期刊
DIABETES
卷 70, 期 4, 页码 932-943出版社
AMER DIABETES ASSOC
DOI: 10.2337/db20-0937
关键词
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资金
- National Institutes of Health [P01 AI042288]
- JDRF [1-SRA-2019-764-A-N, 2-PDF-2016-207A-N]
- American Diabetes Association
- McJunkin Family Charitable Foundation
- Jeffrey Keene Family Professorship
By incorporating genetic risk score, islet autoantibodies, disease duration, and age at onset, the study demonstrated a superior capacity to predict residual beta-cell function in individuals with type 1 diabetes. These findings suggest the need for longitudinal validation of the combinatorial model to inform clinical trial enrollment and benchmarking for preserving or restoring endogenous beta-cell function.
We and others previously demonstrated that a type 1 diabetes genetic risk score (GRS) improves the ability to predict disease progression and onset in at-risk subjects with islet autoantibodies. Here, we hypothesized that GRS and islet autoantibodies, combined with age at onset and disease duration, could serve as markers of residual beta-cell function following type 1 diabetes diagnosis. Generalized estimating equations were used to investigate whether GRS along with insulinoma-associated protein-2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A), and GAD autoantibody (GADA) titers were predictive of C-peptide detection in a largely cross-sectional cohort of 401 subjects with type 1 diabetes (median duration 4.5 years [range 0-60]). Indeed, a combined model with incorporation of disease duration, age at onset, GRS, and titers of IA-2A, ZnT8A, and GADA provided superior capacity to predict C-peptide detection (quasi-likelihood information criterion [QIC] = 334.6) compared with the capacity of disease duration, age at onset, and GRS as the sole parameters (QIC = 359.2). These findings support the need for longitudinal validation of our combinatorial model. The ability to project the rate and extent of decline in residual C-peptide production for individuals with type 1 diabetes could critically inform enrollment and benchmarking for clinical trials where investigators are seeking to preserve or restore endogenous beta-cell function.
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