Abstract: Angiotensin II receptor blockade has been shown to have a beneficial effect on the angiopathies of hypertension and hyperglycemia in patients with type 2 diabetes. On the other hand, blood pressure is difficult to control with monotherapy, especially in patients with diabetes, highlighting the requirement of drug contribution such as losartan/hydrochlorothiazide (LST/HCTZ). However, the effect of LST/HCTZ on the angiopathy-related markers in hypertension and type 2 diabetes is poorly understood. We investigated the effects of LST/HCTZ on these markers in 82 hypertensive patients with and without type 2 diabetes mellitus. Levels of the angiopathy-related markers (platelet-derived microparticles: 11.6 ± 2.7 vs. 17.1 ± 5.6 IU/ml, p < 0.01; RANTES: 73.1 ± 12.2 vs. 88.8 ± 20.4 ng/ml, p < 0.01; monocyte chemotactic peptide-1: 430 ± 104 vs. 492 ± 120 pg/ml, p < 0.05; and soluble E-selectin: 48 ± 19 vs. 62 ± 22 ng/ml, p < 0.01) were significantly increased in hypertensive patients with type 2 diabetes compared to without type 2 diabetes. In addition, the concentrations of adiponectin were significantly decreased in patients with type 2 diabetes (4.71 ± 0.85 vs. 3.19 ± 1.14 μg/ml, p < 0.01). Regardless of the presence of diabetic complications, both systolic and diastolic blood pressure significantly decreased after LST/HCTZ administration (LST/HCTZ 50 mg/day for 12 weeks). The angiopathy-related markers were decreased significantly in patients
with type 2 diabetes after LST/HCTZ treatment, but not in non-type 2 diabetic patients. In addition, LST/HCTZ alleviated hypoadiponectinemia in hypertensive patients with diabetes (before vs. after: 3.19 ± 1.14 vs. 4.28 ± 0.93 mg/ml, p < 0.01) but did not increase adiponectin levels in the non-diabetic hypertensive group, for which the average adiponectin level was normal prior to treatment. These results suggest LST/HCTZ may be beneficial as an adiponectin-dependent anti-atherosclerotic therapy in patients with type 2 diabetes in addition to its anti-hypertensive action.
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