Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and β-cell function in TODAY.
Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and β-cell function in TODAY.
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DOI：
10.2337/dc12-2393
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发表时间：
2013-06
期刊：
影响因子：
16.2
通讯作者：
TODAY Study Group
中科院分区：
文献类型：
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作者：
TODAY Study Group
青少年和青少年2型糖尿病的治疗选择（TODAY）试验表明，与单用二甲双胍相比，二甲双胍加罗格列酮联合治疗提供了更好的血糖控制持久性，治疗失败率显著降低（38.6% vs 51.7%），二甲双胍加生活方式的效果中等。在此，我们描述了在4年期间三种治疗中β细胞功能和胰岛素敏感性测量的时间变化。今天的参与者（699人）定期接受口服葡萄糖耐量试验，以确定胰岛素敏感性（1/空腹胰岛素[1/IF]）、胰岛素原指数（△I30/△G30）或c肽指数（△C30/△G30），以及相对于胰岛素敏感性的β细胞功能（口服处理指数[oDI]）。在前6个月，与单用二甲双胍和二甲双胍加生活方式相比，二甲双胍加罗格列酮对胰岛素敏感性和oDI的改善显著更大；这些改善持续了48个月。无论采用何种治疗方法，与未失败的患者相比，未能维持血糖控制的患者在随机分组时β细胞功能显著降低（约50%），空腹血糖浓度较高，HbA1c较高。与单用二甲双胍和二甲双胍加罗格列酮相比，前6个月内胰岛素敏感性的有益改变和由此产生的β细胞功能负担的降低似乎是其血糖耐久性优于二甲双胍和二甲双胍加生活方式的原因。然而，初始β细胞储备和HbA1c随机化是血糖持久性的独立预测因子。因此，在β细胞功能显著丧失之前保持β细胞功能和降低HbA1c可能有利于青年2型糖尿病的治疗。
The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that combination therapy with metformin plus rosiglitazone provided superior durability of glycemic control compared with metformin alone, with significantly lower treatment failure rates (38.6 vs. 51.7%), and metformin plus lifestyle was intermediate. Herein we describe the temporal changes in measures of β-cell function and insulin sensitivity over a 4-year period among the three treatments. TODAY participants (699) were tested periodically with an oral glucose tolerance test to determine insulin sensitivity (1/fasting insulin [1/IF]), insulinogenic index (△I30/△G30) or C-peptide index (△C30/△G30), and β-cell function relative to insulin sensitivity (oral disposition index [oDI]). During the first 6 months, metformin plus rosiglitazone exhibited a significantly greater improvement in insulin sensitivity and oDI versus metformin alone and versus metformin plus lifestyle; these improvements were sustained over 48 months of TODAY. Irrespective of treatment, those who failed to maintain glycemic control had significantly lower β-cell function (∼50%), higher fasting glucose concentration, and higher HbA1c at randomization compared with those who did not fail. The beneficial change in insulin sensitivity and the resultant lower burden on β-cell function achieved in the first 6 months with metformin plus rosiglitazone appear to be responsible for its superior glycemic durability over metformin alone and metformin plus lifestyle. However, initial β-cell reserve and HbA1c at randomization are independent predictors of glycemic durability. Therefore, efforts to preserve β-cell function before significant loss occurs and to reduce HbA1c may be beneficial in the treatment of youth with type 2 diabetes.