Insulin resistance functionally limits endothelium-dependent coronary vasodilation in nondiabetic patients.
ABSTRACT Insulin resistance (IR) is now considered to be a risk factor for coronary arterial atherosclerosis and is likely to be involved in a limited endothelium-dependent vasodilatory function in peripheral circulation. We investigated whether IR impairs endothelial vasodilator function in the noninfarcted coronary artery. In 14 nondiabetic patients (10 males, 66 +/- 6 years) who were selected from 214 patients underwent IR evaluation by glucose clamp, a Doppler flow wire was used to measure coronary flow changes (percent volume flow index, %VFI) during intracoronary administration of papaverin (10 mg) and stepwise administration of acetylcholine (Ach; 1, 3, 10 microg/ml per minute) into the non-infarcted left circumflex coronary artery. Insulin resistance was comparatively evaluated by an euglycemic hyperinsulinemic glucose clamp (M value, mg/m(2) per minute) or by a 75g-oral glucose tolerance test (120-min immunoreactive insulin; 120' IRI, pmol/l). Eight patients (57%) were defined as having IR on the basis of results obtained by both the glucose clamp method (M values <167 mg/m(2) per minute) and 120' IRI (>384 pmol/l). There was no difference between papaverin-induced %VFI increases in IR and non-IR subjects (328% +/- 43% vs. 361% +/- 87%). However, IR subjects showed significantly lower Ach-induced %VFI increases in a dose-dependent manner (P < 0.05), especially when low (1 microg/ml per minute) and moderate (3 microg/ml per minute) doses of Ach were used (165% +/- 18% or 248% +/- 29% in non-IR subjects vs. 130% +/- 20% or 183% +/- 41% in IR subjects, P < 0.001, respectively). Moreover, %VFI increase at a low dose of Ach infusion significantly correlated with M values or 120' IRI ([%VFI Ach 1 microg] = 85.9 + 0.35 [M values], r = 0.58, P = 0.038; [%VFI Ach 1 microg] = 176.8 - 0.47.[120' IRI], r = -0.57, P = 0.035). Insulin resistance limits endothelium-dependent coronary vasodilation in association with the severity of IR in non-diabetic patients.
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ABSTRACT: The effect of acute hyperglycemia per se on coronary perfusion in humans is undefined. We evaluated the effects of short-term hyperglycemia on myocardial blood flow reserve (MBFR) in healthy nondiabetic volunteers. Twenty-one nondiabetic volunteers (76 % females, mean ± SD, age 48 ± 5 years) had noninvasive MBFR assessment while exposed to pancreatic clamp with somatostatin and replacement glucagon and growth hormone infusions, with frequent interval plasma glucose (PG) monitoring. Insulin was infused at 0.75 mU/kg/min to mimic postprandial plasma insulin concentrations, and glucose was infused to maintain euglycemia (PG 93.9 ± 7.3 mg/dl) followed by hyperglycemia (PG 231.5 ± 18.1 mg/dl). Myocardial contrast echocardiography (MCE) was performed during each glycemic steady state using continuous infusion of Definity at rest and during regadenoson (Lexiscan 5 ml (400 μg) intravenous bolus) infusion to quantify myocardial blood flow (MBF) and determine MBFR. Insulin resistance (IR) was assessed by glucose infusion rate (GIR; mg/kg/min) at euglycemia. Median stress MBF, MBFR, and β reserve were significantly reduced during acute hyperglycemia versus euglycemia (stress MBF 3.9 vs 5.4, P = 0.02; MBFR 2.0 vs 2.7, P < 0.0001; β reserve 1.45 vs 2.4, P = 0.007). Using a median threshold GIR of 5 mg/kg/min, there was a correlation between GIR and hyperglycemic MBFR (r = 0.506, P = 0.019). MBFR, as determined noninvasively by MCE, is significantly decreased during acute hyperglycemia in nondiabetic volunteers, and the magnitude of this reduction is modulated by IR.Heart and Vessels 11/2012; · 2.13 Impact Factor
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ABSTRACT: INTRODUCTION: Weight loss in sexually active women improves their quality of life. At present, no studies have investigated whether weight loss may affect female sexual function in severe obese women. AIM: The aim of this study was to investigate the effects of different programs of weight loss on female sexual dysfunction complaints and on endothelial function in premenopausal obese females. METHODS: Forty-four out of overall 80 obese fertile women (age 18-49 years; mean 36 years) were enrolled because of sexual complaints at Female Sexual Function Index-6 (FSFI-6 score ≤19). Patients were then allocated to different treatments of 8 weeks duration each: an intensive residential program with hypocaloric diet plus controlled physical exercise along with lifestyle modifications at a specialized clinic (Group A, N = 23) and a non-intensive outpatient clinic program consisting of hypocaloric diet and physical exercise at home (Group B, N = 21). Afterward, overall patients were allocated to an extended 8-week follow-up period consisting of outpatient clinic controlled diet plus physical exercise at home. MAIN OUTCOME MEASURES: Primary end points were modifications of FSFI-6 scores and endothelial function as measured by reactive hyperemia (RHI) with EndoPat-2000. Secondary end points were modifications in body composition as measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: After 16 weeks, FSFI-6 score and the frequency of sexual activity were significantly higher in Group A compared with Group B (P < 0.01), and significant improvements in arousal, lubrication, and satisfaction sub-domain scores were also found (P < 0.01). Group A showed improvements in RHI (P < 0.01) and marked improvement in homeostasis model assessment of insulin resistance (P < 0.001), anthropometric parameters as weight (P < 0.01), body mass index (P < 0.01), fat mass (P < 0.0001), and percentage of fat mass (P < 0.005) compared with Group B. A relationship between peak insulin (P < 0.0001) and RHI (P < 0.001) vs. FSFI-6 scores was found, respectively. CONCLUSIONS: A multidisciplinary approach to female obesity appears to be superior to conventional outpatient clinic to produce weight loss and to improve several aspects of sexual dysfunction in obese women. Such changes might be related to persistent improvements in endothelial function and in insulin resistance.Journal of Sexual Medicine 01/2013; · 3.51 Impact Factor
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ABSTRACT: BACKGROUND: Coronary flow reserve (CFR) provides independent prognostic information in diabetic patients with known or suspected coronary artery disease. However, there have been no substantial data to evaluate CFR in prediabetics. Accordingly, we aimed to evaluate CFR in subjects with prediabetes using second harmonic transthoracic Doppler echocardiography. METHODS AND RESULTS: We measured CFR of 65 subjects with prediabetes, 45 patients with overt type 2 diabetes, and 43 sex and age matched normoglycemic healthy subjects with normal glucose tolerance. Ages, gender, existence of hypertension or hypercholesterolemia, smoking status were similar among the groups. CFR was significantly lower in diabetics (2.15±0.39) than in prediabetics (2.39±0.45) and controls (2.75±0.35); in addition, it was significantly lower in prediabetics than controls. Only 2 (5%) of control subjects had abnormal CFR (<2) but 11 (17%) prediabetic subjects and 19 (42%) diabetic patients had abnormal CFR. We found that only age (β=-0.31, P<0.01) and presence of the diabetes (β=-0.57, P<0.01) were significant predictors of lower CFR in a multivariable model that adjusted for other variables. CFR was significantly and inversely correlated with age (r=-0.15, P=0.04), fasting glucose level (r=-0.27, P=0.001), postprandial glucose level (r=0.43, P<0.001), hemoglobin A1C level (r=-0.34, P<0.001), LDL cholesterol level (r=0.22, P=0.009), mitral A velocity (r=-0.27, P=0.001) and Tei index (r=-0.19, P=0.02), whereas mitral E/A ratio, mitral Em (r=0.18, P=0.02), mitral Em/Am ratio (r=0.23, P=0.004) were significantly and positively correlated with CFR. CONCLUSION: CFR is impaired in subjects with prediabetics, but this impairment is not as severe as that in diabetics.Metabolism: clinical and experimental 04/2013; · 3.10 Impact Factor