Takeda N, Yasuda K, Horiya T, Yamada H, Imai T, Kitada M, Miura K
Nihon Naibunpi Gakkai Zasshi. 1986 May 20;62(5):631-48. doi: 10.1507/endocrine1927.62.5_631.
We investigated the mechanism of glucose intolerance in 51 patients with Cushing's syndrome. In an oral 100g glucose tolerance test, although prevalence of decreased glucose tolerance was very high as revealed in 36 of 47 patients (77%) studied, impairment was rather mild in the majority of patients and only 10 patients (21%) were judged as diabetic. Plasma insulin was measured in 12 patients and the mean values of these patients reached above normal levels after oral glucose load. When insulin secreting capacity was assessed by measuring the ratio of the incremental area of insulin above fasting level to the corresponding area of glucose during the test, Cushing's syndrome as a whole exhibited a normal ratio compared to 9 control subjects (113 +/- 115 vs. 144 +/- 78 microU/mg, M +/- SD, ns), but in 3 patients with severe impairment of glucose tolerance reaching the diabetic range, the ratio was lower than normal (27 +/- 20 vs. 144 +/- 78 microU/mg, M +/- SD, p less than 0.05). The hypoglycemic effect of iv insulin was studied in 23 patients and was demonstrated to have decreased. Thus, we confirmed the presence of decreased insulin sensitivity, i.e. insulin resistance in Cushing's syndrome. The age of patients showed positive correlation with the degree of impairment in glucose tolerance and insulin secreting capacity, but not with that of insulin sensitivity, that is, in patients with advanced age, glucose intolerance appeared to be severe with decreased insulin secreting capacity. 125I-insulin binding to red blood cells in 8 patients was examined to elucidate the mechanism of insulin resistance in Cushing's syndrome. Percent specific binding at tracer concentration of insulin in Cushing's syndrome was not different from the value obtained in 19 normal subjects (8.2 +/- 3.0 vs. 7.7 +/- 1.0%, M +/- SD, ns). Receptor concentration and affinity were also normal. From these observations, it is likely that glucose intolerance in Cushing's syndrome is primarily due to the effects of chronic glucocorticoid excess on tissue metabolism of glucose as characterized by the presence of insulin resistance, which is not due to a defect in insulin-receptor binding but rather caused by the alteration in post-receptor mechanism, and increased secretion of insulin can be considered as a compensatory mechanism. In some patients, however, a decrease in insulin secreting capacity, the cause of which is not clear but at least related to the patient's age, is found and seems to lead to severe glucose intolerance.
我们对51例库欣综合征患者糖耐量异常的机制进行了研究。在口服100g葡萄糖耐量试验中，尽管47例接受研究的患者中有36例（77%）糖耐量降低的发生率很高，但大多数患者的损害相当轻微，只有10例患者（21%）被判定为糖尿病。对12例患者测定了血浆胰岛素，这些患者口服葡萄糖负荷后平均值达到正常水平以上。通过测量试验期间胰岛素高于空腹水平的增量面积与相应葡萄糖面积的比值来评估胰岛素分泌能力时，与9名对照受试者相比，库欣综合征总体呈现正常比值（113±115对144±78微单位/毫克，均数±标准差，无显著性差异），但在3例糖耐量严重受损达到糖尿病范围的患者中，该比值低于正常（27±20对144±78微单位/毫克，均数±标准差，P<0.05）。对23例患者研究了静脉注射胰岛素的降糖作用，结果显示其作用减弱。因此，我们证实了库欣综合征存在胰岛素敏感性降低，即胰岛素抵抗。患者年龄与糖耐量损害程度及胰岛素分泌能力呈正相关，但与胰岛素敏感性无关，也就是说，在老年患者中，糖耐量异常似乎因胰岛素分泌能力降低而较为严重。对8例患者检测了125I胰岛素与红细胞的结合情况，以阐明库欣综合征胰岛素抵抗的机制。库欣综合征患者在胰岛素示踪剂浓度下的特异性结合百分比与19名正常受试者所得值无差异（8.2±3.0对7.7±1.0%，均数±标准差，无显著性差异）。受体浓度和亲和力也正常。从这些观察结果来看，库欣综合征患者的糖耐量异常可能主要是由于慢性糖皮质激素过多对葡萄糖组织代谢的影响，其特征为存在胰岛素抵抗，这并非由于胰岛素受体结合缺陷，而是由受体后机制改变所致，胰岛素分泌增加可被视为一种代偿机制。然而，在一些患者中，发现胰岛素分泌能力下降，其原因尚不清楚，但至少与患者年龄有关，这似乎导致了严重的糖耐量异常。
