The Journal of clinical endocrinology and metabolism · 2018
Randomized, Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Metabolic and Inflammatory Indices in HIV.
СтатьяРандомизированное исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Srinivasa Suman, Fitch Kathleen V, Wong Kimberly, O'Malley Timothy K, Maehler Patrick, Branch Karen L, Looby Sara E, Burdo Tricia H, Martinez-Salazar Edgar L, Torriani Martin, Lyons Shannon H, Weiss Julian, Feldpausch Meghan, Stanley Takara L, Adler Gail K, Grinspoon Steven K
Аннотация
CONTEXT: HIV-infected individuals demonstrate increased renin-angiotensin-aldosterone system activation in association with visceral adiposity, insulin resistance, and inflammation. A physiologically based treatment approach targeting mineralocorticoid receptor (MR) blockade may improve metabolic and inflammatory indices in HIV.
OBJECTIVE: To investigate effects of eplerenone on insulin sensitivity, inflammatory indices, and other metabolic parameters in HIV.
DESIGN: Six-month, double-blind, randomized, placebo-controlled trial.
SETTING: Academic clinical research center.
PARTICIPANTS: HIV-infected individuals with increased waist circumference and abnormal glucose homeostasis.
INTERVENTION: Eplerenone 50 mg or placebo daily.
OUTCOME: The primary end point was change in insulin sensitivity measured by the euglycemic-hyperinsulinemic clamp technique. Secondary end points included change in body composition and inflammatory markers.
RESULTS: Forty-six individuals were randomized to eplerenone (n = 25) vs placebo (n = 21). Eplerenone did not improve insulin sensitivity [0.48 (-1.28 to 1.48) vs 0.43 (-1.95 to 2.55) mg/min/μIU/mL insulin; P = 0.71, eplerenone vs placebo] when measured by the gold standard euglycemic-hyperinsulinemic clamp technique. Intramyocellular lipids (P = 0.04), monocyte chemoattractant protein-1 (P = 0.04), and high-density lipoprotein (P = 0.04) improved among those randomized to eplerenone vs placebo. Trends toward decreases in interleukin-6 (P = 0.10) and high-sensitivity C-reactive protein (P = 0.10) were also seen with eplerenone vs placebo. Plasma renin activity and aldosterone levels increased in the eplerenone vs placebo-treated group, demonstrating expected physiology. MR antagonism with eplerenone was well tolerated among the HIV population, with no considerable changes in blood pressure or potassium.
CONCLUSION: MR blockade may improve selected metabolic and inflammatory indices in HIV-infected individuals. Further studies are necessary to understand the clinical potential of MR antagonism in HIV.
OBJECTIVE: To investigate effects of eplerenone on insulin sensitivity, inflammatory indices, and other metabolic parameters in HIV.
DESIGN: Six-month, double-blind, randomized, placebo-controlled trial.
SETTING: Academic clinical research center.
PARTICIPANTS: HIV-infected individuals with increased waist circumference and abnormal glucose homeostasis.
INTERVENTION: Eplerenone 50 mg or placebo daily.
OUTCOME: The primary end point was change in insulin sensitivity measured by the euglycemic-hyperinsulinemic clamp technique. Secondary end points included change in body composition and inflammatory markers.
RESULTS: Forty-six individuals were randomized to eplerenone (n = 25) vs placebo (n = 21). Eplerenone did not improve insulin sensitivity [0.48 (-1.28 to 1.48) vs 0.43 (-1.95 to 2.55) mg/min/μIU/mL insulin; P = 0.71, eplerenone vs placebo] when measured by the gold standard euglycemic-hyperinsulinemic clamp technique. Intramyocellular lipids (P = 0.04), monocyte chemoattractant protein-1 (P = 0.04), and high-density lipoprotein (P = 0.04) improved among those randomized to eplerenone vs placebo. Trends toward decreases in interleukin-6 (P = 0.10) and high-sensitivity C-reactive protein (P = 0.10) were also seen with eplerenone vs placebo. Plasma renin activity and aldosterone levels increased in the eplerenone vs placebo-treated group, demonstrating expected physiology. MR antagonism with eplerenone was well tolerated among the HIV population, with no considerable changes in blood pressure or potassium.
CONCLUSION: MR blockade may improve selected metabolic and inflammatory indices in HIV-infected individuals. Further studies are necessary to understand the clinical potential of MR antagonism in HIV.