Mercado M, Molitch M E, Baumann G
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
Diabetes. 1992 May;41(5):605-9. doi: 10.2337/diab.41.5.605.
Poorly controlled insulin-dependent diabetes mellitus (IDDM) is associated with elevated basal plasma growth hormone (GH), disproportionally low insulin-like growth factor I (IGF-I) levels, and impaired somatic growth. These derangements in the GH-IGF axis imply a state of GH resistance. The mechanism of GH resistance is unknown; it may involve a defect at the level of the GH receptor, unresponsiveness due to a postreceptor defect in GH action, or both. To investigate a potential receptor involvement, we measured plasma high-affinity GH-binding protein (GHBP), which represents a truncated GH receptor and may reflect GH receptor levels in tissues, in patients with IDDM, patients with non-insulin-dependent diabetes (NIDDM), and nondiabetic control subjects. Patients with IDDM had significantly lower plasma GHBP levels than either patients with NIDDM or nondiabetic control subjects (mean value 18.2 vs. 24.6 and 23.8% GH bound/ml plasma, respectively, P less than 0.001). This difference persisted when only lean patients (less than 115% ideal body wt) were included in the analysis. Basal plasma GH levels were significantly elevated in IDDM compared with either patients with NIDDM or nondiabetic control subjects (mean 6.9 vs. 2.1 and 2.0 micrograms/L, respectively, P less than 0.001), whereas IFG-I levels were not significantly different in IDDM and NIDDM. No correlations were found between levels of GHBP and HbA1, duration of diabetes, or plasma GH. GHBP and IGF-I levels were significantly correlated in NIDDM but not in IDDM. We conclude that IDDM is associated with low GHBP levels and that GH resistance found in this disorder may be mediated, at least in part, by a decrease in GH receptor levels.(ABSTRACT TRUNCATED AT 250 WORDS)
胰岛素依赖型糖尿病(IDDM)控制不佳与基础血浆生长激素(GH)升高、胰岛素样生长因子I(IGF-I)水平不成比例地降低以及躯体生长受损有关。GH-IGF轴的这些紊乱意味着存在GH抵抗状态。GH抵抗的机制尚不清楚;它可能涉及GH受体水平的缺陷、由于GH作用的受体后缺陷导致的无反应性,或两者皆有。为了研究潜在的受体参与情况,我们测量了IDDM患者、非胰岛素依赖型糖尿病(NIDDM)患者和非糖尿病对照受试者血浆中的高亲和力GH结合蛋白(GHBP),它代表截短的GH受体,可能反映组织中的GH受体水平。IDDM患者的血浆GHBP水平显著低于NIDDM患者或非糖尿病对照受试者(分别为结合GH的平均值18.2% vs. 24.6%和23.8%/毫升血浆,P<0.001)。当仅纳入体重较轻的患者(低于理想体重的115%)进行分析时,这种差异仍然存在。与NIDDM患者或非糖尿病对照受试者相比,IDDM患者的基础血浆GH水平显著升高(分别为平均值6.9 vs. 2.1和2.0微克/升,P<0.001),而IDDM和NIDDM患者的IFG-I水平无显著差异。未发现GHBP水平与糖化血红蛋白、糖尿病病程或血浆GH之间存在相关性。NIDDM患者中GHBP和IGF-I水平显著相关,但IDDM患者中并非如此。我们得出结论,IDDM与低GHBP水平有关,并且这种疾病中发现的GH抵抗可能至少部分由GH受体水平降低介导。(摘要截短至250字)