Insulin micro-secretion in Type 1 diabetes and related microRNA profiles

Andrzej S. Januszewski; Yoon Hi Cho; Mugdha V. Joglekar; Ryan J. Farr; Emma S. Scott; Wilson K. M. Wong; Luke M. Carroll; Yik W. Loh; Paul Z. Benitez-Aguirre; Anthony C. Keech; David N. O'Neal; Maria E. Craig; Anandwardhan A. Harkidar; Kim C. Donaghue; Alicia J. Jenkins

doi:10.1038/s41598-021-90856-6

Insulin micro-secretion in Type 1 diabetes and related microRNA profiles

Andrzej S. Januszewski, Yoon Hi Cho, Mugdha V. Joglekar, Ryan J. Farr, Emma S. Scott, Wilson K. M. Wong, Luke M. Carroll, Yik W. Loh, Paul Z. Benitez-Aguirre, Anthony C. Keech, David N. O'Neal, Maria E. Craig, Anandwardhan A. Harkidar, Kim C. Donaghue, Alicia J. Jenkins

Western Sydney University

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Abstract

The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n= 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p < 0.0001 and in all (n= 253) participants without diabetes (CON). C-peptide levels, when detectable, were lower in the individuals with diabetes than in the CON group [median lower quartile (LQ)–upper quartile (UQ)] 5.0 (2.6–28.7) versus 650.9 (401.2–732.4) pmol/L respectively, p < 0.0001 and lower in childhood versus adult-onset diabetes [median (LQ–UQ) 4.2 (2.6–12.2) pmol/L vs. 8.0 (2.3–80.5) pmol/L, p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (>20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend< 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes; (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration; and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited.

Original language	English
Article number	11727
Number of pages	11
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-90856-6
Publication status	Published - 2021

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Januszewski, A. S., Cho, Y. H., Joglekar, M. V., Farr, R. J., Scott, E. S., Wong, W. K. M., Carroll, L. M., Loh, Y. W., Benitez-Aguirre, P. Z., Keech, A. C., O'Neal, D. N., Craig, M. E., Harkidar, A. A., Donaghue, K. C., & Jenkins, A. J. (2021). Insulin micro-secretion in Type 1 diabetes and related microRNA profiles. Scientific Reports, 11(1), Article 11727. https://doi.org/10.1038/s41598-021-90856-6

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title = "Insulin micro-secretion in Type 1 diabetes and related microRNA profiles",

abstract = "The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n= 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p < 0.0001 and in all (n= 253) participants without diabetes (CON). C-peptide levels, when detectable, were lower in the individuals with diabetes than in the CON group [median lower quartile (LQ)–upper quartile (UQ)] 5.0 (2.6–28.7) versus 650.9 (401.2–732.4) pmol/L respectively, p < 0.0001 and lower in childhood versus adult-onset diabetes [median (LQ–UQ) 4.2 (2.6–12.2) pmol/L vs. 8.0 (2.3–80.5) pmol/L, p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (>20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend< 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes; (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration; and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited.",

author = "Januszewski, {Andrzej S.} and Cho, {Yoon Hi} and Joglekar, {Mugdha V.} and Farr, {Ryan J.} and Scott, {Emma S.} and Wong, {Wilson K. M.} and Carroll, {Luke M.} and Loh, {Yik W.} and Benitez-Aguirre, {Paul Z.} and Keech, {Anthony C.} and O'Neal, {David N.} and Craig, {Maria E.} and Harkidar, {Anandwardhan A.} and Donaghue, {Kim C.} and Jenkins, {Alicia J.}",

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T1 - Insulin micro-secretion in Type 1 diabetes and related microRNA profiles

AU - Januszewski, Andrzej S.

AU - Cho, Yoon Hi

AU - Joglekar, Mugdha V.

AU - Farr, Ryan J.

AU - Scott, Emma S.

AU - Wong, Wilson K. M.

AU - Carroll, Luke M.

AU - Loh, Yik W.

AU - Benitez-Aguirre, Paul Z.

AU - Keech, Anthony C.

AU - O'Neal, David N.

AU - Craig, Maria E.

AU - Harkidar, Anandwardhan A.

AU - Donaghue, Kim C.

AU - Jenkins, Alicia J.

PY - 2021

Y1 - 2021

N2 - The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n= 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p < 0.0001 and in all (n= 253) participants without diabetes (CON). C-peptide levels, when detectable, were lower in the individuals with diabetes than in the CON group [median lower quartile (LQ)–upper quartile (UQ)] 5.0 (2.6–28.7) versus 650.9 (401.2–732.4) pmol/L respectively, p < 0.0001 and lower in childhood versus adult-onset diabetes [median (LQ–UQ) 4.2 (2.6–12.2) pmol/L vs. 8.0 (2.3–80.5) pmol/L, p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (>20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend< 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes; (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration; and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited.

AB - The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n= 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p < 0.0001 and in all (n= 253) participants without diabetes (CON). C-peptide levels, when detectable, were lower in the individuals with diabetes than in the CON group [median lower quartile (LQ)–upper quartile (UQ)] 5.0 (2.6–28.7) versus 650.9 (401.2–732.4) pmol/L respectively, p < 0.0001 and lower in childhood versus adult-onset diabetes [median (LQ–UQ) 4.2 (2.6–12.2) pmol/L vs. 8.0 (2.3–80.5) pmol/L, p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (>20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend< 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes; (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration; and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited.

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DO - 10.1038/s41598-021-90856-6

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JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 11727

ER -

Insulin micro-secretion in Type 1 diabetes and related microRNA profiles

Abstract

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