Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy

Michael Hecht Olsen, Eigil Fossum, Aud Høieggen, Kristian Wachtell, Elsa Hjerkinn, Shawna D. Nesbitt, Ulrik B. Andersen, Robert A. Phillips, Cynthia L. Gaboury, Hans Ibsen, Sverre E. Kjeldsen, Stevo Julius

Research output: Contribution to journalArticle

53 Citations (Scopus)

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 mm Hg × min × 100, P < 0.05) and M/IG decreased (8.6 versus 12.1 I2/kg × mmol × min, P < 0.05) in patients treated with atenolol, whereas MFVR and M/IG were unchanged (3.5 versus 3.5 mmHg × min × 100 and 12.6 versus 11.1 I2/kg × mmol × 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.

Original languageEnglish (US)
Pages (from-to)891-898
Number of pages8
JournalJournal of Hypertension
Volume23
Issue number4
StatePublished - Apr 2005

Fingerprint

Atenolol
Losartan
Insulin Resistance
Forearm
Vascular Resistance
Hypertension
Blood Vessels
Hypertrophy
Therapeutics
Plethysmography
Left Ventricular Hypertrophy
Skeletal Muscle
Body Mass Index
Blood Pressure
Glucose
Incidence

Keywords

  • Adrenergic receptor blocker
  • Angiotensin antagonist
  • Essential hypertension
  • Hypertrophy
  • Insulin resistance
  • Losartan
  • Vascular resistance

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Olsen, M. H., Fossum, E., Høieggen, A., Wachtell, K., Hjerkinn, E., Nesbitt, S. D., ... Julius, S. (2005). Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy. Journal of Hypertension, 23(4), 891-898.

Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension : ICARUS, a LIFE substudy. / Olsen, Michael Hecht; Fossum, Eigil; Høieggen, Aud; Wachtell, Kristian; Hjerkinn, Elsa; Nesbitt, Shawna D.; Andersen, Ulrik B.; Phillips, Robert A.; Gaboury, Cynthia L.; Ibsen, Hans; Kjeldsen, Sverre E.; Julius, Stevo.

In: Journal of Hypertension, Vol. 23, No. 4, 04.2005, p. 891-898.

Research output: Contribution to journalArticle

Olsen, MH, Fossum, E, Høieggen, A, Wachtell, K, Hjerkinn, E, Nesbitt, SD, Andersen, UB, Phillips, RA, Gaboury, CL, Ibsen, H, Kjeldsen, SE & Julius, S 2005, 'Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy', Journal of Hypertension, vol. 23, no. 4, pp. 891-898.
Olsen, Michael Hecht ; Fossum, Eigil ; Høieggen, Aud ; Wachtell, Kristian ; Hjerkinn, Elsa ; Nesbitt, Shawna D. ; Andersen, Ulrik B. ; Phillips, Robert A. ; Gaboury, Cynthia L. ; Ibsen, Hans ; Kjeldsen, Sverre E. ; Julius, Stevo. / Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension : ICARUS, a LIFE substudy. In: Journal of Hypertension. 2005 ; Vol. 23, No. 4. pp. 891-898.
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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 mm Hg × min × 100, P < 0.05) and M/IG decreased (8.6 versus 12.1 I2/kg × mmol × min, P < 0.05) in patients treated with atenolol, whereas MFVR and M/IG were unchanged (3.5 versus 3.5 mmHg × min × 100 and 12.6 versus 11.1 I2/kg × mmol × 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.",
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T2 - ICARUS, a LIFE substudy

AU - Olsen, Michael Hecht

AU - Fossum, Eigil

AU - Høieggen, Aud

AU - Wachtell, Kristian

AU - Hjerkinn, Elsa

AU - Nesbitt, Shawna D.

AU - Andersen, Ulrik B.

AU - Phillips, Robert A.

AU - Gaboury, Cynthia L.

AU - Ibsen, Hans

AU - Kjeldsen, Sverre E.

AU - Julius, Stevo

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N2 - 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 mm Hg × min × 100, P < 0.05) and M/IG decreased (8.6 versus 12.1 I2/kg × mmol × min, P < 0.05) in patients treated with atenolol, whereas MFVR and M/IG were unchanged (3.5 versus 3.5 mmHg × min × 100 and 12.6 versus 11.1 I2/kg × mmol × 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.

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KW - Adrenergic receptor blocker

KW - Angiotensin antagonist

KW - Essential hypertension

KW - Hypertrophy

KW - Insulin resistance

KW - Losartan

KW - Vascular resistance

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