I growth factor-1 (IGF-1) is synthesized by the liver and kidneys, and also as a paracrine and autocrine substance by endothelial cells and by vascular and cardiac myocytes. It has been well established that IGF-1 promotes insulin sensitivity and glucose availability to body tissues and to normal and ischemic myocardium. Furthermore, by enhancing tyrosine-kinase, phosphoinositol-3-kinase, and nitric oxide synthase, IGF-1 promotes nitric oxide mediated vasodilation. Nitric oxide inhibitors have been shown to prevent IGF-1-induced vasodilation. IGF-1, however, may also induce vasodilation through the opening of membrane potassium channels. Both impaired insulin sensitivity and coronary microvascular dysfunction have been reported in patients with cardiac syndrome X. Thus, in this study, we investigated whether abnormalities in serum IGF-1 levels are present in these patients and whether they are related to insulin levels and insulin sensitivity. • • • We studied 13 patients (56 ! 9 years, 7 men) with typical syndrome X (effort angina, positive exercise test, normal coronary angiography, and no evidence of epicardial artery spasm). The 12-lead electrocardiographic and echocardiographic examinations were normal. Other cardiac or noncardiac diseases, including systemic hypertension and diabetes, were excluded by full clinical and laboratory investigations. All drugs were withdrawn !48 hours before the investigation. As a control group, 12 healthy volunteers (55 ! 10 years, 7 men) recruited from our hospital staff were studied. None had a history of chronic inflammatory diseases, acromegaly, obesity (defined as body mass index kg/m), or any other condition known to affect insulin sensitivity and/or IGF-1 serum levels. The protocol was approved by the hospital ethical committee. Patients and controls were tested in the morning, between 8:00 and 9:00 A.M. After obtaining informed written consent to participate, a fasting venous blood sample was taken for baseline insulin and IGF-1 serum levels. The samples were centrifuged without delay and aliquots stored at #80°C until assayed. Insulin sensitivity was assessed by Bonora’s insulin tolerance test, which is one of the simplest to assess insulin resistance. The test yields reliable results and has been shown to have a good correlation with euglycemic and/or hyperinsulinemic clamp data. A 20-gauge indwelling catheter was introduced in an antecubital vein and an infusion of saline solution was administered. After 30 minutes of rest, an intravenous bolus of 0.1 IU/kg of regular insulin (Humulin R, Eli Lilly, Firenze, Italy) was injected. Blood samples of 0.5 ml were drawn immediately before and 3, 6, 9, 12, 15, 18, 20, and 30 minutes after the insulin bolus to determine plasma glucose. Twenty minutes after the insulin injection, 30 ml of a 33% glucose solution was injected intravenously. Blood glucose levels were measured in real-time using the “Onetouch-hospital” reflectometer (Ortho-Clinical Diagnostics, Monza, Italy), which has been previously validated with standard gluco-oxidase methods. The serum concentrations of insulin and IGF-1 were measured by commercially available immunoenzymatic (IMX Insulin Assay, Abbott Laboratories, Pomezia, Italy) or immunoradiometric (Active NonExtraction IGF-1 IRMA DSL-2800, Diagnostics System Laboratories, Webster, Texas) assays. The samples were tested in batches and in duplicate. The intrasample variability was $10% for both assays. Biochemical variables showed a normal distribution, according to the Kolmogorov-Smirnov test. Therefore, group comparisons were assessed by unpaired t test. Pearson’s correlation was used to examine relations between variables. Two-way analysis of variance with a repeated measure design was used to compare the changes in blood glucose levels in response to the insulin bolus in the 2 groups. Insulin sensitivity was measured as the rate of change in blood glucose concentrations between minutes 3 and 15 after the insulin bolus, as calculated using a leastsquare linear regression method. This parameter is defined as “blood glucose disappearance rate” and is expressed as milligrams per deciliter per minute. Data are shown as mean ! SD. A 2-tailed p value $0.05 was considered statistically significant. Statistica for Windows version 4.0 software (Statsoft, Inc 1993, Vigonza, Italy) was used for analyses. Patients and controls did not differ significantly in age, gender, and body mass index (Table 1). However, fasting IGF-1 levels were significantly lower (p% 0.002) and insulin levels significantly higher (p % 0.004) in patients with syndrome X than in controls (Table 1 and From the Institute of Cardiology, the Institute of Obstaetrics and Gynaecology, and the Hormones Laboratory, Catholic University, Rome, Italy. This study was financially supported by the “Fondazione internazionale per il Cuore,” Rome, Italy. Dr. Conti’s address is: Istituto di Cardiologia, Universita Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italy. E-mail: e_conti02@hotmail.com. Manuscript received September 5, 2001; revised manuscript received and accepted December 24, 2001.
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Jul 5, 2024
Cindy Neuzillet + 22
Open Access