Wu Andrew, Pu Jiajie, Emery Alexandra, Harris Stewart B, Reichert Sonja M, Gerstein Hertzel C, McInnes Natalia, Kramer Caroline K, Zinman Bernard, Retnakaran Ravi
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada.
Department of Family Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Diabetes Obes Metab. 2025 Mar;27(3):1132-1142. doi: 10.1111/dom.16099. Epub 2024 Nov 28.
When administered in early type 2 diabetes (T2DM), the strategy of 'induction' with short-term intensive insulin therapy (IIT) followed by 'maintenance' with metformin thereafter can yield outstanding glycaemic control, with some patients achieving A1c in the normal range of its assay. We thus sought to identify determinants of sustained normalisation of A1c in response to this treatment strategy.
In this study, adults with T2DM of mean duration 1.7 ± 1.4 years received induction IIT (glargine, lispro) for 3 weeks, followed by metformin maintenance either with or without periodic 2-week courses of IIT every 3 months for 2 years. Sustained glycaemic normalisation was defined by A1c <6.0% at 2 years.
Of 101 participants, 26 achieved A1c <6.0% at 2 years. At baseline, these individuals had lower A1c and fasting glucose than the other participants, along with better beta-cell function. During maintenance therapy from 3 weeks to 2 years, they had greater reduction of adiposity (body mass index: p = 0.02; waist circumference: p = 0.02), hepatic insulin resistance (HOMA-IR: p = 0.02) and ALT (p = 0.005), coupled with relative stabilisation of beta-cell function and glycaemia. On logistic regression analyses, significant independent predictors of normalisation of A1c at 2 years were baseline A1c (adjusted odds ratio [aOR] = 0.01 [95% CI 0.001-0.16], p = 0.001) and the changes in waist circumference (aOR = 0.77 [0.63-0.94], p = 0.012) and ALT (aOR = 0.90 [0.82-0.98], p = 0.019) during maintenance therapy from 3 weeks to 2 years.
While lower baseline A1c and greater reduction in central adiposity predicted A1c <6.0% at 2 years as anticipated, the emergence of greater reduction in ALT as a concomitant determinant highlights the role of the liver in the achievement of sustained glycaemic normalisation.
在早期2型糖尿病（T2DM）患者中应用短期强化胰岛素治疗（IIT）进行“诱导”，随后使用二甲双胍进行“维持”治疗，可实现出色的血糖控制，部分患者糖化血红蛋白（A1c）可达到检测正常范围。因此，我们试图确定对该治疗策略有反应的患者实现A1c持续正常化的决定因素。
在本研究中，平均病程为1.7±1.4年的成年T2DM患者接受为期3周的诱导IIT（甘精胰岛素、赖脯胰岛素）治疗，随后使用二甲双胍维持治疗，维持治疗期为2年，期间每3个月有或没有为期2周的IIT疗程。持续血糖正常化定义为2年时A1c<6.0%。
101名参与者中，26人在2年时A1c<6.0%。在基线时，这些个体的A1c和空腹血糖低于其他参与者，同时β细胞功能更好。在从3周至2年的维持治疗期间，他们的肥胖程度（体重指数：p=0.02；腰围：p=0.02）、肝脏胰岛素抵抗（HOMA-IR：p=0.02）和谷丙转氨酶（ALT，p=0.005）下降幅度更大，同时β细胞功能和血糖相对稳定。在逻辑回归分析中，2年时A1c正常化的显著独立预测因素为基线A1c（调整优势比[aOR]=0.01[95%CI 0.001-0.16]，p=0.001）以及从3周至2年维持治疗期间腰围（aOR=0.77[0.63-0.94]，p=0.012）和ALT（aOR=0.90[0.82-0.98]，p=0.019）的变化。
正如预期的那样，较低的基线A1c和更大幅度的中心性肥胖减轻可预测2年时A1c<6.0%，而ALT更大幅度下降作为一个伴随决定因素的出现凸显了肝脏在实现持续血糖正常化中的作用。
