Telmisartan improves vascular function independently of metabolic and antihypertensive effects in hypertensive subjects with impaired glucose tolerance.

BACKGROUND: Hypertensive patients with IGT have increased risk for cardiovascular disease and progression to diabetes mellitus. Clinical trials suggest that the ARB telmisartan uniquely possesses PPARγ agonistic properties and improves insulin resistance as well as vascular endothelial dysfunction. The aim of the present study was to compare vascular effects of telmisartan and losartan in relation to their metabolic and antihypertensive effects in hypertensive patients with IGT. MATERIALS AND METHODS: 24 patients were randomised in a double-blind, prospective, cross-over trial. At baseline and after 12 weeks of either treatment an oGTT, and endothelial function testing was performed. RESULTS: Endothelial function improved significantly by telmisartan treatment but not by losartan treatment (FMD; T: 7.9 ± 0.7%, vs B: 6.4 ± 0.8, p<0.01; vs L: 6.4 ± 0.6, p<0.001) at almost identical antihypertensive effect of both agents. Insulin resistance assessed by HOMA (T: 2.20 ± 0.47 vs B: 3.04 ± 0.60, p<0.01; vs L: 3.38 ± 0.84, T vs L p<0.05) and ISI120 (T: 0.114 ± 0.003 vs B: 0.092 ± 0.002, p<0.001; vs L: 0.090 ± 0.006, T vs L p<0.01) improved significantly after telmisartan only, as did glucose tolerance (p<0.01). The improvement of the endothelial function observed, significantly depended on pretreatment insulin resistance but was independent of improvements of insulin resistance, blood pressure or glucose tolerance. CONCLUSION: In hypertensive patients with IGT telmisartan compared to losartan improved endothelial function and insulin resistance independently, supporting the hypothesis that glucometabolic and vascular insulin resistance are differentially regulated.

Efficacy of a continuous GLP-1 infusion compared with a structured insulin infusion protocol to reach normoglycemia in nonfasted type 2 diabetic patients: a clinical pilot trial.

OBJECTIVE: Continuously administered insulin is limited by the need for frequent blood glucose measurements, dose adjustments, and risk of hypoglycemia. Regimens based on glucagon-like peptide 1 (GLP-1) could represent a less complicated treatment alternative. This alternative might be advantageous in hyperglycemic patients hospitalized for acute critical illnesses, who benefit from near normoglycemic control. RESEARCH DESIGN AND METHODS: In a prospective open randomized crossover trial, we investigated eight clinically stable type 2 diabetic patients during intravenous insulin or GLP-1 regimens to normalize blood glucose after a standardized breakfast. RESULTS: The time to reach a plasma glucose below 115 mg/dl was significantly shorter during GLP-1 administration (252 +/- 51 vs. 321 +/- 43 min, P < 0.01). Maximum glycemia (312 +/- 51 vs. 254 +/- 48 mg/dl, P < 0.01) and glycemia after 2 h (271 +/- 51 vs. 168 +/- 48 mg/dl, P = 0.012) and after 4 h (155 +/- 51 vs. 116 +/- 27 mg/dl, P = 0.02) were significantly lower during GLP-1 administration. CONCLUSIONS: GLP-1 infusion is superior to an established insulin infusion regimen with regard to effectiveness and practicability.

Endothelial dysfunction induced by hyperhomocyst(e)inemia: role of asymmetric dimethylarginine.

BACKGROUND: Endothelial function is impaired by hyperhomocyst(e)inemia. We have previously shown that homocyst(e)ine (Hcy) inhibits NO production by cultured endothelial cells by causing the accumulation of asymmetric dimethylarginine (ADMA). The present study was designed to determine if the same mechanism is operative in humans. METHODS AND RESULTS: We studied 9 patients with documented peripheral arterial disease (6 men; 3 women; age, 64+/-3 years), 9 age-matched individuals at risk for atherosclerosis (older adults; 9 men; age, 65+/-1 years), and 5 young control subjects (younger adults; 5 men; age, 31+/-1 years) without evidence of or risk factors for atherosclerosis. Endothelial function was measured by flow-mediated vasodilatation of the brachial artery before and 4 hours after a methionine-loading test (100 mg/kg body weight, administered orally). In addition, blood was drawn at both time points for measurements of Hcy and ADMA concentrations. Plasma Hcy increased after the methionine-loading test in each group (all, P<0.001). Plasma ADMA levels rose in all subjects, from 0.9+/-0.2 to 1.6+/-0.2 micromol/L in younger adults, from 1.5+/-0.2 to 3.0+/-0.4 micromol/L in older adults, and from 1.8+/-0.1 to 3.9+/-0.3 micromol/L in peripheral arterial disease patients (all, P<0.001). Flow-mediated vasodilatation was reduced from 13+/-2% to 10+/-1% in younger adults, from 6+/-1% to 5+/-1% in older adults, and from 7+/-1% to 3+/-1% in peripheral arterial disease patients (all, P<0.001). Furthermore, we found positive correlations between plasma Hcy and ADMA concentrations (P=0.03, r=0.450), as well as ADMA and flow-mediated vasodilatation (P=0.002, r=0.623). CONCLUSIONS: Our results suggest that experimental hyperhomocyst(e)inemia leads to accumulation of the endogenous NO synthase inhibitor ADMA, accompanied by varying degrees of endothelial dysfunction according to the preexisting state of cardiovascular health.