Martin B C, Warram J H, Krolewski A S, Bergman R N, Soeldner J S, Kahn C R
Joslin Diabetes Center, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
Lancet. 1992 Oct 17;340(8825):925-9. doi: 10.1016/0140-6736(92)92814-v.
Type 2 diabetes mellitus is characterised by resistance of peripheral tissues to insulin and a relative deficiency of insulin secretion. To find out which is the earliest or primary determinant of disease, we used a minimum model of glucose disposal and insulin secretion based on intravenous glucose tolerance tests to estimate insulin sensitivity (SI), glucose effectiveness (ie, insulin-independent glucose removal rate, SG), and first-phase and second-phase beta-cell responsiveness in normoglycaemic offspring of couples who both had type 2 diabetes. 155 subjects from 86 families were followed-up for 6-25 years. More than 10 years before the development of diabetes, subjects who developed the disease had lower values of both SI (mean 3.2 [SD 2.4] vs 8.1 [6.7] 10(-3) I min-1 pmol-1 insulin; p < 0.0001) and SG (1.6 [0.9] vs 2.3 [1.2] 10(-2) min-1, p < 0.0001) than did those who remained normoglycaemic). For the subjects with both SI and SG below the group median, the cumulative incidence of type 2 diabetes during the 25 years was 76% (95% confidence interval 54-99). By contrast, no subject with both SI and SG above the median developed the disease. Subjects with low SI/high SG or high SI/low SG had intermediate risks. Insulin secretion, especially first phase, tended to be increased rather than decreased in this prediabetic phase and was appropriate for the level of insulin resistance. The development of type 2 diabetes is preceded by and predicted by defects in both insulin-dependent and insulin-independent glucose uptake; the defects are detectable when the patients are normoglycaemic and in most cases more than a decade before diagnosis of disease.
2型糖尿病的特征是外周组织对胰岛素抵抗以及胰岛素分泌相对不足。为了找出疾病的最早或主要决定因素，我们基于静脉葡萄糖耐量试验，使用了一个葡萄糖处置和胰岛素分泌的最小模型，来估计双亲均患有2型糖尿病的血糖正常后代的胰岛素敏感性（SI）、葡萄糖有效性（即胰岛素非依赖型葡萄糖清除率，SG）以及第一相和第二相β细胞反应性。对来自86个家庭的155名受试者进行了6至25年的随访。在糖尿病发生前10多年，患糖尿病的受试者的SI（均值3.2 [标准差2.4] 对比8.1 [6.7]×10⁻³ I min⁻¹ pmol⁻¹胰岛素；p < 0.0001）和SG（1.6 [0.9] 对比2.3 [1.2]×10⁻² min⁻¹，p < 0.0001）均低于血糖正常的受试者。对于SI和SG均低于组中位数的受试者，25年间2型糖尿病的累积发病率为76%（95%置信区间54 - 99）。相比之下，SI和SG均高于中位数的受试者无一人患此病。SI低/SG高或SI高/SG低的受试者风险居中。在这个糖尿病前期阶段，胰岛素分泌，尤其是第一相，往往是增加而非减少的，并且与胰岛素抵抗水平相适应。2型糖尿病的发生之前存在胰岛素依赖型和胰岛素非依赖型葡萄糖摄取缺陷，并可由这些缺陷预测；这些缺陷在患者血糖正常时即可检测到，且在大多数情况下在疾病诊断前十多年就已存在。
