Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada.
Am J Physiol Endocrinol Metab. 2013 Dec 1;305(11):E1398-407. doi: 10.1152/ajpendo.00447.2013. Epub 2013 Oct 15.
Short-term intensive insulin therapy (IIT) can improve pancreatic β-cell function when administered early in the course of type 2 diabetes mellitus (T2DM). However, the degree of improvement in response to this therapy varies between patients. Thus, we sought to characterize the determinants of improvement in β-cell function in response to short-term IIT in early T2DM. Sixty-three patients with mean 3.0 ± 2.1 yr duration of T2DM and Hb A1c of 6.8 ± 0.8% underwent 4 wk of IIT consisting of basal insulin detemir and premeal insulin aspart, with oral glucose tolerance test administered at baseline and 1 day post-IIT. β-Cell function before and after IIT was assessed by Insulin Secretion Sensitivity Index-2 (ISSI-2). Reversibility of β-cell dysfunction was defined as percentage change in ISSI-2 of ≥25%. Overall, the study population experienced an increase in ISSI-2 from baseline to post-IIT (P = 0.01), with one-third of participants achieving ≥25% improvement in ISSI-2. Compared with their peers, those with increases in ISSI-2 of ≥25% had greater decrements in fasting glucose (P < 0.0001), Hb A1c (P = 0.001), ALT (P = 0.04), AST (P = 0.02), and HOMA-IR (P < 0.0001). On logistical regression analysis, baseline Hb A1c (OR = 2.83, 95% CI 1.16-6.88, P = 0.02) and change in HOMA-IR (OR = 0.008, 95%CI 0.0004-0.16, P = 0.001) emerged as independent predictors of reversibility of β-cell dysfunction. Indeed, reversibility of β-cell dysfunction was achieved in only those participants in whom IIT yielded an improvement in HOMA-IR. In conclusion, decline in HOMA-IR may be a key determinant of improvement of β-cell function in response to short-term IIT, suggesting a fundamental contribution of insulin resistance to the reversible component of β-cell dysfunction in early T2DM.
短期强化胰岛素治疗（IIT）可改善 2 型糖尿病（T2DM）早期的胰岛β细胞功能。然而，这种治疗反应的改善程度在患者之间存在差异。因此，我们试图描述短期 IIT 治疗早期 T2DM 患者β细胞功能改善的决定因素。63 例 T2DM 病程平均为 3.0±2.1 年，HbA1c 为 6.8±0.8%，接受为期 4 周的 IIT，包括基础胰岛素地特胰岛素和餐时胰岛素门冬氨酸，在基线和 IIT 后 1 天进行口服葡萄糖耐量试验。IIT 前后β细胞功能通过胰岛素分泌敏感指数-2（ISSI-2）进行评估。β细胞功能障碍的逆转定义为 ISSI-2 的变化百分比≥25%。总体而言，研究人群的 ISSI-2 从基线到 IIT 后有所增加（P=0.01），三分之一的参与者的 ISSI-2 改善≥25%。与他们的同龄人相比，ISSI-2 增加≥25%的患者空腹血糖（P<0.0001）、HbA1c（P=0.001）、丙氨酸转氨酶（ALT）（P=0.04）、天冬氨酸转氨酶（AST）（P=0.02）和 HOMA-IR（P<0.0001）下降幅度更大。在逻辑回归分析中，基线 HbA1c（OR=2.83，95%CI 1.16-6.88，P=0.02）和 HOMA-IR 的变化（OR=0.008，95%CI 0.0004-0.16，P=0.001）是β细胞功能障碍逆转的独立预测因子。实际上，只有那些 IIT 能改善 HOMA-IR 的患者才能实现β细胞功能的逆转。总之，HOMA-IR 的下降可能是短期 IIT 治疗后β细胞功能改善的关键决定因素，提示胰岛素抵抗对早期 T2DM 中β细胞功能障碍的可逆转成分具有重要贡献。
