Precision Medicine in Type 2 Diabetes: Clinical Markers of Insulin Resistance Are Associated With Altered Short- and Long-term Glycemic Response to DPP-4 Inhibitor Therapy.
Precision Medicine in Type 2 Diabetes: Clinical Markers of Insulin Resistance Are Associated With Altered Short- and Long-term Glycemic Response to DPP-4 Inhibitor Therapy.
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DOI：
10.2337/dc17-1827
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发表时间：
2018-04
期刊：
影响因子：
16.2
通讯作者：
MASTERMIND Consortium
中科院分区：
文献类型：
--
作者：
Dennis JM;Shields BM;Hill AV;Knight BA;McDonald TJ;Rodgers LR;Weedon MN;Henley WE;Sattar N;Holman RR;Pearson ER;Hattersley AT;Jones AG;MASTERMIND Consortium
2型糖尿病治疗的“精确”方法旨在根据患者特征进行靶向治疗。我们研究了胰岛素抵抗和分泌的测量是否与对DPP 4抑制剂治疗的血糖反应相关。在一项前瞻性研究中，我们评估了胰岛素抵抗和胰岛素分泌标志物是否与6个月血糖反应相关，该研究对开始DPP 4抑制剂治疗的非胰岛素治疗参与者（PRIBA，n=254）进行了研究，并对英国电子医疗记录中常规可用的标志物进行了复制（CPRD，n= 23，001）。在CPRD中，我们评估了基线标志物与3年缓解持久性之间的关联。为了检测结果的特异性，我们对GLP-1受体激动剂（PRIBA n=339，CPRD n= 4，464）进行了重复分析。在PRIBA中，较高胰岛素抵抗的标志物（较高的空腹C肽（p=0.03）、HOMA 2胰岛素抵抗（p=0.01）和甘油三酯（p<0.01））与6个月时对DPP 4抑制剂的HbA 1c反应降低相关。在CPRD中，较高的甘油三酯和BMI与HbA 1c反应降低相关（均p<0.01）。在两个数据集中，由肥胖（BMI≥ 30 kg/m2）和高甘油三酯（≥ 2.3 mmol/L）定义的亚组的6个月缓解率降低（PRIBA HbA 1c降低5.3[95%CI 1.8，8.6]mmol/mol（0.5%）（肥胖，高甘油三酯）vs 11.3[8.4，14.1] mmol/mol（1.0%）（非肥胖，正常甘油三酯），p=0.01）。在CPRD中，肥胖、高甘油三酯亚组的持久反应也较低（风险比1.28[1.16，1.41]，p<0.001）。胰岛素抵抗标志物与GLP-1受体激动剂反应之间无相关性。较高胰岛素抵抗的标志物始终与对DPP 4抑制剂的血糖反应降低相关。这一发现为精确糖尿病方法应用于DPP 4抑制剂治疗提供了一个起点。PRIBA ClinicalTrials.gov标识符：NCT 01503112
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 DPP4-inhibitor therapy. We evaluated whether markers of insulin resistance and insulin secretion were associated with 6 month glycemic response in a prospective study of non-insulin treated participants starting DPP4-inhibitor therapy (PRIBA, n=254), with replication for routinely available markers in UK electronic healthcare records (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 GLP-1 receptor agonists (PRIBA n=339, CPRD n=4,464). 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 DPP4 inhibitors. In CPRD higher triglycerides and BMI were associated with reduced HbA1c response (both p<0.01). A subgroup defined by obesity (BMI≥30kg/m2) and high triglycerides (≥2.3mmol/L) had reduced 6 month response in both datasets (PRIBA HbA1c reduction 5.3[95%CI 1.8,8.6]mmol/mol (0.5%) (obese, high triglycerides) vs 11.3[8.4,14.1] mmol/mol (1.0%) (non-obese, 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. Markers of higher insulin resistance are consistently associated with reduced glycemic response to DPP4-inhibitors. This finding provides a starting point for the application of a precision diabetes approach to DPP4-inhibitor therapy. PRIBA ClinicalTrials.gov identifier: NCT01503112
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