Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future.
Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future.
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DOI：
10.1016/s0140-6736(13)62154-6
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发表时间：
2014-03-22
期刊：
影响因子：
168.9
通讯作者：
Del Prato, Stefano
中科院分区：
文献类型：
--
作者：
Kahn, Steven E.;Cooper, Mark E.;Del Prato, Stefano
葡萄糖代谢的正常调节是由一个涉及胰岛β细胞和胰岛素敏感组织的反馈回路决定的，其中组织对胰岛素的敏感性决定了β细胞反应的大小。当胰岛素抵抗存在时，β细胞通过增加胰岛素输出来维持正常的葡萄糖耐量。只有当β细胞在胰岛素抵抗的情况下不能释放足够的胰岛素时，葡萄糖水平才会上升。虽然β细胞功能障碍具有明显的遗传成分，但环境变化起着至关重要的作用。现代研究方法也揭示了己糖、氨基酸和脂肪酸在决定胰岛素抵抗和β细胞功能障碍中的重要性，以及微生物组改变的潜在作用。许多新的治疗方法已经被开发出来，但是需要更有效的疗法来减缓β细胞功能的逐渐丧失。最近的临床试验提供了关于预防和治疗2型糖尿病的方法以及这些干预措施的一些不良影响的重要信息。然而，需要对药物和减肥手术进行额外的长期研究，以确定预防和治疗的新方法，从而减少2型糖尿病的有害影响。
Normal regulation of glucose metabolism is determined by a feedback loop involving the islet β-cell and insulin-sensitive tissues in which tissue sensitivity to insulin determines the magnitude of the β-cell response. When insulin resistance is present, the β-cell maintains normal glucose tolerance by increasing insulin output. It is only when the β-cell is incapable of releasing sufficient insulin in the presence of insulin resistance that glucose levels rise. While β-cell dysfunction has a clear genetic component, environmental changes play a vital role. Modern approaches have also informed regarding the importance of hexoses, amino acids and fatty acids in determining insulin resistance and β-cell dysfunction as well as the potential role of alterations in the microbiome. A number of new treatment approaches have been developed, but more effective therapies that slow the progressive loss of β-cell function are needed. Recent clinical trials have provided important information regarding approaches to prevent and treat type 2 diabetes as well as some of the adverse effects of these interventions. However, additional long-term studies of medications and bariatric surgery are required in order to identify novel approaches to prevention and treatment, thereby reducing the deleterious impact of type 2 diabetes.