scholarly journals Variability in Estimated Modelled Insulin Secretion

2021 ◽  
pp. 193229682199112
Author(s):  
Jennifer J. Ormsbee ◽  
Hannah J. Burden ◽  
Jennifer L. Knopp ◽  
J. Geoffrey Chase ◽  
Rinki Murphy ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Kinetic Parameters ◽  
Pancreatic Beta Cells ◽  
Compartment Model ◽  
Interquartile Range ◽  
Cumulative Distribution ◽  
Model Framework ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Model Based

Background: The ability to measure insulin secretion from pancreatic beta cells and monitor glucose-insulin physiology is vital to current health needs. C-peptide has been used successfully as a surrogate for plasma insulin concentration. Quantifying the expected variability of modelled insulin secretion will improve confidence in model estimates. Methods: Forty-three healthy adult males of Māori or Pacific peoples ancestry living in New Zealand participated in an frequently sampled, intravenous glucose tolerance test (FS-IVGTT) with an average age of 29 years and a BMI of 33 kg/m2. A 2-compartment model framework and standardized kinetic parameters were used to estimate endogenous pancreatic insulin secretion from plasma C-peptide measurements. Monte Carlo analysis (N = 10 000) was then used to independently vary parameters within ±2 standard deviations of the mean of each variable and the 5th and 95th percentiles determined the bounds of the expected range of insulin secretion. Cumulative distribution functions (CDFs) were calculated for each subject for area under the curve (AUC) total, AUC Phase 1, and AUC Phase 2. Normalizing each AUC by the participant’s median value over all N = 10 000 iterations quantifies the expected model-based variability in AUC. Results: Larger variation is found in subjects with a BMI > 30 kg/m2, where the interquartile range is 34.3% compared to subjects with a BMI ≤ 30 kg/m2 where the interquartile range is 24.7%. Conclusions: Use of C-peptide measurements using a 2-compartment model and standardized kinetic parameters, one can expect ~±15% variation in modelled insulin secretion estimates. The variation should be considered when applying this insulin secretion estimation method to clinical diagnostic thresholds and interpretation of model-based analyses such as insulin sensitivity.

Development of hyperinsulinemia and insulin resistance during the early stage of weight gain

2008 ◽  
Vol 294 (3) ◽  
pp. E568-E575 ◽  
Author(s):  
Johannes Erdmann ◽  
Bianca Kallabis ◽  
Ulrich Oppel ◽  
Oleg Sypchenko ◽  
Stefan Wagenpfeil ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Weight Gain ◽  
Early Stage ◽  
Normal Range ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Glucose Levels ◽  
Hyperglycemic Clamp ◽  
First Time

Obesity is associated with insulin resistance and hyperinsulinemia, which is considered to be a core component in the pathophysiology of obesity-related comorbidities. As yet it is unknown whether insulin resistance and hyperinsulinemia already develop during weight gain within the normal range. In 10 healthy male subjects the effect of intentional weight gain by 2 BMI points was examined on insulin. C-peptide and glucose levels following a meal, 75 g of glucose, and a two-step hyperglycemic clamp increased plasma glucose by 1.38 and 2.75 mmol/l, respectively. Baseline insulin, C-peptide, and glucose concentrations were significantly higher after weight gain from 21.8 to 23.8 kg/m2 BMI within 41/2 mo. Calculations of insulin secretion and clearance indicate that reduced insulin clearance contributes more to post-weight gain basal hyperinsulinemia than insulin secretion. Following oral or intravenous stimulation insulin concentrations were significantly higher post-weight gain during all three test conditions, whereas C-peptide and glucose levels did not differ. Calculations of insulin secretion and clearance demonstrated that higher stimulated insulin concentrations are entirely due to clearance but not secretion. Despite significantly higher insulin levels, the rate of intravenous glucose required to maintain the defined elevation of glucose levels was either identical (1.38 mmol/l) or even significantly lower (2.75 mmol/l) following weight gain. The present study demonstrates for the first time that insulin resistance already develops during weight gain within the normal range of body weight. The associated basal and stimulated hyperinsulinemia is the result of differentiated changes of insulin secretion and clearance, respectively.

Plasma C-peptide and insulin in trained and untrained subjects

1981 ◽  
Vol 50 (1) ◽  
pp. 71-77 ◽  
Author(s):  
A. Wirth ◽  
C. Diehm ◽  
H. Mayer ◽  
H. Morl ◽  
I. Vogel ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Plasma Insulin ◽  
Time Course ◽  
Recovery Period ◽  
Rebound Effect ◽  
Insulin Response ◽  
Work Load ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
C Peptide

Plasma insulin and C-peptide were simultaneously determined under various conditions in 11 endurance-trained athletes and 12 nonathletes. Both groups performed an exhaustive ergometer test and an endurance test with 38% of the maximal achieved work load for 45 min. An intravenous glucose tolerance test was also performed. In the basal state, athletes had low plasma insulin and C-peptide concentrations. During exercise, insulin and C-peptide decreased similarly in both groups. In the recovery period, insulin and C-peptide rose within a few minutes. There were differences between the extent as well as the time course of this "rebound" effect after exhaustive or endurance exercise that might be related to glucose alterations. The insulin response but not the C-peptide response after glucose injection was blunted in trained subjects. Results indicate that basal plasma insulin concentrations are lower in athletes due to reduced insulin secretion. During exercise, insulin secretion is diminished independent of the training state. The blunted response of insulin after glucose administration in athletes is due to an enhanced plasma clearance.

Insulin and C-Peptide Levels After Oral and Intravenous Glucose: Contribution of Enteroinsular Axis to Insulin Secretion

Diabetes ◽  
1986 ◽  
Vol 35 (5) ◽  
pp. 612-616 ◽  
Author(s):  
S. M. Hampton ◽  
L. M. Morgan ◽  
J. A. Tredger ◽  
R. Cramb ◽  
V. Marks
Keyword(s):  
Insulin Secretion ◽  
Enteroinsular Axis ◽  
Intravenous Glucose ◽  
C Peptide

scholarly journals Increased insulin clearance in mice with double deletion of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors

2018 ◽  
Vol 314 (5) ◽  
pp. R639-R646 ◽  
Author(s):  
Andrea Tura ◽  
Roberto Bizzotto ◽  
Yuchiro Yamada ◽  
Yutaka Seino ◽  
Giovanni Pacini ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Clearance ◽  
Second Phase ◽  
Incretin Hormones ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Double Deletion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
First Phase Insulin Secretion

To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO ( n = 31) and wild-type (WT) C57BL6J mice ( n = 45) were intravenously injected with d-glucose (0.35 g/kg). Blood was sampled for 50 min and assayed for glucose, insulin, and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection. Assessment of C-peptide kinetics revealed that C-peptide clearance was 1.66 ± 0.10 10−3 1/min. After intravenous glucose administration, insulin clearance during first phase insulin secretion was markedly higher in DIRKO than in WT mice (0.68 ± 0.06 10−3 l/min in DIRKO mice vs. 0.54 ± 0.03 10−3 1/min in WT mice, P = 0.02). In contrast, there was no difference between the two groups in insulin clearance during second phase insulin secretion ( P = 0.18). In conclusion, this study evaluated C-peptide kinetics in the mouse and exploited a mathematical model to estimate insulin clearance. Results showed that DIRKO mice have higher insulin clearance than WT mice, following intravenous injection of glucose. This suggests that incretin hormones reduce insulin clearance at physiological, nonstimulated levels.

scholarly journals Influence of Tacrolimus on Glucose Metabolism before and after Renal Transplantation: A Prospective Study

2001 ◽  
Vol 12 (3) ◽  
pp. 583-588 ◽  
Author(s):  
ELLY M. VAN DUIJNHOVEN ◽  
JOHANNES M. M. BOOTS ◽  
MAARTEN H. L. CHRISTIAANS ◽  
BRUCE H. R. WOLFFENBUTTEL ◽  
JOHANNES P. VAN HOOFF
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Prospective Longitudinal Study ◽  
C Peptide ◽  
Before And After ◽  
Prospective Longitudinal

Abstract. Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the influence of tacrolimus on glucose metabolism before and after transplantation. Eighteen Caucasian dialysis patients underwent an intravenous glucose tolerance test before and 5 d after the start of tacrolimus. Insulin sensitivity index (kG), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus were measured. After transplantation, the occurrence of posttransplantation diabetes mellitus (PTDM) was prospectively monitored. Statistical analysis was performed using the Wilcoxon signed ranks test and Spearman's rho for correlation. Before tacrolimus, kG was indeterminate in three patients. During tacrolimus, kG decreased in 16 of 18 patients, from a median of 1.74 mmol/L per min to 1.08 mmol/L per min (P < 0.0001). The correlation between C-peptide and insulin data was excellent. Insulin secretion decreased from 851.0 mU × min/L to 558.0 mU × min/L (P = 0.014), whereas insulin resistance did not change. Insulin sensitivity correlated negatively with tacrolimus trough level. After transplantation, three patients developed PTDM; before tacrolimus, two had an indeterminate and one a low normal kG. During tacrolimus administration, kG decreased in almost all patients as a result of a diminished insulin secretion response to a glucose load, whereas insulin resistance did not change. Patients with an abnormal or indeterminate kG seem to be at risk of developing PTDM while on tacrolimus.

scholarly journals The Incretin Effect in Female Mice With Double Deletion of GLP-1 and GIP Receptors

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Bo Ahrén ◽  
Yuichiro Yamada ◽  
Yutaka Seino
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Insulin Response ◽  
Oral Glucose ◽  
Incretin Effect ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Female Mice

Abstract To establish the contribution of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) for the incretin effect after oral glucose, studies were undertaken in female mice with genetic deletion of receptors for GIP and GLP-1 (double incretin receptor knockout [DIRKO] mice) and their wild-type (WT) counterparts. Insulin secretion was explored after oral glucose (doses ranging from 0 to 100 mg), after intravenous glucose (doses ranging from 0 to 0.75 g/kg), and after oral and intravenous glucose at matching circulating glucose. DIRKO mice had glucose intolerance after oral glucose challenges in association with impaired beta-cell function. Suprabasal area under the curve for C-peptide (AUCC-peptide) correlated linearly with suprabasal AUCglucose both in WT (r = 0.942, P = .017) and DIRKO mice (r = 0.972, P = .006). The slope of this regression was lower in DIRKO than in WT mice (0.012 ± 0.006 vs 0.031 ± 0.006 nmol C-peptide/mmol glucose, P = .042). In contrast, there was no difference in the insulin response to intravenous glucose between WT and DIRKO mice. Furthermore, oral and intravenous glucose administration at matching glucose levels showed that the augmentation of insulin secretion after oral glucose (the incretin effect) in WT mice (11.8 ± 2.3 nmol/L min) was entirely absent in DIRKO mice (3.3 ± 1.2 nmol/L min). We conclude that GIP and GLP-1 are required for normal glucose tolerance and beta-cell function after oral glucose in mice, that they are the sole incretin hormones after oral glucose at higher dose levels, and that they contribute by 65% to insulin secretion after oral glucose.

scholarly journals Patterns of Insulin Secretion During First-Phase Insulin Secretion in Normal Chinese Adults

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Yuan ◽  
Shuoning Song ◽  
Tianyi Zhao ◽  
Yanbei Duo ◽  
Shihan Wang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Linear Trend ◽  
Insulin Response ◽  
Density Lipoprotein ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Significant Difference ◽  
First Phase Insulin Secretion

BackgroundThe increase in diabetes worldwide is alarming. Decreased acute insulin response to intravenous glucose tolerance test (IVGTT) during first-phase insulin secretion (FPIS) is a characteristic of diabetes. However, knowledge of the insulin secretion characteristics identified by different time to glucose peak in subjects with different metabolic state is sparse.AimsThis study aimed to find different patterns of FPIS in subjects with normal glucose tolerance (NGT) and analyzed the relationship between insulin secretion patterns and the risk for development of type 2 diabetes mellitus (T2DM).MethodsA total of 126 subjects were divided into three groups during a 10-min IVGTT, including NGT with time to glucose peak after 3 min (G1, n = 21), NGT with time to glucose peak at 3 min (G2, n = 95), and prediabetes or diabetes with time to glucose peak at 3 min (G3, n = 10). Glucose, insulin, and C-peptide concentrations at 0, 3, 5, 7, and 10 min during the IVGTT were tested. IVGTT-based indices were calculated to evaluate the insulin secretion and insulin sensitivity.ResultsAge, body mass index (BMI), waist-to-hip ratio, triglyceride (TG), and hemoglobin A1c (HbA1c) of subjects were gradually higher, while high-density lipoprotein cholesterol (HDL-C) was gradually lower from G1 to G3 (p for linear trend &lt;0.05), and the differences between G1 and G2 were also statistically significant (p &lt; 0.05). Glucose peak of most participants in G1 converged at 5 min, and the curves shape of insulin and C-peptide in G2 were the sharpest among three groups. There was no significant difference in all IVGTT-based indices between G1 and G2, but AUCIns, AUCIns/AUCGlu, and △Ins3/△Glu3 in G2 were the highest, and the p-value for linear trend of those indices among three groups were statistically significant (p &lt; 0.05).ConclusionsTwo patterns of FPIS were in subjects with NGT, while subjects with later time to glucose peak during FPIS might be less likely to develop T2DM in the future.

scholarly journals First-Phase Insulin and Amylin after Bariatric Surgery: A Prospective Randomized Trial on Patients with Insulin Resistance or Diabetes after Gastric Bypass or Sleeve Gastrectomy

Obesity Facts ◽  
2020 ◽  
Vol 13 (6) ◽  
pp. 584-595
Author(s):  
Rahel Nussbaumer ◽  
Anne Christin Meyer-Gerspach ◽  
Ralph Peterli ◽  
Thomas Peters ◽  
Christoph Beglinger ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gastric Bypass ◽  
Insulin Secretion ◽  
Sleeve Gastrectomy ◽  
Glycemic Control ◽  
Insulin Release ◽  
Severe Obesity ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Postoperative Change

<b><i>Background:</i></b> Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear. <b><i>Objective:</i></b> To determine whether the improvement in glycemic control on the level of endocrine pancreatic function is due to an increased first-phase insulin secretion comparing LRYGB to LSG. <b><i>Setting:</i></b> University of Basel Hospital and St. Clara Research Ltd., Basel, Switzerland. <b><i>Methods:</i></b> Sixteen morbidly obese patients with severe obesity and different degrees of insulin resistance were randomized to LSG or LRYGB, and islet cell functions were tested by intravenous glucose and intravenous arginine administration before and 4 weeks after surgery. <b><i>Results:</i></b> Fasting insulin and glucose levels and homeostasis model assessment insulin resistance were significantly lower in both groups after surgery compared to baseline, while no change was seen in fasting C-peptide, amylin, and glucagon. After intravenous glucose stimulation, no statistically significant pre- to postoperative change in area under the curve (AUC 0–60 min) was seen for insulin, glucagon, amylin, and C-peptide. No statistically significant pre- to postoperative change in incremental AUC for first-phase insulin release (AUC 0–10 min), second-phase insulin secretion (AUC 10–60 min), and insulin/glucose ratio could be shown in either group. Arginine-stimulated insulin and glucagon release showed no pre- to postoperative change. <b><i>Conclusion:</i></b> Intravenous glucose and arginine administrations show no pre- to postoperative changes of insulin release, amylin, glucagon, or C-peptide concentrations, and no differences between LRYGB and LSG were found. The postoperative improvement in glycemic control is not caused by changes in endocrine pancreatic hormone secretion.

A minimal model of insulin secretion and kinetics to assess hepatic insulin extraction

2006 ◽  
Vol 290 (1) ◽  
pp. E169-E176 ◽  
Author(s):  
Gianna Toffolo ◽  
Marco Campioni ◽  
Rita Basu ◽  
Robert A. Rizza ◽  
Claudio Cobelli
Keyword(s):  
Insulin Secretion ◽  
Minimal Model ◽  
Insulin Delivery ◽  
Intravenous Glucose Tolerance Test ◽  
Insulin Degradation ◽  
Second Phase ◽  
Hepatic Extraction ◽  
Minimal Models ◽  
Intravenous Glucose ◽  
C Peptide

The liver is the principal site of insulin degradation, and assessing its ability to extract insulin is important to understand several pathological states. Noninvasive quantification of hepatic extraction (HE) in an individual requires comparing the profiles of insulin secretion (ISR) and posthepatic insulin delivery rate (IDR). To do this, we propose here the combined use of the classical C-peptide minimal model with a new minimal model of insulin delivery and kinetics. The models were identified on insulin-modified intravenous glucose tolerance test (IM-IVGTT) data of 20 healthy subjects. C-peptide kinetics were fixed to standard population values, whereas insulin kinetics were assessed in each individual, along with IDR parameters, thanks to the presence of insulin decay data observed after exogenous insulin administration. From the two models, profiles of ISR and IDR were predicted, and ISR and IDR indexes of β-cell responsivity to glucose in the basal state, as well as during first- and second-phase secretion, were estimated. HE profile, obtained by comparing ISR and IDR profiles, showed a rapid suppression immediately after the glucose administration. HE indexes, obtained by comparing ISR and IDR indexes, indicated that the liver is able to extract 70 ± 9% of insulin passing through it in the basal state and 54 ± 14% during IM-IVGTT. In conclusion, insulin secretion, kinetics, and hepatic extraction can be reliably assessed during an IM-IVGTT by using insulin and C-peptide minimal models.

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