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Horm Metab Res 2011; 43(5): 319-324
DOI: 10.1055/s-0031-1271695
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Hydrochlorothiazide Compared to Candesartan Treatment Increases Adipose Tissue Gene Expression and Circulating Levels of Serum Amyloid A in Hypertensive Patients

J. Palming1 , P-A. Jansson1 , F. Renström2 , A. Johansson1 , L. Johansson3 , 4 , C. Karlsson3 , L. Lind5 , J. W. Eriksson1 , 3
  • 1The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
  • 2Department of Medicine, Umeå University Hospital, Umeå, Sweden
  • 3AstraZeneca R & D, Mölndal, Sweden
  • 4Department of Radiology, Uppsala University Hospital, Uppsala, Sweden
  • 5Department of Medicine, Uppsala University Hospital, Uppsala, Sweden
Further Information

Publication History

received 06.10.2010

accepted 13.01.2011

Publication Date:
17 February 2011 (online)

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Abstract

Treatment of hypertension with angiotensin receptor blockers has been shown to reduce the risk of developing type 2 diabetes in comparison to thiazide diuretics and beta adrenergic blockers. Therefore, we wanted to study the effect of antihypertensive drugs on adipose tissue with respect to insulin resistance. In the MEDICA (MEchanisms for the DIabetes preventing effects of CAndesartan) study, 22 hypertensive, nondiabetic patients with abdominal obesity (10 men, 12 women) were randomized into 12-week treatment periods with candesartan, hydrochlorothiazide, and placebo according to a 3-way cross-over design. Subcutaneous adipose tissue biopsies were taken after 8 weeks treatment to analyze gene expression, glucose uptake capacity, insulin-signaling, and adipocyte size. Adipose tissue gene expression of serum amyloid A (SAA) was higher after hydrochlorothiazide treatment compared to candesartan (p=0.036), and this was in accordance with our previous finding on circulating SAA levels. Serum levels of E selectin were increased after hydrochlorothiazide compared to candesartan treatment (p=0.002) and lower after candesartan compared to placebo (p=0.002). In adipocytes, there were no significant differences between the treatments with respect to cell size, glucose uptake capacity, or insulin-signaling. In comparison to candesartan, hydrochlorothiazide raised the adipose tissue gene expression of SAA and the serum level of SAA as well as E selectin in hypertensive patients. Less adipose and systemic inflammation may be one explanation why candesartan is favorable in comparison to thiazide diuretics with respect to development of insulin resistance and type 2 diabetes.

Key words

E selectin - C reactive protein - antihypertensive therapy - MEDICA

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Correspondence

J. W. Eriksson

The Lundberg Laboratory for

Diabetes Research

Sahlgrenska University Hospital

Blå stråket 5

413 45 Gothenburg

Sweden

Phone: +46/708/467706

Fax: +46/31/410573

Email: jan.eriksson@medic.gu.se

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