Kutoh Eiji, Fukushima Takuya
Biomedical Center, Edogawa-ku, 132-0034 Tokyo, Japan.
Endocrine. 2009 Jun;35(3):333-40. doi: 10.1007/s12020-009-9174-2. Epub 2009 Apr 15.
The aim of this study was to study the effects of pioglitazone on several diabetic parameters with subjects possessing distinct levels of insulin. Treatment naive patients with type 2 diabetes received 15-30 mg/day pioglitazone monotherapy. At 3 months, levels of insulin, C-peptide, HbA1c, HOMA-R, HOMA-B and BMI were compared with those at baseline between the low (below 5.9 microU/ml, n = 48), medium (11.9-6 microU/ml n = 39) and high (above 12 microU/ml, n = 33) insulin groups. At baseline, differences existed in the levels of HbA1c, insulin, C-peptide, HOMA-R, HOMA-B, and BMI between these groups. In the high-insulin group significant reductions of insulin/C-peptide levels were observed, while in the low-insulin group significant increases of insulin/C-peptide were observed. In the medium-insulin group, no significant changes were observed. In contrast, the HbA1c levels significantly and similarly decreased in all the groups. Significant correlations between the changes of insulin/C-peptide levels with pioglitazone and the baseline insulin/C-peptide levels were observed. HOMA-R showed greater reductions in the high-insulin group, while HOMA-B showed greater increases in the low-insulin group in comparison to other groups. Multiple regression analysis revealed that the baseline insulin level is the predominant determinant of the changes of insulin levels with pioglitazone. These results suggest that pioglitazone appears to have two effects: to reduce insulin resistance (and lower insulin) and to improve beta-cell function (and increase insulin). The predominance of these effects appears to be determined by the insulin levels. Based on these data, a novel physiological model showing that pioglitazone may shift the natural history of diabetes toward an earlier stage (rejuvenation of beta-cell function) will be presented.
本研究旨在探讨吡格列酮对不同胰岛素水平受试者的多种糖尿病参数的影响。初治的2型糖尿病患者接受15 - 30毫克/天的吡格列酮单药治疗。3个月时，比较低胰岛素水平组（低于5.9微单位/毫升，n = 48）、中等胰岛素水平组（11.9 - 6微单位/毫升，n = 39）和高胰岛素水平组（高于12微单位/毫升，n = 33）的胰岛素、C肽、糖化血红蛋白（HbA1c）、胰岛素抵抗指数（HOMA - R）、胰岛β细胞功能指数（HOMA - B）和体重指数（BMI）水平与基线水平的差异。基线时，这些组之间的HbA1c、胰岛素、C肽、HOMA - R、HOMA - B和BMI水平存在差异。在高胰岛素水平组中，观察到胰岛素/C肽水平显著降低，而在低胰岛素水平组中，观察到胰岛素/C肽水平显著升高。在中等胰岛素水平组中，未观察到显著变化。相比之下，所有组的HbA1c水平均显著且相似地降低。观察到吡格列酮治疗后胰岛素/C肽水平变化与基线胰岛素/C肽水平之间存在显著相关性。与其他组相比，HOMA - R在高胰岛素水平组中降低幅度更大，而HOMA - B在低胰岛素水平组中升高幅度更大。多元回归分析显示，基线胰岛素水平是吡格列酮治疗后胰岛素水平变化的主要决定因素。这些结果表明，吡格列酮似乎有两种作用：降低胰岛素抵抗（并降低胰岛素水平）和改善β细胞功能（并增加胰岛素水平）。这些作用的优势似乎由胰岛素水平决定。基于这些数据，将提出一个新的生理模型，该模型表明吡格列酮可能使糖尿病的自然病程向更早阶段转变（β细胞功能恢复活力）。
