scholarly journals Metabolomics analysis reveals altered metabolites in lean compared with obese adolescents and additional metabolic shifts associated with hyperinsulinaemia and insulin resistance in obese adolescents: a cross-sectional study

Metabolomics ◽  
2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Elisabeth Müllner ◽  
Hanna E. Röhnisch ◽  
Claudia von Brömssen ◽  
Ali A. Moazzami
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Glucose Tolerance ◽  
Insulin Response ◽  
Oral Glucose ◽  
Response Level ◽  
Metabolic Alterations ◽  
Obese Adolescents ◽  
Branched Chain ◽  
Metabolomics Analysis

Abstract Introduction Hyperinsulinaemia and insulin resistance (IR) are strongly associated with obesity and are forerunners of type 2 diabetes. Little is known about metabolic alterations separately associated with obesity, hyperinsulinaemia/IR and impaired glucose tolerance (IGT) in adolescents. Objectives To identify metabolic alterations associated with obesity, hyperinsulinaemia/IR and hyperinsulinaemia/IR combined with IGT in obese adolescents. Methods 81 adolescents were stratified into four groups based on body mass index (lean vs. obese), insulin responses (normal insulin (NI) vs. high insulin (HI)) and glucose responses (normal glucose tolerance (NGT) vs. IGT) after an oral glucose tolerance test (OGTT). The groups comprised: (1) healthy lean with NI and NGT, (2) obese with NI and NGT, (3) obese with HI and NGT, and (4) obese with HI and IGT. Targeted nuclear magnetic resonance-based metabolomics analysis was performed on fasting and seven post-OGTT plasma samples, followed by univariate and multivariate statistical analyses. Results Two groups of metabolites were identified: (1) Metabolites associated with insulin response level: adolescents with HI (groups 3–4) had higher concentrations of branched-chain amino acids and tyrosine, and lower concentrations of serine, glycine, myo-inositol and dimethylsulfone, than adolescents with NI (groups 1–2). (2) Metabolites associated with obesity status: obese adolescents (groups 2–4) had higher concentrations of acetylcarnitine, alanine, pyruvate and glutamate, and lower concentrations of acetate, than lean adolescents (group 1). Conclusions Obesity is associated with shifts in fat and energy metabolism. Hyperinsulinaemia/IR in obese adolescents is also associated with increased branched-chain and aromatic amino acids.

scholarly journals Prehepatic secretion and disposal of insulin in obese adolescents as estimated by three-hour, eight-sample oral glucose tolerance tests

2016 ◽  
Vol 311 (1) ◽  
pp. E82-E94 ◽  
Author(s):  
Josef A. Vogt ◽  
Christian Domzig ◽  
Martin Wabitsch ◽  
Christian Denzer
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Metabolic Regulation ◽  
The Body ◽  
Oral Glucose ◽  
Published Data ◽  
Oral Glucose Tolerance ◽  
Insulin Metabolism ◽  
Obese Adolescents

The body compensates for early-stage insulin resistance by increasing insulin secretion. A reliable and easy-to-use mathematical assessment of insulin secretion and disposal could be a valuable tool for identifying patients at risk for the development of type 2 diabetes. Because the pathophysiology of insulin resistance is incompletely understood, assessing insulin metabolism with minimal assumptions regarding its metabolic regulation is a major challenge. To assess insulin secretion and indexes of insulin disposal, our marginalized and regularized absorption approach (MRA) was applied to a sparse sampling oral glucose tolerance test (OGTT) protocol measuring the insulin and C-peptide concentrations. Identifiability and potential bias of metabolic parameters were estimated from published data with dense sampling. The MRA was applied to OGTT data from 135 obese adolescents to demonstrate its clinical applicability. Individual prehepatic basal and dynamic insulin secretion and clearance levels were determined with a precision and accuracy greater than 10% of the nominal value. The intersubject variability in these parameters was approximately four times higher than the intrasubject variability, and there was a strong negative correlation between prehepatic secretion and plasma clearance of insulin. MRA-based analysis provides reliable estimates of insulin secretion and clearance, thereby enabling detailed glucose homeostasis characterization based on restricted datasets that are obtainable during routine patient care.

scholarly journals Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy

2002 ◽  
pp. 397-405 ◽  
Author(s):  
A Johansson ◽  
T Olsson ◽  
K Cederquist ◽  
H Forsberg ◽  
JJ Holst ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Myotonic Dystrophy ◽  
Insulin Response ◽  
Oral Glucose ◽  
Islet Function ◽  
Insulin Resistant ◽  
Significant Difference ◽  
Repeat Expansions ◽  
Ctg Repeat

OBJECTIVE: Although the incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), as well as glucagon and cortisol, are known to influence islet function, the role of these hormones in conditions of insulin resistance and development of type 2 diabetes is unknown. An interesting model for the study of hormonal perturbations accompanying marked insulin resistance without concomitant diabetes is myotonic dystrophy (DM1). DESIGN: The work was carried out in an out-patient setting. METHODS: An oral glucose tolerance test was performed in 18 males with DM1 and 18 controls to examine the release of incretins and counter-regulatory hormones. Genetic analyses were also performed in patients. RESULTS: We found that the increment in GLP-1 after oral glucose was significantly greater in patients, while there was no significant difference in GIP or glucagon responses between patients and controls, although long CTG repeat expansions were associated with a more pronounced GIP response. Interestingly, the GLP-1 response to oral glucose correlated with the insulin response in patients but not in controls whereas, in controls, the insulin response closely correlated with the GIP response. Furthermore, cortisol and ACTH levels increased paradoxically in patients after glucose; this was more pronounced in patients with long CTG repeat expansions. CONCLUSIONS: This study showed that the GLP-1 and ACTH/cortisol responses to oral glucose are abnormal in insulin-resistant DM1 patients and that CTG triplet repeats are linked to GIP release. These abnormalities may contribute both to the severe insulin resistance and hyperinsulinemia in DM1 and to the preservation of adequate islet function, enabling glucose tolerance to be normal in spite of this marked insulin resistance in DM1.

Insulin resistance in aged man: Relationship between impaired glucose tolerance and decreased insulin activity on branched-chain amino acids

Metabolism ◽  
1987 ◽  
Vol 36 (11) ◽  
pp. 1096-1100 ◽  
Author(s):  
Giulio Marchesini ◽  
Stefano Cassarani ◽  
Giovanni A. Checchia ◽  
Giampaolo Bianchi ◽  
Vincenzo Bua ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Branched Chain Amino Acids ◽  
Insulin Activity ◽  
Branched Chain

Effect of 10 days of physical inactivity on glucose tolerance in master athletes

1990 ◽  
Vol 68 (5) ◽  
pp. 1833-1837 ◽  
Author(s):  
M. A. Rogers ◽  
D. S. King ◽  
J. M. Hagberg ◽  
A. A. Ehsani ◽  
J. O. Holloszy
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Physical Inactivity ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Master Athletes ◽  
Short Term ◽  
Glucose Response

Master athletes who exercise regularly appear to avoid the development of insulin resistance and deterioration of glucose tolerance (GT) commonly seen with aging. To evaluate the possibility that exercise prevents rather than masks the aging-related changes responsible for development of insulin resistance, we investigated the effects of 10 days of physical inactivity in 14 master athletes aged 61 +/- 2 (SE) yr. The response of 10 of these men to inactivity was similar to that of young athletes, with an unchanged plasma glucose response and a significantly greater insulin response to an oral glucose tolerance test (OGTT) after 10 days of inactivity. These 10 athletes appeared to have been protected against the aging-related changes in GT because their plasma glucose and insulin levels during the OGTT after 10 days of inactivity were not significantly different from those of young lean sedentary men. In contrast, a deterioration in GT occurred in four of the master athletes during 10 days of inactivity; this was sufficiently marked in two of them to be classified as impaired GT. We conclude that regular exercise may 1) protect against the development of insulin resistance and decline in GT with aging in individuals with normal GT and 2) normalize GT by means of short-term effects of exercise in some individuals with abnormal GT.

scholarly journals Metabolomic Profiling in Response to an Oral Glucose Tolerance Test Reveals Pathways Associated With Obesity and Insulin Resistance During the Pubertal Transition

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 506-506
Author(s):  
Jennifer LaBarre ◽  
Emily Hirschfeld ◽  
Gayatri Iyer ◽  
Alla Karnovsky ◽  
William Herman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Response Group ◽  
Pubertal Transition ◽  
Group 1

Abstract Objectives To reveal alterations in metabolic pathways in response to an oral glucose tolerance test (OGTT) underlying the development of insulin resistance during the pubertal transition. Methods Participants were recruited as healthy controls (HC, n = 55, aged 8.3–18.0 years, BMI percentile 5–85%) and overweight and obese individuals (OVOB, n = 228, aged 8.1–17.9 years, BMI percentile ≥ 85%). Participants were grouped based on their peak insulin response to the OGTT, stratified by peak at t30 (Group 1, n = 163), t60 (Group 2, n = 75), and t120 minutes (Group 3, n = 44). Untargeted metabolomics profiled 267 annotated metabolites and > 3000 unannotated features in plasma at t0 and t60 minutes. Regression classified changes in metabolites across the time-course, assessing the influence of BMI and insulin response (FDR < 0.05). The connectivity of the metabolome was determined using differential network enrichment analysis (DNEA), stratified by insulin response group. Results At fasting, 32% of the metabolites differed between HC and OVOB, including elevated kynurenine, leucine/isoleucine, methionine, tyrosine, short-chain acylcarnitines, and diacylglycerols in OVOB. At t60, only 4% of the metabolites differed between HC and OVOB participants, suggesting a “normalization” of the metabolome, with exceptions of acylcarnitines and FA oxidation (FAO) intermediates. Although no metabolites differed significantly between insulin response group, differential subnetworks were observed, including increased connectivity between FA and FAO intermediates in Group 1 at t60, suggesting differential regulation in post-prandial FAs. Conclusions Profiling the metabolome response to an OGTT may highlight metabolic dysfunction prior to type 2 diabetes and will be used in future longitudinal analyses predicting insulin resistance trajectory. Funding Sources The National Institute of Child Health and Human Development, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institutes of Health

scholarly journals QOL-43. ENDOCRINE AND METABOLIC CHANGES IN CHILDREN TREATED FOR MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii439-iii439
Author(s):  
Alexey Kalinin ◽  
Natalia Strebkova ◽  
Olga Zheludkova
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Impaired Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Hormone Deficiency ◽  
Oral Glucose ◽  
Oral Glucose Tolerance

Abstract We examined 63 patients (40 males/23 females) after complex treatment of medulloblastoma. Patients had a median age (range) of 11.3 (5.5 ÷ 17.9) years. The median time after the end of treatment was 3.7 (1.5 ÷ 11.6) years. Endocrine disorders were detected with the following frequency: growth hormone deficiency - 98.41% (62 of 63 patients), thyroid hormone deficiency – 69.8% (44/63), adrenal hormone deficiency - 17.4% (11/63). Three cases (4.7%) of premature sexual development were also detected. Lipids levels, beta-cell function and insulin resistance (IR) during 2-h oral glucose tolerance test were evaluated. A mono frequent bioelectrical impedanciometer was used to measure body composition. Overweight (SDS BMI> 1) was observed only in 16 patients (3 girls and 13 boys), obesity (SDS BMI> 2) in 1 boy. Dyslipidemia was found in 34 patients (54%). All patients underwent oral glucose tolerance test. Insulin resistance (ISI Matsuda <2.5 and/or HOMA-IR> 3.2) was detected in 7 patients (11/1%), impaired glucose tolerance (120 min glucose ≥7.8 mmol / l) was observed in 2 patients with IR and in 2 patients without IR. At the same time, IR and impaired glucose tolerance were encountered in only 5 children with overweight and no one with obesity. All patients with impaired glucose tolerance had normal values of fasting glucose (4.3 ÷ 5.04 mmol / l) and HbA1c (4.8 ÷ 5.8%). A bioelectrical impedanciometer was used to measure body composition in 49 cases, the percentage of adipose tissue was increased in 14 patients (28%) with normal BMI.

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