Objective: Blocking the renin-angiotensin system (RAS) may reduce the risk of developing type-2 diabetes, but data are inconclusive and the mechanisms involved are unclear. RAS and RAS inhibition also influence the IGF-I system, which is important in glucose homeostasis. We investigated the effects of the angiotensin-receptor antagonist, losartan, on insulin resistance and IGF-I levels. Design and methods: In this hypothesis-generating study, five individuals with impaired fasting glucose received 100 mg losartan during 8 weeks. Before and after the treatment period, insulin sensitivity was assessed using the homeostasis model assessment of insulin resistance (HOMA), as well as the 2-h continuous infusion of glucose with model assessment (CIGMA). Furthermore, serum levels of free and total IGF-I, IGF-binding protein-3 (IGFBP-3), lipids and HbAlc were measured. Results: After the treatment period, the HOMA score for insulin resistance had decreased from 5.3 ± 1.1 to 3.7 ± 0.9 (P = 0.004) and the 2-h CIGMA score from 23.4 ± 3.1 to 15.9 ± 2.1 (P = 0.07). The serum levels of free IGF-I had increased from 57 ± 18.8 to 134 ± 31.3 pmol/l (P = 0.04). In terms of percentage, the decrease of HOMA correlated with the increase in free IGF-I levels (Pearson's correlation coefficient r= - 0.8; P = 0.07). A trend in the same direction was observed with 2-h CIGMA. No differences were observed in lipids, total IGF-I, IGFBP-3 or HbAlc. Conclusions: Losartan raised serum levels of free IGF-I, which might contribute to the improvement of insulin resistance associated with losartan treatment. These observations, if confirmed in broader studies, will help our understanding of the pathogenesis of type-2 diabetes mellitus, as well as the role of angiotensin-receptor antagonists in its prevention.

doi.org/10.1530/eje.1.02219, hdl.handle.net/1765/56727
European Journal of Endocrinology
Department of Internal Medicine

Zandbergen, A., Lamberts, S., Janssen, J., & Bootsma, A. (2006). Short-term administration of an angiotensin-receptor antagonist in patients with impaired fasting glucose improves insulin sensitivity and increases free IGF-I. European Journal of Endocrinology, 155(2), 293–296. doi:10.1530/eje.1.02219