Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada.
Division of Endocrinology, University of Toronto, Toronto, Canada.
Nat Commun. 2023 Jul 27;14(1):4514. doi: 10.1038/s41467-023-40287-w.
In early type 2 diabetes, the strategy of "induction" with short-term intensive insulin therapy followed by "maintenance" with metformin can stabilize pancreatic beta-cell function in some patients but not others. We thus sought to elucidate determinants of sustained stabilization of beta-cell function. In this secondary analysis of ClinicalTrials.Gov NCT02192424, adults with ≤5-years diabetes duration were randomized to 3-weeks induction insulin therapy (glargine/lispro) followed by metformin maintenance either with or without intermittent 2-week courses of insulin every 3-months for 2-years. Sustained stabilization (higher beta-cell function at 2-years than at baseline) was achieved in 55 of 99 participants. Independent predictors of sustained stabilization were the change in beta-cell function during induction and changes in hepatic insulin resistance and alanine aminotransferase during maintenance. Thus, initial reversibility of beta-cell dysfunction during induction and subsequent preservation of hepatic insulin sensitivity during maintenance are associated with sustained stabilization of beta-cell function following short-term insulin and metformin.ClinicalTrials.Gov NCT02192424.
在 2 型糖尿病早期，采用短期强化胰岛素治疗诱导，随后用二甲双胍维持的“诱导-维持”策略可以稳定一些患者的胰岛β细胞功能，但不能稳定另一些患者的胰岛β细胞功能。因此，我们试图阐明持续稳定胰岛β细胞功能的决定因素。在这项 ClinicalTrials.Gov NCT02192424 的二次分析中，病程≤5 年的成年人被随机分为三组：3 周诱导胰岛素治疗（甘精胰岛素/赖脯胰岛素），随后用二甲双胍维持，或在 2 年期间每 3 个月用胰岛素间歇治疗 2 周。在 99 名参与者中，有 55 名实现了β细胞功能的持续稳定（2 年时的β细胞功能高于基线）。持续稳定的独立预测因素是诱导期β细胞功能的变化以及维持期肝胰岛素抵抗和丙氨酸氨基转移酶的变化。因此，诱导期β细胞功能障碍的初始可逆性以及维持期肝胰岛素敏感性的后续保存与短期胰岛素和二甲双胍治疗后β细胞功能的持续稳定相关。ClinicalTrials.Gov NCT02192424。
