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 1 is compensation: insulin secretion increases to maintain normoglycemia in the face of insulin resistance and/or decreasing beta-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 approximately 5.0-6.5 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.

中文翻译：

---

进展为糖尿病期间 β 细胞功能障碍演变的五个阶段

本文提出了糖尿病发展的五个阶段，每个阶段的特点是 β 细胞量、表型和功能的不同变化。第 1 阶段是补偿：面对胰岛素抵抗和/或 β 细胞量减少时，胰岛素分泌增加以维持正常血糖。这个阶段的特征是维持分化的功能，完整的急性葡萄糖刺激胰岛素分泌 (GSIS)。第 2 阶段发生在葡萄糖水平开始上升，达到约 5.0-6.5 mmol/l 时；这是一种稳定的 β 细胞适应状态，伴随着 β 细胞质量的丧失和功能的破坏，GSIS 和 β 细胞去分化减少就证明了这一点。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迅速上升至第 4 阶段的坦率糖尿病，其特征是稳定的失代偿和更严重的 β 细胞去分化。最后，第 5 阶段的特征是严重的失代偿，表示随着进展为酮症，β 细胞量显着减少。跨阶段 1-4 的运动可以是任一方向。例如，接受治疗的 2 型糖尿病患者可以从第 4 阶段进入第 1 阶段或第 2 阶段。对于 1 型糖尿病，随着缓解的发展，通常会发现从第 4 阶段进展到第 2 阶段。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深入了解。跨阶段 1-4 的运动可以是任一方向。例如，接受治疗的 2 型糖尿病患者可以从第 4 阶段进入第 1 阶段或第 2 阶段。对于 1 型糖尿病，随着缓解的发展，通常会发现从第 4 阶段进展到第 2 阶段。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深入了解。跨阶段 1-4 的运动可以是任一方向。例如，接受治疗的 2 型糖尿病患者可以从第 4 阶段进入第 1 阶段或第 2 阶段。对于 1 型糖尿病，随着缓解的发展，通常会发现从第 4 阶段进展到第 2 阶段。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深入了解。