Proinsulin to C-Peptide Ratio in the First Year After Diagnosis of Type 1 Diabetes.
J Clin Endocrinol Metab
; 106(11): e4318-e4326, 2021 10 21.
Article
in En
| MEDLINE
| ID: mdl-34228132
ABSTRACT
OBJECTIVE:
The proinsulin to C-peptide (PIC) ratio is reputedly a biomarker of ß-cell endoplasmic reticulum (ER) stress.OBJECTIVE:
This study examined the natural history of the PIC ratio and its correlation with residual ß-cell function in childhood new-onset type 1 diabetes (T1D). Over the first year of T1D, the temporal trend in fasting and nutrient-stimulated PI data is limited.METHODS:
PI was a secondary pre-planned analysis of our 1-year, randomized, double-blind, placebo-controlled gamma aminobutyric acid (GABA) trial in new-onset T1D. Of the 99 participants in the primary study, aged 4 to 18 years, 30 were placebo. This study only involved the 30 placebo patients; all were enrolled within 5 weeks of T1D diagnosis. A liquid mixed meal tolerance test was administered at baseline and 5 and 12 months for determination of C-peptide, PI, glucose, and hemoglobin A1C.RESULTS:
Both the fasting (Pâ =â 0.0003) and stimulated (Pâ =â 0.00008) PIC ratios increased from baseline to 12 months, indicating escalating ß-cell ER stress. The baseline fasting PI correlated with the fasting change in C-peptide at 12 months (Pâ =â 0.004) with a higher PI correlating with greater decline in C-peptide. Patients with an insulin-adjusted A1Câ >9% (hence, not in remission) had higher fasting PIC ratios. Younger age at diagnosis correlated with a higher PIC ratio (Pâ =â 0.04).CONCLUSION:
Children with new-onset T1D undergo progressive ß-cell ER stress and aberrant proinsulin processing, as evidenced by increasing PIC ratios. Moreover, the PIC ratio reflects more aggressive ß-cell onslaught with younger age, as well as diminished glycemic control.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proinsulin
/
C-Peptide
/
Diabetes Mellitus, Type 1
/
Insulin-Secreting Cells
/
Endoplasmic Reticulum Stress
Type of study:
Clinical_trials
/
Diagnostic_studies
Limits:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2021
Document type:
Article
Affiliation country: