Persistence of Prolonged C-peptide Production in Type 1 Diabetes as Measured With an Ultrasensitive C-peptide Assay

• Published in: Diabetes care Vol. 35; no. 3; pp. 465 - 470
• Main Authors: Wang, Limei, Lovejoy, Nicholas Fraser, Faustman, Denise L
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.2012
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Analysis; Antibodies; Autoantibodies; Autoimmunity; bioassays; Biological and medical sciences; Biological Assay; Biological Assay - methods; biomarkers; blood; blood serum; c-peptide; C-Peptide - blood; Child; detection limit; Diabetes; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; hyperglycemia; insulin secretion; insulin-dependent diabetes mellitus; islets of Langerhans; Male; Medical sciences; Metabolic diseases; metabolism; methods; Middle Aged; Miscellaneous; multivariate analysis; Older people; Original Research; patients; Public health. Hygiene; Public health. Hygiene-occupational medicine; regression analysis; renal function; Reproducibility of Results; Type 1 diabetes; Viral antibodies; Young Adult; zinc; Endocrinopathy; Human; Immunopathology; Nutrition; Autoimmune disease; Metabolic diseases; C-Peptide; Assay; Persistence; Type 1 diabetes; Production; Endocrinology; Prolonged
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc11-1236

OBJECTIVE: To examine persistence of C-peptide production by ultrasensitive assay years after onset of type 1 diabetes and factors associated with preserving β-cell function. RESEARCH DESIGN AND METHODS: Serum C-peptide levels, a marker of insulin production and surviving β-cells, were measured in human subjects (n = 182) by ultrasensitive assay, as was β-cell functioning. Twenty-two times more sensitive than standard assays, this assay’s lower detection limit is 1.5 pmol/L. Disease duration, age at onset, age, sex, and autoantibody titers were analyzed by regression analysis to determine their relationship to C-peptide production. Another group of four patients was serially studied for up to 20 weeks to examine C-peptide levels and functioning. RESULTS: The ultrasensitive assay detected C-peptide in 10% of individuals 31–40 years after disease onset and with percentages higher at shorter duration. Levels as low as 2.8 ± 1.1 pmol/L responded to hyperglycemia with increased C-peptide production, indicating residual β-cell functioning. Several other analyses showed that β-cells, whose C-peptide production was formerly undetectable, were capable of functioning. Multivariate analysis found disease duration (β = –2.721; P = 0.005) and level of zinc transporter 8 autoantibodies (β = 0.127; P = 0.015) significantly associated with C-peptide production. Unexpectedly, onset at >40 years of age was associated with low C-peptide production, despite short disease duration. CONCLUSIONS: The ultrasensitive assay revealed that C-peptide production persists for decades after disease onset and remains functionally responsive. These findings suggest that patients with advanced disease, whose β-cell function was thought to have long ceased, may benefit from interventions to preserve β-cell function or to prevent complications.