Short-term administration of an angiotensin-receptor antagonist in patients with impaired fasting glucose improves insulin sensitivity and increases free IGF-I.
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


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.
Zandbergen
Adrienne A M
AA
Department of Internal Medicine, Erasmus University Medical Centre, Dr Molewaterplein 40 3015 GD Rotterdam, The Netherlands. adrienne_zandbergen@yahoo.com
Lamberts
Steven W J
SW
Janssen
Joop A M J L
JA
Bootsma
Aart H
AH
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001786:Blood Glucose; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000517:prevention & control; D005215:Fasting; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D007334:Insulin-Like Growth Factor I; D019808:Losartan