Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes  

Oleh:

Sims, Emily K. ; Chaudhry, Zunaira ; Watkins, Renecia ; Syed, Farooq ; Evans-Molina, Carmella

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Diabetes Care vol. 39 no. 09 (Sep. 2016), page 1519-1526.
Topik: Type 1 Diabetes; T1D

Ketersediaan

Perpustakaan FK Nomor Panggil: D05.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

OBJECTIVE We tested whether an elevation in the serum proinsulin–to–C-peptide ratio (PI:C), a biomarker of ß-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. RESEARCH DESIGN AND METHODS Fasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody-positive relatives without diabetes of individuals with type 1 diabetes. Samples were obtained ~12 months before diabetes onset from PTP progressors in whom diabetes developed (n = 60), and were compared with age-, sex-, and BMI-matched nonprogressors who remained normoglycemic (n = 58). PI:C ratios were calculated as molar ratios and were multiplied by 100% to obtain PI levels as a percentage of C levels. RESULTS Although absolute PI levels did not differ between groups, PI:C ratios were significantly increased in antibody-positive subjects in whom there was progression to diabetes compared with nonprogressors (median 1.81% vs. 1.17%, P = 0.03). The difference between groups was most pronounced in subjects who were =10 years old, where the median progressor PI:C ratio was nearly triple that of nonprogressors; 90.0% of subjects in this age group within the upper PI:C quartile progressed to the development of diabetes. Logistic regression analysis, adjusted for age and BMI, demonstrated increased odds of progression for higher natural log PI:C ratio values (odds ratio 1.44, 95% CI 1.02, 2.05). CONCLUSIONS These data suggest that ß-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children. Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 diabetes in the presymptomatic phase.

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