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

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

doi:10.1038/s41598-021-90856-6

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 (< 18 y.o.), and diabetes duration was stratified as ≤ 10 years, 10–20 years and > 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.

Highlights

Type 1 diabetes arises from the autoimmune-induced loss of insulin producing pancreatic cells, with ≈70% loss at clinical p resentation[1]
C-peptide was detectable in all CON subjects and in 55.3% (193 of 349) of participants with diabetes (63.8% (159 of 249) of adults and 34.0% (34 of 100) of youth, p < 0.0001)
Using a relatively recently available ultrasensitive C-peptide assay in a cross-sectional study we demonstrated insulin microsecretion in 55.3% of people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes

Summary

Introduction

Type 1 diabetes arises from the autoimmune-induced loss of insulin producing pancreatic cells, with ≈70% loss at clinical p resentation[1]. We measured C-peptide levels in a cross-sectional study of paediatric and adult participants with Type 1 diabetes and people without diabetes (controls, CON). There was no difference in detectable C-peptide rates with diabetes duration in participants diagnosed below and above 13 years of age, a common age of diabetes onset and puberty[15] (ESM Fig. 1).

Results

Conclusion