The metabolic cost of lowering blood pressure with hydrochlorothiazide

Diabetology & Metabolic Syndrome

Lidia S Szczepaniak¹  Ronald G Victor¹  Jaime Wiebel²  Edward W Szczepaniak¹  Ildiko Lingvay²  Angela L Price² 

[1] Cedars -Sinai Medical Center, The Heart Institute, Los Angeles, California, USA;Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA

关键词: Insulin secretion;    Insulin sensitivity;    Proton magnetic resonance spectroscopy;    Hydrochlorothiazide;    Valsartan;    Type 2 diabetes;   

Others  :  812727
DOI  :  10.1186/1758-5996-5-35

 received in 2013-07-09, accepted in 2013-07-05,  发布年份 2013

【 摘 要 】

Background

The landmark Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) placed a new spotlight on thiazide diuretics as the first-line therapy for hypertension. This is concerning as thiazide-diuretics may contribute to comorbidities associated with the current epidemic of obesity. Previous randomized clinical trials have linked thiazide diuretic treatment to insulin resistance, metabolic syndrome, and increased incidence of type 2 diabetes.

Methods

This proof of concept, longitudinal, randomized, double–blind study evaluated the effects of the angiotensin II receptor blocker Valsartan and the specific thiazide diuretic Hydrochlorothiazide (HCTZ) on hepatic triglyceride level (primary outcome), as well as triglyceride levels within other organs including the heart, skeletal muscle, and pancreas. Additionally, we evaluated whether myocardial function, insulin sensitivity, and insulin secretion were affected by these treatments.

Results

Hepatic TG levels increased by 57% post HCTZ treatment: ∆hTG _HCTZ = 4.12% and remained unchanged post Valsartan treatment: ∆hTG _V = 0.06%. The elevation of hepatic TG levels after HCTZ treatment was additionally accompanied by a reduction in insulin sensitivity: ∆SI _HCTZ = -1.14. Treatment with Valsartan resulted in improved insulin sensitivity: ∆SI _V = 1.24. Treatment-induced changes in hepatic TG levels and insulin sensitivity were statistically significant between groups (p_hTG = 0.0098 and p_SI = 0.0345 respectively). Disposition index, DI, remained unchanged after HCTZ treatment: ∆DI _HCTZ = -141 but it was increased by a factor of 2 after treatment with Valsartan: ∆DI _V =1018). However, the change between groups was not statistically significant. Both therapies did not modify abdominal visceral and subcutaneous fat mass as well as myocardial structure and function. Additionally, myocardial, pancreatic, and skeletal muscle triglyceride deposits remained unchanged in both therapeutic arms.

Conclusions

Our findings are two-fold and relate to hepatic steatosis and insulin sensitivity. HCTZ treatment worsened hepatic steatosis measured as hepatic triglyceride content and reduced insulin sensitivity. Valsartan treatment did not affect hepatic triglyceride levels and improved insulin sensitivity. The results of this study reinforce the message that in patients at risk for type 2 diabetes it is particularly important to choose an antihypertensive regimen that lowers blood pressure without exacerbating patient’s metabolic profile.

【 授权许可】

   
2013 Price et al.; licensee BioMed Central Ltd.

【 图 表 】

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