Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System, University of Washington, Seattle, WA, USA.
Diabetes Division, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
Lancet. 2014 Mar 22;383(9922):1068-83. doi: 10.1016/S0140-6736(13)62154-6. Epub 2013 Dec 3.
Glucose metabolism is normally regulated by a feedback loop including islet β cells and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude of β-cell response. If insulin resistance is present, β cells maintain normal glucose tolerance by increasing insulin output. Only when β cells cannot release sufficient insulin in the presence of insulin resistance do glucose concentrations rise. Although β-cell dysfunction has a clear genetic component, environmental changes play an essential part. Modern research approaches have helped to establish the important role that hexoses, aminoacids, and fatty acids have in insulin resistance and β-cell dysfunction, and the potential role of changes in the microbiome. Several new approaches for treatment have been developed, but more effective therapies to slow progressive loss of β-cell function are needed. Recent findings from clinical trials provide important information about methods to prevent and treat type 2 diabetes and some of the adverse effects of these interventions. However, additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful effects of this disease.
葡萄糖代谢通常受到一个反馈回路的调节，其中包括胰岛β细胞和胰岛素敏感组织，在这个回路中，组织对胰岛素的敏感性会影响β细胞反应的程度。如果存在胰岛素抵抗，β细胞通过增加胰岛素分泌来维持正常的葡萄糖耐量。只有当β细胞在存在胰岛素抵抗的情况下无法释放足够的胰岛素时，血糖浓度才会升高。尽管β细胞功能障碍有明显的遗传成分，但环境变化也起着至关重要的作用。现代研究方法有助于确定己糖、氨基酸和脂肪酸在胰岛素抵抗和β细胞功能障碍中的重要作用，以及微生物组变化的潜在作用。已经开发出几种新的治疗方法，但需要更有效的疗法来减缓β细胞功能的进行性丧失。临床试验的最新发现提供了有关预防和治疗 2 型糖尿病的方法的重要信息，以及这些干预措施的一些不良反应。然而，需要进行更多的长期药物和减肥手术研究，以确定预防和治疗 2 型糖尿病的新方法，从而减少这种疾病的有害影响。
