Berrish T S, Hetherington C S, Alberti K G, Walker M
Human Diabetes and Metabolism Research Centre, University of Newcastle upon Tyne, UK.
Diabetologia. 1995 Jun;38(6):699-704. doi: 10.1007/BF00401842.
Recent evidence suggests that the postprandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion (delta 0-10 min insulin area divided by delta 0-10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2-19.4] vs 9.1 [2.6-14.5] mU.mmol-1; p < 0.01). During the clamp, circulating insulin (93 +/- 8 [mean +/- SEM] and 81 +/- 10 mU.l-1) and glucagon (54 +/- 4 and 44 +/- 6 ng.l-1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78 +/- 0.27 vs 4.47 +/- 0.53 mg.kg-1.min-1; p < 0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38 +/- 0.10 and 0.30 +/- 0.18 mg.kg-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
近期证据表明，糖耐量受损者的餐后高血糖主要是由于基础肝糖输出抑制受损所致。这反过来似乎继发于第一相胰岛素分泌减少，尽管肝胰岛素敏感性降低（这是非胰岛素依赖型糖尿病的一个特征）可能也起一定作用。8名糖耐量受损的轻度超重受试者和8名年龄、体重匹配的糖耐量正常的对照受试者接受了静脉葡萄糖耐量试验，以评估第一相胰岛素分泌。通过150分钟的高胰岛素-正常血糖钳夹试验检测胰岛素敏感性。从150分钟开始输注生长抑素以抑制内源性胰岛素分泌，并用持续输注替代胰高血糖素和胰岛素。输注添加了双氘代葡萄糖的葡萄糖（标记输注技术）以维持正常血糖。糖耐量受损受试者的第一相胰岛素分泌（0 - 10分钟胰岛素面积除以0 - 10分钟葡萄糖面积）显著降低（中位数[范围]：1.2[0.2 - 19.4]对9.1[2.6 - 14.5]mU·mmol-1；p < 0.01）。在钳夹期间，循环胰岛素（93±8[平均值±标准误]和81±10 mU·L-1）和胰高血糖素（54±4和44±6 ng·L-1）水平相当。糖耐量受损受试者的总葡萄糖处置减少（2.78±0.27对4.47±0.53 mg·kg-1·min-1；p < 0.02），且主要是由于非氧化葡萄糖处置减少。然而，钳夹期间肝糖输出率相当（0.38±0.10和0.30±0.18 mg·kg-1·min-1）。（摘要截断于250字）
