アブストラクト | OBJECTIVE: A precision approach to type 2 diabetes therapy would aim to target treatment according to patient characteristics. We examined if measures of insulin resistance and secretion were associated with glycemic response to dipeptidyl peptidase 4 (DPP-4) inhibitor therapy. RESEARCH DESIGN AND METHODS: We evaluated whether markers of insulin resistance and insulin secretion were associated with 6-month glycemic response in a prospective study of noninsulin-treated participants starting DPP-4 inhibitor therapy (Predicting Response to Incretin Based Agents [PRIBA] study; n = 254), with replication for routinely available markers in U.K. electronic health care records (Clinical Practice Research Datalink [CPRD]; n = 23,001). In CPRD, we evaluated associations between baseline markers and 3-year durability of response. To test the specificity of findings, we repeated analyses for glucagon-like peptide 1 (GLP-1) receptor agonists (PRIBA, n = 339; CPRD, n = 4,464). RESULTS: In PRIBA, markers of higher insulin resistance (higher fasting C-peptide [P = 0.03], HOMA2 insulin resistance [P = 0.01], and triglycerides [P < 0.01]) were associated with reduced 6-month HbA1c response to DPP-4 inhibitors. In CPRD, higher triglycerides and BMI were associated with reduced HbA1c response (both P < 0.01). A subgroup defined by obesity (BMI >/=30 kg/m(2)) and high triglycerides (>/=2.3 mmol/L) had reduced 6-month response in both data sets (PRIBA HbA1c reduction 5.3 [95% CI 1.8, 8.6] mmol/mol [0.5%] [obese and high triglycerides] vs. 11.3 [8.4, 14.1] mmol/mol [1.0%] [nonobese and normal triglycerides]; P = 0.01). In CPRD, the obese, high- triglycerides subgroup also had less durable response (hazard ratio 1.28 [1.16, 1.41]; P < 0.001). There was no association between markers of insulin resistance and response to GLP-1 receptor agonists. CONCLUSIONS: Markers of higher insulin resistance are consistently associated with reduced glycemic response to DPP-4 inhibitors. This finding provides a starting point for the application of a precision diabetes approach to DPP-4 inhibitor therapy. |
ジャーナル名 | Diabetes care |
投稿日 | 2018/2/2 |
投稿者 | Dennis, John M; Shields, Beverley M; Hill, Anita V; Knight, Bridget A; McDonald, Timothy J; Rodgers, Lauren R; Weedon, Michael N; Henley, William E; Sattar, Naveed; Holman, Rury R; Pearson, Ewan R; Hattersley, Andrew T; Jones, Angus G |
組織名 | Health Statistics Group, University of Exeter Medical School, Exeter, U.K.;National Institute for Health Research Exeter Clinical Research Facility,;University of Exeter Medical School, Exeter, U.K.;Blood Sciences, Royal Devon and Exeter Hospital, Exeter, U.K.;Institute of Biomedical and Clinical Science, University of Exeter Medical;School, Exeter, U.K.;Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow,;U.K.;Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism,;University of Oxford, Oxford, U.K.;Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School,;University of Dundee, Dundee, U.K.;University of Exeter Medical School, Exeter, U.K. angus.jones@exeter.ac.uk. |
Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/29386249/ |