Cardiovascular and renal complications of type 2 diabetes in obesity: role of sympathetic nerve activity and insulin resistance.
Overweight and obesity is a growing "world-wide epidemic problem". Because as many as, two-thirds of the adult population and a growing number of children are overweight. The prevalence of diabetes, especially type 2 diabetes and hypertension have significantly increased with the prevalence of obesity. Obesity accompanying type 2 diabetes and hypertension are known to be closely linked with insulin resistance and elevated sympathetic nervous activity. It has been well documented that obesity, hypertension, and diabetes are high risk factors for subsequent cardiovascular and renal complications. Many patients are both diabetic and hypertensive, while they are obese, but not all diabetic patients have hypertension, indicating that insulin resistance is not only a mechanism for blood pressure elevation in diabetic-hypertensive patients. Several investigators have reported that sympathetic nervous activation relates to cardiovascular complications in patients with hypertension, diabetes, and obesity, and that sympathetic nerve activity accompanying insulin resistance is closely linked with left ventricular hypertrophy in healthy subjects. In addition, sympathetic nerve activation may predict future renal injury in healthy normotensive subjects. These findings suggest that elevated sympathetic nerve activity associated with insulin resistance may contribute to the onset and maintenance of cardiovascular and renal complications in diabetes, and hypertension in obesity. Further, genetic polymorphisms of the beta2- and beta3-adrenoceptor gene have been associated with type-2 diabetes and insulin resistance in many epidemiological studies and might be another factor responsible for the close relationship between insulin resistance and heightened sympathetic nerve activity. Thus, focusing on the interactions between insulin resistance, sympathetic nervous activity and beta-adrenoceptor polymorphisms might help in understanding the precise relationships between insulin resistance and sympathetic nerve activity in type 2 diabetes and obesity-related hypertension. The purpose of this article is to provide a synthesis of the current findings on the mechanisms of the onset and maintenance of cardiovascular and renal complications in obesity, diabetes and hypertension. A better understanding of the relationships of sympathetic nervous system activity and insulin resistance might help with the clinical treatment of diabetes and hypertension in obesity. Further, to clarify the pathogenesis and mechanisms of the association between obesity, diabetes, and hypertension may lead to reductions in cardiovascular and renal risk.
Masuo
Kazuko
K
Nucleus Network Ltd., Baker IDI Heart and Diabetes Research Institute, Melbourne, Victoria 3004, Australia. kmasuo@bakeridi.edu.au
Rakugi
Hiromi
H
Ogihara
Toshio
T
Esler
Murray D
MD
Lambert
Gavin W
GW
D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D007333:Insulin Resistance; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D012307:Risk Factors; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2