Vascular disease in the metabolic syndrome: do we need to target the microcirculation to treat large vessel disease?
The metabolic syndrome of vascular risk is threatening large numbers of ever-younger people. To date, the syndrome has been chiefly viewed as a potential risk marker that confers a heightened probability of developing type 2 diabetes and occlusive atherothrombotic disease of large- and medium-sized arteries. Accumulating evidence suggests that the components of the metabolic syndrome may also adversely affect the microvasculature through several inter-related mechanisms. These include the following observations: classic risk factors for macrovascular disease such as high blood pressure and dyslipidaemia also accelerate microvascular complications of diabetes, lesser disturbances of glucose metabolism (i.e. impaired glucose tolerance) may be associated with some forms of microvascular dysfunction, non-glucose intermediary metabolites may promote renovascular hypertension thereby damaging the microvasculature, and insulin resistance appears to be directly associated with microvascular dysfunction. In turn, microvascular complications such as nephropathy and autonomic neuropathy may promote the development and progression of atherosclerosis. We argue that the vascular implications of the metabolic syndrome should be broadened to include the microvasculature. The hypothesis that vascular events can be prevented, or at least deferred, through earlier therapeutic intervention in pre-diabetic subjects with glucose intolerance is amenable to testing in clinical trials.
Krentz
Andrew J
AJ
Institute of Developmental Sciences, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
Clough
Geraldine
G
Byrne
Christopher D
CD
D019440:Anti-Obesity Agents / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D018450:Disease Progression; D018149:Glucose Intolerance / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008833:Microcirculation / Q000187:drug effects*; D011236:Prediabetic State / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D014652:Vascular Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D019440:Anti-Obesity Agents; D000959:Antihypertensive Agents; D002317:Cardiovascular Agents; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents