Kautzky-Willer A, Tura A, Winzer C, Wagner O F, Ludvik B, Hanusch-Enserer U, Prager R, Pacini G
Department of Internal Medicine III, Medical University of Vienna, Austria.
Diabetes Obes Metab. 2006 Sep;8(5):561-7. doi: 10.1111/j.1463-1326.2005.00568.x.
This study was designed to assess the usefulness of a model-based index of insulin sensitivity during an oral glucose tolerance test (OGTT) in the identification of possible changes in this metabolic parameter produced by pharmacological agents known to be potent insulin sensitizers, that is metformin (M) and thiazolidinedione (T). The association of these agents with several other factors related to glucose metabolism was also investigated, as well as the relation of insulin sensitivity and secretion with markers of endothelial function such as different adhesion molecules (cAMs), that is vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-Selectin.
Twenty type 2 diabetic patients treated with diet only underwent a 3-h OGTT for measurement of plasma glucose, insulin, proinsulin, C-peptide and cAMs before and after administration of randomly given M (n = 9; 1700 mg/day) or T (n = 11; 600 mg/day). After 16 weeks of treatment, a second OGTT was performed. Insulin sensitivity was calculated with homeostasis model assessment and with oral glucose insulin sensitivity (OGIS), which quantifies dynamic glucose clearance per unit change of insulin. Insulin secretion was assessed by modelling technique. Differences in these parameters before and after treatment, as well as possible relationships with cAMs, were assessed.
Basal and stimulated plasma glucose decreased after therapy in both the groups by approximately 20%. Basal insulin resistance also decreased. Insulin sensitivity in dynamic conditions (OGIS: ml/min/m(2)) increased with M (289.3 +/- 18.8 vs. 234.7 +/- 18.1, p < 0.02) and tended to improve with T (323.5 +/- 18.1 vs. 286.8 +/- 22.1, p = 0.09). Total insulin secretion over the OGTT [TIS: nmol/l(3 h)] tended to decrease with M (17.1 +/- 2.5 vs. 27.3 +/- 0.3, p = 0.08) but not with T (23.6 +/- 3.5 vs. 22.5 +/- 2.7). Plasma concentrations of E-Selectin decreased in T (38.0 +/- 2.3 vs. 51.2 +/- 6.1 ng/ml, p < 0.05). No correlation was found between insulin sensitivity and cAMs.
Model-based indices of insulin sensitivity and secretion during an OGTT can be able to detect changes observed in patients under treatment with pharmacological agents such as M or T. Both the drugs improved glucose control similarly. Decreased plasma E-Selectin concentrations were seen in patients on T therapy only.
本研究旨在评估口服葡萄糖耐量试验（OGTT）期间基于模型的胰岛素敏感性指数在识别已知强效胰岛素增敏剂（即二甲双胍（M）和噻唑烷二酮（T））所引起的该代谢参数可能变化方面的实用性。还研究了这些药物与其他几个与葡萄糖代谢相关因素的关联，以及胰岛素敏感性和分泌与内皮功能标志物（如不同的黏附分子（cAMs），即血管细胞黏附分子 -1、细胞间黏附分子 -1 和 E - 选择素）之间的关系。
仅接受饮食治疗的 20 例 2 型糖尿病患者在随机给予 M（n = 9；1700 毫克/天）或 T（n = 11；600 毫克/天）前后进行 3 小时 OGTT，以测量血浆葡萄糖、胰岛素、胰岛素原、C 肽和 cAMs。治疗 16 周后，进行第二次 OGTT。使用稳态模型评估和口服葡萄糖胰岛素敏感性（OGIS）计算胰岛素敏感性，OGIS 量化胰岛素单位变化时的动态葡萄糖清除率。通过建模技术评估胰岛素分泌。评估治疗前后这些参数的差异以及与 cAMs 的可能关系。
两组治疗后基础和刺激后的血浆葡萄糖均下降约 20%。基础胰岛素抵抗也降低。动态条件下（OGIS：毫升/分钟/平方米）的胰岛素敏感性在使用 M 时增加（289.3±18.8 对 234.7±18.1，p < 0.02），在使用 T 时趋于改善（323.5±18.1 对 286.8±22.1，p = 0.09）。OGTT 期间的总胰岛素分泌[TIS：纳摩尔/升（3 小时）]在使用 M 时趋于下降（17.1±2.5 对 27.3±0.3，p = 0.08），但在使用 T 时未下降（23.6±3.5 对 22.5±2.7）。T 组中 E - 选择素的血浆浓度下降（38.0±2.3 对 51.2±
