C.N.R. Institute of Neuroscience, Padua, Italy.
Department of Statistical Sciences, University of Padua, Padua, Italy.
J Clin Endocrinol Metab. 2022 Jun 16;107(7):2092-2100. doi: 10.1210/clinem/dgac213.
Loss of the incretin effect (IE) in type 2 diabetes (T2D) contributes to hyperglycemia and the mechanisms underlying this impairment are unclear.
To quantify the IE impairment in T2D and to investigate the factors associated with it using a meta-analytic approach.
PubMed, Scopus, and Web-of-Science were searched. Studies measuring IE by the gold-standard protocol employing an oral glucose tolerance test (OGTT) and an intravenous glucose infusion at matched glucose levels were selected. We extracted IE, sex, age, body mass index (BMI), and hemoglobin A1c, fasting values, and area under curve (AUC) of glucose, insulin, C-peptide, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1). In subjects with T2D, we also recorded T2D duration, age at diagnosis, and the percentage of subjects taking antidiabetic medications.
The IE weighted mean difference between subjects with T2D and those with normal glucose tolerance (NGT) was -27.3% (CI -36.5% to -18.1%; P < .001; I2 = 86.6%) and was affected by age (P < .005). By meta-regression of combined NGT and T2D data, IE was inversely associated with glucose tolerance (lower IE in T2D), BMI, and fasting GIP (P < .05). By meta-regression of T2D studies only, IE was associated with the OGTT glucose dose (P < .0001). IE from insulin was larger than IE from C-peptide (weighted mean difference 11.2%, CI 9.2-13.2%; P < .0001; I2 = 28.1%); the IE difference was inversely associated with glucose tolerance and fasting glucose.
The IE impairment in T2D vs NGT is consistent though considerably variable, age being a possible factor affecting the IE difference. Glucose tolerance, BMI, and fasting GIP are independently associated with IE; in subjects with T2D only, the OGTT dose is a significant covariate.
2 型糖尿病（T2D）中肠促胰岛素效应（IE）的丧失导致高血糖，其受损的机制尚不清楚。
采用荟萃分析方法定量评估 T2D 中 IE 受损情况，并探讨与 IE 受损相关的因素。
检索 PubMed、Scopus 和 Web-of-Science，选择采用口服葡萄糖耐量试验（OGTT）和静脉葡萄糖输注匹配血糖水平的金标准方案测量 IE 的研究。我们提取了 IE、性别、年龄、体重指数（BMI）、糖化血红蛋白（HbA1c）、空腹值和血糖、胰岛素、C 肽、葡萄糖依赖性胰岛素释放肽（GIP）和胰高血糖素样肽 1（GLP-1）的曲线下面积（AUC）。在 T2D 患者中，我们还记录了 T2D 病程、诊断时年龄以及服用抗糖尿病药物的患者比例。
T2D 患者与糖耐量正常（NGT）患者之间的 IE 加权平均差异为-27.3%（CI -36.5%至-18.1%；P < 0.001；I2=86.6%），且受年龄影响（P < 0.005）。通过对合并 NGT 和 T2D 数据的荟萃回归分析，IE 与葡萄糖耐量（T2D 中 IE 降低）、BMI 和空腹 GIP 呈负相关（P < 0.05）。仅通过对 T2D 研究的荟萃回归分析，IE 与 OGTT 葡萄糖剂量相关（P < 0.0001）。胰岛素介导的 IE 大于 C 肽介导的 IE（加权平均差异 11.2%，CI 9.2-13.2%；P < 0.0001；I2=28.1%）；IE 差异与葡萄糖耐量和空腹血糖呈负相关。
T2D 与 NGT 相比，IE 受损一致但差异较大，年龄可能是影响 IE 差异的一个因素。葡萄糖耐量、BMI 和空腹 GIP 与 IE 独立相关；仅在 T2D 患者中，OGTT 剂量是一个重要的协变量。
