OBJECTIVE—We studied the relationships between plasma IGF-I concentrations and insulin sensitivity in subjects with various degrees of glucose tolerance. RESEARCH DESIGN AND METHODS—A total of 357 nondiabetic subjects, 54 subjects with impaired glucose tolerance and 98 newly diagnosed type 2 diabetic subjects, were consecutively recruited, and anthropometric and biochemical characteristics were collected. RESULTS—IGF-I concentrations were negatively correlated with age, BMI, waist-to-hip ratio, triglyceride levels, and systolic and diastolic blood pressure. IGF-I concentrations were positively correlated with HDL cholesterol and homeostasis model assessment of insulin sensitivity (HOMA-S). The correlations remained significant after adjusting for sex, age, and BMI. Correlations for HOMA-S with these metabolic and anthropometric variables were of a similar degree and direction to those for IGF-I concentrations. Stepwise linear regression analysis in a model, which included well-known modulators of insulin sensitivity such as sex, age, BMI, glucose tolerance status, family history of diabetes, waist-to-hip ratio, systolic and diastolic blood pressure, HDL cholesterol, and triglyceride levels, revealed that IGF-I concentrations were independently associated with insulin sensitivity accounting for 10.8% of its variation (P < 0.0001). IGF-I concentrations were significantly lower in subjects with World Health Organization (WHO)-defined metabolic syndrome compared with subjects without metabolic syndrome (P < 0.0001). Logistic regression analysis showed that each unit increase in log-transformed IGF-I concentrations was associated with a 90.5% reduction in the risk of WHO-defined metabolic syndrome. CONCLUSIONS—These data indicate that IGF-I has the characteristics to be a marker for the insulin resistance syndrome. This suggests that low IGF-I levels may be a useful marker for identifying subjects at risk for cardiovascular disease.

Aims To investigate the additive prognostic impact of both forearm endothelial dysfunction and left ventricular mass (LVM) for future cardiovascular events. Methods and results We enrolled 324 Caucasian, never treated, hypertensive outpatients. Endothelial function, by intra-arterial infusion of acetylcholine (ACh), and echocardiographic LVM were investigated. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) and LVM indexed by body surface area (LVMI). Cardiovascular events assessed were: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, transient cerebral ischaemic attack, unstable angina, coronary revascularization procedures, and symptomatic aorto-iliac occlusive disease. During a mean follow-up of 45.2±23.6 months, there were 47 new cardiovascular events (3.8 events/100 patient-years). The event rate was 6.8, 2.8, and 1.6% in the tertiles of ACh-stimulated FBF (log-rank test, P=0.0009), and 1.4, 3.4, and 6.6% in the tertiles of LVMI (log-rank test, P=0.0002), respectively. Besides, a significant interaction was documented between FBF and LVMI. In fact, the cardiovascular risk increases up to 11.4% in patients with low FBF and high LVMI. Conclusion For the first time, we demonstrate that the co-existence of LVH and endothelial dysfunction in hypertensive patients increases significantly the risk of subsequent cardiovascular events.

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) interfere with cardiac mass (left ventricular mass; LVM) development. We investigated the role of the GH/IGF-1 axis on LVM and ventricular geometry in a group of 230 never-treated hypertensive patients. Partition values for left ventricular hypertrophy (LVH) were 125 g/m2 for both women and men. Insulin resistance was estimated by the homeostasis model assessment (HOMA) index. A significant inverse correlation was observed between IGF-1 and both fasting insulin (r = −0.249; P < 0.0001) and GH (r = −0.218; P < 0.0001). Systolic blood pressure (157.3 ± 13.6 versus 149.4 ± 12.8 mmHg; P < 0.001), fasting insulin (17.4 ± 8.5 versus 11.4 ± 6.0 μU/l; P < 0.0001), HOMA (4.4 ± 2.3 versus 2.9 ± 1.6; P < 0.0001) and GH (1.0 ± 1.0 versus 0.4 ± 0.5 ng/ml; P < 0.0001) were significantly higher in patients with LVH; on the contrary, IGF-1 values (119.1 ± 47.8 versus 160.1 ± 75.5 ng/ml; P < 0.0001) were higher in patients without LVH. In a logistic regression analysis, the strongest independent predictors of LVH were GH [relative risk (RR) = 2.078; 95% confidence interval (CI) = 1.364–3.163], HOMA (RR = 1.345; 95% CI = 1.133–1.596), IGF-1 (RR = 0.993; 95% CI = 0.998–0.999) and systolic blood pressure (RR = 1.036; 95% CI = 1.013–1.060). IGF-1 showed an opposite trend in patients with eccentric and concentric hypertrophy. Present data demonstrate that the increase in LVM prevalent in human essential hypertension is directly associated with serum GH levels and inversely related to circulating IGF-1.