Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio.
PLoS One
; 11(12): e0166702, 2016.
Article
en En
| MEDLINE
| ID: mdl-27907006
ABSTRACT
BACKGROUND:
The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulinC-peptide ratio (PIC). The present study aims to optimize precision of PIC measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release.METHODS:
Between-day imprecision (n = 20) and split-sample analysis (n = 95) were used to compare TT-TRFIA (AutoDelfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche). High-risk multiple autoantibody-positive first-degree relatives (n = 49; age 5-39) were tested for fasting PIC, HOMA2-IR and hyperglycemic clamp and followed for 20-57 months (interquartile range).RESULTS:
TT-TRFIA values for proinsulin, C-peptide and PIC correlated significantly (r2 = 0.96-0.99; P<0.001) with results obtained with separate methods. TT-TRFIA achieved better between-day %CV for PIC at three different levels (4.5-7.1 vs 6.7-9.5 for separate methods). In high-risk relatives fasting PIC was significantly and inversely correlated (rs = -0.596; P<0.001) with first-phase C-peptide release during clamp (also with second phase release, only available for age 12-39 years; n = 31), but only after normalization for HOMA2-IR. In ROC- and Cox regression analysis, HOMA2-IR-corrected PIC predicted 2-year progression to diabetes equally well as clamp-derived C-peptide release.CONCLUSIONS:
The reproducibility of PIC benefits from the automated simultaneous determination of both hormones. HOMA2-IR-corrected PIC may serve as a minimally invasive alternative to the more tedious hyperglycemic clamp test.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proinsulina
/
Péptido C
/
Diabetes Mellitus Tipo 1
/
Hiperglucemia
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Bélgica