Objectives: Insulin resistance (IR) and obesity are very common metabolic abnormalities, which are often associated with reduced GH secretion. GH reduces intraabdominal fat and its deficiency may contribute to the metabolic syndrome. IGF-1 improves IR but IGFBPs have a potential role in regulating its bioactivity although only little information exists. We postulate that the elevated insulin levels in IR may persistently suppress GH provided its regulation remains insulin sensitive. We therefore tested the sensitivity of the GH axis to insulin suppression.
Methods: 181 healthy subjects underwent assessment of fasting total IGF-1, fasting IGFBP3 and fasting and post-OGTT GH and insulin levels (57 men; age 19-76; BMI 29.8±0.5). IR was estimated by calculating three indicies: HOMA, QUICKI and ISI.
Results: All three indicies for IR were well correlated (r=0,6-0,9, P<0.001). IGFBP3 and log-transformed nadir GH but not IGF-1 were significant predictors for insulin sensitivity (r=0.35, P<0.001; r=−0.23, P<0.01 respectively) even after correction for IGF-I levels. We explain the positive correlation between IGFBP3 and IR through its ability to reduce free IGF-1 levels since a positive correlation between IGF-1/BP3-ratio, as an indicator for free IGF-1 levels, with QUICKI is observed (r=0.16, P<0.05). Moreover, the negative correlation between nadir GH and IR may be due to a higher insulin/glucose-induced GH suppression after glucose ingestion since a negative correlation between nadir GH and peak post-glucose insulin level is seen (r=0.33, P<0.001).
Conclusion: Our data indicate that GH secretion remains sensitive to insulin in IR. IGFBP3 and nadir GH are more predictive than total IGF-1 of IR. We show for the first time that higher IGFBP3 and lower free IGF-1 estimated by IGF-1/BP3 ratio are associated with a higher IR indicating a role of endogenous IGF-1in glucose homeostasis.
01 - 05 Apr 2006
European Society of Endocrinology