Dataset Information

Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: A pilot study.

ABSTRACT:

Aims

Increased proinsulin (PI) compared to C-peptide (CP) concentrations have been reported, both prior to type 1 diabetes mellitus (T1D) onset, as well as early in disease. In this pilot study, we sought to define the normal PI secretion in a healthy cohort and compare this to a local T1D cohort and a separate well-defined nationally representative T1D cohort with measurable CP.

Methods

Thirteen healthy subjects and 12 T1D subjects with T1D >3 years from the local T1D cohort completed mixed meal tolerance tests (MMTT) with PI and CP measured over 90 and 240 minutes. The change in CP (maximum versus baseline, ?CP) during MMTT in the T1D Exchange T1D cohort was stratified according to non-fasting PI concentrations, based on a fasting PI threshold, as defined by the healthy control group.

Results

The maximum fasting PI in the control group was 6 pmol/L. Individuals from the T1D Exchange with a non-fasting PI ? 6 pmol/L had a lower ?CP during a MMTT, compared to those with a PI < 6 pmol/L. While only three individuals from the local T1D cohort had measurable CP and PI during the MMTT, those with a greater ?CP had lower PI secretion.

Conclusion

While all T1D subjects from the T1D Exchange secreted measurable non-fasting PI, those with a greater non-fasting PI demonstrated a decrease in ?CP during the MMTT. PI may be preferentially secreted compared to CP in some individuals with long standing T1D.

SUBMITTER: Sullivan CA

PROVIDER: S-EPMC6226191 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: A pilot study.

Sullivan Catherine A CA Cacicedo Jose M JM Rajendran Iniya I Steenkamp Devin W DW

PloS one 20181109 11

<h4>Aims</h4>Increased proinsulin (PI) compared to C-peptide (CP) concentrations have been reported, both prior to type 1 diabetes mellitus (T1D) onset, as well as early in disease. In this pilot study, we sought to define the normal PI secretion in a healthy cohort and compare this to a local T1D cohort and a separate well-defined nationally representative T1D cohort with measurable CP.<h4>Methods</h4>Thirteen healthy subjects and 12 T1D subjects with T1D >3 years from the local T1D cohort comp ...[more]

PMID: 30412637

Similar Datasets

Project description:BackgroundLatent autoimmune diabetes in adults (LADA) is characterized by autoimmunity, late-onset and intermediate beta-cell deprivation rate between type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM). Herein, we investigated proinsulin (PI) secretion patterns and the endoplasmic reticulum (ER) dysfunction biomarker, PI-to-C-peptide (PI:CP) ratio, to elucidate beta-cell intrinsic pathogenesis mechanisms in different types of diabetes.MethodsTotal serum fasting PI (FPI) were measured in adult-onset and newly-diagnosed diabetes patients, including 60 T1DM, 60 LADA and 60 T2DM. Thirty of each type underwent mixed meal tolerance tests (MMTTs), and hence 120 min postprandial PI (PPI) were detected. PI:CP ratio = PI (pmol/L) ÷ CP (pmol/L) × 100%. PI-related measurements among types of diabetes were compared. Correlation between PI-related measurements and beta-cell autoimmunity were analyzed. The possibility of discriminating LADA from T1DM and T2DM with PI-related measurements were tested.ResultsFPI and PPI were significantly higher in LADA than T1DM (P<0.001 for both comparisons), but lower than those in T2DM (P<0.001 and P=0.026, respectively). Fasting PI:CP ratio was significantly higher in T1DM than both LADA and T2DM (median 3.25% vs. 2.13% and 2.32%, P=0.011 and P=0.017, respectively). In LADA, positive autoantibody numbers increased by both fasting and postprandial PI:CP ratio (P=0.007 and P=0.034, respectively). Areas under receiver operation characteristic curves (AUCROC) of FPI and PPI for discriminating LADA from adult-onset T1DM were 0.751 (P<0.001) and 0.838 (P<0.001), respectively. Between LADA and T2DM, AUCROC of FPI and PPI were 0.685 (P<0.001) and 0.741 (P=0.001), respectively.ConclusionsIn the development of autoimmune diabetes, interplays between ER stress and beta-cell autoimmunity are potentially responsible for severer beta-cell destruction. PI-related measurements could help in differentiating LADA from adult-onset T1DM and T2DM.

Dataset Information

Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: A pilot study.

Aims

Methods

Results

Conclusion

Publications

Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: A pilot study.

Similar Datasets

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