Novel insulin sensitivity index derived from oral glucose tolerance test

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.     

Prediction of clamp-derived insulin sensitivity from the oral glucose insulin sensitivity index

Aims/hypothesis

The euglycaemic–hyperinsulinaemic clamp is the gold-standard method for measuring insulin sensitivity, but is less suitable for large clinical trials. Thus, several indices have been developed for evaluating insulin sensitivity from the oral glucose tolerance test (OGTT). However, most of them yield values different from those obtained by the clamp method. The aim of this study was to develop a new index to predict clamp-derived insulin sensitivity (M value) from the OGTT-derived oral glucose insulin sensitivity index (OGIS).

Methods

We analysed datasets of people that underwent both a clamp and an OGTT or meal test, thereby allowing calculation of both the M value and OGIS. The population was divided into a training and a validation cohort (n?=?359 and n?=?154, respectively). After a stepwise selection approach, the best model for M value prediction was applied to the validation cohort. This cohort was also divided into subgroups according to glucose tolerance, obesity category and age.

Results

The new index, called PREDIcted M (PREDIM), was based on OGIS, BMI, 2 h glucose during OGTT and fasting insulin. Bland–Altman analysis revealed a good relationship between the M value and PREDIM in the validation dataset (only 9 of 154 observations outside limits of agreement). Also, no significant differences were found between the M value and PREDIM (equivalence test: p?<?0.0063). Subgroup stratification showed that measured M value and PREDIM have a similar ability to detect intergroup differences (p?<?0.02, both M value and PREDIM).

Conclusions/interpretation

The new index PREDIM provides excellent prediction of M values from OGTT or meal data, thereby allowing comparison of insulin sensitivity between studies using different tests.

     

Comparative evaluation of simple insulin sensitivity methods based on the oral glucose tolerance test

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.     

Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents

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.     

肥胖青少年胰岛素敏感性分析

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…     

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

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 .     

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

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     

Oral glucose tolerance test and insulin sensitivity in low insulin responders

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.     

Relative contribution of insulin sensitivity and beta-cell function to plasma glucose and insulin concentrations during the oral glucose tolerance test.

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.     

Insulin release and peripheral sensitivity at the oral glucose tolerance test

With the use of a 75 g oral glucose tolerance test, both insulin release (IRG) and the degree of peripheral sensitivity (SI) were evaluated simultaneously in groups with normal (NGT) and impaired (IGT) glucose tolerance as well as NIDDM. IRG was expressed as the ratio of the area under the insulin curve to that of the glucose curve above fasting levels. The peripheral glucose uptake rate (M) during the OGTT was measured as the difference between the glucose load and the increase in the amount of glucose in the glucose space during the oral glucose tolerance test (OGTT). SI was expressed as the ratio of the metabolic clearance rate (M/mean blood glucose) to log mean serum insulin. In the non-obese groups, both mean IRG and mean SI values were decreased with an increasing degree of hyperglycemia from NGT to NIDDM. Decreased mean SI values were also found in obese subjects. IGT-subjects given 3 months of diet and exercise achieved improved SI values. A non-obese NIDDM-group had higher mean IRG and mean SI values after 6 months of treatment with glipizide. The results were comparable to data obtained with more complicated techniques, such as the insulin clamp and suppression tests, and should be easy to apply on a large scale in epidemiological studies.     

Insulin secretion and insulin sensitivity on the oral glucose tolerance test (OGTT) in middle-aged Japanese

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.     

Assessment of insulin sensitivity and beta-cell function from measurements in the fasting state and during an oral glucose tolerance test

Aims/hypothesis. We aimed to find if the relation between insulin sensitivity and beta-cell function assessed from fasting and OGTT measurements has a physiological shape (hyperbolic with the reference methods). Methods. Healthy women without diabetic first-degree relatives underwent a 75 g OGTT with plasma glucose and insulin (n = 35) concentrations being measured at 0, 30, 60 and 120 min. Beta-cell function and insulin sensitivity were estimated using previously described indices from fasting (1 for beta-cell function, 6 for insulin sensitivity) and OGTT measurements (3 for beta-cell function and 5 for insulin sensitivity). A hyperbolic relation was tested for the 21 beta-cell function-insulin sensitivity pairs using a non-lineal regression method. Results. The assessment of beta-cell function from OGTT was impossible in seven women and one had outlier indices. For the remaining 27 women, only 8 combinations adjusted to a hyperbolic relation. The best adjustment was achieved using the fasting glucose to insulin ratio as the estimation of insulin sensitivity and the homeostasis model assessment (HOMA) index (single fasting sample) as the estimation of beta-cell function (r ² 0.802, k 869.71, p < 0.001). Conclusion/interpretation. In this group of healthy women, the estimation of insulin sensitivity and beta-cell function by most methods using OGTT-derived glucose and insulin measurements did not adjust to a hyperbolic relation but all fasting indices combinations did. Beta-cell function estimated with the HOMA index and insulin sensitivity with fasting glucose to insulin ratio had the best adjustment. [Diabetologia (2000) 43: 1507–1511] Received: 29 June 2000 and in revised form: 16 August 2000     

Measuring insulin sensitivity in postmenopausal women covering a range of glucose tolerance: comparison of indices derived from the oral glucose tolerance test with the euglycemic-hyperinsulinemic clamp

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.     

Estimating insulin secretion in youth using simple indices derived from the oral glucose tolerance test

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 index_{t30 min} (r = 0.80), insulin/glucose ratio_{t30 min} (r = 0.71) and ratio of the area under the curve for insulin to glucose_{t0-30 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.     

Validation of simple indices to assess insulin sensitivity based on the oral glucose tolerance test in the Japanese population

The homeostasis model assessment (HOMA) represents a simple index for evaluating insulin sensitivity, but clinical use is limited. Insulin sensitivity indices calculated from plasma glucose and plasma insulin concentrations after an oral glucose tolerant test (OGTT) have been proposed, but have not been validated in the Japanese population. We compared these indices with the euglycemic hyperinsulinemic clamp technique to evaluate the predicting insulin sensitivities in 77 Japanese subjects with varying degrees of glucose tolerance (normal glucose tolerance, n=40; impaired glucose tolerance, n=22; and type 2 diabetes mellitus, n=15). Insulin sensitivity was measured by the euglycemic hyperinsulinemic glucose clamp technique using an artificial pancreas, and expressed as the M-value. Weak inverse correlations existed between the HOMA index and M-values (r=-0.227, P=0.0468). An alternative index calculated by Matsuda's formula correlated with the M-value (r=0.450, P=0.0001). A second index calculated by Stumvoll's formula also correlated with the M-value (r=0.641, P=0.0001). Finally, a third index calculated by Gutt's formula also significantly correlated with the M-value (r=0.526, P=0.0001). All three indices are applicable for clinical use. The second index is the most sensitive measure of insulin sensitivity in the Japanese population.     

正常糖耐量者口服葡萄糖-胰岛素释放试验的胰岛素分泌曲线特点的研究

目的研究口服葡萄糖一胰岛素释放试验（OGIRT）的胰岛素（Ins）分泌曲线特点,初步探讨适用于I临床评价个体胰岛素敏感性和8细胞分泌功能的方法。方法对12例正常糖耐量者行OGIRT和静脉糖耐量试验（IVGTT）,观察OGIRT、IVGTT血浆Ins分泌峰值时间分布频数,分析胰岛素敏感性和B细胞功能各指标相关指数。结果OGIRT血浆Ins分泌高峰出现于35-45min,无明显第二分泌峰。经多因素线性回归分析表明20、30、35minIns增值与葡萄糖增值的比值（ΔI20／ΔG20、ΔI30／ΔG30、ΔI35／ΔG35）与第一相（1PH）胰岛素分泌、葡萄糖及胰岛素曲线下面积比值（SGI）、胰岛素作用指数（IAI）、HOMA—IR、胰岛素分泌指数均不相关（P〉0．05）,ΔI40／ΔG40与SGI、IAI、HOMA-IR显著相关（P均〈0．01）。结论OGIRT可能不能反映1PH;OGIRTΔI40／ΔG40比I20／ΔG20、△I30／ΔG30能更好地评估β细胞功能。     

A simple method for quantitation of insulin sensitivity and insulin release from an intravenous glucose tolerance test.

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)