title: Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy.
abstract: OBJECTIVE
  Hypertension and insulin resistance might be associated through peripheral vascular hypertrophy/rarefaction which compromises skeletal muscle blood flow and decreases glucose uptake, inducing insulin resistance. We hypothesized that treatment with losartan as compared to atenolol would improve insulin sensitivity through regression of peripheral vascular hypertrophy/rarefaction.
  
  
  METHODS
  In 70 hypertensive patients with electrocardiographic left ventricular hypertrophy, we measured minimal forearm vascular resistance (MFVR) by plethysmography and insulin sensitivity (M/IG) by a 2-h isoglycemic hyperinsulinemic clamp at baseline and after 1, 2 and 3 years of blinded treatment with atenolol- or losartan-based regimens.
  
  
  RESULTS
  Blood pressures were reduced similarly in the two treatment groups. After 3 years, MFVR was increased (3.7 versus 3.2 mmHg x min x 100, P < 0.05) and M/IG decreased (8.6 versus 12.1 l/kg x mmol x min, P < 0.05) in patients treated with atenolol, whereas MFVR and M/IG were unchanged (3.5 versus 3.5 mmHg x min x 100 and 12.6 versus 11.1 l/kg x mmol x min, both P = NS) in patients treated with losartan. As compared to atenolol, losartan treatment was associated with less increase in MFVR (4.3 versus 27%, P < 0.05) and less decrease in M/IG (24 versus -14%, P < 0.01). The relative change in M/IG was inversely associated with the relative change in MFVR (r = -0.16, P < 0.05) independently of the relative change in body mass index (r = -0.29, P < 0.001).
  
  
  CONCLUSIONS
  As compared to atenolol, losartan treatment was associated with less peripheral vascular hypertrophy/rarefaction and higher insulin sensitivity. The relative change in MFVR and M/IG were inversely related, supporting the hypothesis that peripheral vascular changes in hypertension may induce insulin resistance. The ability of losartan to preserve insulin sensitivity may explain the lower incidence of new onset diabetes in patients treated with losartan in the LIFE study.
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Glostrup University Hospital, Copenhagen, Denmark. mho@dadlnet.dk
authors.forename: Michael H
authors.initials: MH
authors.lastname: Olsen
authors.forename: Eigil
authors.initials: E
authors.lastname: Fossum
authors.forename: Aud
authors.initials: A
authors.lastname: Høieggen
authors.forename: Kristian
authors.initials: K
authors.lastname: Wachtell
authors.forename: Elsa
authors.initials: E
authors.lastname: Hjerkinn
authors.forename: Shawna D
authors.initials: SD
authors.lastname: Nesbitt
authors.forename: Ulrik B
authors.initials: UB
authors.lastname: Andersen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Phillips
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Gaboury
authors.forename: Hans
authors.initials: H
authors.lastname: Ibsen
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
authors.forename: Stevo
authors.initials: S
authors.lastname: Julius
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001262:Atenolol / Q000008:administration & dosage*; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D019808:Losartan / Q000008:administration & dosage*; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D007328:Insulin; D001262:Atenolol; D019808:Losartan