title: Hydrochlorothiazide compared to candesartan treatment increases adipose tissue gene expression and circulating levels of serum amyloid A in hypertensive patients.
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.
authors.affiliation: The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Palming
authors.forename: P-A
authors.initials: PA
authors.lastname: Jansson
authors.forename: F
authors.initials: F
authors.lastname: Renström
authors.forename: A
authors.initials: A
authors.lastname: Johansson
authors.forename: L
authors.initials: L
authors.lastname: Johansson
authors.forename: C
authors.initials: C
authors.lastname: Karlsson
authors.forename: L
authors.initials: L
authors.lastname: Lind
authors.forename: J W
authors.initials: JW
authors.lastname: Eriksson
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000682:Amyloid / Q000097:blood*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D000682:Amyloid; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D006852:Hydrochlorothiazide; C081643:candesartan