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 (< 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.

The Link Between Glycemic Control Measures and Eye Microvascular Complications in a Clinical Cohort of Type 2 Diabetes with MicroRNA-223 Signature

“…Others have explored the association between C-peptide and circulating miR-223 alongside other miRNAs in patients with T1D versus healthy controls. The expression level of miR-223 was substantially increased in diabetic patients versus controls in correlation with C-peptide levels [50]. Our results support that miRNA assessment may be a useful addition to the routine diagnosis particularly given that genetics, environmental and lifestyle measures differ by ethnicity.…”

The link between glycemic control measures and eye microvascular complications in a clinical cohort of type 2 diabetes with microRNA-223-3p signature

“…Others have explored the association between C-peptide and circulating miR-223-3p alongside other miRNAs in patients with T1D versus healthy controls. The expression level of miR-223-3p was substantially increased in diabetic patients versus controls in correlation with C-peptide levels [ 51 ]. Our results support that miRNA assessment may be a useful addition to the routine diagnosis particularly given that genetics, environmental and lifestyle measures differ by ethnicity.…”

Identification of a suitable endogenous control miRNA in bone aging and senescence

“…Following the discovery of lin-4 , the first miRNA to be discovered that repressed lin-14 message in C. elegans , thousands of miRNAs have been identified in various plants and animal species including humans that regulate a wide range of biological functions such as cell proliferation, apoptosis, regeneration, and metabolism ( Bartel, 2004 ; Lee et al, 1993 ; Wightman et al, 1993 ). Moreover, their ability to circulate throughout the body in cell-free encapsulated vesicles called extracellular vesicles or exosomes (30–150 nm-diameter) have made them potent signaling molecules, disease biomarkers, and essential prognostic and therapeutic tools in chronic age-related diseases such as osteoporosis, cardiovascular diseases, type I and II diabetes, and cancers ( Bottani et al, 2019 ; Condrat et al, 2020 ; Foessl et al, 2019 ; Januszewski et al, 2021 ; Mandourah et al, 2018 ; Margaritis et al, 2021 ; Materozzi et al, 2018 ).…”