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Mechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids

Aims/hypothesis This study aimed to examine the metabolic health of young apparently healthy non-obese adults to better understand mechanisms of hyperinsulinaemia. Methods Non-obese (BMI 

Journal Title: Diabetologia 2019, Vol.62 (12), p.2310-2324
Main Author: Hamley, Steven
Other Authors: Kloosterman, Danielle , Duthie, Tamara , Dalla Man, Chiara , Visentin, Roberto , Mason, Shaun A. , Ang, Teddy , Selathurai, Ahrathy , Kaur, Gunveen , Morales-Scholz, Maria G. , Howlett, Kirsten F. , Kowalski, Greg M. , Shaw, Christopher S. , Bruce, Clinton R.
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0012-186X
Link: https://www.ncbi.nlm.nih.gov/pubmed/31489455
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title: Mechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids
format: Article
creator:
  • Hamley, Steven
  • Kloosterman, Danielle
  • Duthie, Tamara
  • Dalla Man, Chiara
  • Visentin, Roberto
  • Mason, Shaun A.
  • Ang, Teddy
  • Selathurai, Ahrathy
  • Kaur, Gunveen
  • Morales-Scholz, Maria G.
  • Howlett, Kirsten F.
  • Kowalski, Greg M.
  • Shaw, Christopher S.
  • Bruce, Clinton R.
subjects:
  • Adolescent
  • Adult
  • Amino acids
  • Amino Acids - blood
  • Beta cells
  • Blood Glucose - metabolism
  • Cholesterol
  • Diabetes
  • endocrine system diseases
  • Fasting
  • Fasting - blood
  • Female
  • Glucose
  • Glucose tolerance
  • Glucose Tolerance Test
  • Human Physiology
  • Humans
  • Hyperinsulinaemia
  • Hyperinsulinism - blood
  • Hyperinsulinism - metabolism
  • Insulin
  • Insulin - blood
  • Insulin resistance
  • Insulin Resistance - physiology
  • Insulin secretion
  • Insulin Secretion - physiology
  • Insulin sensitivity
  • Internal Medicine
  • Lipids - blood
  • Male
  • Medicine
  • Medicine & Public Health
  • Metabolic Diseases
  • Minimal model
  • nutritional
  • Plasma amino acids
  • Prediabetes
  • Secretion
  • Young Adult
  • Young adults
ispartof: Diabetologia, 2019, Vol.62 (12), p.2310-2324
description: Aims/hypothesis This study aimed to examine the metabolic health of young apparently healthy non-obese adults to better understand mechanisms of hyperinsulinaemia. Methods Non-obese (BMI 
language: eng
source:
identifier: ISSN: 0012-186X
fulltext: no_fulltext
issn:
  • 0012-186X
  • 1432-0428
url: Link


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titleMechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids
creatorHamley, Steven ; Kloosterman, Danielle ; Duthie, Tamara ; Dalla Man, Chiara ; Visentin, Roberto ; Mason, Shaun A. ; Ang, Teddy ; Selathurai, Ahrathy ; Kaur, Gunveen ; Morales-Scholz, Maria G. ; Howlett, Kirsten F. ; Kowalski, Greg M. ; Shaw, Christopher S. ; Bruce, Clinton R.
creatorcontribHamley, Steven ; Kloosterman, Danielle ; Duthie, Tamara ; Dalla Man, Chiara ; Visentin, Roberto ; Mason, Shaun A. ; Ang, Teddy ; Selathurai, Ahrathy ; Kaur, Gunveen ; Morales-Scholz, Maria G. ; Howlett, Kirsten F. ; Kowalski, Greg M. ; Shaw, Christopher S. ; Bruce, Clinton R.
descriptionAims/hypothesis This study aimed to examine the metabolic health of young apparently healthy non-obese adults to better understand mechanisms of hyperinsulinaemia. Methods Non-obese (BMI < 30 kg/m 2 ) adults aged 18–35 years ( N  = 254) underwent a stable isotope-labelled OGTT. Insulin sensitivity, glucose effectiveness and beta cell function were determined using oral minimal models. Individuals were stratified into quartiles based on their insulin response during the OGTT, with quartile 1 having the lowest and quartile 4 the highest responses. Results Thirteen per cent of individuals had impaired fasting glucose (IFG; n  = 14) or impaired glucose tolerance (IGT; n  = 19), allowing comparisons across the continuum of insulin responses within the spectrum of normoglycaemia and prediabetes. BMI (~24 kg/m 2 ) was similar across insulin quartiles and in those with IFG and IGT. Despite similar glycaemic excursions, fasting insulin, triacylglycerols and cholesterol were elevated in quartile 4. Insulin sensitivity was lowest in quartile 4, and accompanied by increased insulin secretion and reduced insulin clearance. Individuals with IFG had similar insulin sensitivity and beta cell function to those in quartiles 2 and 3, but were more insulin sensitive than individuals in quartile 4. While individuals with IGT had a similar degree of insulin resistance to quartile 4, they exhibited a more severe defect in beta cell function. Plasma branched-chain amino acids were not elevated in quartile 4, IFG or IGT. Conclusions/interpretation Hyperinsulinaemia within normoglycaemic young, non-obese adults manifests due to increased insulin secretion and reduced insulin clearance. Individual phenotypic characterisation revealed that the most hyperinsulinaemic were more similar to individuals with IGT than IFG, suggesting that hyperinsulinaemic individuals may be on the continuum toward IGT. Furthermore, plasma branched-chain amino acids may not be an effective biomarker in identifying hyperinsulinaemia and insulin resistance in young non-obese adults.
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languageeng
publisherBerlin/Heidelberg: Springer Berlin Heidelberg
subjectAdolescent ; Adult ; Amino acids ; Amino Acids - blood ; Beta cells ; Blood Glucose - metabolism ; Cholesterol ; Diabetes ; endocrine system diseases ; Fasting ; Fasting - blood ; Female ; Glucose ; Glucose tolerance ; Glucose Tolerance Test ; Human Physiology ; Humans ; Hyperinsulinaemia ; Hyperinsulinism - blood ; Hyperinsulinism - metabolism ; Insulin ; Insulin - blood ; Insulin resistance ; Insulin Resistance - physiology ; Insulin secretion ; Insulin Secretion - physiology ; Insulin sensitivity ; Internal Medicine ; Lipids - blood ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Minimal model ; nutritional ; Plasma amino acids ; Prediabetes ; Secretion ; Young Adult ; Young adults
ispartofDiabetologia, 2019, Vol.62 (12), p.2310-2324
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1Diabetologia is a copyright of Springer, (2019). All Rights Reserved. © 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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1Kloosterman, Danielle
2Duthie, Tamara
3Dalla Man, Chiara
4Visentin, Roberto
5Mason, Shaun A.
6Ang, Teddy
7Selathurai, Ahrathy
8Kaur, Gunveen
9Morales-Scholz, Maria G.
10Howlett, Kirsten F.
11Kowalski, Greg M.
12Shaw, Christopher S.
13Bruce, Clinton R.
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descriptionAims/hypothesis This study aimed to examine the metabolic health of young apparently healthy non-obese adults to better understand mechanisms of hyperinsulinaemia. Methods Non-obese (BMI < 30 kg/m 2 ) adults aged 18–35 years ( N  = 254) underwent a stable isotope-labelled OGTT. Insulin sensitivity, glucose effectiveness and beta cell function were determined using oral minimal models. Individuals were stratified into quartiles based on their insulin response during the OGTT, with quartile 1 having the lowest and quartile 4 the highest responses. Results Thirteen per cent of individuals had impaired fasting glucose (IFG; n  = 14) or impaired glucose tolerance (IGT; n  = 19), allowing comparisons across the continuum of insulin responses within the spectrum of normoglycaemia and prediabetes. BMI (~24 kg/m 2 ) was similar across insulin quartiles and in those with IFG and IGT. Despite similar glycaemic excursions, fasting insulin, triacylglycerols and cholesterol were elevated in quartile 4. Insulin sensitivity was lowest in quartile 4, and accompanied by increased insulin secretion and reduced insulin clearance. Individuals with IFG had similar insulin sensitivity and beta cell function to those in quartiles 2 and 3, but were more insulin sensitive than individuals in quartile 4. While individuals with IGT had a similar degree of insulin resistance to quartile 4, they exhibited a more severe defect in beta cell function. Plasma branched-chain amino acids were not elevated in quartile 4, IFG or IGT. Conclusions/interpretation Hyperinsulinaemia within normoglycaemic young, non-obese adults manifests due to increased insulin secretion and reduced insulin clearance. Individual phenotypic characterisation revealed that the most hyperinsulinaemic were more similar to individuals with IGT than IFG, suggesting that hyperinsulinaemic individuals may be on the continuum toward IGT. Furthermore, plasma branched-chain amino acids may not be an effective biomarker in identifying hyperinsulinaemia and insulin resistance in young non-obese adults.
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19Hyperinsulinism - metabolism
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22Insulin resistance
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37Secretion
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titleMechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids
authorHamley, Steven ; Kloosterman, Danielle ; Duthie, Tamara ; Dalla Man, Chiara ; Visentin, Roberto ; Mason, Shaun A. ; Ang, Teddy ; Selathurai, Ahrathy ; Kaur, Gunveen ; Morales-Scholz, Maria G. ; Howlett, Kirsten F. ; Kowalski, Greg M. ; Shaw, Christopher S. ; Bruce, Clinton R.
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8Kaur, Gunveen
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atitleMechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids
jtitleDiabetologia
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abstractAims/hypothesis This study aimed to examine the metabolic health of young apparently healthy non-obese adults to better understand mechanisms of hyperinsulinaemia. Methods Non-obese (BMI < 30 kg/m 2 ) adults aged 18–35 years ( N  = 254) underwent a stable isotope-labelled OGTT. Insulin sensitivity, glucose effectiveness and beta cell function were determined using oral minimal models. Individuals were stratified into quartiles based on their insulin response during the OGTT, with quartile 1 having the lowest and quartile 4 the highest responses. Results Thirteen per cent of individuals had impaired fasting glucose (IFG; n  = 14) or impaired glucose tolerance (IGT; n  = 19), allowing comparisons across the continuum of insulin responses within the spectrum of normoglycaemia and prediabetes. BMI (~24 kg/m 2 ) was similar across insulin quartiles and in those with IFG and IGT. Despite similar glycaemic excursions, fasting insulin, triacylglycerols and cholesterol were elevated in quartile 4. Insulin sensitivity was lowest in quartile 4, and accompanied by increased insulin secretion and reduced insulin clearance. Individuals with IFG had similar insulin sensitivity and beta cell function to those in quartiles 2 and 3, but were more insulin sensitive than individuals in quartile 4. While individuals with IGT had a similar degree of insulin resistance to quartile 4, they exhibited a more severe defect in beta cell function. Plasma branched-chain amino acids were not elevated in quartile 4, IFG or IGT. Conclusions/interpretation Hyperinsulinaemia within normoglycaemic young, non-obese adults manifests due to increased insulin secretion and reduced insulin clearance. Individual phenotypic characterisation revealed that the most hyperinsulinaemic were more similar to individuals with IGT than IFG, suggesting that hyperinsulinaemic individuals may be on the continuum toward IGT. Furthermore, plasma branched-chain amino acids may not be an effective biomarker in identifying hyperinsulinaemia and insulin resistance in young non-obese adults.
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pubSpringer Berlin Heidelberg
pmid31489455
doi10.1007/s00125-019-04990-y
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