Insulin resistance and impaired regulation of hemodynamic parameters

摘要

Insulin resistance (IR) is associated with poor cardiovascular prognosis. Various factors may be involved, including metabolic disorders, changes in cation contents of smooth muscle cells and changes in hemodynamic conditions. There is substantial evidence for cardiovascular autonomic disorders and endothelium dysfunction in the ER syndrome.In nondiabetic overweight subjects, heart rate variability (HRV) is decreased in more than 40% of the cases, and this disorder is associated with a higher IR index (HOMA). Sympathetic activity evaluated by the low-frequency peak of systolic blood pressure changes (spectral analysis) correlates with IR index. The HOORN study has shown that HRV is abnormal in the subjects with glucose intolerance. Insulin may be involved in the changes of vagosympathetic balance, and the role of free fatty acids has also been suggested. The Fredericia study has provided arguments for the role of genetic factors in autonomic dysfunction.Endothelium function also seems to be impaired in the IR syndrome. In overweight subjects, a decrease in coronary endothelium-dependent vasodilation has been reported, and we found that the cutaneous endothelium-dependent vasodilation is decreased and correlates negatively with HOMA index. Capillary filtration of albumin is increased in overweight women and improved by metformin. In Zucker fatty rats, we recently found a similar increase in capillary filtration of albumin. Some experimental data and therapeutic trials suggest that endothelium dysfunction may be improved by thiazolidinediones.Both autonomic and endothelium dysfunctions may have important cardiac consequences. Autonomic dysfunction is associated with a decrease in circadian blood pressure variations, and sympathetic activity correlates with arterial rigidity. Together with a depression of endothelium-dependent vasodilation, these disorders may contribute to left ventricle hypertrophy. Finally, several prospective studies have demonstrated the prognostic value of autonomic disorders and endothelium dysfunction of the coronary arteries.Thus, changes in hemodynamic conditions may account for the poor cardiovascular prognosis related to TR. Common genetic factors might be implicated in IR and such cardiovascular changes.