Department of Endocrinology, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China; Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China.
Diabetes Metab Res Rev. 2013 Nov;29(8):664-72. doi: 10.1002/dmrr.2443.
Studies with metformin suggest a favourable change in β-cell function over sulphonylureas in the early course of obese type 2 diabetes mellitus (T2DM), but it remains unclear whether a similar effect is observed in non-obese individuals. Here we investigated the effects of metformin or glipizide gastrointestinal therapeutics system extended-release formulation (GITS) on β-cell function in non-obese patients with newly diagnosed T2DM.
A total of 160 newly diagnosed patients with fasting glucose 7.0-13.0 mmol/L and body mass index <30 kg/m(2) from five centres in China were randomized to metformin or glipizide GITS for 24 weeks. Early insulin secretion [the ratio of area under the curve (AUC) of insulin to glucose during 0-30 min (InsAUC30 /GluAUC30 )] and insulin sensitivity [Matsuda index (ISIM )] were assessed during the standard meal tolerance test before and after therapy. Plasma glucagon-like peptide-1(GLP-1) and glucagon levels were also measured.
Metformin improved InsAUC30 /GluAUC30 significantly (from 8.1 ± 0.6 pmol/mmol to 10.7 ± 0.7 pmol/mmol, p < 0.05), comparable to results with glipizide GITS. In the metformin-treated lean (body mass index < 25 kg/m(2) ) subgroup, the increase in ISIM was not significant, but the improvement in InsAUC30 /GluAUC30 was of great magnitude. Increased GLP-1 responses during meal tolerance test and decreased fasting glucagon level were observed after metformin treatment. Correlation analysis showed that the improvement of InsAUC30 /GluAUC30 was associated with the changes in HbA1c (r = -0.374, p = 0.000), ISIM (r = 0.356, p = 0.001), and ΔGLP-10-30 (r = 0.225, p = 0.02).
Metformin improved β-cell function in non-obese subjects with newly diagnosed T2DM, which was partly independent of the change in insulin sensitivity in these subjects. This study provides evidence-based data to support metformin use in non-obese patients with T2DM as the first-line agent, which can improve both insulin sensitivity and β-cell function.
二甲双胍治疗肥胖 2 型糖尿病（T2DM）患者的早期β细胞功能改善优于磺脲类药物，但非肥胖患者是否存在类似效果尚不清楚。本研究旨在探讨二甲双胍或格列吡嗪控释片（GITS）对新诊断的非肥胖 T2DM 患者β细胞功能的影响。
来自中国 5 个中心的 160 例新诊断的空腹血糖 7.0-13.0mmol/L 和体重指数<30kg/m²的患者被随机分为二甲双胍或格列吡嗪 GITS 治疗组，治疗 24 周。在治疗前后的标准餐耐量试验中评估早期胰岛素分泌[0-30min 时胰岛素与血糖曲线下面积的比值（InsAUC30/GluAUC30）]和胰岛素敏感性[Matsuda 指数（ISIM）]。同时还测量了血浆胰高血糖素样肽-1（GLP-1）和胰高血糖素水平。
二甲双胍能显著改善 InsAUC30/GluAUC30（从 8.1±0.6pmol/mmol 增加到 10.7±0.7pmol/mmol，p<0.05），与格列吡嗪 GITS 的结果相当。在二甲双胍治疗的非肥胖（体重指数<25kg/m²）亚组中，ISIM 的改善不显著，但 InsAUC30/GluAUC30 的改善幅度较大。在用二甲双胍治疗后，观察到餐耐量试验中 GLP-1 反应增加和空腹胰高血糖素水平降低。相关性分析表明，InsAUC30/GluAUC30 的改善与 HbA1c（r=-0.374，p=0.000）、ISIM（r=0.356，p=0.001）和 ΔGLP-10-30（r=0.225，p=0.02）的变化有关。
二甲双胍改善了新诊断的非肥胖 T2DM 患者的β细胞功能，这在一定程度上独立于这些患者的胰岛素敏感性变化。本研究为支持二甲双胍作为非肥胖 T2DM 患者一线药物的使用提供了循证数据，可改善胰岛素敏感性和β细胞功能。
