 1 and a glucose clamp on the morning of d 2. Their mean (+/-SD) age and body mass index were 30.8 +/- 8.3 yr and 22.0 +/- 3.9 kg/m(2), respectively. The mean (+/-SD) glucose disposal rate and ISI determined by glucose clamp were 27.46 +/- 16.55 micro mol/kg.min and 7.39 +/- 2.72 micro mol/kg.min/pmol.liter, respectively. Pearson's correlation coefficient between our ISI(OGTT) and ISI(Clamp) was 0.869 (P < 0.0001) which was stronger than those corresponding values calculated from HOMA, QUICKI, Belfiore, Cederholm, Gutt, Matsuda, and Stumvoll, the respective values of which were 0.404, 0.434, 0.643, 0.533, 0.584, 0.734, and 0.508. In conclusion, the ISI(OGTT) derived from our equation is more suitable than others in assessing insulin sensitivity in subjects with normal glucose tolerance. Further studies in subjects with impaired glucose tolerance and diabetes mellitus should be performed to confirm the validity of this equation.  相似文献   

9.
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11.
This study compares indices of insulin sensitivity derived from fasting and oral glucose tolerance test (OGTT) glucose and insulin measurements, with respect to the reference measure (M/I), obtained from the euglycemic-hyperinsulinemic clamp, in postmenopausal women with varying glucose tolerance status. Fasting plasma insulin index, homeostasis model assessment index, and OGTT-derived indices (insulin 120-minute, Matsuda, metabolic clearance rate [MCR] of glucose, insulin sensitivity [ISI], and Cederholm indices) were calculated and compared with the M/I value in 112 postmenopausal women. All indices examined were significantly correlated with M/I (0.28 < or = r(2) < or = 0.56). Association studies revealed that on average, 48% of women were grouped in the same tertile of insulin sensitivity when using M/I and fasting plasma insulin index, and 54% when using M/I and insulin 120-minute index. However, concordance with M/I tertiles were 57%, 58%, 64%, 64%, and 68% for homeostasis model assessment, Matsuda, MCR, ISI, and Cederholm indices, respectively. Finally, correlation coefficients between M/I and insulin sensitivity indices were generally lower in women with normal glucose tolerance compared with women with impaired glucose tolerance or type 2 diabetes mellitus. These results suggest that in postmenopausal women, surrogate indices of insulin sensitivity obtained from OGTT data and incorporating a measurement of body weight or body mass index) (Cederholm, ISI, and MCR indices) appear to be superior to those without OGTT data or body weight-body mass index measurements and, therefore, could offer a better estimate of insulin sensitivity, allowing an improved clinical evaluation of this population at higher risk of cardiovascular disease and type 2 diabetes mellitus.  相似文献   

12.
We have investigated the reproducibility of (1) insulin sensitivity (S*I) and glucose effectiveness (S*G) as measured by the stable-label (one compartment) minimal model, and (2) insulin sensitivity (S*Ib), plasma clearance rate (PCR), basal hepatic output (HGOb), and total hepatic glucose output (HGO0–240) as measured by the novel stable-label two compartment model of glucose disappearance during labelled intravenous glucose tolerance test (IVGTT) using 6,6-2H-glucose. Ten normal male subjects were studied on two occasions one week apart. Both models provided estimates of all indices with acceptable precision (CV of parameter estimates ≤50 %). The within subject CVs of S*I and S*Ib were comparable (17 % vs 19 %) as were the within subject CVs of S*G and PCR (13 % vs 16 %). A highly significant linear relationship was observed between S*Ib and S*I (0.303 ± 0.046 ml kg−1 min−1 per mU l−1 vs 13.04 ± 1.89 10−4 min−1 per mU l−1, y = 0.0037 x + 0.0002, r = 0.90, p <0.001; mean ± SE), but not between PCR and S*G (1.98 ± 0.15 ml kg−1 min−1 vs 0.0089 ± 0.0005 min−1, rs = 0.34, NS). The two compartment model provided a plausible time-profile of hepatic glucose output during IVGTT, reproducible estimates of HGOb (1.96 ± 0.18 mg kg−1 min−1, 15 %; mean ± SE, within subject CV), and a highly reproducible HGO0–240 (7 %; within subject CV). We conclude that the stable-label (one compartment) minimal model and the stable-label two compartment model provide reproducible estimates of parameters of glucose kinetics in normal subjects. Insulin sensitivity indices estimated by the two models are strongly linearly related. © 1998 John Wiley & Sons, Ltd.  相似文献   

13.
目的:本文探讨转换酶抑制剂及ATl受体拮抗剂对血管紧张素Ⅱ(A ngⅡ)受体的作用.方法:SHR与WKY大鼠服用两种不同药物(benaxepril和losartan),检测动物肾皮质AT1 mRNA表达情况和AT1受体密度.原发性高血压患者服用benaxepril或losartan后检测血小板AT1 mRNA的表达情况.结果:SHR喂用benazepril后肾脏AT1 mRNA和AT1受体密度均无明显变化,而喂用losartan后肾脏AT1 mRNA及AT1受体密度则明显降低.SHR肾AT1受体密度在benazepril组无明显变化,而在losartan组明显降低.相应的高血压患者服用benaxepril后血小板AT1 mRNA无明显变化,而losartan组benaxepril后血小板AT1 mRNA的表达明显降低.结论:AT1RA能下调AngⅡ受体密度而ACEI则无此作用,ACEI和AT1RA对肾皮质RAS系统作用机制是不同的.测定人血小板的AT1 mRNA是反映AT1受体状况的有用指标 .  相似文献   

14.
目的:本文探讨转换酶抑制剂及AT1受体拮抗剂对血管紧张素Ⅱ(AngⅡ)受体的作用。方法:SHR与WKY大鼠服用两种不同药物(benaxepril和losartan),检测动物肾皮质AT1mRNA表达情况和AT1受体密度。原发性高血压患者服用benaxepril或losartan后检测血小板AT1mRNA的表达情况。结果:SHR喂用benazepril后肾脏AT1mRNA和QT1受体密度均无明显变化  相似文献   

15.
Plasma glucose and insulin concentrations have been used in genetic studies as quantitative phenotypic traits and also as surrogates for insulin sensitivity and beta-cell function. However, the significance of these traits in relation to insulin sensitivity and beta-cell function was unknown. We examined how insulin sensitivity and beta-cell function affected plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). This is a cross-sectional study enrolling 105 glucose-tolerant subjects (64 females; age, 18 to 40 years; body mass index, 17.58 to 37.57 kg/m(2); waist-to-hip ratio, 0.649 to 1.033 cm/cm). They participated in both OGTTs and hyperglycemic clamps. The relationship between plasma glucose and insulin concentrations and indices of insulin sensitivity and beta-cell function was examined. Univariate analyses showed that insulin sensitivity index (ISI) had some influence on plasma insulin concentrations (r(2) =.2623 to.3814) during the OGTT; however, it had only modest impacts on plasma glucose levels at 60, 90, and 120 minutes (r(2) =.0537 to.1300). Neither first phase (1stIR) nor second phase insulin response (2ndIR) affected plasma glucose concentrations. Multivariate analyses showed an independent impact (all P <.0001) of ISI on plasma glucose concentrations at 60, 90, and 120 minutes and on plasma insulin concentrations at every time point except at 30 minutes. Except for plasma insulin concentration at 30 minutes, of which 24% of the variation can be explained by 1stIR, beta-cell function (either 1stIR or 2ndIR) only had a very modest impact on 30-, 60-, 90- and 120-minute plasma glucose concentrations and on plasma insulin concentration at 60 minutes. In glucose-tolerant subjects, ISI plays an important role in determining postchallenged plasma glucose concentrations at 60, 90, and 120 minutes, as well as plasma insulin concentrations at fasting, 60, 90, and 120 minutes. However, beta-cell function is only reflected in plasma insulin concentration at 30 minutes through 1stIR. Therefore, we conclude that it is essential to measure beta-cell function in vivo if one plans to study the genetic influence of beta-cell dysfunction.  相似文献   

16.
Summary Oral glucose tolerance test (OGTT) results were compared between 4,667 middle-aged males attending a preventive medical screening and intervention program in Malm? and the subjects in this sample who reported a history of previous operation for gastric or duodenal ulcer (n=158, or 3.4%), 76% of the operated subjects were smokers in comparison with 50% in the general cohort of males of the same age. The glucose and insulin responses in the OGTT in both the smoking and non-smoking operated cases showed higher early peak values and a subsequent rapid drop of the levels with lower 120-min values of both glucose and insulin compared to the average screening cohort. This type of response to an oral glucose load had previously been well known in the acute and immediate postoperative stages of gastric and duodenal resection, but it had not been shown before that it seems to be a permanent effect and may chronically influence the results of OGTTs in the population. Gastro-duodenal surgery should be included among the factors which may significantly affect the chronic results and thereby also the clinical interpretation of the OGTTs in the population. Supported by the Swedish Tobacco Company.  相似文献   

17.
Oral and iv glucose tolerance, insulin response to iv and oral glucose load as well as insulin sensitivity were evaluated in 58 'low insulin responders'. They were selected from a group of 226 healthy subjects with normal fasting blood glucose and normal iv glucose tolerance test on the basis of a low insulin response during a standardized glucose infusion test (GIT). The insulin response to GIT was analysed by parameter identification in a mathematical model (parameter KI). Insulin sensitivity was also measured by computer analysis of GIT (parameter KG) and, in a limited group of subjects, by a somatostatin infusion test. Thirty-three low insulin responders had normal OGTT, whereas 5 demonstrated borderline-1, 16 borderline-2, and 4 decreased OGTT. The first group of subjects demonstrated normal or enhanced insulin sensitivity. Borderline and decreased OGTT, in most instances, was accompanied by decreased insulin sensitivity, implying that a subgroup of low insulin responders exhibited signs of both impaired insulin response to glucose and insulin resistance. Since these defects characterize manifest type-2 diabetes, these subjects possibly may run a high risk to develop this type of diabetes. On the other hand, low insulin response in combination with increased insulin sensitivity may reflect adaptation of the secretory capacity of B-cells to the need of insulin.  相似文献   

18.
In a material of 3596 oral glucose tolerance tests (OGTT) performed in a population investigation of middle-aged males in Malm?, fasting and 120 min values of blood glucose and plasma insulin immunoreactivity (IRI) were studied while taking factors like body weight, smoking, alcohol, gastric resection and selfreported diabetes heredity into account. The fasting as well as the 120 min levels of both glucose and IRI were markedly influenced by body weight and smoking habits but not by the hereditary background. At 120 min, but not in the fasting state, there was a linear correlation between the IRI and glucose levels. The increase of IRI on glucose was significantly steeper in most of the hereditary subjects in comparison with their non-hereditary controls.  相似文献   

19.
OBJECTIVES The assessment of insulin sensitivity requires an accurate and reproducible technique. The short insulin tolerance test is a simple and rapid method for screening large numbers of subjects when the fasting glucose level is normal. Conventionally, an insulin dose of 0·1 units/kg is used, but this may result in symptomatic hypoglycaemia in healthy thin subjects who are insulin sensitive. In order to overcome this problem we have employed a lower dose of insulin and have studied the reproducibility of this modified technique comparing it with the euglycaemic hyperinsulinaemic clamp. DESIGN Subjects were studied on two separate occasions, once by a short insulin tolerance test and on a second occasion by either a euglycaemic hyperinsulinaemic clamp (insulin infusion of 40 mU/m2/min) or a repeat short insulin tolerance test. PATIENTS Eleven healthy subjects were studied twice with a short insulin tolerance test. A further 10 healthy subjects received a short insulin tolerance test on one day and a euglycaemic hyperinsulinaemic clamp study on another occasion. MEASUREMENTS Insulin sensitivity was measured in the short insulin tolerance test using the slope of arterialized blood glucose concentration from 3 to 15 minutes after an intravenous bolus of short-acting insulin, 0·05 units/kg body weight. In the clamp study, insulin sensitivity was derived from the average amount of glucose infused at steady state (M) and the mean plasma insulin level (l). RESULTS In the short insulin tolerance test no subject developed symptomatic or biochemical hypoglycaemia, defined as a blood glucose < 2·2 mmol/l. The (mean ± SEM) insulin sensitivities for the 11 subjects studied twice were 174±10 and 179±11 μmol/l/min with a coefficient of variation of 6·9±2·6%. There was a close correlation between insulin sensitivity derived from the short insulin tolerance test and that obtained from the euglycaemic clamp studies (so-called M/l ratio) in the same subjects (r= 0·81; P < 0·005). CONCLUSION The short insulin tolerance test employing 0·05 units/kg insulin is a safe, valid and reproducible method for the assessment of insulin sensitivity.  相似文献   

20.
Both insulin secretion and insulin sensitivity are important in the development of diabetes but current methods used for their measurements are complex and cannot be used for epidemiological surveys. This study describes a simplified approach for the estimation of first phase insulin release and insulin sensitivity from a standard 40-min intravenous glucose tolerance test (IVGTT), and compares these parameter estimations with the sophisticated minimal model analysis of a frequently sampled 3-h IVGTT and the euglycaemic clamp technique. For the simplified IVGTT, first phase insulin release was measured as the insulin area above basal post glucose load unit-1 incremental change (i.e. peak rise) in plasma glucose over 0-10 min, and insulin sensitivity as a rate of glucose disappearance (Kg) unit-1 insulin increase above basal from 0-40 min post-glucose load in 18 subjects who were studied twice, either basally or in a perturbed pathophysiological state (i.e. pre- and post-ultramarathon race, n = 5; pre- and post-20 h pulsatile hyperinsulinaemia, n = 8; pre- and post-thyrotoxic state, n = 5). A further 12 subjects were compared by IVGTT, and glucose clamp. In addition, seven dogs were studied three times by IVGTT during normal saline infusion and after short-term (1/2 hour) or long-term (72 hour) adrenaline infusions. First phase insulin release and insulin sensitivity estimated from the simplified IVGTT as calculated by the two methods correlated closely (rs = 0.89 and rs = 0.87, respectively), although less precisely in markedly insulin-resistant subjects and the slopes and y intercepts of the linear regression lines were similar in the basal and perturbed states.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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