Five stages of evolving β-cell dysfunction during progression to diabetes
Five stages of evolving β-cell dysfunction during progression to diabetes
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DOI：
10.2337/diabetes.53.suppl_3.s16
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发表时间：
2004-12-01
期刊：
影响因子：
7.7
通讯作者：
Bonner-Weir, S
中科院分区：
文献类型：
--
作者：
Weir, GC;Bonner-Weir, S
本文提出了糖尿病进展的五个阶段，每个阶段的特征在于β细胞质量、表型和功能的不同变化。第一阶段是补偿：胰岛素分泌增加，以维持正常的胰岛素抵抗和/或减少细胞质量。该阶段的特征在于维持分化功能，具有完整的急性葡萄糖刺激的胰岛素分泌（GSIS）。第2阶段发生在葡萄糖水平开始升高时，达到5.0 -6.5 mmol/l;这是β细胞适应的稳定状态，伴有β细胞质量损失和功能破坏，表现为GSIS减少和β细胞去分化。第3阶段是早期失代偿的短暂不稳定时期，其中葡萄糖水平相对快速地上升至第4阶段的明显糖尿病，其特征在于具有更严重的β细胞去分化的稳定失代偿。最后，第5阶段的特征在于严重的代偿失调，代表β细胞质量的显著减少，并进展为酮症。跨越阶段1-4的移动可以在任一方向上。例如，患有2型糖尿病的个体可以从阶段4移动到阶段1或阶段2。对于1型糖尿病，随着病情的缓解，通常会从4期进展到2期。这些阶段的描述提供了对糖尿病进展和缓解的病理生理学的了解。
This article proposes five stages in the progression of diabetes, each of which is characterized by different changes in beta-cell mass, phenotype, and function. Stage I is compensation: insulin secretion increases to maintain normoglycemia in the face of insulin resistance and/or decreasing -cell mass. This stage is characterized by maintenance of differentiated function with intact acute glucose-stimulated insulin secretion (GSIS). Stage 2 occurs when glucose levels start to rise, reaching similar to5.0-6.5 mmol/l; this is a stable state of beta-cell adaptation with loss of beta-cell mass and disruption of function as evidenced by diminished GSIS and beta-cell dedifferentiation. Stage 3 is a transient unstable period of early decompensation in which glucose levels rise relatively rapidly to the frank diabetes of stage 4, which is characterized as stable decompensation with more severe beta-cell dedifferentiation. Finally, stage 5 is characterized by severe decompensation representing a profound reduction in beta-cell mass with progression to ketosis. Movement across stages 1-4 can be in either direction. For example, individuals with treated type 2 diabetes can move from stage 4 to stage 1 or stage 2. For type 1 diabetes, as remission develops, progression from stage 4 to stage 2 is typically found. Delineation of these stages provides insight into the pathophysiology of both progression and remission of diabetes.