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

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 as10 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.

Automated summary

The study compared plasma C-peptide levels in individuals with and without diabetes, finding greater beta-cell function loss in younger-onset Type 1 diabetes. Adults with diabetes had persistent insulin secretion, while those with childhood-onset diabetes and longer duration possibly had regenerative secretion.Relationships between C-peptide levels and circulating miRs were observed, suggesting the need for further clinical and basic science studies.