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    Markers of beta-Cell Failure Predict Poor Glycemic Response to GLP-1 Receptor Agonist Therapy in Type 2 Diabetes

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    URI
    http://hdl.handle.net/11287/594002
    Author
    Jones, Angus G.
    McDonald, Timothy J.
    Shields, Beverley M
    Hill, Anita V.
    Hyde, C. J.
    Knight, Bridget A.
    Hattersley, Andrew T.
    Priba Study Group
    Date
    2015-08-04
    Journal
    Diabetes care
    Type
    Journal Article
    Publisher
    Diabetes Care
    DOI
    10.2337/dc15-0258
    Metadata
    Show full item record
    Abstract
    OBJECTIVE: To assess whether clinical characteristics and simple biomarkers of beta-cell failure are associated with individual variation in glycemic response to GLP-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We prospectively studied 620 participants with type 2 diabetes and HbA1c >/=58 mmol/mol (7.5%) commencing GLP-1RA therapy as part of their usual diabetes care and assessed response to therapy over 6 months. We assessed the association between baseline clinical measurements associated with beta-cell failure and glycemic response (primary outcome HbA1c change 0-6 months) with change in weight (0-6 months) as a secondary outcome using linear regression and ANOVA with adjustment for baseline HbA1c and cotreatment change. RESULTS: Reduced glycemic response to GLP-1RAs was associated with longer duration diabetes, insulin cotreatment, lower fasting C-peptide, lower postmeal urine C-peptide-to-creatinine ratio, and positive GAD or IA2 islet autoantibodies (P </= 0.01 for all). Participants with positive autoantibodies or severe insulin deficiency (fasting C-peptide </=0.25 nmol/L) had markedly reduced glycemic response to GLP-1RA therapy (autoantibodies, mean HbA1c change -5.2 vs. -15.2 mmol/mol (-0.5 vs. -1.4%), P = 0.005; C-peptide <0.25 nmol/L, mean change -2.1 vs. -15.3 mmol/mol (-0.2 vs. -1.4%), P = 0.002). These markers were predominantly present in insulin-treated participants and were not associated with weight change. CONCLUSIONS: Clinical markers of low beta-cell function are associated with reduced glycemic response to GLP-1RA therapy. C-peptide and islet autoantibodies represent potential biomarkers for the stratification of GLP-1RA therapy in insulin-treated diabetes.
    Citation
    Diabetes Care. 2015 Aug 4. [Epub ahead of print]
    Publisher URL
    http://www.ncbi.nlm.nih.gov/pubmed/26242184
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    • 2015 RD&E publications
    • Diabetes and endocrinology
    • Honorary contracts publications

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