Improved quantification of muscle insulin sensitivity using oral glucose tolerance test data: the MISI Calculator.
Ontology highlight
ABSTRACT:
SUBMITTER: O'Donovan SD
PROVIDER: S-EPMC6598992 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveWe investigated the natural history of glucokinase (GCK)-related maturity-onset diabetes of the young type 2 (MODY2), notably the factors associated with deterioration of hyperglycemia over time.Research design and methodsWe report an 11-year follow-up of glucose tolerance and indexes of insulin secretion and insulin sensitivity derived from oral glucose tolerance tests in 33 MODY2 subjects.ResultsThe variation between tests of glucose tolerance (expressed as the area under the glucose curve) was 6.9 +/- 3.2% (mean +/- SEM), but individual results ranged from -20 to 61%. Deterioration of glucose tolerance between tests was associated with decreased insulin sensitivity, while insulin secretion remained stable.ConclusionsGlucose tolerance can remain stable over many years in subjects with MODY2 due to the relative stability of the GCK-related beta-cell defect. However, the development of insulin resistance may have an important role in the deterioration of the glucose tolerance and in the long-term evolution of the disorder.
| S-EPMC2453674 | biostudies-literature
Project description:IntroductionThe Oral Minimal Model (OMM), a differential-equations based mathematical model of glucose-insulin dynamics, utilizes data from a frequently sampled oral glucose tolerance test (OGTT) to quantify insulin sensitivity ( SI ). OMM-based estimates of SI can detect differences in insulin resistance (IR) across population groups and quantify effects of clinical or behavioral interventions. These estimates of SI have been validated in healthy adults using data from OGTTs with durations from 2 to 7 h. However, data demonstrating how protocol duration affects SI estimates in highly IR populations such as adolescents with obesity are limited.MethodsA 6-h frequently sampled OGTT was performed in adolescent females with obesity. Two, 3-, and 4- hour implementations of OMM assuming an exponentially-decaying rate of glucose appearance beyond measured glucose concentrations were compared to the 6-h implementation. A 4- hour OMM implementation with truncated data (4h Tr) was also considered.ResultsData from 68 participants were included (age 15.8 ± 1.2 years, BMI 35.4 ± 5.6 kg/m2). Although SI values were highly correlated for all implementations, they varied with protocol duration (2h: 2.86 ± 3.31, 3h: 2.55 ± 2.62, 4h: 2.81 ± 2.59, 4h tr: 3.13 ± 3.14, 6h: 3.06 ± 2.85 x 10-4 dl/kg/min per U/ml). SI estimates based on 2 or 3 h of data underestimated SI values, whereas 4-h SI estimates more closely approximated 6-h SI values.DiscussionThese results suggest that OGTT protocol duration should be considered when implementing OMM to estimate SI in adolescents with obesity and other IR populations.
| S-EPMC7817496 | biostudies-literature
Project description:Impaired glucose tolerance (IGT) is diagnosed by a standardized oral glucose tolerance test (OGTT). However, the OGTT is laborious, and when not performed, glucose tolerance cannot be determined from fasting samples retrospectively. We tested if glucose tolerance status is reasonably predictable from a combination of demographic, anthropometric, and laboratory data assessed at one time point in a fasting state.Given a set of 22 variables selected upon clinical feasibility such as sex, age, height, weight, waist circumference, blood pressure, fasting glucose, HbA1c, hemoglobin, mean corpuscular volume, serum potassium, fasting levels of insulin, C-peptide, triglyceride, non-esterified fatty acids (NEFA), proinsulin, prolactin, cholesterol, low-density lipoprotein, HDL, uric acid, liver transaminases, and ferritin, we used supervised machine learning to estimate glucose tolerance status in 2,337 participants of the TUEF study who were recruited before 2012. We tested the performance of 10 different machine learning classifiers on data from 929 participants in the test set who were recruited after 2012. In addition, reproducibility of IGT was analyzed in 78 participants who had 2 repeated OGTTs within 1?year.The most accurate prediction of IGT was reached with the recursive partitioning method (accuracy?=?0.78). For all classifiers, mean accuracy was 0.73?±?0.04. The most important model variable was fasting glucose in all models. Using mean variable importance across all models, fasting glucose was followed by NEFA, triglycerides, HbA1c, and C-peptide. The accuracy of predicting IGT from a previous OGTT was 0.77.Machine learning methods yield moderate accuracy in predicting glucose tolerance from a wide set of clinical and laboratory variables. A substitution of OGTT does not currently seem to be feasible. An important constraint could be the limited reproducibility of glucose tolerance status during a subsequent OGTT.
| S-EPMC5868129 | biostudies-literature
Project description:Obesity is associated with metabolic inflexibility, the inability to switch from lipid to glucose oxidation during physiological conditions favoring excess glucose and insulin, which could contribute to the increased incidence of type 2 diabetes. Despite this knowledge, the role of skeletal muscle metabolites during these physiological conditions remain unclear and warrant further investigation. The purpose of this pilot study is to determine if: 1) there are differences in skeletal muscle glycolysis and TCA metabolites and amino acids between lean and obese individuals in the fasted state, and 2) if these metabolites change after 50 min of glucose ingestion, and 3) if there are differences in these metabolites between lean and obese individuals after 50 min of glucose ingestion.
2017-08-02 | ST000836 | MetabolomicsWorkbench
Project description:OBJECTIVE To determine if glucose and C-peptide values obtained as part of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study could be used to estimate insulin sensitivity during late pregnancy. RESEARCH DESIGN AND METHODS A total of 78 women enrolled in the HAPO study were recruited for this ancillary study. Venous plasma samples were drawn after an 8- to 10-h fast (time 0) and at 30, 60, 90, and 120 min after a 75-g glucose challenge, which was performed at 24-32 weeks' gestation. Samples were analyzed for plasma glucose, insulin, and C-peptide. Insulin sensitivity was estimated using the established Matsuda and DeFronzo insulin sensitivity index for oral glucose tolerance tests (IS(OGTT)). Insulin sensitivity was also calculated from two other commonly used indexes of insulin sensitivity (that for homeostasis model assessment [IS(HOMA)] and that for quantitative insulin sensitivity check index [IS(QUICKI)]). A new insulin sensitivity index was calculated using the glucose and C-peptide concentrations at 0 and 60 min to derive IS(HOMA C-pep), IS(QUICKI C-pep), and IS(OGTT C-pep). These indexes were then correlated with insulin sensitivity estimated from the IS(OGTT). RESULTS The strongest correlation with the IS(OGTT) was obtained for IS(OGTT C-pep) (r = 0.792, P < 0.001). Further, the correlations of IS(HOMA) (C-pep) and IS(QUICKI C-pep) with IS(OGTT) were also significant (r = 0.676, P < 0.001 and r = 0.707, P < 0.001, respectively). CONCLUSIONS These data suggest that calculated IS(OGTT C-pep) is an excellent predictor of insulin sensitivity in pregnancy and can be used to estimate insulin sensitivity in over 25,000 women participating in the HAPO study.
| S-EPMC2827494 | biostudies-literature
Project description:Aims/hypothesisHomozygous staggerer (sg/sg) mice, which have decreased and dysfunctional Ror? (also known as Rora) expression in all tissues, display a lean and dyslipidaemic phenotype. They are also resistant to (high fat) diet-induced obesity. We explored whether retinoic acid receptor-related orphan receptor (ROR) ? action in skeletal muscle was involved in the regulation of glucose metabolism.MethodsWe used a three-armed genomic approach, including expression profiling, ingenuity analysis and quantitative PCR validation to identify the signalling pathway(s) in skeletal muscle that are perturbed in sg/sg mice. Moreover, western analysis, functional insulin and glucose tolerance tests, and ex vivo glucose uptake assays were used to phenotypically characterise the impact of aberrant v-AKT murine thymoma viral oncogene homologue (AKT) signalling.ResultsHomozygous and heterozygous (sg/sg and sg/+) animals exhibited decreased fasting blood glucose levels, mildly improved glucose tolerance and increased insulin sensitivity. Illumina expression profiling and bioinformatic analysis indicated the involvement of ROR? in metabolic disease and phosphatidylinositol 3-kinase-AKT signalling. Quantitative PCR and western analysis validated increased AKT2 (mRNA and protein) and phosphorylation in sg/sg mice in the basal state. This was associated with increased expression of Tbc1d1 and Glut4 (also known as Slc2a4) mRNA and protein. Finally, in agreement with the phenotype, we observed increased (absolute) levels of AKT and phosphorylated AKT (in the basal and insulin stimulated states), and of (ex vivo) glucose uptake in skeletal muscle from sg/sg mice relative to wild-type littermates.Conclusions/interpretationWe propose that Ror? plays an important role in regulation of the AKT2 signalling cascade, which controls glucose uptake in skeletal muscle.
| S-EPMC3071927 | biostudies-literature
Project description:AimDPP4 inhibitors are widely prescribed as treatments for type 2 diabetes. Because drug responses vary among individuals, we initiated investigations to identify genetic variants associated with the magnitude of drug responses.MethodsSitagliptin (100 mg) was administered to 47 healthy volunteers. Several endpoints were measured to assess clinically relevant responses - including the effect of sitagliptin on glucose and insulin levels during an oral glucose tolerance test (OGTT).ResultsThis pilot study confirmed that sitagliptin (100 mg) decreased the area under the curve for glucose during an OGTT (p=0.0003). Furthermore, sitagliptin promoted insulin secretion during the early portion of the OGTT as reflected by an increase in the ratio of plasma insulin at 30 min divided by plasma insulin at 60 min (T30:T60) from 0.87+/-0.05 to 1.62+/-0.36 mU/L (p=0.04). The magnitude of sitagliptin's effect on insulin secretion (as judged by the increase in the T30:T60 ratio for insulin) was correlated with the magnitude of sitagliptin-induced increase in the area under the curve for intact plasma GLP1 levels during the first hour of the OGTT. This study confirmed previously reported sex differences in glucose and insulin levels during an OGTT. Specifically, females exhibited higher levels of glucose and insulin at the 90-180 min time points. However, we did not detect significant sex-associated differences in the magnitude of sitagliptin-induced changes in T30:T60 ratios for either glucose or insulin.ConclusionsT30:T60 ratios for insulin and glucose during an OGTT provide useful indices to assess pharmacodynamic responses to DPP4 inhibitors.
| S-EPMC10557823 | biostudies-literature
Project description:BackgroundInsulin resistance (IR) is predictive for type 2 diabetes and associated with various metabolic abnormalities in fasting conditions. However, limited data are available on how IR affects metabolic responses in a non-fasting setting, yet this is the state people are mostly exposed to during waking hours in the modern society. Here, we aim to comprehensively characterise the metabolic changes in response to an oral glucose test (OGTT) and assess the associations of these changes with IR.MethodsBlood samples were obtained at 0 (fasting baseline, right before glucose ingestion), 30, 60, and 120 min during the OGTT. Seventy-eight metabolic measures were analysed at each time point for a discovery cohort of 4745 middle-aged Finnish individuals and a replication cohort of 595 senior Finnish participants. We assessed the metabolic changes in response to glucose ingestion (percentage change in relative to fasting baseline) across the four time points and further compared the response profile between five groups with different levels of IR and glucose intolerance. Further, the differences were tested for covariate adjustment, including gender, body mass index, systolic blood pressure, fasting, and 2-h glucose levels. The groups were defined as insulin sensitive with normal glucose (IS-NGT), insulin resistant with normal glucose (IR-NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and new diabetes (NDM). IS-NGT and IR-NGT were defined as the first and fourth quartile of fasting insulin in NGT individuals.ResultsGlucose ingestion induced multiple metabolic responses, including increased glycolysis intermediates and decreased branched-chain amino acids, ketone bodies, glycerol, and triglycerides. The IR-NGT subgroup showed smaller responses for these measures (mean + 23%, interquartile 9-34% at 120 min) compared to IS-NGT (34%, 23-44%, P < 0.0006 for difference, corrected for multiple testing). Notably, the three groups with glucose abnormality (IFG, IGT, and NDM) showed similar metabolic dysregulations as those of IR-NGT. The difference between the IS-NGT and the other subgroups was largely explained by fasting insulin, but not fasting or 2 h glucose. The findings were consistent after covariate adjustment and between the discovery and replication cohort.ConclusionsInsulin-resistant non-diabetic individuals are exposed to a similar adverse postprandial metabolic milieu, and analogous cardiometabolic risk, as those with type 2 diabetes. The wide range of metabolic abnormalities associated with IR highlights the necessity of diabetes diagnostics and clinical care beyond glucose management.
| S-EPMC6883544 | biostudies-literature
Project description:Insulin-like growth factor 1 (IGF1) is a key factor for tissue growth and fuel metabolism. The potential function of central IGF1 remains unclear. We previously observed that IGF1 expression is increased in the hypothalamus of obese mice lacking STAT5 in the central nervous system (CNS). In this study, we explored the potential metabolic function of central IGF1 by intracerebroventricular (ICV) injection of IGF1, over-expression of central IGF1 by administering an adeno-associated virus (AAV), and ICV injection of an anti-IGF1 antibody. Mice that over-expressed central IGF1 displayed increased appetite, improved glucose tolerance and insulin sensitivity, decreased Pomc levels in the hypothalamus, and increased UCP1 expression in brown fat tissue. This is the first study demonstrating that central IGF1 regulates several important metabolic functions.
| S-EPMC5865549 | biostudies-literature
Project description:The associations of body mass index (BMI) and liver fat (LF) with circulating prandial metabolomic markers are incompletely understood.We aimed to characterize circulating metabolite excursions during an oral glucose tolerance test (OGTT) and evaluate whether the metabolomic signatures of BMI discordance coassociate with LF content.We measured 80 metabolite parameters by nuclear magnetic resonance, together with glucose and insulin, during a 2-hour OGTT in 64 monozygotic (MZ) and 73 dizygotic (DZ) twin pairs (aged 22.8 to 36.2 years). Metabolite excursions during the OGTT were compared within BMI-discordant (intrapair difference, BMI ? 3 kg/m2) cotwins separately within MZ and DZ pairs. Insulin-based indices were calculated from the OGTT. LF was measured by magnetic resonance spectroscopy in 25 BMI-discordant MZ pairs. Metabolite profiles were compared with respect to LF discordance (?LF% ? 2%).We replicated many previously reported OGTT-induced metabolite excursions in all 274 individuals and report novel lipoprotein excursions. The associations between some metabolite excursions and BMI differed in MZ and DZ twins. In BMI-discordant MZ pairs (mean ?BMI = 4.9 kg/m2) who were concordant for LF (?0.2%), few metabolites differed between the cotwins: very-low-density lipoprotein (VLDL) cholesterol and apolipoprotein B were elevated, and high-density lipoprotein size and concentration were decreased in the cotwins with higher BMI. In contrast, in BMI-discordant MZ pairs (?BMI = 6.1 kg/m2) who were discordant for LF (?6.8%), cotwins with higher BMI exhibited lower insulin sensitivity and widespread metabolomic differences: elevations in small VLDL and low-density lipoprotein particles, fatty acids (FAs), and isoleucine. Within all 64 MZ twin pairs, lower insulin sensitivity associated with higher levels of VLDLs, triglycerides, FAs, and isoleucine.BMI-discordant MZ twin pairs who also are discordant for LF have more pronounced within-pair differences in metabolomics profiles during an OGTT than BMI-discordant pairs without LF discordance.
| S-EPMC6287394 | biostudies-other