Endocrine Abstracts

Objectives: Insulin resistance (IR) is a very common metabolic abnormality in obesity, which is often associated with reduced growth hormone (GH) secretion. GH deficiency is associated with increased in intra-abdominal fat and several parameters of the metabolic syndrome. IGF-I improves IR but the IGF-binding proteins are supposed to regulate its bioactivity although only little information exists. We postulated that the elevated insulin levels due to IR do not only suppress GH but also IGF-I bioactivity, and therefore we tested the effect of insulin on serum levels of bioactive IGF-I.

Methods: 24 healthy subjects (12 men; age 21–72 years; BMI 25.9±0.9 kg/m2) and 19 patients with impaired glucose tolerance (IGT; 8 men; age 26–71; BMI 28.9±1.2) were studied using an OGTT and a hyperinsulinemic euglycemic clamp. IR was estimated by calculating the homeostatic model assessment (HOMA-IR) index and the glucose infusion rate (GIR). IGF-I bioactivity was estimated using a novel IGF-I kinase receptor activation assay (KIRA) under fasting conditions and during the steady state of the clamp. Ethical Committee approval was obtained.

Results: Insulin significantly decreased IGF-I bioactivity in IGT patients (1.8±0.2 vs. 1.5±0.2 μg/l, P=0.004) and in healthy controls (1.8±0.2 vs 1.6±0.2 μg/l, P=0.001). Age, BMI and fasting IGF-I bioactivity did not significantly differ between groups. However, patients with IGT showed a higher HOMA-IR and a lower GIR (2.3±0.4 vs. 1.3±0.2 and 2.5±0.3 vs. 4.7±0.3 mg/kg min, P<0.05, respectively). Moreover, inverse correlations were seen between bioactive IGF-I levels and age (r=−0.38, P=0.01), BMI (r=−0.46, P=0.002) and waist to hip ratio (r=−0.51, P=0.01).

Conclusion: Our data indicate that insulin infusion acutely decreased serum IGF-I bioactivity in humans. Hyperinsulinemia as seen in IR may per se be responsible for this reduction. Estimation of IGF-I bioavailability using the KIRA method may, therefore, have a predictive value in the diagnosis of the metabolic syndrome.