Role of Adipose Tissue Insulin Resistance in the Natural History of Type 2 Diabetes: Results From the San Antonio Metabolism Study
Role of Adipose Tissue Insulin Resistance in the Natural History of Type 2 Diabetes: Results From the San Antonio Metabolism Study
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DOI：
10.2337/db16-1167
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发表时间：
2017-04-01
期刊：
影响因子：
7.7
通讯作者：
DeFronzo, Ralph A.
中科院分区：
文献类型：
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作者：
Gastaldelli, Amalia;Gaggini, Melania;DeFronzo, Ralph A.
在从正常葡萄糖耐量（NGT）向2型糖尿病（T2 DM）的转变中，β细胞功能障碍和外周胰岛素抵抗（IR）的作用已得到充分证实。然而，功能失调的脂肪组织的影响尚未完全阐明。本研究的目的是在大量NGT、糖耐量受损（IGT）和T2 DM受试者中评价胰岛素抗脂解作用抵抗（脂肪组织IR [Adipo-IR]）的作用。302例不同糖耐量的受试者接受了口服葡萄糖耐量试验（OGTT）和正常血糖胰岛素钳夹试验。我们评估了Adipo-IR（空腹和平均OGTT血浆游离脂肪酸[FFA] x胰岛素浓度）、外周IR（1/[松田指数]和（M/I）（-1）值）和β细胞功能（计算为血浆胰岛素增量与葡萄糖的比率[OGTT/IR（Delta I/Delta G除以IR）]）。肥胖NGT和IGT受试者的空腹Adipo-IR比消瘦NGT受试者增加2倍（分别为8.0 +/- 1.1和9.2 +/- 0.7 vs. 4.1 +/- 0.3），T2 DM受试者增加3倍（11.9 +/- 0.6; P < 0.001）。Δ I/Δ G 4 IR的进行性下降与OGTT期间FFA抑制的进行性损害相关，而平均血糖浓度的升高仅在受试者明显糖尿病时才变得明显。NGT患者开始的β细胞功能的进行性下降与FFA和空腹Adipo-IR的进行性增加相关。
In the transition from normal glucose tolerance (NGT) to type 2 diabetes mellitus (T2DM), the role of beta-cell dysfunction and peripheral insulin resistance (IR) is well established. However, the impact of dysfunctional adipose tissue has not been fully elucidated. The aim of this study was to evaluate the role of resistance to the antilipolytic effect of insulin (adipose tissue IR [Adipo-IR]) in a large group of subjects with NGT, impaired glucose tolerance (IGT), and T2DM. Three hundred two subjects with varying glucose tolerance received an oral glucose tolerance test (OGTT) and euglycemic insulin clamp. We evaluated Adipo-IR (fasting and mean OGTT plasma free fatty acid [FFA] x insulin concentrations), peripheral IR (1/[Matsuda index] and (M/I)(-1) value), and beta-cell function (calculated as the ratio of the increment in plasma insulin to glucose [OGTT/IR (Delta I/Delta G divided by IR)]). Fasting Adipo-IR was increased twofold in obese subjects with NGT and IGT versus lean subjects with NGT (8.0 +/- 1.1 and 9.2 +/- 0.7 vs. 4.1 +/- 0.3, respectively) and threefold in subjects with T2DM (11.9 +/- 0.6; P < 0.001). Progressive decline in Delta I/Delta G 4 IR was associated with a progressive impairment in FFA suppression during OGTT, whereas the rise in mean plasma glucose concentration only became manifest when subjects became overtly diabetic. The progressive decline in beta-cell function that begins in individuals with NGT is associated with a progressive increase in FFA and fasting Adipo-IR.