Aggressive antihypertensive strategies based on hydrochlorothiazide, candesartan or lisinopril decrease left ventricular mass and improve arterial compliance in patients with type II diabetes mellitus and hypertension.

We investigated the effects of aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril on left ventricular mass (LVM) index and arterial stiffness in hypertensive type II diabetic individuals. Seventy hypertensive type II diabetic individuals were treated with three antihypertensive strategies in a randomized, double-blind, double-dummy design. Blood pressure was titrated to levels below 130/85 mm Hg or a decrease in systolic pressure of 10% with a diastolic pressure below 85 mm Hg. After titration, patients were treated for 12 months. Mean blood pressures were 157/93, 151/94 and 149/93 mm Hg at baseline in the hydrochlorothiazide (n = 24), candesartan (n = 24) and lisinopril (n = 22) groups, and 135/80, 135/82 and 131/80 mm Hg after titration. About 70% reached target blood pressures, with the median use of three antihypertensive drugs. Left ventricular mass index and all estimates of arterial stiffness showed significant improvement after 12 months: that is, LVM index (-11 g/m(2); -8%); carotid distensibility coefficient (DC; +2.8 x 10(-3) kPa(-1); +27%), compliance coefficient (CC; +0.13 mm2/kPa; +21%) and elastic modulus (-0.19 kPa; -16%); femoral DC (+1.6 x 10(-3) kPa(-1); +50%) and CC (+0.08 mm2/kPa; +26%); brachial DC (+2.1 x 10(-3) kPa(-1); +39%) and CC (+0.03 mm2/kPa; +27%) and total systemic arterial compliance (+0.29 ml/mm Hg; +16%). No differences in outcome variables between treatment groups were observed. Aggressive antihypertensive treatment, although difficult to achieve, resulted in substantial reductions of LVM index and arterial stiffness in relatively uncomplicated hypertensive type II diabetic individuals. Strategies based on renin-angiotensin system inhibitors were not clearly superior to conventional (i.e. diuretic-based) strategies.

Liver alanine aminotransferase, insulin resistance and endothelial dysfunction in normotriglyceridaemic subjects with type 2 diabetes mellitus.

BACKGROUND: Plasma levels of liver transaminases, including alanine aminotransferase (ALT), are elevated in most cases of nonalcoholic fatty liver disease (NAFLD). Elevated ALT levels are associated with insulin resistance, and subjects with NAFLD have features of the metabolic syndrome that confer high-risk cardiovascular disease. Alanine aminotransferase predicts the development of type 2 diabetes (DM2) in subjects with the metabolic syndrome. However, the role of elevated ALT levels in subjects with overt DM2 has yet not been explored. MATERIALS AND METHODS: In a cross-sectional study, 64 normotriglyceridaemic subjects with DM2 were studied with regard to the relation between liver transaminases with whole-body insulin sensitivity, measured with the euglycaemic hyperinsulinaemic clamp and with brachial artery flow-mediated dilation (FMD) as a marker of endothelial dysfunction. RESULTS: On average, patients were normotriglyceridaemic (plasma triglycerides 1.3 +/- 0.4 mmol L-1) and had good glycaemic control (HbA1c 6.2 +/- 0.8%). The mean ALT level was 15.0 +/- 7.5 U L-1, and the mean aspartate aminotransferase concentration equalled 10.6 +/- 2.6 U L-1. Alanine aminotransferase levels were negatively associated with whole-body insulin sensitivity as well as with FMD (both P = 0.03, in multivariate analyses; regression coefficients beta [95%CI]: -0.76 [-1.4 to -0.08] and -0.31 [-0.58 to -0.03] respectively). CONCLUSIONS: In metabolically well-controlled patients with DM2, ALT levels are related to decreased insulin-sensitivity and an impaired conduit vessel vascular function.

Aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril as initial choice in hypertensive type II diabetic individuals: effects on albumin excretion, endothelial function and inflammation in a double-blind, randomized clinical trial.

We investigated the effects of aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril on urinary albumin excretion, endothelial function and inflammatory activity in hypertensive type II diabetic individuals. A total of 70 hypertensive type II diabetic individuals were treated with three antihypertensive strategies in a randomized, double-blind, double-dummy design. Blood pressure was titrated to levels below 130/85 mmHg or a decrease in systolic pressure of 10% with a diastolic pressure below 85 mmHg. After titration, patients were treated for 12 months. Mean blood pressures changed from 157/93, 151/94 and 149/93 at baseline to 135/80, 135/82 and 131/80 mmHg after titration in the hydrochlorothiazide (n=24), candesartan (n=24) and lisinopril (n=22) groups. About 70% reached target blood pressures. However, only 45% had blood pressures <130/85 mmHg. Urinary albumin excretion and levels of soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 decreased (GEE regression coefficients, -2.40 mg/24 h (P<0.001), -85 ng/ml (P=0.01) and -50 ng/ml (P=0.02)), but brachial artery endothelium-dependent and -independent vasodilation and levels of von Willebrand factor and C-reactive protein did not change (GEE regression coefficients, 0.21 mm (P=0.07), 0.04 mm (P=0.43), 0.04 IU/ml (P=0.33) and -1.15 mg/l (P=0.64)). No differences in outcome variables between treatment groups were observed. These data show that achievement of target blood pressures below 130/85 mmHg in hypertensive type II diabetes is difficult. Aggressive antihypertensive therapy can improve urinary albumin excretion, endothelial function and inflammatory activity in hypertensive type II diabetic individuals, regardless of the type of antihypertensive therapy used.

Associations of metabolic variables with arterial stiffness in type 2 diabetes mellitus: focus on insulin sensitivity and postprandial triglyceridaemia.

BACKGROUND: Type 2 diabetes mellitus is associated with an increased risk of atherothrombotic disease, which may in part be mediated through increased arterial stiffness. We investigated to what extent increased arterial stiffness is associated with cardiovascular risk factors that commonly cluster in type 2 diabetes. DESIGN: In this cross-sectional, observational study we assessed, in 81 subjects with type 2 diabetes, local distensibility and compliance of the common carotid and femoral arteries, and carotido-femoral transit time. We subsequently investigated whether these measures of arterial stiffness were determined by diabetes duration, blood pressure, lipid levels (including fasting and postprandial triglyceridaemia), hyperglycaemia, BMI, waist-to-hip ratio, insulin resistance (as measured by a euglycaemic, hyperinsulinaemic clamp), hyperinsulinaemia, cigarette smoking, or the use of alcohol. RESULTS: In multivariate analysis, insulin-mediated glucose uptake was positively [standardized beta, 0.21 (P = 0.05)] associated with the carotid artery compliance coefficient, and the use of alcohol was negatively associated with the femoral artery compliance coefficient [standardized beta, -0.25 (P = 0.03)]. Except for mean arterial pressure, which was negatively associated with all outcome variables, the other cardiovascular risk factors that we investigated were not significantly associated with the distensibility coefficients of both the carotid and femoral artery, or with the carotido-femoral transit time. CONCLUSIONS: In subjects with type 2 diabetes mellitus, insulin resistance and the use of alcohol were associated with increased arterial stiffness, which supports the hypothesis that increased arterial stiffness can act as a mediating factor in the association between type 2 diabetes mellitus and increased risk of atherothrombotic disease. We found no evidence for an association between fasting or postprandial triglyceridaemia and arterial stiffness.