lisinopril and Insulin-Resistance

The role of the RAAS in development and maintenance of blood pressure is well established. In addition, the deleterious effects of angiotensin II on the heart, vasculature, and kidneys have been clearly defined. There seems to be a close relationship between endothelial dysfunction, insulin resistance (a precursor to diabetes and coronary artery disease) and angiotensin II. The signaling pathways for insulin in the vascular wall interacts with the angiotensin signaling, giving rise to potential mechanisms for development of diabetes and resulting harmful effects. A large number of clinical trials using ACE inhibitors or ARBs have shown significant reduction in secondary endpoints in the development of new onset of diabetes. Ongoing prospective studies involving ARBs (eg, the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research trial) and ACE inhibitors (eg, the Diabetes Re-duction Assessment with Ramipril and Rosiglita-zone Medication trial) are testing the ability of certain agents to prevent type 2 diabetes. In the meantime, it is important to recognize insulin resistance and metabolic syndrome as entities that increase the risk for cardiovascular disease. In addition to lifestyle modifications, managing endothelial dysfunction and protecting the vasculature will help prevent diabetes and cardiovascular disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Endothelium, Vascular; Humans; Insulin Resistance; Life Style; Lisinopril; Metabolic Syndrome; Renin-Angiotensin System; Risk Factors

Metabolic syndrome is common in patients with hypertension and increases the risk of developing diabetes mellitus. The objective of this study (the MARCADOR study) was to compare the effects of manidipine 20  mg with the extemporary combination of manidipine 10  mg/lisinopril 10  mg, amlodipine 10  mg and telmisartan 80  mg on insulin sensitivity, as well as metabolic, inflammatory and prothrombotic markers, in hypertensive non-diabetic patients with metabolic syndrome.. This study had a prospective, randomized, open-label, blinded endpoint (PROBE) design. A total of 120 patients aged 35-75 years with stage I-II essential hypertension (systolic blood pressure [BP] 140-179  mmHg, diastolic BP 90-109  mmHg) and metabolic syndrome were recruited from general practitioner clinics in Northern Gran Canaria Island, Spain and randomized to receive amlodipine 10  mg (n = 30), telmisartan 80  mg (n = 30), manidipine 20  mg (n = 30) or (low-dose) manidipine 10  mg/lisinopril 10  mg (n = 30), all administered once daily. At baseline and after 14 weeks of treatment, BP, insulin sensitivity, lipid profile, and albumin and metanephrin excretion as well as several other metabolic, inflammatory, prothrombotic and growth/adhesion markers were measured. The primary endpoint was the change in insulin sensitivity.. A total of 115 patients completed the study. All treatments significantly lowered BP from baseline. Compared with amlodipine, manidipine had significantly superior effects (p < 0.05) on insulin resistance (-26.5% vs -3.0%), albumin/creatinine ratio (-28.2% vs -3.6%), low-density lipoprotein (LDL) cholesterol (-6.8% vs +1.7%), and several other metabolic, inflammatory and prothrombotic markers. Manidipine was associated with a slightly greater increase in insulin sensitivity than manidipine/lisinopril, but manidipine/lisinopril was significantly more effective than manidipine and telmisartan for improving a number of metabolic, inflammatory, prothrombotic and growth/adhesion markers. Amlodipine was associated with a significantly greater incidence of adverse effects compared with telmisartan, manidipine and manidipine/lisinopril (26.7% vs 3.3%, 3.3% and 13.3%, respectively).. In patients with hypertension and metabolic syndrome, manidipine, both alone and in combination with the ACE inhibitor lisinopril, is significantly superior to amlodipine for improving insulin sensitivity as well as several metabolic, inflammatory and prothrombotic markers. Furthermore, the combination of manidipine and lisinopril appears to have greater efficacy than manidipine alone and telmisartan with respect to the improvement of metabolic, inflammatory and prothrombotic markers.

Topics: Adult; Aged; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Biomarkers; Blood Pressure; Dihydropyridines; Drug Combinations; Female; Humans; Hypertension; Insulin Resistance; Lisinopril; Male; Metabolic Syndrome; Middle Aged; Nitrobenzenes; Piperazines; Prospective Studies; Spain; Telmisartan

Angiotensin II and insulin resistance (IR) have clinical implications in the pathophysiology of chronic heart failure (CHF). However, it is still unclear whether the combination of an angiotensin-receptor blocker and angiotensin-converting enzyme inhibitor (ACEI) improves IR in CHF patients who do not receive β-blockers. Thus, the aim of the present study was to evaluate the effects of losartan on glucose metabolism and inflammatory cytokines in CHF patients treated with ACEI but not β-blockers.. The effect of losartan treatment for 16 weeks on IR was analyzed in 16 CHF patients in a randomized crossover trial. Insulin level and homeostasis model IR index (HOMA-IR) decreased significantly (P<0.05), but fasting plasma glucose did not change significantly. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels were significantly decreased with losartan (P<0.05). Furthermore, the changes in IL-6 and MCP-1 levels were significantly correlated with the reduction in HOMA-IR (P<0.05), but the change in TNF-α levels was not significantly correlated.. The addition of losartan to ACEI therapy improved IR and decreased inflammatory cytokines in CHF patients who did not receive β-blockers.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Blood Glucose; Chemokine CCL2; Chronic Disease; Cross-Over Studies; Drug Therapy, Combination; Enalapril; Female; Heart Failure; Humans; Imidazolidines; Inflammation Mediators; Insulin; Insulin Resistance; Interleukin-6; Japan; Lisinopril; Losartan; Male; Middle Aged; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

The aim of this study was to compare the effects of the ACE-inhibitor lisinopril and the angiotensin II receptor antagonist losartan on insulin sensitivity in the treatment of non diabetic hypertensives.. Twenty-five non diabetic subjects with mild to moderate hypertension, 11 females and 14 males, aged 44-63 years, after a 4-week wash-out period on placebo, were randomized to receive lisinopril 20 mg once daily or losartan 50 mg once daily for 6 weeks. Following another 4-week wash-out period, patients were crossed to the alternative regimen for further 6 weeks. At the end of the placebo and of the active treatment periods, blood pressure (BP) was measured (by standard mercury sphygmomanometer, Korotkoff I and V) and insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp technique. Glucose infusion rate (GIR) during the last 30 min of clamp and total glucose requirement (TGR) were evaluated.. Both lisinopril and losartan significantly reduced SBP (by a mean of 20.2 and 17.2 mmHg, respectively) and DBP (by a mean of 15.2 and 12.3 mmHg, respectively), with no difference between the two treatments. GIR, used as an indicator of insulin sensitivity, was significantly increased by lisinopril (+1.5 mg min(-1) kg(-1), P<0.05 vs baseline) but not by losartan (+0.42 mg min(-1) kig(-1), NS), the difference between the two drugs being statistically significant (P<0.05). TGR was increased by lisinopril (+7.3 g, P<0.05 vs baseline), whereas losartan did not significantly modify it (+1.9 g, NS).. In conclusion, with all cautions due to an absence in this study of a randomized placebo phase, our findings suggest that lisinopril improved insulin sensitivity whereas losartan did not affect it.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Glucose; Blood Pressure; Body Weight; Cross-Over Studies; Double-Blind Method; Female; Humans; Hypertension; Insulin; Insulin Resistance; Lipid Metabolism; Lisinopril; Losartan; Male; Middle Aged

Patients with high blood pressure tend to be insulin resistant, glucose intolerant, hyperinsulinemic, and dyslipidemic. Since these metabolic defects are accentuated by obesity, we thought it important to compare the effects of 3 months' treatment with either lisinopril (20 mg/day) or low dose hydrochlorothiazide (12.5 mg/day) on blood pressure and glucose, insulin, and lipoprotein metabolism in obese patients with hypertension. There were 14 patients in each group, and they were similar (mean +/- SE) in age (54 +/- 3 v 50 +/- 4 years), gender (nine men/five women), and body mass index (33.4 +/- 0.8 v 33.9 +/- 0.9 kg/m2). Patients treated with lisinopril had a somewhat greater fall in both systolic (18 +/- 3 v 10 +/- 3 mm Hg) and diastolic (12 +/- 2 v 8 +/- 1 mm Hg) blood pressure, but only the change in systolic pressure was statistically significant (P < .05). Plasma glucose, insulin, and triglyceride concentrations were measured at hourly intervals from 8 AM to 4 PM (breakfast at 8 AM and lunch at 12 PM), and there was a modest increase in all three variables following hydrochlorothiazide treatment (P < .05 to P < .09). However, daylong plasma glucose, insulin, and triglyceride concentration did not change with lisinopril treatment. Finally, neither the ability of insulin to mediate glucose disposal nor fasting lipid and lipoprotein concentrations, changed with either treatment. In conclusion blood pressure decreased significantly following treatment with either lisinopril (20 mg/day) or hydrochlorothiazide (12.5 mg/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Blood Glucose; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hydrochlorothiazide; Hypertension; Insulin; Insulin Resistance; Lipid Metabolism; Lisinopril; Male; Middle Aged; Obesity; Risk Factors

To investigate the effects of antihypertensive treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril on insulin sensitivity and related metabolic variables, the insulin sensitivity index (SI), determined with the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure were assessed in 24 lean, non-diabetic patients with essential hypertension. Following a double-blind, randomised crossover design, these parameters were measured after a 4-week run-in period, after 8 weeks of lisinopril or placebo, and after an additional 8 weeks on placebo or lisinopril, respectively. Furthermore, the level of physical fitness was estimated using the Conconi bicycle ergometer test. SI was low in this study population (5.6 vs 13.3 x 10(-4).min-1.mU-1.l-1 in normal lean control subjects). It did not differ between the placebo run-in phase, the lisinopril phase, and the placebo crossover phase (5.8, 5.5, and 5.4 x 10(-4).min-1.mU-1.l-1, respectively). Moreover, during the administration of lisinopril, no significant changes occurred in fasting plasma insulin and glucose, areas under the glucose and insulin curves, glucose disappearance rate, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions. Heart rate at rest, body weight, and anaerobic threshold remained stable throughout the study. Compliance assessed by pill-counting exceeded 90% at all visits. These findings demonstrate that the ACE inhibitor lisinopril is neutral with regard to insulin sensitivity, plasma insulin and glucose, and lipoprotein metabolism in patients with essential hypertension.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Cholesterol; Cross-Over Studies; Double-Blind Method; Female; Humans; Hypertension; Insulin; Insulin Resistance; Lipoproteins; Lisinopril; Male; Middle Aged

Women with polycystic ovary syndrome (PCOS), the most common endocrinopathy in reproductive age, are characterized by increased cardiometabolic risk. Similar hormonal and metabolic changes were found in their siblings. The purpose of our study was to compare blood pressure-lowering and pleiotropic effects of lisinopril between sisters of women with PCOS and their unrelated peers. The study included two age-, body mass index-, and blood pressure-matched groups of women with grade 1 hypertension: 26 sisters of PCOS probands (Group 1) and 26 individuals without a family history of PCOS (Group 2), receiving 10-40 mg of lisinopril daily. Blood pressure, glucose homeostasis markers, plasma levels of lipids (androgens, estradiol, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen, and uric acid), and urinary albumin-to-creatinine ratio (UACR) were measured before lisinopril treatment and 6 months later. At baseline, the study groups differed in insulin sensitivity, testosterone, free androgen index (FAI), hsCRP, homocysteine, and UACR. Blood pressure-lowering properties of lisinopril did not differ between the groups. The decrease in homocysteine and UACR, although observed in both groups, was stronger in Group 2 than in Group 1. Only in women without a family history of PCOS lisinopril improved insulin sensitivity and reduce hsCRP, fibrinogen, and uric acid. The remaining markers did not change throughout the study. Cardiometabolic effects of lisinopril correlated with testosterone, free androgen index, and changes in insulin sensitivity. The obtained results suggest that cardiometabolic effects of lisinopril may be slightly less pronounced in sisters of women with PCOS than in women without a family history of this disorder.

Topics: Androgens; Body Mass Index; C-Reactive Protein; Cardiometabolic Risk Factors; Cardiovascular Diseases; Female; Fibrinogen; Humans; Insulin; Insulin Resistance; Lisinopril; Polycystic Ovary Syndrome; Risk Factors; Siblings; Testosterone; Uric Acid

The insulin-like growth factor I possesses biologic actions that resemble those of insulin. Tissue access of the factor depends on the distribution of the circulating bound factor between its binding protein 3 that remains within the intravascular space and its binding protein I that is able to cross the endothelium. Preliminary results have shown that tissue availability of insulin-like growth factor I is a determinant of glucose regulation in essential hypertension. To investigate whether the tissue availability of circulating insulin-like growth factor I in patients with essential hypertension is related to insulin resistance and whether chronic angiotensin converting enzyme inhibition influences tissue availability of the factor and insulin resistance in these patients.. We studied 29 patients with essential hypertension and 20 age-matched and sex-matched normotensive subjects. The measurements were repeated for 25 patients after 12 months of treatment with lisinopril. Tissue availability of circulating insulin-like growth factor I was assessed by analyzing its distribution between its binding proteins 3 and 1. An insulin resistance index was estimated using the homeostasis model analysis of fasting insulin-glucose interactions. Levels of serum insulin-like growth factor I binding proteins 3 and 1, plasma insulin-like growth factor I, and insulin were determined by specific radioimmunoassays.. Baseline insulin resistance index was significantly higher in the hypertensive patients than it was in the normotensive controls. With the upper 100% confidence limit of the normotensive population as the cutoff point, a subgroup of 12 hypertensives had an abnormally high insulin resistance index. Compared with patients with normal insulin resistance indexes, patients with greater than normal indexes were characterized by lower binding protein 1 levels, similar binding protein 3 levels, lower binding protein 1 : binding protein 3 ratio and similar insulin-like growth factor I levels. The serum binding protein 1 level and the binding protein 1 : binding protein 3 ratio were inversely correlated to the insulin resistance index for the whole group of hypertensives. After treatment with lisinopril hypertensive patients with higher than normal insulin resistance indexes at baseline exhibited normalization of this parameter and significant increases of binding protein 1 levels and binding protein 1 : binding protein 3 ratio, with no significant changes in insulin-like growth factor I levels. These parameters remained unchanged for the remaining patients.. These results suggest that tissue availability of circulating insulin-like growth factor I is a determinant of insulin sensitivity in patients with essential hypertension. Whereas the patients with normal insulin sensitivity exhibit greater than normal tissue access of circulating insulin-like growth factor I, patients with insulin resistance present normal tissue access of the factor. Our findings suggest that the ability of angiotensin converting enzyme inhibitors to restore insulin sensitivity in essential hypertensives may be related to their ability to facilitate the tissue availability of circulating insulin-like growth factor I.

Topics: Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Female; Follow-Up Studies; Glucagon; Growth Hormone; Humans; Hypertension; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Lisinopril; Male; Middle Aged; Radioimmunoassay

Topics: Acanthosis Nigricans; Androgens; Child; Cholesterol; Diabetes Mellitus, Type 2; Female; Humans; Hyperandrogenism; Hyperlipidemias; Insulin Resistance; Lisinopril; Male; Menarche; Middle Aged; Obesity; Pedigree; Pelvis; Steroids; Triglycerides; Ultrasonography

The purpose of this study was to determine whether antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril would alter cell Na+ transport kinetics, metabolic parameters associated with insulin resistance, or both in young adults with mild hypertension. Sixteen young adults (mean age 29 +/- 4 years) were treated with placebo for 8 weeks, then with lisinopril for 12 weeks. Metabolic risk factors examined included plasma lipid levels, plasma insulin concentration during an oral glucose tolerance test, and insulin sensitivity determined by an euglycemic hyperinsulinemic clamp procedure. Red blood cells were assayed for Na+/H+ exchange, Na+/Li+ exchange, Na(+)-K+ pump activity, and Na(+)-K(+)-Cl- cotransport before and during treatment. Blood pressure decreased from 142 +/- 4/98 +/- 2 mm Hg before treatment to 131 +/- 3/85 +/- 1 mm Hg during lisinopril treatment (P < .001). During lisinopril treatment, there was a significant reduction in total cholesterol (from 177 +/- 8 to 161 +/- 8 mg/dL, P < .008), in low density lipoprotein-cholesterol (from 107 +/- 7 to 91 +/- 7 mg/dL, P < .002), and in insulin at 60 min into the oral glucose tolerance test (from 132 +/- 18 to 99 +/- 15 microU/mL, P < .05). There was a marginally significant increase in insulin sensitivity during lisinopril treatment (P < .08). The assays of cell Na+ transport showed a significant reduction in maximal activity (Vmax) for Na+/H+ exchange (from 33.7 +/- 3.8 to 19.7 +/- 2.6 mmol/L cell/h, P < .003).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; Blood Pressure; Chlorides; Female; Humans; Hydrogen-Ion Concentration; Hypertension; Insulin Resistance; Intracellular Fluid; Ion Transport; Lipids; Lisinopril; Male; Sodium; Sodium-Hydrogen Exchangers; Sodium-Potassium-Exchanging ATPase