Dipeptidyl peptidase-4 inhibitor sitagliptin improves pancreatic ß-cell function in hypertensive diabetic patients treated with angiotensin receptor blockers.

INTRODUCTION: Dipeptidyl peptidase (DPP)-4 inhibitors, a novel oral anti-diabetic agents, exert a protective effect on pancreatic ß-cell function in patients with type 2 diabetic mellitus (T2DM). However, their beneficial effect in hypertensive T2DM patients treated with angiotensin receptor blockers (ARBs) has not been investigated. METHODS: In this open-label multicenter randomized study, a total of 55 hypertensive T2DM patients treated with ARBs were randomly assigned to receive the DPP-4 inhibitor sitagliptin or sulfonylurea (SU). RESULTS: After 24 weeks of treatment, a significant reduction in fasting blood glucose was only observed in the sitagliptin group, while HbA1c was significantly reduced in both groups. Homeostasis model assessment of insulin resistance was not significantly improved in either group. Indicators of pancreatic ß-cell function, including proinsulin to insulin ratio and homeostasis model assessment of ß-cell function, were significantly improved in the sitagliptin group, but not in the SU group. The beneficial effects of sitagliptin were observed in hypoglycemic drug naïve patients, but not in patients who had received SU monotherapy prior to the study. CONCLUSION: Treatment with the DPP-4 inhibitor sitagliptin might exert beneficial effects on pancreatic ß-cell function in ARB-treated T2DM patients and its efficacy might be more pronounced in hypoglycemic drug naïve patients.

Vascular angiotensin II type 2 receptor attenuates atherosclerosis via a kinin/NO-dependent mechanism.

INTRODUCTION: The angiotensin II (Ang II) type 1 receptor exerts pro-atherogenic action by augmenting oxidative stress, whereas the Ang II type 2 receptor (AT2)-mediated effect on atherosclerosis remains controversial. MATERIALS AND METHODS: AT2 transgenic (AT2-Tg) mice, which overexpress AT2 in their vascular smooth muscle cells, were crossed with apoE-deficient (apoE(-/-)) mice to generate AT2 transgenic apoE(-/-) mice (AT2-Tg/apoE(-/-)). RESULTS: A subpressor dose of Ang II infusion exaggerated atherosclerosis development in apoE(-/-) mice, which was markedly suppressed in AT2-Tg/apoE(-/-) mice. Inhibitors of nitric oxide (NO) synthase (L-NAME) or bradykinin type 2 receptor completely abolished AT2-mediated anti-atherogenic actions. The vascular cell adhesion molecule-1 expression levels and degree of monocyte/macrophage accumulation in the intima were also considerably reduced in AT2-Tg/apoE(-/-) mice; these phenomena were completely reversed by L-NAME treatment. Ang II infusion significantly enhanced the accumulation of dihydroethidium-positive mononuclear cells in the intima and mRNA expression levels of Nox2, a phagocytic cell-type NADPH oxidase subunit in apoE(-/-) mice, which was completely inhibited in AT2-Tg/apoE(-/-) mice. CONCLUSIONS: Vascular AT2 stimulation exerts anti-atherogenic actions in an endothelial kinin/NO-dependent manner, and its anti-oxidative effect is likely to be exerted by inhibiting the accumulation of superoxide-producing mononuclear leukocytes.

Long-term antihypertensive efficacy of losartan/hydrochlorothiazide combination therapy on home blood pressure control.

Angiotensin receptor blocker (ARB)/hydrochlorothiazide (HCTZ) combination therapy has been shown to produce a prompt reduction in clinic blood pressure (BP) without serious adverse effects; however, long-term antihypertensive efficacy on home BP has not been fully investigated. In this open-label multicenter observational study, a total of 151 hypertensive patients uncontrolled with antihypertensive regimens including standard dose of ARBs were switched to the fixed-dose combination of losartan (50 mg)/HCTZ (12.5 mg) (mean age 66.9 ± 9.5 years, 51% male, 19% with diabetes mellitus, and 57% with dyslipidemia). After 3 months, losartan/HCTZ treatment significantly reduced mean home systolic BP/diastolic BP from a baseline level of 153 ± 11/85 ± 9 mm Hg to 136 ± 12/77 ± 10 mm Hg (P < .001) and mean clinic BP from 158 ± 9/87 ± 9 to 136 ± 12/77 ± 10 (P < .001), which were maintained through the study period of 12 months (132 ± 11/75 ± 9 and 136 ± 12/77 ± 10; home and clinic BP at 12 months, respectively, P < .001). Furthermore, younger patients (< 65 years) receiving ARB monotherapy at the start of the study showed a significantly greater reduction in home BP, but not in clinic BP, compared with elderly patients (≥ 65 years). In conclusion, losartan/HCTZ combination therapy exerted a 1-year long-term efficacy on home BP as well as clinic BP. In patients uncontrolled with ARB monotherapy, the antihypertensive efficacy on home BP is more pronounced in younger patients compared with that in elderly patients.

A case of Takayasu's arteritis and aortic regurgitation, which presented much difficulty in the diagnosing process because of complicated osteomyelitis and non-typical manifestations.

A 49-year-old woman presenting with leg edema and progressive dyspnea on exertion was found to have a diastolic murmur. Echocardiography revealed increased left ventricular volume and severe aortic regurgitation (AR). She also had pain in her chest and left shoulder. Gallium scintigraphy showed increased uptake in the sternum, and further examination indicated chronic osteomyelitis in the sternum and the proximal portion of bilateral clavicles. Aortic valve replacement was performed and the ascending aorta was found to have inflammatory wall thickening with adhesion formation. Histological study and other postoperative examinations revealed Takayasu's arteritis (TA). Involvement of bone is rarely described in TA, and typical manifestations such as claudication of extremities, decreased brachial artery pulse, and arteriogram abnormality were absent, which made the preoperative diagnosis difficult. Here we report a case of severe AR due to TA which presented much difficulty in the diagnosing process, because a rare complicated illness, osteomyelitis was clinically apparent and there were few clinical manifestations related to TA.