Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized placebo-controlled double-blind trial

• Published in: PloS one 2012-06, Vol.7 (6), p.e39930
• Main Authors: Goossens, Gijs H, Moors, Chantalle C M, van der Zijl, Nynke J, Venteclef, Nicolas, Alili, Rohia, Jocken, Johan W E, Essers, Yvonne, Cleutjens, Jack P, Clément, Karine, Diamant, Michaela, Blaak, Ellen E
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipocytes - pathology; Adipogenesis; Adiponectin; Adipose tissue; Adipose Tissue - blood supply; Adipose Tissue - drug effects; Adipose Tissue - pathology; Adipose Tissue - physiopathology; Angiogenesis; Angiotensin; Angiotensin II; Angiotensins; Antihypertensive Agents - pharmacology; Biology; Biomarkers - blood; Biomarkers - metabolism; Biopsy; Blood flow; Blood Pressure - drug effects; Body fat; Capillaries - drug effects; Capillaries - pathology; Cardiovascular diseases; Cell Hypoxia - drug effects; Cell Size - drug effects; Chemotactic Factors - pharmacology; Clinical trials; Diabetes; Diabetes mellitus; Double-Blind Method; Double-blind studies; Fasting; Fasting - blood; Fatty acids; Female; Gene expression; Gene Expression Regulation - drug effects; Glucose; Glucose - metabolism; Health risks; Homeostasis; Humans; Hypertension; Immunoglobulin M; Infiltration; Inflammation; Inflammation - metabolism; Inflammation - pathology; Insulin; Insulin - pharmacology; Insulin resistance; Internal medicine; Leptin; Lipids; Lipolysis - drug effects; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Macrophages - pathology; Male; Markers; Medicine; Metabolism; Middle Aged; Nutrition research; Physiological aspects; Placebos; Postprandial Period; Randomization; Renin; Risk reduction; Rodents; Sensitivity; Studies; Tetrazoles - pharmacology; Toxicology; Tumor necrosis factor-α; Type 2 diabetes; Valine - analogs & derivatives; Valine - pharmacology; Valsartan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0039930

Blockade of the renin-angiotensin system (RAS) reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT) function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM). We performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d) or placebo (PLB) for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF) ((133)Xe wash-out), systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp). VAL treatment markedly reduced adipocyte size (P