Lillioja S, Mott D M, Howard B V, Bennett P H, Yki-Järvinen H, Freymond D, Nyomba B L, Zurlo F, Swinburn B, Bogardus C
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, AZ 85016.
N Engl J Med. 1988 May 12;318(19):1217-25. doi: 10.1056/NEJM198805123181901.
Impaired glucose tolerance often presages the development of non-insulin-dependent diabetes mellitus. We have studied insulin action and secretion in 24 Pima Indians before and after the development of impaired glucose tolerance and in 254 other subjects representing the whole spectrum of glucose tolerance, including subjects with overt non-insulin-dependent diabetes. The transition from normal to impaired glucose tolerance was associated with a decrease in glucose uptake during hyperinsulinemia, from 0.018 to 0.016 mmol per minute (from 3.3 to 2.8 mg per kilogram of fat-free body mass per minute) (P less than 0.0003). Mean plasma insulin concentrations increased during an oral glucose-tolerance test, from 1200 to 1770 pmol per liter (from 167 to 247 microU per milliliter). In 151 subjects with normal glucose tolerance, the insulin concentration measured during an oral glucose-tolerance test correlated with the plasma glucose concentration (r = 0.48, P less than or equal to 0.0001). This relation was used to predict an insulin concentration of 1550 pmol per liter (216 microU per milliliter) in subjects with impaired glucose tolerance (actual value, 1590 pmol per liter [222 microU per milliliter]; P not significant), suggesting that these subjects had normal secretion of insulin. In contrast, plasma insulin concentrations in the diabetics decreased as glucose concentrations increased (r = -0.75, P less than or equal to 0.0001), suggesting deficient secretion of insulin. This relative insulin deficiency first appears at the lower end of the second (diabetic) mode seen in population frequency distributions of plasma glucose concentrations. Our data show that impaired glucose tolerance in our study population is primarily due to impaired insulin action. In patients with non-insulin-dependent diabetes mellitus, by contrast, impaired insulin action and insulin secretory failure are both present.
糖耐量受损往往预示着非胰岛素依赖型糖尿病的发生。我们研究了24名皮马印第安人在糖耐量受损发生前后的胰岛素作用和分泌情况，并研究了254名代表糖耐量全谱的其他受试者，包括显性非胰岛素依赖型糖尿病患者。从正常糖耐量转变为糖耐量受损与高胰岛素血症期间葡萄糖摄取量的减少有关，从每分钟0.018毫摩尔降至每分钟0.016毫摩尔（从每千克去脂体重每分钟3.3毫克降至2.8毫克）（P<0.0003）。口服葡萄糖耐量试验期间，平均血浆胰岛素浓度从每升1200皮摩尔升至每升1770皮摩尔（从每毫升167微单位升至247微单位）。在151名糖耐量正常的受试者中，口服葡萄糖耐量试验期间测得的胰岛素浓度与血浆葡萄糖浓度相关（r = 0.48，P≤0.0001）。利用这种关系预测糖耐量受损受试者的胰岛素浓度为每升1550皮摩尔（每毫升216微单位）（实际值为每升1590皮摩尔[每毫升222微单位]；P无显著性差异），表明这些受试者胰岛素分泌正常。相比之下，则糖尿病患者的血浆胰岛素浓度随着葡萄糖浓度的升高而降低（r = -0.75，P≤0.0001），提示胰岛素分泌不足。这种相对胰岛素缺乏首先出现在血浆葡萄糖浓度人群频率分布中所见的第二个（糖尿病）模式的较低端。我们的数据表明，我们研究人群中的糖耐量受损主要是由于胰岛素作用受损。相比之下，在非胰岛素依赖型糖尿病患者中，胰岛素作用受损和胰岛素分泌衰竭均存在。
