Title
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Prediction of impending type 1 diabetes through automated dual-label measurement of proinsulin:C-peptide ratio
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Author
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Abstract
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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 proinsulin:C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C 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 539) were tested for fasting PI:C, HOMA2-IR and hyperglycemic clamp and followed for 2057 months (interquartile range). Results TT-TRFIA values for proinsulin, C-peptide and PI:C correlated significantly (r2 = 0.960.99; P<0.001) with results obtained with separate methods. TT-TRFIA achieved better between-day %CV for PI:C at three different levels (4.57.1 vs 6.79.5 for separate methods). In high-risk relatives fasting PI:C 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 1239 years; n = 31), but only after normalization for HOMA2-IR. In ROC- and Cox regression analysis, HOMA2-IR-corrected PI:C predicted 2-year progression to diabetes equally well as clamp-derived C-peptide release. Conclusions The reproducibility of PI:C benefits from the automated simultaneous determination of both hormones. HOMA2-IR-corrected PI:C may serve as a minimally invasive alternative to the more tedious hyperglycemic clamp test. |
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Language
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English
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Source (journal)
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PLoS ONE
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Publication
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2016
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ISSN
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1932-6203
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DOI
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10.1371/JOURNAL.PONE.0166702
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Volume/pages
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11
:12
(2016)
, 14 p.
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Article Reference
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e0166702
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ISI
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000389482700036
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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