ROLE OF GLUCOSE AND INSULIN RESISTANCE IN DEVELOPMENT OF TYPE-2 DIABETES-MELLITUS - RESULTS OF A 25-YEAR FOLLOW-UP-STUDY
ROLE OF GLUCOSE AND INSULIN RESISTANCE IN DEVELOPMENT OF TYPE-2 DIABETES-MELLITUS - RESULTS OF A 25-YEAR FOLLOW-UP-STUDY
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DOI：
10.1016/0140-6736(92)92814-v
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发表时间：
1992-10-17
期刊：
影响因子：
168.9
通讯作者：
KAHN, CR
中科院分区：
文献类型：
--
作者：
MARTIN, BC;WARRAM, JH;KAHN, CR
2型糖尿病的特征是外周组织对胰岛素的抵抗和胰岛素分泌的相对不足。为了找出哪一个是疾病的最早或主要决定因素，我们使用了基于静脉葡萄糖耐量试验的葡萄糖处理和胰岛素分泌的最小模型来估计胰岛素敏感性（S（I））、葡萄糖有效性（GOS）和胰岛素敏感性（GOS）。（即，胰岛素非依赖性葡萄糖清除率，S（G）），以及均患有2型糖尿病的夫妇的正常血糖后代的第一和第二时相β细胞反应性。长达6-25年。在糖尿病发病前10年以上，患糖尿病的受试者的S（I）（平均3.2 [SD 2.4] vs 8.1 [6.7] 10（-3）l min-1 pmol-1胰岛素; p < 0.0001）和S（G）（1.6 [0.9] vs 2.3 [1.2] 10（-2）min-1，p < 0.0001）。对于S（I）和SG均低于组中位数的受试者，25年期间2型糖尿病的累积发病率为76%（95%置信区间54-99）。相比之下，没有S（I）和S（G）均高于中位数的受试者发生疾病。低S（I）/高S（G）或高S（I）/低S（G）的受试者具有中等风险。胰岛素分泌，特别是第一阶段，往往增加，而不是减少在这个糖尿病前期阶段，是适当的胰岛素抵抗的水平。2型糖尿病的发展之前和预测的缺陷，在胰岛素依赖性和胰岛素非依赖性葡萄糖摄取;缺陷是可检测的，当患者是正常血糖，在大多数情况下，超过十年前诊断的疾病。
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 (S(I)), glucose effectiveness (ie, insulin-independent glucose removal rate, S(G)), 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 S(I) (mean 3.2 [SD 2.4] vs 8.1 [6.7] 10(-3) l min-1 pmol-1 insulin; p < 0.0001) and S(G) (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 S(I) 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 S(I) and S(G) above the median developed the disease. Subjects with low S(I)/high S(G) or high S(I)/low S(G) 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.