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 < 0.001). This difference persisted when only lean patients (< 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 μg/L, respectively, P < 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. Insulinopenia may be the principal reason for GHBP/receptor deficiency.

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