Exp Clin Endocrinol Diabetes 2006; 114 - P15_189
DOI: 10.1055/s-2006-933074

Growth hormone and IGFBP-3 but not IGF-1 are independent predictors of insulin sensitivity in healthy subjects: on the role of hGH in the metabolic syndrome

MA Arafat 1, F Perschel 2, C Schöfl 1, M Weickert 3, J Purschwitz 1, H Rochlitz 1, J Spranger 3, M Möhlig 3, AFH Pfeiffer 1
  • 1Benjamin Franklin Medical Center, Charité University, Department of Endocrinology, Diabetes and Nutrition, Berlin, Germany
  • 2Benjamin Franklin Medical Center, Charité University, Department of Clinical Chemistry and Pathobiochemistry, Berlin, Germany
  • 3German Institute of Human Nutrition, Department of Clinical Nutrition, Nuthetal, Germany

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: Seventy healthy subjects underwent assessment of fasting total IGF-1, fasting IGFBP3 and fasting and post-OGTT GH and insulin levels (26 men; age 25–73; BMI 28.9±0.7). IR was estimated by calculating indicies: HOMA, QUICKI and ISI. Bivariate and multiple linear regression analyses were performed to estimate the effects of different predictors of IR.

Results: In healthy subjects all three indicies for IR were well correlated (r=0.68–0.88, p<0.0001). IGFBP3 and log-transformed nadir GH levels but not total IGF-1 levels were significant predictors of insulin sensitivity (r=0.354–0.372, p<0.005; r=0.277–0.373, P<0.05 respectively) even after correction for total IGF-I levels. We explain the positive correlation between IGFBP3 and IR through its ability to reduce free IGF-1 levels since a negative correlation between IGF-1/BP3-ratio, as an indicator for free IGF-1 levels, with IR is indicated (r=0.271–0.289, 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=0.313, p=0.008).

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-1 in glucose homeostasis.