The shape of the glucose concentration curve during an oral glucose tolerance test predicts risk for type 1 diabetes

Aims/hypothesis

We aimed to examine: (1) whether specific glucose-response curve shapes during OGTTs are predictive of type 1 diabetes development; and (2) the extent to which the glucose-response curve is influenced by insulin secretion.

Methods

Autoantibody-positive relatives of people with type 1 diabetes whose baseline OGTT met the definition of a monophasic or biphasic glucose-response curve were followed for the development of type 1 diabetes (n = 2627). A monophasic curve was defined as an increase in OGTT glucose between 30 and 90 min followed by a decline of ≥ 0.25 mmol/l between 90 and 120 min. A biphasic response curve was defined as a decrease in glucose after an initial increase, followed by a second increase of ≥ 0.25 mmol/l. Associations of type 1 diabetes risk with glucose curve shapes were examined using cumulative incidence curve comparisons and proportional hazards regression. C-peptide responses were compared with and without adjustments for potential confounders.

Results

The majority of participants had a monophasic curve at baseline (n = 1732 [66%] vs n = 895 [34%]). The biphasic group had a lower cumulative incidence of type 1 diabetes (p < 0.001), which persisted after adjustments for age, sex, BMI z score and number of autoantibodies (p < 0.001). Among the monophasic group, the risk of type 1 diabetes was greater for those with a glucose peak at 90 min than for those with a peak at 30 min; the difference persisted after adjustments (p < 0.001). Compared with the biphasic group, the monophasic group had a lower early C-peptide (30–0 min) response, a lower C-peptide index (30–0 min C-peptide/30–0 min glucose), as well as a greater 2 h C-peptide level (p < 0.001 for all).

Conclusions/interpretation

Those with biphasic glucose curves have a lower risk of progression to type 1 diabetes than those with monophasic curves, and the risk among the monophasic group is increased when the glucose peak occurs at 90 min than at 30 min. Differences in glucose curve shapes between the monophasic and biphasic groups appear to be related to C-peptide responses.

     

Correlation between fasting plasma glucose and two-hour plasma glucose during oral glucose tolerance test in South Indians

The diagnostic criteria for diabetes have been recently revised and the fasting plasma glucose (FPG) level reduced to 126 mg/dL, since the earlier cutoff of 140 mg/dL was considered to correspond to a much higher level than the 2-hour postglucose (2 h PG) value of 200 mg/dL. However, there are few data directly correlating FPG and 2 h PG during an oral glucose tolerance test (OGTT). This study reports on a retrospective analysis of 5,936 OGTTs performed at a diabetes center in South India and attempts to correlate the FPG and 2 h PG values. Using a 2 h PG of 200 mg/dL or higher as the diagnostic criterion, 46.7% of the cohort had diabetes. The corresponding values using the old FPG of 140 mg/dL or higher and the new FPG of 126 mg/dL or higher were 31.7% and 39.8%, respectively. If the FPG was further reduced to 118 mg/dL, the "diabetic yield" increased to 45.8%, ie, it approached the figures based on a 2 h PG of > or =200 mg/dL. Various regression equations were used to correlate FPG and 2 h PG values. When FPG was used as the dependent variable, the semilogarithmic regression equation provided the best fit, and using this model, the 2 h PG of 200 mg/dL corresponds to a FPG of 118 mg/dL. When the 2 h PG was used as the dependent variable, the log-log model provided the best fit, and using this model, a 2 h PG of 200 mg/dL corresponds to a FPG of 118 mg/dL. Thus, a FPG of 118 mg/dL seems to correlate with a 2 h PG of 200 mg/dL in South Indians.     

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。     

Predictive ability of fasting plasma glucose for a diabetic 2-h postload glucose value in oral glucose tolerance test: spectrum effect

The performance of diagnostic tests may vary according to patient characteristics. The aim of this study is to find out the factors, if any, that may affect the performance of fasting plasma glucose (FPG) to predict a diabetic 2-h postload glucose level (> or =200 mg/dl) in oral glucose tolerance test (OGTT). One hundred ninety-six patients with known risk factors for diabetes mellitus to whom OGTT was applied were included. Factors that may have an effect on the performance of FPG in prediction of a diabetic value in OGTT were determined by using logistic regression and likelihood ratios (LRs). The cutoff of FPG predicting a 2-h postload glucose of > or =200 mg/dl was calculated by receiver operating characteristic curve as 110 mg/dl (sensitivity, 76.7%; specificity, 75.9%). Waist-to-hip ratio (WHR) and body mass index (BMI) influenced sensitivity, whereas age, family history, and presence of hyperlipidemia affected specificity of FPG. Significant factors for positive LR were age and hyperlipidemia, whereas sex, smoking, hyperlipidemia, physical inactivity, WHR, and BMI influenced negative LR. Fasting plasma glucose performance as a diagnostic test can be affected by many factors that are clearly stated as risk factors for diabetes mellitus. These data emphasize how the interpretation of a diagnostic test varies as the patient characteristics vary; the criteria that we confidently rely on may not be that reliable, changing between just two different patients.     

Changes in plasma amino acids during the oral glucose tolerance test in hepatic diseases

We have measured the plasma concentration of neutral amino acids before and after an oral glucose tolerance test (100 g) in patients with liver cirrhosis (LC), chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), acute hepatitis in the acute stage (AHa) and acute hepatitis in the convalescent stage (AHc) and normal controls. The ratio of the concentration of an amino acid to the sum of those of the other neutral amino acids that compete during transport through the blood brain barrier (BBB), which was reported to correlate well with the brain level of the amino acid, was compared in patients with various liver diseases. The ratios of Trp (Trp/Tyr + Phe + Ile + Leu + Val), Tyr, Phe, and Val increased after glucose loading in all subjects, except Tyr in normal controls, which slightly decreased. On the other hand, Ile and Leu ratios decreased (Trp; tryptophan, Tyr; tyrosine, Phe; phenylalanine, Ile; isoleucine, Leu; leucine, Val; valine). LC showed a characteristic pattern; the ratios of Trp and Tyr were highest among all diseases at 3 hours after glucose loading, and those of Ile, Leu and Val were lowest. We assumed that delta an amino acid ratio = the amino acid ratio at 3 hrs after glucose loading minus the amino acid ratio at 0 hr. In LC, delta Trp ratio and delta Tyr ratio were highest, while delta Val ratio was lowest. The delta Phe ratios in AHa and AHc were significantly higher than those in healthy controls. From these results, the uptake of Trp and Tyr might be supposed to be highest and that of Val was lowest in LC, after glucose loading.     

Outcome of glucose tolerance condition in patients with normal glucose tolerance with either persistently high or low 1-h postchallenge glucose levels in 75 g oral glucose tolerance test

International Journal of Diabetes in Developing Countries - This study aimed to investigate whether persistently high 1-h postchallenge glucose (PG) levels in a 75&nbsp;g oral glucose tolerance...     

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.     

The normal range of the plasma immunoreactive glucagon level during a 75 g oral glucose tolerance test

In order to establish a normal value of plasma glucagon immunoreactivity (GI) and glucagon-like immunoreactivity (GLI) during a newly adopted 75 g OGTT, 50 normals (N), 102 individuals with IGT and 20 diabetics (D) were subjected to the OGTT, and their plasma GI and GLI levels were determined at various intervals by radioimmunoassay using 2 kinds of the C-terminal region specific antibody, OAL123 and 30K, and of the antibody specific for the N-terminal and/or central region of glucagon, OAL196, respectively. The basal levels of OAL123-GI and 30K-GI and OAL196-GLI in the 3 groups were as follows; N, 114.3, 80.8, and 335.5; IGT, 107.6, 76.1, and 338.5; and D, 135.7, 76.9, and 342.2 pg/ml. After glucose administration, a significant decrease in plasma GI and increase in plasma GLI were observed in the 3 groups, although their changes from the basal levels were variable. The plasma samples of inexplicably high GI concentration were chromatographed to clarify the nature of the hyperglucagonemia. The apparent GI was mostly eluted in the Vo component, but negligibly at the 3500 mol.wt. glucagon fraction. There was a marked difference in the Vo peak depending upon the antiserum used. These facts suggest that plasma GI values are dependent on the amount of BPG present in particular samples, and the antibody used.     

Paradoxical release of growth hormone during oral glucose tolerance test in patients with abnormal glucose tolerance

Oral glucose tolerance tests were performed on 24 patients characterized as having abnormal glucose tolerance (AGT) and on 27 control subjects. Serums for glucose, growth hormone and insulin determinations were serially obtained for 4 hr after glucose administration. As serum glucose declined 2 hr or more after glucose ingestion a rise in growth hormone, as has been previously described, was observed in 40% of control subjects and 12% of AGT patients. However, of interest was a paradoxical early increase in growth hormone levels noted in 44% of lean AGT subjects occurring during the first 2 hr of the test with glucose levels rising. This response was seen in only one of 8 obese patients with AGT and in none of the control subjects. An abnormality in the hypothalamic glucose receptors in the ventromedial nucleus is a possible explanation for the changes observed. It is possible that this early inappropriate increase in growth hormone release may in some nonobese subjects with AGT contribute to the abnormal oral glucose tolerance tests observed.     

Relation between plasma insulin and blood glucose in a cross-sectional population study of the oral glucose tolerance test

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.