Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Pettiti M, Natali A, Mari A, DeFronzo R A
Metabolism Unit, C.N.R. Institute of Clinical Physiology and Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy.
Diabetologia. 2003 Sep;46(9):1211-9. doi: 10.1007/s00125-003-1169-6. Epub 2003 Jul 23.
AIMS/HYPOTHESIS: Impaired glucose tolerance (IGT) is an insulin-resistant state and a risk factor for Type 2 diabetes. The relative roles of insulin resistance and insulin deficiency in IGT have been disputed.
In 40 IGT subjects and 63 sex-, age-, and weight-matched controls with normal glucose tolerance (NGT), we measured (i) indices of insulin sensitivity of fasting glucose production (by tracer glucose) and glucose disposal (M value on a 240 pmol x min(-1) x m(-2) insulin clamp) and (ii) indices of beta-cell function (glucose sensitivity, rate sensitivity, and potentiation) derived from model analysis (Am J Physiol 283:E1159-E1166, 2002) of the insulin secretory response (by C-peptide deconvolution) to oral glucose.
In comparison with NGT, IGT were modestly insulin resistant (M=29+/-2 vs 35+/-2 micromol x min(-1) x kg(FFM)(-1), p=0.01); insulin sensitivity of glucose production also was reduced, in approximate proportion to M. Despite higher baseline insulin secretion rates, IGT was characterized by a 50% reduction in glucose sensitivity [53 (36) vs 102 (123) pmol x min(-1) x m(-2) x mM(-1), median (interquartile range), p=0.001] and impaired potentiation [1.6 (0.8) vs 2.0 (1.5) units, p<0.04] of insulin release, whereas rate sensitivity [1.15 (1.15) vs 1.38 (1.28) nmol x m(-2) x mM(-1)] was not significantly reduced. Glucose sensitivity made the single largest contribution (approximately 50%) to the observed variability of glucose tolerance.
CONCLUSION/INTERPRETATION: In IGT the defect in glucose sensitivity of insulin release quantitatively predominates over insulin resistance in the genesis of the reduced tolerance to oral glucose.
目的/假设：糖耐量受损（IGT）是一种胰岛素抵抗状态，也是2型糖尿病的一个风险因素。胰岛素抵抗和胰岛素缺乏在IGT中的相对作用一直存在争议。
在40名IGT受试者和63名年龄、性别、体重匹配的糖耐量正常（NGT）对照者中，我们测量了：（i）空腹葡萄糖生成（通过示踪葡萄糖）和葡萄糖处置（在240 pmol×min⁻¹×m⁻²胰岛素钳夹下的M值）的胰岛素敏感性指标；以及（ii）通过对口服葡萄糖的胰岛素分泌反应（通过C肽反卷积）进行模型分析（《美国生理学杂志》283：E1159 - E1166，2002）得出的β细胞功能指标（葡萄糖敏感性、速率敏感性和增强作用）。
与NGT相比，IGT存在轻度胰岛素抵抗（M = 29 ± 2 vs 35 ± 2 μmol×min⁻¹×kg(FFM)⁻¹，p = 0.01）；葡萄糖生成的胰岛素敏感性也降低，大致与M成比例。尽管基线胰岛素分泌率较高，但IGT的特征是葡萄糖敏感性降低50% [53（36）vs 102（123）pmol×min⁻¹×m⁻²×mM⁻¹，中位数（四分位间距），p = 0.001]，胰岛素释放的增强作用受损[1.6（0.8）vs 2.0（1.5）单位，p < 0.04]，而速率敏感性[1.15（1.15）vs 1.38（1.28）nmol×m⁻²×mM⁻¹]没有显著降低。葡萄糖敏感性对观察到的糖耐量变异性的单一最大贡献约为50%。
结论/解读：在IGT中，胰岛素释放的葡萄糖敏感性缺陷在口服葡萄糖耐受性降低的发生过程中，在数量上比胰岛素抵抗更为突出。
