Increased human urotensin II levels are correlated with carotid atherosclerosis in essential hypertension.

BACKGROUND: Circulating blood levels of human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, are increased in patients with essential hypertension. Our previous studies showed that U-II accelerates human macrophage foam cell formation and vascular smooth muscle cell proliferation, suggesting development of atherosclerotic plaque. In this study, we demonstrated a correlation between plasma U-II level and progression of atherosclerosis in hypertensive patients. METHODS: The intima-media thickness (IMT) and plaque score in the carotid artery, blood pressure (BP), plasma levels of U-II, and atherosclerotic parameters were determined in 50 hypertensive patients and 31 normotensive controls. RESULTS: Plasma U-II level, maximum IMT, plaque score, systolic BP, and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly greater in hypertensive patients than normotensive controls. Age, gender, body mass index, and serum levels of high-sensitive C-reactive protein (CRP), HDL and LDL cholesterols, small dense LDL, triglycerides, lipoprotein(a), insulin, and fasting plasma glucose level were not significantly different between the two groups. In all subjects, plasma U-II level showed significant positive correlations with systolic BP, maximum IMT, plaque score, and HOMA-IR. Multiple logistic regression analysis indicated that the contribution of plasma U-II levels to carotid plaque formation (plaque score >/=1.1) was significantly still greater with a 60% increase than those of established risk factors, such as age, systolic BP, high-sensitive CRP, small dense LDL, and HOMA-IR. CONCLUSIONS: Our results suggest that increased levels of U-II may play a crucial role in the development of carotid atherosclerosis in hypertensive patients.

Clinical effect of combination therapy of pioglitazone and an alpha-glucosidase inhibitor.

This study evaluated the efficacy of adding pioglitazone 30 mg to the therapy of patients with type 2 diabetes mellitus whose glycaemic control was poor on an alpha-glucosidase inhibitor (alpha-GI) alone or in combination with a sulphonylurea (SU). The patients (n = 20) had a HbA(1c) level between 7.0 and 12.0% and the fasting plasma glucose was 7.8 mmol/l or higher. They were treated with 30 mg pioglitazone once daily for 16 weeks. The decrease in HbA(1c) at week 16 of treatment was 0.8% (7.8% at baseline dropping to 7.1% at week 16; p < or = 0.01). An increase in leptin was observed 4 weeks after starting the post-study period (p < or = 0.05). Tumour necrosis factor-alpha (TNF-alpha) and body fat percentage did not show any significant alterations. Correlations between the decrease in HbA1c at week 16 and characteristic variables of patients were examined. A correlation with leptin (p = -0.5632, p < or = 0.05) levels was found. Five patients experienced adverse drug reactions, such as oedema, hypoglycaemia and increased creatine phosphokinase (CK), all of which were mild in severity. The addition of pioglitazone in diabetics whose glycaemic control was poor on a alpha-GI alone or with a alpha-GI and SU combination resulted in a significant decrease in HbA1c, and the treatment was well-tolerated. Our findings also suggest that leptin levels could be useful for assessing responders to pioglitazone.

Very low-density lipoprotein-apoprotein CI is increased in diabetic nephropathy: comparison with apoprotein CIII.

BACKGROUND: Recent studies have suggested that apoprotein (apo) CI in very low-density lipoprotein (VLDL) plays an important role in causing hypertriglyceridemia independent of apo CIII, which is associated with coronary heart disease (CHD). Because the incidence of CHD is increased in diabetic patients and is even higher when diabetic nephropathy is developed, we measured apo CI levels in VLDL from type 2 diabetic patients, with various degree of nephropathy, and compared the results with those for healthy controls or nondiabetic patients with chronic renal failure (CRF). METHODS: This study enrolled healthy control subjects, type 2 diabetic patients with normoalbuminuria, microalbuminuria, overt proteinuria, and CRF on hemodialysis and nondiabetic hemodialysis patients. VLDL (density <1.006) was separated by ultracentrifugation. Then the apo CI, CIII, and B concentrations in VLDL were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The apo CI, CIII, and B concentrations in VLDL were respectively 3-, 2-, and 2-fold higher, respectively, in diabetic patients with overt proteinuria than in controls. Hemodialysis patients with diabetic nephropathy had levels of apo CI, CIII, and B in VLDL that were 2.6-, 2.7- and 2-fold higher, respectively, than those in controls. Nondiabetic hemodialysis patients also had a 2.7-fold higher level of VLDL apo CIII, whereas VLDL apo CI and VLDL apo B were not significantly increased. VLDL apo CI was significantly correlated with VLDL apo B independently of VLDL apo CIII level. CONCLUSION: An increase of VLDL apo CIII is a prominent feature of dyslipidemia in CRF patients, regardless of whether they are diabetic or nondiabetic, whereas an increase of VLDL apo CI is more specific to diabetic nephropathy and is closely associated with an increase of VLDL particle numbers, a new risk factor for CHD.