Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
Clin Endocrinol (Oxf). 2010 Sep;73(3):339-45. doi: 10.1111/j.1365-2265.2010.03811.x. Epub 2010 Apr 23.
By using tracer techniques, we explored the metabolic mechanisms by which pioglitazone treatment for 16 weeks improves oral glucose tolerance in patients with type 2 diabetes when compared to subjects without diabetes.
In all subjects, before and after treatment, we measured rates of tissue glucose clearance (MCR), oral glucose appearance (RaO) and endogenous glucose production (EGP) during a (4-h) double tracer oral glucose tolerance test (OGTT) (1-(14)C-glucose orally and 3-(3)H-glucose intravenously). Basal hepatic insulin resistance index (HepIR) was calculated as EGPxFPI. beta-cell function was assessed as the incremental ratio of insulin to glucose (DeltaI/DeltaG) during the OGTT.
Pioglitazone decreased fasting plasma glucose concentration (10.5 +/- 0.7 to 7.8 +/- 0.6 mM, P < 0.0003) and HbA1c (9.7 +/- 0.7 to 7.5 +/- 0.5%, P < 0.003) despite increased body weight and no change in plasma insulin concentrations. This was determined by a decrease both in fasting EGP (20.0 +/- 1.1 to 17.3 +/- 0.8 micromol/kg(ffm) min, P < 0.005) and HepIR (from 8194 declined by 49% to 3989, P < 0.002). During the OGTT, total glucose Ra during the 0- to 120-min time period following glucose ingestion decreased significantly because of a reduction in EGP. During the 0- to 240-min time period, pioglitazone caused only a modest increase in MCR (P < 0.07) but markedly increased DeltaI/DeltaG (P = 0.003). The decrease in 2h-postprandial hyperglycaemia correlated closely with the increase in DeltaI/DeltaG (r = -0.76, P = 0.004) and tissue clearance (r = -0.74, P = 0.006) and with the decrease in HepIR (r = 0.62, P = 0.006).
In diabetic subjects with poor glycaemic control, pioglitazone improves oral glucose tolerance mainly by enhancing the suppression of EGP and improving beta-cell function.
通过示踪技术，我们探讨了吡格列酮治疗 16 周改善 2 型糖尿病患者口服葡萄糖耐量的代谢机制，与无糖尿病患者相比。
在所有受试者中，在治疗前后，我们在（4 小时）双示踪口服葡萄糖耐量试验（1-（14）C-葡萄糖口服和 3-（3）H-葡萄糖静脉内）期间测量组织葡萄糖清除率（MCR）、口服葡萄糖出现（RaO）和内源性葡萄糖产生（EGP）的速率。基础肝胰岛素抵抗指数（HepIR）计算为 EGPxFPI。β细胞功能评估为 OGTT 期间胰岛素与葡萄糖的增量比（DeltaI/DeltaG）。
吡格列酮降低空腹血糖浓度（10.5 +/- 0.7 至 7.8 +/- 0.6 mM，P < 0.0003）和 HbA1c（9.7 +/- 0.7 至 7.5 +/- 0.5%，P < 0.003），尽管体重增加且血浆胰岛素浓度无变化。这是通过降低空腹 EGP（20.0 +/- 1.1 至 17.3 +/- 0.8 μmol/kg（ffm）min，P < 0.005）和 HepIR（从 8194 下降 49%至 3989，P < 0.002）来实现的。在 OGTT 期间，由于 EGP 减少，葡萄糖摄入后 0 至 120 分钟期间的总葡萄糖 Ra 显著降低。在 0 至 240 分钟期间，吡格列酮仅导致 MCR 适度增加（P < 0.07），但明显增加 DeltaI/DeltaG（P = 0.003）。餐后 2 小时高血糖的降低与 DeltaI/DeltaG 的增加密切相关（r = -0.76，P = 0.004）和组织清除率（r = -0.74，P = 0.006）以及 HepIR 的降低（r = 0.62，P = 0.006）。
在血糖控制不佳的糖尿病患者中，吡格列酮主要通过增强 EGP 的抑制和改善β细胞功能来改善口服葡萄糖耐量。
