Effects of pioglitazone and metformin on β-cell function in nondiabetic subjects at high risk for type 2 diabetes
Effects of pioglitazone and metformin on β-cell function in nondiabetic subjects at high risk for type 2 diabetes
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DOI：
10.1152/ajpendo.00221.2006
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发表时间：
2007-01-01
影响因子：
5.1
通讯作者：
Elbein, Steven C.
中科院分区：
文献类型：
--
作者：
Rasouli, Neda;Kern, Philip A.;Elbein, Steven C.
吡格列酮和二甲双胍对2型糖尿病高危非糖尿病患者β细胞功能的影响[J] .中国生理与内分泌杂志，2009,29(2):359- 359。首次发表于2006年9月12日；doi:10.1152/ajpendo.00221.2006。噻唑烷二酮（TZDs）和二甲双胍分别降低了糖尿病风险受试者的糖尿病发病率，改善了外周或肝脏胰岛素敏感性。它们是否也能直接改善β细胞的功能尚不清楚。体外研究显示，TZDs和二甲双胍可改善β细胞功能；然而，TZDs或二甲双胍对人类β细胞功能的影响仍不确定。我们假设TZDs和二甲双胍都直接影响β细胞功能。我们通过口服和静脉葡萄糖耐量试验以及葡萄糖增强精氨酸刺激试验来评估糖耐量受损或有妊娠糖尿病史受试者的β细胞功能和胰岛素敏感性（SI）。与二甲双胍相比，吡格列酮可改善S-I、葡萄糖耐量和胰岛素不依赖型葡萄糖处理[葡萄糖有效性（SG）]。吡格列酮和二甲双胍均未显著改善胰岛素抵抗的β细胞代偿[处置指数（DI）]，但DI的变化与基线SI显著相关。在葡萄糖水平（AIR(max)）最大增强时，精氨酸对胰岛素分泌的反应倾向于二甲双胍后增加，吡格列酮后减少；然而，当调整SI时，变化并不显著。我们的研究结果表明，在有糖尿病风险的非糖尿病受试者中，吡格列酮，而不是二甲双胍，通过改善SI和SG显著改善葡萄糖耐量。我们没有发现任何证据表明吡格列酮或二甲双胍可以改善β细胞功能。改善的β细胞代偿主要在基线时SI最低的受试者亚组中观察到。
Effects of pioglitazone and metformin on beta-cell function in nondiabetic subjects at high risk for type 2 diabetes. Am J Physiol Endocrinol Metab 292:E359-E365, 2007. First published September 12, 2006;doi:10.1152/ajpendo.00221.2006. Thiazolidinediones (TZDs) and metformin decreased the incidence of diabetes in subjects at risk for developing diabetes and improved peripheral or hepatic insulin sensitivity, respectively. Whether they also directly improved beta-cell function is not clear. In vitro studies showed improved beta-cell function in response to TZDs and metformin; however, the effects of TZDs or metformin on beta-cell function in humans are still uncertain. We hypothesized that both TZDs and metformin directly affect beta-cell function. We evaluated beta-cell function and insulin sensitivity (SI) in subjects with impaired glucose tolerance or a history of gestational diabetes using oral and intravenous glucose tolerance tests in addition to the glucose-potentiated arginine stimulation test. In contrast to metformin, pioglitazone improved S-I, glucose tolerance, and insulin-independent glucose disposal [glucose effectiveness (SG)]. Neither pioglitazone nor metformin significantly improved beta-cell compensation for insulin resistance [disposition index (DI)], but the change in DI significantly correlated with baseline SI. Insulin secretion in response to arginine at maximally potentiating glucose levels (AIR(max)) tended to increase after metformin and to decrease after pioglitazone; however, when adjusted for SI, the changes were not significant. Our results demonstrate that, in nondiabetic subjects at risk for diabetes, pioglitazone, but not metformin, significantly improved glucose tolerance by improving SI and SG. We did not find any evidence that either pioglitazone or metformin improved beta-cell function. Improved beta-cell compensation was observed primarily in the subgroup of subjects that had the lowest SI at baseline.