Insulin Sensitivity In Hypertensive Patients Research Articles

Prevalence of insulin resistance among hypertensive patients undergoing antihypertensive therapy

Background: Hypertensive patients undergoing antihypertensive therapy are more prone to insulin resistance (IR). Thus, it is essential to monitor its prevalence, metabolic consequences and to individualize antihypertensive therapy to negate its potential adverse effects. Therefore, the presented study assessed the prevalence of IR among hypertensive patients undergoing antihypertensive therapy. Methodology: This prospective study involved 200 patients of either sex, diagnosed with essential hypertension, and undergoing treatment. Data regarding age, gender, medical history, body mass index (BMI), and waist circumference were collected. Laboratory investigations for fasting blood sugar levels, serum fasting Insulin levels, lipid profile, and glycosylated hemoglobin were performed. Homeostatic model assessment of IR (HOMA IR) was calculated. Statistical analysis was performed by using R software (Version. 3.6.0). Results: The prevalence of IR in hypertensive nondiabetic patients was 39%. The mean age and BMI of patients were 58.70 ± 16.64 year and 23.10 ± 2.57 kg/m2, respectively. The mean fasting blood sugar levels were 108.24 ± 20.99 mg/ dl. The mean HOMA IR levels were >2.8. IR was more in users of beta?blockers than in angiotensin?converting enzyme (ACE) inhibitors and calcium channel blockers, as a significant association was observed between the class of hypertensive drugs and presence of IR (P < 0.05). A significant association (P < 0.05) was observed between the duration of hypertension and IR indicated by HOMA IR >2.5 in patients on beta?blockers and on ACE inhibitors. Conclusion: Antihypertensive drugs like beta?blockers decrease insulin sensitivity in hypertensive patients leading to increased prevalence of IR.

Effects of azilsartan compared with telmisartan on insulin resistance in patients with essential hypertension and type 2 diabetes mellitus: An open-label, randomized clinical trial.

BackgroundBased on non-clinical data, it is expected that azilsartan, an angiotensin II receptor blocker, will help improve insulin resistance in addition to its hypotensive action. The present study is aimed to explore the effect of azilsartan compared to telmisartan on insulin sensitivity in hypertensive patients in the clinical setting.MethodsThis multicenter, randomized, open-label, parallel-group exploratory study was conducted in Japan. We randomized adult patients (≥20 years old) with grade I or II essential hypertension and coexisting type 2 diabetes (1:1) to receive either oral azilsartan (20 mg/day;17 patients) or telmisartan (40 mg/day;16 patients) for 12 weeks. The primary endpoint was the change in the homeostasis model assessment ratio of insulin resistance (HOMA-R) from the baseline at the end of the treatment period. We also evaluated its safety and efficacy on other diabetes-related variables and blood pressure.FindingsThe mean changes in HOMA-R at the end of treatment were 0.22 (95% CI, −1.09–1.52) in the azilsartan group and −0.23 (95% CI, −0.72–0.27) in the telmisartan group. We found no clinically remarkable changes between the groups in diabetes-related variables such as fasting blood glucose, fasting insulin, HbA1c (NGSP), HOMA-β, or 1,5-anhydroglucitol. Reductions in clinic systolic and diastolic blood pressure were observed at week 4 and the reduced levels were maintained throughout the treatment period in both groups. No serious treatment-emergent adverse events (TEAEs) were observed. Only one drug-related TEAE (mild decrease in blood pressure) was reported in one patient in the azilsartan group.ConclusionNeither azilsartan nor telmisartan had any clinically remarkable effects on insulin resistance parameters when administered for 12 weeks to patients with grade I or II essential hypertension and coexisting type 2 diabetes mellitus. Azilsartan (20 mg/day) and telmisartan (40 mg/day) exerted comparable antihypertensive effects.Trial registrationClinicalTrials.gov NCT02079805

A meta-analysis of the effects of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers on insulin sensitivity in hypertensive patients without diabetes

AimsThis study sought to compare the effects of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on insulin sensitivity (IS) in hypertensive patients without diabetes. MethodsStudies on the observation of IS in hypertensive patients without diabetes who received ACEI and ARB prior to December 2013 was collected using computer-based retrieval of the PUBMED, EMBASE, and COCHRANE databases. The primary indicators included IS, fasting plasma glucose (FPG), and fasting plasma insulin (FPI). The secondary indicators included systolic blood pressure (SBP) and diastolic blood pressure (DBP). A meta-analysis was performed using the STATA and Review Manager 5.2 software. The effects of these two drugs on IS in hypertensive patients without diabetes were analyzed using the fixed effect model and the random effect model. ResultsA total of 203 cases of patients involved in 4 clinical studies were included. As compared to ARB, ACEI treatment resulted in more effective improvement of IS in hypertensive patients without diabetes (SMD: 0.45, 95% CI 0.17–0.73), although these two drugs did not show significant differences with regards to FPG (WMD: 0.00, 95% CI −0.19–0.20), FPI (WMD: −0.34, 95% CI −1.31–0.63), SBP (WMD: 2.85, 95% CI −1.55–7.24), and DBP (WMD: 0.81, 95% CI −1.12–2.75). ConclusionIn patients showing no significant difference in blood pressure control, the comparison between ACEI and ARB showed that the former type of drug more effectively relieved IS in hypertensive patients without diabetes.

A Comparative Study of Olmesartan and Valsartan on Insulin Sensitivity in Hypertensive Patients with Diabetes Mellitus or Impaired Glucose Tolerance (OVIS Study)

Activation of renin angiotensin system is implicated in insulin resistance. In mega trials, it has been suggested that angiotensin receptor blockers may be beneficial on insulin sensitivity in hypertensive patients. We conducted a multicenter, open-label, parallel-group trial to compare the effects of olmesartan and valsartan on insulin sensitivity and adiponectin levels in 206 hypertensive patients with diabetes mellitus or impaired glucose tolerance. Patients were randomly assigned to either olmesartan 20 mg/day or valsartan 80 mg/day treatment for 24 weeks. Blood pressure, fasting glucose, fasting insulin, glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), and serum adiponectin levels were measured. The efficacy was evaluated in 197 patients (olmesartan, n=98; valsartan, n=99). At baseline, all parameters except for systolic blood pressure (SBP) and serum triglyceride did not differ between the 2 groups. HbA1c decreased slightly after a 24-week treatment with valsartan, but not olmesartan, while the decrease did not significantly differ in the two groups. There was no difference in the change from the baseline between olmesartan and valsartan groups concerning fasting glucose, fasting insulin, HOMA-IR, and adiponectin levels after 24-week treatment. The decrease in SBP tended to be greater in the olmesartan group than in the valsartan group even with adjustment for the baseline difference. In conclusion, there was no significant difference in insulin sensitivity or adiponectin levels between the olmesartan and valsartan groups. In the standard dose, olmesartan significantly decreased SBP as compared with valsartan.

Systematic review of the effect of telmisartan on insulin sensitivity in hypertensive patients with insulin resistance or diabetes

Telmisartan is an angiotensin receptor blocker (ARB) originally developed for the treatment of hypertension. It can also partially activate peroxisome proliferator-activated receptor (PPAR)-γ, which may improve insulin sensitivity. This effect may prove useful in hypertensive patients with insulin resistance or diabetes mellitus. Such activity is more marked than that observed with other ARBs. This systematic review and meta-analysis evaluated the benefit of telmisartan on insulin sensitivity compared with that of other ARBs in hypertensive patients who had either insulin resistance or diabetic states. Clinical trials of telmisartan were identified through electronic searches (MEDLINE, CINAHL, Scopus, and The Cochrane Library) up to and including May 2011. Studies were included if they met the following inclusion criteria: (i) randomized controlled trials that compared telmisartan with other ARBs in hypertensive patients who had insulin resistance or type 2 diabetes mellitus; (ii) using telmisartan as an add-on therapy or a monotherapy for treating hypertension; and (iii) reporting fasting plasma glucose (FPG) and fasting plasma insulin (FPI), or homeostasis model assessment of insulin resistance (HOMA-IR), or adiponectin as an outcome measure. Treatment effect was estimated with the mean difference in the final value of FPG, FPI, HOMA-IR and adiponectin between the telmisartan and the control groups. Eight trials involving a total of 763 patients met the inclusion criteria. Telmisartan was superior to other ARBs in reducing FPG level (mean difference, -8·63 mg/dL; 95% CI -12·29 mg/dL to -4·98 mg/dL; P < 0·00001) and increasing adiponectin level (mean difference, 0·93 μg/dL; 95% CI 0·28 μg/dL to 1·59 μg/dL; P = 0·005). At 80 mg dose, telmisartan may reduce FPI level and HOMA-IR. The available evidence suggests a beneficial effect of telmisartan in improving insulin sensitivity in hypertensive patients with insulin resistance or diabetes as demonstrated by the decrease in FPG and increase in adiponectin levels. The effect in decreasing FPG was greater with 80 mg dose than with the 40 mg dose. FPI and insulin resistance may be improved with 80 mg of telmisartan.

Telmisartan effectively improves insulin sensitivity in hypertensive patients with insulin resistance

The angiotensin II receptor blocker (ARB) telmisartan has been shown to activate peroxisome proliferator-activated receptor γ and increase adiponectin protein content in adipocytes. We tested the hypothesis that telmisartan can increase the serum level of adiponectin and improve insulin resistance. The study participants were 25 consecutive hypertensive patients (8 females, 17 males; 65 ± 10 years). Insulin resistance was defined as a patient showing ≥2.5 in the homeostasis model assessment (HOMA) index. We divided subjects into non-insulin resistance (n = 10) and insulin resistance groups (n = 15) based on the HOMA index. Telmisartan was administered (40 mg/day) was administered for 24 weeks. In the insulin resistance group, telmisartan treatment resulted in a significant decrease in the HOMA index and serum level of C-reactive protein, and it increased the serum level of adiponectin (P < 0.05, respectively). Such improvements were not observed in the non-insulin resistance group. Stepwise multiple regression analysis showed that the increase in the serum level of adiponectin was independently associated with reduction in the HOMA index. Our findings suggest that telmisartan improves insulin resistance that parallels an increase in the serum level of adiponectin in hypertensive patients with insulin resistance. It may therefore have advantages in treating such populations.

Different Effects of Aliskiren and Losartan on Fibrinolysis and Insulin Sensitivity in Hypertensive Patients with Metabolic Syndrome

The aim of this study was to compare the effect of aliskiren and losartan on fibrinolysis and insulin sensitivity (IS) in hypertensive patients with metabolic syndrome. After 2-week placebo period, 76 outpatients with mild to moderate hypertension and metabolic syndrome were randomized to aliskiren 300 mg od or losartan 100 mg od for 12 weeks. Clinic blood pressure (BP), plasma PAI-1 antigen, and tPA activity were evaluated after 2, 4, 8, and 12 weeks of treatment. At the end of each treatment period patients performed an euglycemic hyperinsulinemic clamp and IS was assessed by glucose infusion rate (GIR). Both aliskiren and losartan induced a significant and similar SBP/DBP reduction (-15.6/10.7 mmHg and -15.5/10.5 mmHg, p<0.001 vs. baseline, respectively). Both drugs decreased PAI-1 antigen and activity after 2 weeks of treatment; subsequently, only the decreasing effect of aliskiren was sustained throughout the 12 weeks [-7.5 ng/ml (-31%) p<0.05 vs. baseline], while with losartan PAI-1 increased at week 12 [+3.6 ng/ml (+15%), p<0.05 vs. baseline and p<0.01 vs. aliskiren)]. The tPA activity showed no significant change with aliskiren and a decrease with losartan [-0.04 IU/ml (-8%), p<0.05 vs. baseline and p<0.01 vs. aliskiren]. Aliskiren significantly increased GIR [+1.4 mg/min/kg (+28%), p<0.01 vs. baseline] while losartan did not change it [+0.2 mg/min/kg (+4%), NS vs. baseline, p<0.05 vs. aliskiren)]. These results indicated that in this type of patients, despite similar BP reduction, aliskiren improved the fibrinolytic balance as well as IS, while losartan worsened the fibrinolytic balance and did not affect IS. The clinical relevance of these different effects remains to be clarified.

Effects of Antihypertensives on Glucose Metabolism

Treatment with different antihypertensive drug classes has varied effects on glucose metabolism. Thiazide diuretic use in hypertensives has been associated with the development of glucose intolerance and diabetes. Some findings suggest that the probability of worsening glucose metabolism and the development of new diabetes after thiazide initiation is associated with increasing body mass index. Nonselective or beta(1) selective beta-blockers may also lead to decreased insulin sensitivity in hypertensive patients. Newer beta-blockers that cause vasodilatation and beta-blockers that have intrinsic sympathomimetic activity may not have these deleterious effects on insulin sensitivity and glucose metabolism. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers may exert beneficial effects on glycemic control through a variety of mechanisms related to the inhibition of angiotensin II. These agents may be particularly useful in patients with microalbuminuria to slow the progression of renal disease. While there may be some small differences among different classes of calcium channel blockers, there is little net effect of these agents on glucose metabolism. The prevalence of obesity, hypertension, and type 2 diabetes mellitus is increasing in the US. In this setting, it is important to individualize antihypertensive therapy and to monitor its metabolic consequences so that potential adverse effects that would negate some of the benefits of blood-pressure lowering are minimized.

Comparative Effects of Telmisartan and Valsartan on Insulin Resistance in Hypertensive Patients with Metabolic Syndrome

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that includes hyperglycemia, dyslipidemia, hypertension and increased waist circumference. Individuals with this syndrome are at increased risk for development of cardiovascular disease. Since an insulin-resistance state has a critical role in the development of MetS, there is growing concern about insulin-sensitizing effects of antihypertensives, including angiotensin II receptor blockers (ARBs). Telmisartan has been reported to have an effect on the activity of peroxisome proliferator-activated receptor gamma, a well-known target for insulin-sensitizing antidiabetic drugs. The aim of this study was to determine the effects of administration of two different ARBs at low doses (telmisartan at 20 mg/day and valsartan at 40 mg/day) on insulin sensitivity. Patients with MetS meeting the Japanese criteria were treated with telmisartan or valsartan for 4 weeks in combination with lifestyle modification. A significant reduction in blood pressure was found after 4 weeks of both treatments. The homeostasis model assessment of insulin resistance (HOMA-R) was significantly reduced by telmisartan compared to the baseline value (3.11+/-2.06 vs 2.56+/-1.48, p=0.031) but was not significantly changed by valsartan. A statistically significant correlation was found between HOMA-R at baseline and changes in HOMA-R after 4 weeks of treatment only in telmisartan-treated subjects. Body mass index, glycosylated hemoglobin and lipid profile were not changed by either treatment. Our data revealed that treatment with telmisartan even at a low dose improves insulin sensitivity in hypertensive patients with MetS. This ameliorating effect of telmisartan on glucose metabolism clinically deserves to be considered.

Anti-inflammatory and metabolic effects of candesartan in hypertensive patients

Background Angiotensin II type 1 (AT1) receptor blocker therapy prevented or retarded the progression of coronary heart disease. The mechanisms of this benefit may relate to the ability of AT1 receptor blockers to reduce inflammation and insulin resistance. Methods We administered placebo or candesartan 16 mg daily during 2 months to 45 patients with mild to moderate hypertension. This study was randomized, double-blind, placebo-controlled, crossover in design. Results Candesartan therapy significantly lowered both systolic and diastolic blood pressure. Compared with placebo, candesartan therapy significantly lowered plasma hsCRP levels relative to baseline measurements from 1.10 to 0.70 mg/l ( P = 0.024) and soluble CD40 ligand levels by 30 ± 11% ( P < 0.001). There were significant inverse correlations between body mass index and baseline plasma adiponectin levels ( r = − 0.480, P = 0.009). There were significant correlations between baseline adiponectin levels and baseline insulin ( r = − 0.317, P = 0.034) or baseline Quantitative Insulin-Sensitivity Check Index (QUICKI), a surrogate index of insulin sensitivity ( r = 0.371, P = 0.012). Compared with placebo, candesartan therapy significantly lowered fasting insulin levels ( P = 0.011) and increased plasma levels of adiponectin by 15 ± 4% ( P = 0.012) and increased QUICKI by 8 ± 2% ( P = 0.007). There were significant correlations between percent changes in adiponectin levels and percent changes in insulin ( r = − 0.340, P = 0.022) or QUICKI ( r = 0.325, P = 0.029). Conclusions Candesartan therapy significantly reduced inflammation and increased adiponectin levels and improved insulin sensitivity in hypertensive patients.

Clinical significance of calcium channel blocker in patients with metabolic syndrome

Diabetes mellitus, hyperlipidemia and hypertension are often coexisting, especially in obese subjects. Based on the close relationship between these abnormalities, the new definition of "Metabolic Syndrome" was established this April, in which "Metabolic Syndrome" was defined to have 2 of 3 abnormalities such as hypertriglyceridemia (>150 mg/dL) and/or low HDL-cholesterolemia (<40 mg/dL), hypertension (>130/85 mmHg) and high fasting glucose levels (>110 mg/dL) in addition to abdominal obesity (waist circumference >85 cm in men and >90 cm in women). It seems to be very important to select hypotensive agents which improve insulin sensitivity in hypertensive patients with "Metabolic Syndrome".

Prevention of Type 2 Diabetes Mellitus Through Inhibition of the Renin-Angiotensin System

Type 2 diabetes mellitus is becoming a major health problem associated with excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a key objective in the near future. Besides lifestyle changes, various pharmacological treatments have proven their efficacy in placebo-controlled clinical trials, including antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity agents such as orlistat. Arterial hypertension, a clinical entity in which insulin resistance is common, is strongly associated with type 2 diabetes and may precede the disease by several years. While antihypertensive agents such as diuretics or beta-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, newer antihypertensive agents exert neutral or even slightly positive metabolic effects. Numerous clinical trials have investigated the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on insulin sensitivity in hypertensive patients, with or without diabetes, with no consistent results. Almost half of the studies with ACE inhibitors in hypertensive nondiabetic individuals demonstrated a slight but significant increase in insulin sensitivity as assessed by insulin-stimulated glucose disposal during a euglycaemic hyperinsulinaemic clamp, while the other half failed to reveal any significant change. The effects of ARAs on insulin sensitivity are neutral in most studies. Mechanisms of improvement of glucose tolerance and insulin sensitivity through the inhibition of the renin-angiotensin system (RAS) are complex. They may include improvement of blood flow and microcirculation in skeletal muscles and, thereby, enhancement of insulin and glucose delivery to the insulin-sensitive tissues, facilitating insulin signalling at the cellular level and improvement of insulin secretion by the beta cells. Six recent large-scale clinical studies reported a remarkably consistent reduction in the incidence of type 2 diabetes in hypertensive patients treated with either ACE inhibitors or ARAs for 3-6 years, compared with a thiazide diuretic, beta-adrenoceptor antagonist, the calcium channel antagonist amlodipine or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or beta1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001) in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial with valsartan compared with amlodipine. All these studies considered the development of diabetes as a secondary endpoint, except the HOPE trial where it was a post hoc analysis. These encouraging observations led to the initiation of two large, prospective, placebo-controlled randomised clinical trials whose primary outcome is the prevention of type 2 diabetes: the DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan. Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) will also investigate as a secondary endpoint whether it is possible to prevent the development of type 2 diabetes by blocking the RAS with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent consistent observations of a 14-34% reduction of the development of diabetes in hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a theoretical point of view, they emphasise that there are many aspects of the pathogenesis, prevention and treatment of type 2 diabetes that still need to be uncovered. From a practical point of view, they may offer a new strategy to reduce the ongoing epidemic and burden of type 2 diabetes.

QUICKI is a useful index of insulin sensitivity in subjects with hypertension.

Insulin resistance may link disorders of metabolic homeostasis such as diabetes and obesity with disorders of hemodynamic homeostasis such as hypertension. Thus it is of interest to validate simple methods for quantifying insulin sensitivity in hypertensive patients. The quantitative insulin-sensitivity check index (QUICKI) is a novel mathematical transformation of fasting blood glucose and insulin levels. In obese and diabetic subjects, QUICKI has a significantly better linear correlation with glucose clamp determinations of insulin sensitivity than minimal-model estimates. To determine whether QUICKI is also useful in hypertensive subjects, we performed glucose clamps and frequently sampled intravenous glucose tolerance tests (FSIVGTT) on 27 hypertensive subjects taken off antihypertensive medication. Indexes of insulin sensitivity derived from glucose clamp studies (SIClamp) were compared with QUICKI, minimal-model analysis of FSIVGTTs (SIMM), and homeostasis model assessment (HOMA). The correlation between QUICKI and SIClamp ( r = 0.84) was significantly better than that between SIMM and SIClamp( r = 0.65; P &lt; 0.028). The correlation between QUICKI and SIClamp was comparable to that between 1/HOMA and SIClamp ( r = 0.82). When studies were repeated in 14 subjects who had resumed antihypertensive medications, the percent changes in SIClamp for each of these patients were significantly correlated with percent changes in QUICKI ( r = 0.61) and HOMA ( r = −0.54) but not SIMM ( r = −0.18). We conclude that QUICKI is a simple, robust index of insulin sensitivity that is useful for evaluating and following the insulin resistance of hypertensive subjects in both research studies and clinical practice.

Insulin resistance and hypertension.

The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance (IR) under the disorder of glucose metabolism and hypertension were studied. By glucose tolerance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucose tolerance curve (AUCG) to area under insulin release curve (AUCI) were calculated and analyzed. The results showed that ISI was decreased to varying degrees in the patients with hypertension, the mildest in the group of NGT with hypertension, followed by the group of IGT without hypertension, the group of IGT with hypertension and DM (P = 0). There was very significant difference in the ratio of AUCG/AUCI between the hypertensive patients with NGT and controls (P = 0). It was concluded that a significant IR existed during the development of IGT both in hypertension and nonhypertension. The increase of total insulin secretion (AUCI) was associated with nonhypertension simultaneously. IR of the hypertensive patients even existed in NGT and was worsened with the deterioration of glucose metabolism disorder, but the AUCI in the HT group changed slightly. A relative deficiency of insulin secretion or dysfunction of beta-cell of islet existed in IGT and DM of the hypertensive patients.

A double blind comparison of the effects of amlodipine and enalapril on insulin sensitivity in hypertensive patients

This study compares the effects of a calcium channel blocker (amlodipine) and an angiotensin converting enzyme inhibitor (enalapril) on in vivo insulin sensitivity in patients with essential hypertension. Forty-six patients with mild and moderate hypertension were studied. After a 2-week single-blind placebo phase, they were randomly assigned to double-blind therapy with either amlodipine (2.5 to 10 mg/day) or enalapril (5 to 40 mg/day) for 16 weeks. Both groups were comparable in terms of demographic characteristics, degree of obesity, metabolic parameters, and arterial blood pressure. Insulin sensitivity was measured at baseline and at week 16 during the active phase using euglycemic hyperinsulinemic clamps. Arterial blood pressure decreased similarly in both groups. Whole body glucose uptake (M-value) increased with amlodipine from 3.63 ± 0.32 (mean ± SEM) to 3.97 ± 0.31 mg/kg/min ( P = .02). A similar tendency was observed with enalapril: from 3.59 ± 0.32 to 3.94 ± 0.30 mg/kg/min ( P = .09). A trend to lower steady-state insulin level during the second clamp (compared to baseline) was observed in both groups. The clamp-derived insulin sensitivity index (that corrects for steady-state insulin levels and glucose levels during the clamp) increased similarly in both groups: from 1.15 ± 0.11 to 1.39 ± 0.13 with amlodipine ( P = .03) and from 1.25 ± 0.13 to 1.49 ± 0.16 with enalapril ( P = .01). LDL cholesterol decreased with amlodipine (mean change, −11.3 mg/dL, P = .004). Amlodipine and enalapril were associated with increments in insulin sensitivity. Amlodipine provided an additional benefit with decreased low density lipoprotein cholesterol levels.

D43 Comparative effects of atenolol and nebivolol on blood pressure and insulin sensitivity in hypertensive patients with glucose intolerance

D43 Comparative effects of atenolol and nebivolol on blood pressure and insulin sensitivity in hypertensive patients with glucose intolerance

Effect of nebivolol and atenolol on blood pressure and insulin sensitivity in hypertensive patients with diabetes mellitus.

Effect of nebivolol and atenolol on blood pressure and insulin sensitivity in hypertensive patients with diabetes mellitus.

Influence of ACE inhibition on glucose tolerance in patients with stable chronic renal failure

ACE inhibitors improve glucose tolerance and insulin sensitivity in hypertensive patients with normal renal function. Hypertensive patients with renal failure are a high-risk group who are particularly glucose intolerant and insulin resistant. We have therefore studied whether ACE inhibition improve glucose tolerance in this group as well. In a double-blind placebo-controlled crossover study 10 patients with stable moderate chronic renal failure (mean endogenous creatinine clearance 40 +/- 16 ml/min/1.73 m2) were examined. Patients were randomly allocated to receive either placebo or the ACE inhibitor perindopril (2 mg/day per os) for 14 days. After 7 days of wash-out they received the alternative medications in random order for another 14 days. Before and after each of the two treatment periods (day 1 and day 15) an intravenous glucose tolerance test (i.v. GTT) with concomitant determination of insulin levels was performed. The glucose disappearance rate (K value) was calculated to express changes in glucose tolerance. An i.v. GTT was also performed in a group of healthy volunteers. The mean K value was significantly (P < 0.05) lower, i.e. glucose tolerance was impaired, in patients compared with healthy controls. In addition, baseline and peak insulin levels after the i.v. GTT were significantly higher (P < 0.05) in patients than in healthy subjects. The K values in patients before and after placebo treatment (1.33 +/- 0.31 and 1.41 +/- 0.45 respectively) were not significantly different from the values with perindopril treatment (1.35 +/- 0.37 and 1.41 +/- 0.48 respectively). Furthermore, no significant differences between placebo and perindopril treatment were found with respect to the insulin response to the glucose load. The peak (5 min) insulin concentrations after the i.v. glucose load were 49.0 +/- 19.2 microU/ml (day 1) and 50.0 +/- 24.9 (day 15) with placebo and 49.2 +/- 19.3 (day 1) and 46.8 +/- 17.9 (day 15) with perindopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive therapy with enalapril improves glucose storage and insulin sensitivity in hypertensive patients with non—insulin-dependent diabetes mellitus

A double-blind, placebo-controlled, 4-week trial was performed to determine the antihypertensive and metabolic effects of enalapril (20 to 40 mg/d) in 16 hypertensive patients with non—insulin-dependent diabetes mellitus (NIDDM) aged 55 ± 2 years and with a body mass index of 29 ± 1 kg/m 2. Glucose utilization was determined after an overnight fast and during insulin stimulation at 0 and 4 weeks (methods: euglycemic clamp, [3- 3H]glucose infusion, indirect calorimetry). Enalapril decreased systolic (166 ± 4 v 152 ± 5 mm Hg, P < .05) and diastolic (102 ± 2 v 95 ± 2 mm Hg, P < .05) blood pressure. Peripheral insulin sensitivity, ie, insulin stimulation of glucose utilization, increased approximately 30%, or by 4.3 ± 1.7 μmol/kg · min (13.1 ± 2.0 v 17.4 ± 3.5 μmol/kg · min, P < .05, 0 v 4 weeks) during enalapril treatment, but remained unchanged during placebo treatment (15.4 ± 2.8 v 15.3 ± 2.7 μmol/kg · min, respectively). The increase in glucose utilization during enalapril treatment was fully explained by an increase of 4.1 ± 1.7 μmol/kg · min in glucose storage (4.1 ± 1.2 v 8.1 ± 2.9 μmol/kg · min, P < .05) while glucose oxidation remained unchanged. High-density lipoprotein (HDL) cholesterol increased by 8% ( P < .05) and hemoglobin A 1c (HbA 1c) improved slightly (7.7% ± 0.7% v 7.3% ± 0.7%, P < .05) in the enalapril group, but not in the placebo group. We conclude that enalapril improves insulin sensitivity by increasing glucose storage in hypertensive patients with NIDDM. These data indicate that the beneficial metabolic effects of angiotensin-converting enzyme (ACE) inhibitors are not restricted to nondiabetic patients, and that insulin resistance is partially reversible in hypertensive NIDDM patients.

The Role of the Renin-Angiotensin System in Insulin Sensitivity in Normotensive Subjects

Nonobese patients with essential hypertension have been reported to be insulin resistant. Because blockade of the renin-angiotensin system has been demonstrated to improve insulin sensitivity in hypertensive patients, the authors evaluated the effects of angiotensin-II administration and of angiotensin-converting enzyme inhibition with enalapril on insulin-mediated glucose uptake in normotensive men. The results showed no change in insulin sensitivity with either 0.3 ng/kg/min or 1 ng/kg/min angiotensin-II administration or with enalapril therapy. The authors conclude that neither physiologic amounts of angiotensin-II nor converting enzyme inhibition alter insulin sensitivity in normotensive men.