Hemostatic function

Abstract: Introduction to Pathophysiology PART ONE: CENTRAL CONCEPTS OF PATHOPHYSIOLOGY: CELLS AND TISSUES Unit I: The Cell * Cellular Biology * Altered Cellular and Tissue Biology * The Cellular Environment: Fluids and Electrolytes, Acids and Bases Unit II: Genes and Gene-Environment Interaction * Genes and Genetic Diseases * Genes, Environment, Life-style, and Common Diseases Unit III: Mechanisms of Self-Defense * Innate Immunity: Inflammation * Adaptive Immunity * Alterations in Immunity and Inflammation * Infection * Stress and Disease Unit IV: Cellular Proliferation: Cancer * Biology, Clinical Manifestations, and Treatment of Cancer * Cancer Epidemiology * Cancer in Children PART TWO: PATHOPHYSIOLOGIC ALTERATIONS: ORGANS AND SYSTEMS Unit V: The Neurologic System * Structure and Function of the Neurologic System * Pain, Temperature Regulation, Sleep, and Sensory Function * Alterations in Cognitive Systems, Cerebral Hemodynamics and Motor Function * Disorders of the Central and Peripheral Nervous Systems and the Neuromuscular Junction * Neurobiology of Schizophrenia, Mood Disorders, and Anxiety Disorders * Alterations of Neurologic Function in Children Unit VI: The Endocrine System * Mechanisms of Hormonal Regulation * Alterations of Hormonal Regulation Unit VII: The Reproductive Systems * Structure and Function of the Reproductive Systems * Alterations of the Reproductive Systems * Sexually Transmitted Infections Unit VIII: The Hematologic System * Structure and Function of the Hematologic System * Alterations of Erythrocyte Function * Alterations of Leukocyte, Lymphoid, and Hemostatic Function * Alterations of Hematologic Function in Children Unit IX: The Cardiovascular and Lymphatic Systems * Structure and Function of the Cardiovascular and Lymphatic Systems * Alterations of Cardiovascular Function * Alterations of Cardiovascular Function in Children Unit X: The Pulmonary System * Structure and Function of the Pulmonary System * Alterations of Pulmonary Function * Alterations of Pulmonary Function in Children Unit XI: The Renal and Urologic System * Structure and Function of the Renal and Urologic Systems * Alterations of Renal and Urinary Tract Function * Alterations of Renal and Urinary Tract Function in Children Unit XII: The Digestive System * Structure and Function of the Digestive System * Alterations of Digestive Function * Alterations of Digestive Function in Children Unit XIII: The Musculoskeletal System * Structure and Function of the Musculoskeletal System * Alterations of Musculoskeletal Function * Alterations of Musculoskeletal Function in Children Unit XIV: The Integumentary System * Structure, Function, and Disorders of the Integument * Alterations of the Integument in Children Unit XV: Multiple Interacting Systems * Shock, Multiple Organ Dysfunction Syndrome, and Burns in Adults * Shock, Multiple Organ Dysfunction Syndrome, and Burns in Children

Abstract: ContextIncreased risk for cardiovascular disease in persons with glucose intolerance (impaired glucose tolerance and type 2 diabetes mellitus) is not fully explained by concomitant elevations in traditional atherosclerosis risk factors. Hyperinsulinemia associated with glucose intolerance may increase risk directly, or its effect could be mediated through impaired hemostatic function.ObjectiveTo evaluate associations between fasting insulin levels and hemostatic factors in subjects with normal and impaired glucose homeostasis.DesignCross-sectional analysis conducted between January 1991 and June 1995.SettingThe population-based Framingham Offspring Study.SubjectsA total of 1331 men and 1631 women aged 26 to 82 years, without diagnosed diabetes or cardiovascular disease and classified as having normal glucose tolerance (80.2%) or glucose intolerance (impaired glucose tolerance and impaired fasting glucose combined, 15.2%; previously undiagnosed diabetes, 4.7%) using an oral glucose tolerance test.Main Outcome MeasuresTrends across quintiles of fasting insulin in levels of plasminogen activator inhibitor 1 (PAI-1) antigen, tissue-type plasminogen activator (tPA) antigen, von Willebrand factor (vWF) antigen, factor VII antigen, fibrinogen, and plasma viscosity. We stratified analyses by sex and glucose tolerance status and adjusted hemostatic factor levels for obesity, lipid levels, and traditional cardiovascular disease risk factors.ResultsMean levels of all hemostatic factors (except for fibrinogen in men) increased across fasting insulin quintiles among subjects with normal glucose tolerance (P<.001 for trend). Levels of PAI-1 and tPA antigens, but not other hemostatic factors, were higher comparing subjects with glucose intolerance with those with normal glucose tolerance (P<.001). Among subjects with glucose intolerance, levels of PAI-1 and tPA antigen in men and women (P<.01 for trend) and vWF antigen in men (P<.05 for trend) increased significantly across insulin quintiles, but levels of factor VII antigen, fibrinogen, and plasma viscosity did not increase.ConclusionsElevated levels of fasting insulin are associated with impaired fibrinolysis and hypercoagulability in subjects with normal glucose tolerance. Hyperinsulinemia is associated primarily with impaired fibrinolysis in subjects with glucose intolerance. Excess risk for cardiovascular disease associated with hyperinsulinemia and glucose intolerance may be mediated in part by enhanced potential for acute thrombosis.