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日本2型糖尿病患者对胰高血糖素样肽-1受体激动剂治疗反应的预测。

Prediction of response to GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes.

作者信息

Imai Kenjiro, Tsujimoto Tetsuro, Goto Atsushi, Goto Maki, Kishimoto Miyako, Yamamoto-Honda Ritsuko, Noto Hiroshi, Kajio Hiroshi, Noda Mitsuhiko

机构信息

Department of Diabetes, Endocrinology, and Metabolism, Center Hospital, National Center for Global Health and Medicine, Tokyo, Japan.

Department of Diabetes Research, Diabetes Research Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan.

出版信息

Diabetol Metab Syndr. 2014 Oct 15;6(1):110. doi: 10.1186/1758-5996-6-110. eCollection 2014.

Abstract

BACKGROUND

Glucagon-like peptide-1 (GLP-1) receptor agonists can maintain good glycemic control in some diabetic. Here we compared the clinical characteristics and parameters reflecting glucose metabolism at the time of the initiation of GLP-1 receptor agonist therapy between patients who responded well to therapy and those who did not.

METHODS

The records of 43 patients with type 2 diabetes who started receiving GLP-1 receptor agonist therapy during hospitalization were retrospectively reviewed. Glucagon stimulation tests were performed, and patients were started on liraglutide or exenatide therapy. Preprandial blood glucose levels were measured on days 2 and 3 of GLP-1 receptor agonist therapy. We used the Cox proportional hazard model to compare clinical parameters between responders (HbA1c level <8% at more than 3 months after the initiation of treatment) and non-responders (HbA1c level ≥8% at more than 3 months after the initiation of treatment or a switch to insulin therapy at any time).

RESULTS

Twenty-six of the 43 patients were classified as non-responders. At baseline, mean HbA1c levels were 9.9% among responders and 9.7% among non-responders. Compared with treatment with only diet or metformin, the hazard ratio [HR] for non-response was 5.3 (95% confidence interval [CI]: 1.16-24.6, P = 0.03) for insulin therapy and 5.0 (95% CI: 1.13-22.16, P = 0.03) for sulfonylurea therapy. Compared with the lowest tertile, the HRs for non-response in the highest tertile were 3.1 (95% CI: 1.04-8.97, P = 0.04) for the mean preprandial blood glucose level on days 2 and 3 and 3.4 (95% CI: 1.05-11.01, P = 0.04) for the body mass index. The response was not significantly associated with the duration of diabetes or the glucagon stimulation test results. A receiver operating curve analysis showed that the mean preprandial blood glucose level had the highest area under the curve value (=0.72) for the prediction of non-responders.

CONCLUSIONS

In patients with poorly controlled diabetes, the response to GLP-1 receptor agonist therapy was significantly associated with the treatment used before the initiation of therapy, the body mass index, and the mean preprandial blood glucose level during the 2 days after the initiation of therapy.

摘要

背景

胰高血糖素样肽-1(GLP-1)受体激动剂可使部分糖尿病患者维持良好的血糖控制。在此,我们比较了对治疗反应良好的患者与反应不佳的患者在开始GLP-1受体激动剂治疗时的临床特征及反映糖代谢的参数。

方法

回顾性分析43例住院期间开始接受GLP-1受体激动剂治疗的2型糖尿病患者的病历。进行了胰高血糖素刺激试验,并让患者开始接受利拉鲁肽或艾塞那肽治疗。在GLP-1受体激动剂治疗的第2天和第3天测量餐前血糖水平。我们使用Cox比例风险模型比较反应者(治疗开始后3个月以上糖化血红蛋白水平<8%)和无反应者(治疗开始后3个月以上糖化血红蛋白水平≥8%或在任何时间改用胰岛素治疗)之间的临床参数。

结果

43例患者中有26例被分类为无反应者。基线时,反应者的平均糖化血红蛋白水平为9.9%,无反应者为9.7%。与仅采用饮食或二甲双胍治疗相比,胰岛素治疗无反应的风险比[HR]为5.3(95%置信区间[CI]:1.16 - 24.6,P = 0.03),磺脲类药物治疗为5.0(95% CI:1.13 - 22.16,P = 0.03)。与最低三分位数相比,第2天和第3天平均餐前血糖水平最高三分位数的无反应HR为3.1(95% CI:1.04 - 8.97,P = 0.04),体重指数的无反应HR为3.4(95% CI:1.05 - 11.01,P = 0.04)。反应与糖尿病病程或胰高血糖素刺激试验结果无显著相关性。受试者工作特征曲线分析表明,平均餐前血糖水平对无反应者预测的曲线下面积值最高(=0.72)。

结论

在血糖控制不佳的糖尿病患者中,对GLP-1受体激动剂治疗的反应与治疗开始前使用的治疗方法、体重指数以及治疗开始后2天内的平均餐前血糖水平显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae35/4209043/4ed3ffd36418/13098_2014_370_Fig1_HTML.jpg

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