Heald A H, Narayanan R P, Lowes D, Jarman E, Onyekwelu E, Qureshi Z, Laing I, Anderson S G
Department of Medicine, Leighton Hospital, Crewe, UK.
Exp Clin Endocrinol Diabetes. 2012 Jul;120(7):420-3. doi: 10.1055/s-0032-1309046. Epub 2012 May 25.
Exenatide, a glucagon-like peptide-1 (GLP-1) analogue, is an effective glucoregulator for treating overweight individuals, not at target HbA1 c. This prospective study aimed to determine whether estimates of beta cell function (HOMA-B) and insulin sensitivity (HOMA-S) predict response to Exenatide treatment.Prospective data on 43 type 2 diabetes patients were collected for up to 2.8 years in UK primary care. HOMA-B and HOMA-S were estimated prior to initiating Exenatide, with monitoring of cardio-metabolic risk factors.Mean (SD) age and BMI pre-treatment were 54.1±10.5 years and 35.7±7.5 kg/m2 respectively. HbA1c decreased (mean reduction 0.9%, p=0.04; p for trend=0.01) in 61% of patients. In univariate analyses, HOMA-S as a measure of insulin sensitivity was inversely (β=- 0.41, p 0.009) related to change in HbA1c, with no relation for HOMA-B.In a random effects regression model that included age at baseline, weight, LDL-C, HDL-C and triglycerides, change in HbA1c (β= - 0.14, p<0.001) and HDL-C (β= - 0.52, p=0.011) were independently associated with increasing insulin sensitivity (r2=0.52). Thus patients with greater measured insulin sensitivity achieved greater reduction in HbA1c independent of the factors described above.In logistic regression those in the highest tertile of log-HOMA-S were 45% more likely to have a fall in HbA1c with an odds ratio (OR) of 0.55 (95% CI 0.47-0.66) p<0.0001 (log likelihood ratio for the model χ2=71.6, p<0.0001).Patients with greater measured insulin sensitivity achieve greater reduction in HbA1c with Exenatide. Determination of insulin sensitivity may assist in guiding outcome expectation in overweight patients treated with GLP-1 analogues.
艾塞那肽是一种胰高血糖素样肽-1（GLP-1）类似物，是治疗超重但糖化血红蛋白（HbA1c）未达标的个体的有效血糖调节剂。这项前瞻性研究旨在确定β细胞功能估计值（HOMA-B）和胰岛素敏感性（HOMA-S）是否能预测对艾塞那肽治疗的反应。
在英国初级医疗保健机构中收集了43例2型糖尿病患者长达2.8年的前瞻性数据。在开始使用艾塞那肽之前评估HOMA-B和HOMA-S，并监测心血管代谢危险因素。治疗前的平均（标准差）年龄和体重指数分别为54.1±10.5岁和35.7±7.5kg/m²。61%的患者糖化血红蛋白降低（平均降低0.9%，p=0.04；趋势p=0.01）。在单变量分析中，作为胰岛素敏感性指标的HOMA-S与糖化血红蛋白的变化呈负相关（β=-0.41，p=0.009），而HOMA-B与之无关。
在一个纳入基线年龄、体重、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯的随机效应回归模型中，糖化血红蛋白的变化（β=-0.14，p<0.001）和HDL-C的变化（β=-0.52，p=0.011）与胰岛素敏感性增加独立相关（r²=0.52）。因此，测量的胰岛素敏感性较高的患者，其糖化血红蛋白的降低幅度更大，且与上述因素无关。
在逻辑回归分析中，log-HOMA-S最高三分位数的患者糖化血红蛋白下降的可能性高出45%，优势比（OR）为0.55（95%可信区间0.47-0.66），p<0.0001（模型的对数似然比χ²=71.6，p<0.0001）。
胰岛素敏感性较高的患者使用艾塞那肽治疗时糖化血红蛋白降低幅度更大。确定胰岛素敏感性可能有助于指导使用GLP-1类似物治疗的超重患者的预后预期。
