Clayton K L, Holly J M, Carlsson L M, Jones J, Cheetham T D, Taylor A M, Dunger D B
Department of Paediatrics, University of Oxford, UK.
Clin Endocrinol (Oxf). 1994 Oct;41(4):517-24. doi: 10.1111/j.1365-2265.1994.tb02584.x.
It has been proposed that the dissociation between growth hormone secretion and insulin-like growth factor-I (IGF-I) concentrations in insulin-dependent diabetes mellitus arises because of partial resistance at the GH receptor. In order to explore this hypothesis further we have examined the relations between IGF-I, GH-binding protein (GHBP), and GH secretion in normal subjects and patients with diabetes during puberty.
Blood samples for the estimation of IGF-I and GHBP levels were obtained from 104 patients with diabetes and 89 puberty matched controls. Thirty-four of the controls and 42 of the patients with diabetes also underwent an overnight GH secretory profile with measurements of GH every 15-20 minutes between 2000 and 0800 h.
In multivariate analysis using sex, puberty stage, and presence or absence of diabetes as dependent variables, diabetes was associated with increased GH levels (F = 23.04, P < 0.001), reduced IGF-I (F = 10.89, P < 0.001), and reduced GHBP levels (F = 31.36, P < 0.001). A negative relation between GH and GHBP levels (r = -0.44, P < 0.01) was found in normal subjects but this was absent in those with diabetes. Both GHBP and IGF-I levels in the diabetic subjects were correlated with total insulin dose (r = 0.4, P < 0.001, and r = 0.46, P < 0.001, respectively). Yet there was no direct correlation between GHBP and IGF-I concentrations. The variation in IGF-I levels was also related to glycosylated haemoglobin levels in the diabetics (r = -0.27, P = 0.01). In a stepwise multiple regression analysis insulin dose contributed 23%, HbA1 4.4% and C-peptide levels 3.7% to the variation in IGF-I levels.
In adolescents with insulin dependent diabetes mellitus, the elevated GH concentrations are associated with low circulating IGF-I and GHBP concentrations and the normal reciprocal relation between GHBP and GH is no longer evident. Although IGF-I and GHBP are both related to insulin dose, there is no direct correlation between these variables. This may indicate that GHBP reflects GH receptor numbers but not necessarily post receptor events, and the weak positive correlation between GH and IGF-I indicates that increased growth hormone secretion may compensate for reduced receptor numbers.
有人提出，胰岛素依赖型糖尿病患者生长激素分泌与胰岛素样生长因子-I（IGF-I）浓度之间的解离是由于生长激素受体存在部分抵抗。为了进一步探讨这一假说，我们研究了正常受试者和青春期糖尿病患者中IGF-I、生长激素结合蛋白（GHBP）与生长激素分泌之间的关系。
从104例糖尿病患者和89例青春期匹配的对照者中采集血样，以测定IGF-I和GHBP水平。34名对照者和42名糖尿病患者还进行了夜间生长激素分泌情况监测，于20:00至08:00期间每隔15 - 20分钟测量一次生长激素。
在以性别、青春期阶段及是否患有糖尿病为自变量的多变量分析中，糖尿病与生长激素水平升高（F = 23.04，P < 0.001）、IGF-I降低（F = 10.89，P < 0.001）以及GHBP水平降低（F = 31.36，P < 0.001）相关。在正常受试者中发现生长激素与GHBP水平呈负相关（r = -0.44，P < 0.01），但糖尿病患者中不存在这种关系。糖尿病患者的GHBP和IGF-I水平均与胰岛素总剂量相关（分别为r = 0.4，P < 0.001和r = 0.46，P < 0.001）。然而，GHBP与IGF-I浓度之间无直接相关性。糖尿病患者中IGF-I水平的变化也与糖化血红蛋白水平相关（r = -0.27，P = 0.01）。在逐步多元回归分析中，胰岛素剂量对IGF-I水平变化的贡献率为23%，糖化血红蛋白为4.4%，C肽水平为3.7%。
在胰岛素依赖型糖尿病青少年中，生长激素浓度升高与循环中IGF-I和GHBP浓度降低相关，且GHBP与生长激素之间正常的相互关系不再明显。虽然IGF-I和GHBP均与胰岛素剂量有关，但这些变量之间无直接相关性。这可能表明GHBP反映的是生长激素受体数量，而不一定反映受体后事件，生长激素与IGF-I之间的弱正相关表明生长激素分泌增加可能补偿了受体数量的减少。
