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

2.50
Hdl Handle:
http://hdl.handle.net/11287/594002
Title:
Markers of beta-Cell Failure Predict Poor Glycemic Response to GLP-1 Receptor Agonist Therapy in Type 2 Diabetes
Authors:
Jones, Angus G.; McDonald, Timothy J. ( 0000-0003-3559-6660 ) ; Shields, Beverley M; Hill, Anita V.; Hyde, C. J.; Knight, Bridget A.; Hattersley, Andrew T.; Priba Study Group
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:
Diabetes Care
Journal:
Diabetes care
Issue Date:
4-Aug-2015
URI:
http://hdl.handle.net/11287/594002
DOI:
10.2337/dc15-0258
PubMed ID:
26242184
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/26242184
Type:
Journal Article
Language:
Eng
ISSN:
1935-5548
Appears in Collections:
2015 RD&E publications; Diabetes/Endocrine Services; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorJones, Angus G.en
dc.contributor.authorMcDonald, Timothy J.en
dc.contributor.authorShields, Beverley Men
dc.contributor.authorHill, Anita V.en
dc.contributor.authorHyde, C. J.en
dc.contributor.authorKnight, Bridget A.en
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorPriba Study Groupen
dc.date.accessioned2016-01-19T12:38:28Zen
dc.date.available2016-01-19T12:38:28Zen
dc.date.issued2015-08-04en
dc.identifier.citationDiabetes Care. 2015 Aug 4. [Epub ahead of print]en
dc.identifier.issn1935-5548en
dc.identifier.pmid26242184en
dc.identifier.doi10.2337/dc15-0258en
dc.identifier.urihttp://hdl.handle.net/11287/594002en
dc.description.abstractOBJECTIVE: 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.en
dc.language.isoEngen
dc.publisherDiabetes Careen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/26242184en
dc.titleMarkers of beta-Cell Failure Predict Poor Glycemic Response to GLP-1 Receptor Agonist Therapy in Type 2 Diabetesen
dc.typeJournal Articleen
dc.identifier.journalDiabetes careen

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