Limitations of the fasting proinsulin to insulin ratio as a measure of β-cell health in people with and without impaired glucose tolerance.
Adult
Biomarkers
Blood Glucose
/ metabolism
C-Peptide
/ blood
Case-Control Studies
Diabetes Mellitus, Type 2
/ blood
Fasting
/ blood
Female
Glucose Intolerance
/ blood
Humans
Insulin
/ blood
Insulin Resistance
Insulin Secretion
Insulin-Secreting Cells
/ metabolism
Male
Middle Aged
Proinsulin
/ blood
disposition index
endoplasmic reticulum stress
insulin
insulin action
proinsulin
unfolded protein response
Journal
European journal of clinical investigation
ISSN: 1365-2362
Titre abrégé: Eur J Clin Invest
Pays: England
ID NLM: 0245331
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
revised:
02
12
2020
received:
27
10
2020
accepted:
04
12
2020
pubmed:
9
12
2020
medline:
31
12
2021
entrez:
8
12
2020
Statut:
ppublish
Résumé
The fasting proinsulin to insulin ratio is elevated in people with type 2 diabetes and has been suggested as a marker of β-cell health. However, its utility in discriminating between individuals with varying degrees of β-cell dysfunction is unclear. Proinsulin has a very different half-life to insulin and unlike insulin does not undergo hepatic extraction prior to reaching the systemic circulation. Given these limitations, we sought to examine the relationship between fasting and postprandial concentrations of β-cell polypeptides (proinsulin, insulin and C-peptide) in people with normal and impaired glucose tolerance in differing metabolic environments. Subjects were studied on two occasions in random order while undergoing an oral challenge. During one study day, free fatty acids were elevated (to induce insulin resistance) by infusion of Intralipid with heparin. Proinsulin to insulin and proinsulin to C-peptide ratios were calculated for the 0-, 30-, 60- and 240-minute time points. Insulin action (Si) and β-cell responsivity (Φ) indices were calculated using the oral minimal model. The fasting proinsulin to c-peptide or fasting proinsulin to insulin ratios did not differ between groups and did not predict subsequent β-cell responsivity to glucose during the glycerol or Intralipid study days in either group. Among nondiabetic individuals, the fasting proinsulin to insulin ratio is not a useful marker of β-cell function.
Sections du résumé
BACKGROUND
BACKGROUND
The fasting proinsulin to insulin ratio is elevated in people with type 2 diabetes and has been suggested as a marker of β-cell health. However, its utility in discriminating between individuals with varying degrees of β-cell dysfunction is unclear. Proinsulin has a very different half-life to insulin and unlike insulin does not undergo hepatic extraction prior to reaching the systemic circulation. Given these limitations, we sought to examine the relationship between fasting and postprandial concentrations of β-cell polypeptides (proinsulin, insulin and C-peptide) in people with normal and impaired glucose tolerance in differing metabolic environments.
DESIGN
METHODS
Subjects were studied on two occasions in random order while undergoing an oral challenge. During one study day, free fatty acids were elevated (to induce insulin resistance) by infusion of Intralipid with heparin. Proinsulin to insulin and proinsulin to C-peptide ratios were calculated for the 0-, 30-, 60- and 240-minute time points. Insulin action (Si) and β-cell responsivity (Φ) indices were calculated using the oral minimal model.
RESULTS
RESULTS
The fasting proinsulin to c-peptide or fasting proinsulin to insulin ratios did not differ between groups and did not predict subsequent β-cell responsivity to glucose during the glycerol or Intralipid study days in either group.
CONCLUSIONS
CONCLUSIONS
Among nondiabetic individuals, the fasting proinsulin to insulin ratio is not a useful marker of β-cell function.
Identifiants
pubmed: 33289929
doi: 10.1111/eci.13469
pmc: PMC8169515
mid: NIHMS1654141
doi:
Substances chimiques
Biomarkers
0
Blood Glucose
0
C-Peptide
0
Insulin
0
Proinsulin
9035-68-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13469Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR000135
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK082396
Pays : United States
Organisme : NIH HHS
ID : DK82396
Pays : United States
Organisme : Università degli Studi di Padova
ID : CPDA145405
Organisme : NIDDK NIH HHS
ID : R01 DK126206
Pays : United States
Organisme : NIH HHS
ID : DK116231
Pays : United States
Organisme : NIH HHS
ID : DK78646
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK116231
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK078646
Pays : United States
Informations de copyright
© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.
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