VA Puget Sound Health Care System, Seattle, Washington, USA.
Department of Medicine, University of Washington, Seattle, Washington, USA.
Obesity (Silver Spring). 2022 Aug;30(8):1579-1588. doi: 10.1002/oby.23475.
The extent to which weight loss contributes to increases in insulin sensitivity (IS) and β-cell function after surgical or medical intervention has not been directly compared in individuals with impaired glucose tolerance or newly diagnosed type 2 diabetes.
The Restoring Insulin Secretion (RISE) Study included adults in the Beta-Cell Restoration Through Fat Mitigation Study (n = 88 randomized to laparoscopic gastric banding or metformin [MET]) and the Adult Medication Study (n = 267 randomized to placebo, MET, insulin glargine/MET, or liraglutide + MET [L + M]). IS and β-cell responses were measured at baseline and after 12 months by modeling of oral glucose tolerance tests and during arginine-stimulated hyperglycemic clamps. Linear regression models assessed differences between and within treatments over time.
BMI decreased in all treatment groups, except placebo, at 12 months. IS increased in all arms except placebo and was inversely correlated with changes in BMI. L + M was the only treatment arm that enhanced multiple measures of β-cell function independent of weight loss. Insulin secretion decreased in the laparoscopic gastric banding arm proportional to increases in IS, with no net benefit on β-cell function.
Reducing demand on the β-cell by improving IS through weight loss does not reverse β-cell dysfunction. L + M was the only treatment that enhanced β-cell function.
在糖耐量受损或新诊断的 2 型糖尿病患者中,尚未直接比较手术或药物干预后体重减轻对胰岛素敏感性(IS)和β细胞功能增加的影响。
恢复胰岛素分泌研究(RISE)包括在脂肪减轻β细胞恢复研究(n=88 随机分为腹腔镜胃带或二甲双胍[MET])和成人药物研究(n=267 随机分为安慰剂、MET、甘精胰岛素/MET 或利拉鲁肽+MET[L+M])中的成年人。通过口服葡萄糖耐量试验和精氨酸刺激高血糖钳夹试验在基线和 12 个月时测量 IS 和β细胞反应。线性回归模型评估了不同治疗组之间和治疗组内随时间的差异。
除了安慰剂组,所有治疗组的 BMI 在 12 个月时均下降。除了安慰剂组,IS 均增加,且与 BMI 的变化呈负相关。L+M 是唯一一种独立于体重减轻而增强β细胞功能的多种指标的治疗方法。腹腔镜胃带组的胰岛素分泌随 IS 的增加而按比例下降,β细胞功能无净获益。
通过减轻体重来提高 IS 以降低β细胞的需求并不能逆转β细胞功能障碍。L+M 是唯一增强β细胞功能的治疗方法。