Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes
| Autor: | Renecia A. Watkins, Raghavendra G. Mirmira, Zunaira Chaudhry, Carmella Evans-Molina, Linda A. DiMeglio, Emily K. Sims, Fangqian Ouyang, Jay M. Sosenko, Susan M. Perkins, Farooq Syed, Janice S. Blum |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Diabetes mellitus Internal medicine Internal Medicine medicine Humans Longitudinal Studies Young adult Child Proinsulin Autoantibodies Advanced and Specialized Nursing Type 1 diabetes C-Peptide C-peptide business.industry Clinical Care/Education/Nutrition/Psychosocial Research Odds ratio Fasting medicine.disease Pedigree 030104 developmental biology Endocrinology Diabetes Mellitus Type 1 chemistry Quartile Cohort Disease Progression Blood Banks Female business Biomarkers |
| Zdroj: | Diabetes Care |
| ISSN: | 1935-5548 0149-5992 |
| Popis: | OBJECTIVE We tested whether an elevation in the serum proinsulin–to–C-peptide ratio (PI:C), a biomarker of β-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 β-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. |
| Databáze: | OpenAIRE |
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