Glucose effectiveness is a critical pathogenic factor leading to glucose intolerance and type 2 diabetes: An ignored hypothesis

F. P. Alford*, J. E. Henriksen, C. Rantzau, H. Beck-Nielsen

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftKommentar/debatFormidling

Resumé

Background: Although the ability of glucose to mediate its own in vivo metabolism is long documented, the quantitative measurement of whole body glucose-mediated glucose disposal at basal insulin levels (glucose effectiveness [GE]), followed the introduction of the Minimal Model intravenous glucose tolerance test technique. Methods: A literature review, combined with our own studies, of the role of GE in glucose metabolism in normal and "at risk" individuals, was undertaken to determine GE's contribution to glucose homeostasis. Results: GE accounts for ~45% to 65% of glucose disposal in man. A negative association between GE and insulin meditated glucose disposal (Si), is present in normal subjects without a family history of type 2 diabetes mellitus but is absent in normoglycaemic "at risk" relatives with a positive family history of diabetes mellitus. Intracellular GE disposal is mediated by mass action of glucose through the skeletal muscle membrane via facilitated Glut 4 transporters. However, GE is frequently forgotten as a significant contributor to the development of glucose intolerance in "at risk" individuals. Only limited studies have examined the role of a lower GE in such normoglycemic subjects with preexisting mild insulin resistance and β-cell dysfunction. These studies demonstrate that in "at risk" individuals, an initial low GE is a key contributor and predictor of future glucose intolerance, whereas an initial raised GE is protective against future glucose intolerance. Conclusion: In "at risk" individuals, a low GE and genetically determined vulnerable β-cell function are more critical determinants of future glucose intolerance than their preexisting insulin-resistant state.

OriginalsprogEngelsk
Artikelnummere2989
TidsskriftDiabetes - Metabolism: Research and Reviews (Print Edition)
Vol/bind34
Udgave nummer4
Antal sider5
ISSN1520-7552
DOI
StatusUdgivet - maj 2018

Fingeraftryk

Glucose Intolerance
Medical problems
Type 2 Diabetes Mellitus
Glucose
Insulin
Metabolism

Bibliografisk note

Copyright © 2018 John Wiley & Sons, Ltd.

Citer dette

@article{c54e8bf96ce24fc7bde269ae86b5fc8b,
title = "Glucose effectiveness is a critical pathogenic factor leading to glucose intolerance and type 2 diabetes: An ignored hypothesis",
abstract = "Background: Although the ability of glucose to mediate its own in vivo metabolism is long documented, the quantitative measurement of whole body glucose-mediated glucose disposal at basal insulin levels (glucose effectiveness [GE]), followed the introduction of the Minimal Model intravenous glucose tolerance test technique. Methods: A literature review, combined with our own studies, of the role of GE in glucose metabolism in normal and {"}at risk{"} individuals, was undertaken to determine GE's contribution to glucose homeostasis. Results: GE accounts for ~45{\%} to 65{\%} of glucose disposal in man. A negative association between GE and insulin meditated glucose disposal (Si), is present in normal subjects without a family history of type 2 diabetes mellitus but is absent in normoglycaemic {"}at risk{"} relatives with a positive family history of diabetes mellitus. Intracellular GE disposal is mediated by mass action of glucose through the skeletal muscle membrane via facilitated Glut 4 transporters. However, GE is frequently forgotten as a significant contributor to the development of glucose intolerance in {"}at risk{"} individuals. Only limited studies have examined the role of a lower GE in such normoglycemic subjects with preexisting mild insulin resistance and β-cell dysfunction. These studies demonstrate that in {"}at risk{"} individuals, an initial low GE is a key contributor and predictor of future glucose intolerance, whereas an initial raised GE is protective against future glucose intolerance. Conclusion: In {"}at risk{"} individuals, a low GE and genetically determined vulnerable β-cell function are more critical determinants of future glucose intolerance than their preexisting insulin-resistant state.",
keywords = "Australia/epidemiology, Blood Glucose/metabolism, Diabetes Mellitus, Type 2/epidemiology, Glucose Intolerance/epidemiology, Glucose Tolerance Test, Humans, Insulin Resistance, Prediabetic State/epidemiology",
author = "Alford, {F. P.} and Henriksen, {J. E.} and C. Rantzau and H. Beck-Nielsen",
note = "Copyright {\circledC} 2018 John Wiley & Sons, Ltd.",
year = "2018",
month = "5",
doi = "10.1002/dmrr.2989",
language = "English",
volume = "34",
journal = "Diabetes - Metabolism: Research and Reviews (Print Edition)",
issn = "1520-7552",
publisher = "John Wiley & Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Glucose effectiveness is a critical pathogenic factor leading to glucose intolerance and type 2 diabetes

T2 - An ignored hypothesis

AU - Alford, F. P.

AU - Henriksen, J. E.

AU - Rantzau, C.

AU - Beck-Nielsen, H.

N1 - Copyright © 2018 John Wiley & Sons, Ltd.

PY - 2018/5

Y1 - 2018/5

N2 - Background: Although the ability of glucose to mediate its own in vivo metabolism is long documented, the quantitative measurement of whole body glucose-mediated glucose disposal at basal insulin levels (glucose effectiveness [GE]), followed the introduction of the Minimal Model intravenous glucose tolerance test technique. Methods: A literature review, combined with our own studies, of the role of GE in glucose metabolism in normal and "at risk" individuals, was undertaken to determine GE's contribution to glucose homeostasis. Results: GE accounts for ~45% to 65% of glucose disposal in man. A negative association between GE and insulin meditated glucose disposal (Si), is present in normal subjects without a family history of type 2 diabetes mellitus but is absent in normoglycaemic "at risk" relatives with a positive family history of diabetes mellitus. Intracellular GE disposal is mediated by mass action of glucose through the skeletal muscle membrane via facilitated Glut 4 transporters. However, GE is frequently forgotten as a significant contributor to the development of glucose intolerance in "at risk" individuals. Only limited studies have examined the role of a lower GE in such normoglycemic subjects with preexisting mild insulin resistance and β-cell dysfunction. These studies demonstrate that in "at risk" individuals, an initial low GE is a key contributor and predictor of future glucose intolerance, whereas an initial raised GE is protective against future glucose intolerance. Conclusion: In "at risk" individuals, a low GE and genetically determined vulnerable β-cell function are more critical determinants of future glucose intolerance than their preexisting insulin-resistant state.

AB - Background: Although the ability of glucose to mediate its own in vivo metabolism is long documented, the quantitative measurement of whole body glucose-mediated glucose disposal at basal insulin levels (glucose effectiveness [GE]), followed the introduction of the Minimal Model intravenous glucose tolerance test technique. Methods: A literature review, combined with our own studies, of the role of GE in glucose metabolism in normal and "at risk" individuals, was undertaken to determine GE's contribution to glucose homeostasis. Results: GE accounts for ~45% to 65% of glucose disposal in man. A negative association between GE and insulin meditated glucose disposal (Si), is present in normal subjects without a family history of type 2 diabetes mellitus but is absent in normoglycaemic "at risk" relatives with a positive family history of diabetes mellitus. Intracellular GE disposal is mediated by mass action of glucose through the skeletal muscle membrane via facilitated Glut 4 transporters. However, GE is frequently forgotten as a significant contributor to the development of glucose intolerance in "at risk" individuals. Only limited studies have examined the role of a lower GE in such normoglycemic subjects with preexisting mild insulin resistance and β-cell dysfunction. These studies demonstrate that in "at risk" individuals, an initial low GE is a key contributor and predictor of future glucose intolerance, whereas an initial raised GE is protective against future glucose intolerance. Conclusion: In "at risk" individuals, a low GE and genetically determined vulnerable β-cell function are more critical determinants of future glucose intolerance than their preexisting insulin-resistant state.

KW - Australia/epidemiology

KW - Blood Glucose/metabolism

KW - Diabetes Mellitus, Type 2/epidemiology

KW - Glucose Intolerance/epidemiology

KW - Glucose Tolerance Test

KW - Humans

KW - Insulin Resistance

KW - Prediabetic State/epidemiology

U2 - 10.1002/dmrr.2989

DO - 10.1002/dmrr.2989

M3 - Comment/debate

C2 - 29451713

AN - SCOPUS:85044262751

VL - 34

JO - Diabetes - Metabolism: Research and Reviews (Print Edition)

JF - Diabetes - Metabolism: Research and Reviews (Print Edition)

SN - 1520-7552

IS - 4

M1 - e2989

ER -