METABOLIC SYNDROME AND MACROANGIOPATHY .2 . THERAPEUTIC STRATEGIES

The pathogenesis of macroangiopathy is diverse, various risk factors a re known. The metabolic syndrome describes the association of obesity, hypertension, dyslipidemia, glucose intolerance and hyperinsulinemia. In this syndrome, resistance of insulin stimulated glucose uptake and the compensatory hyperinsulinemia play a central role. The metabolic syndrome requires a re-evaluation of the cardiovascular risk managemen t of detecting and treating single factors and a change towards a more integrative approach. Life style modifications such as diet, weight l oss and regular physical activity are the best interventions possible and should therefore be the first in line. They effectively reduce the vicious circle of insulin resistance, hyperinsulinemia and do,vn-regu lation of the receptors, the combination of all interventions being mo st promising. In general, if drug intervention is necessary, one shoul d consider the potential metabolic effects of the substances used. For instance, when treating hypertension, substrates like the thiazide di uretics and conventional betablocker should be avoided, as they could induce or further deteriorate insulin resistance (iatrogenic insulin r esistance). Alpha(1)-blocking agents, vasodilating betablockers and AC E-inhibitors were shown to be metabolically inert or even improve insu lin sensitivity; therefore these agents should be preferred. Today sev eral compounds are available which directly or indirectly interfer wit h the vicious circle of insulin resistance/hyperinsulinemia: substrate s which slow down intestinal glucose absorption (guar, acarbose) will reduce the reactive hyperinsulinemia. Metformin improves insulin effec tiveness, as it controls glycemia without increasing hyperinsulinemia; due to the risk of lactic acidosis, its use is somewhat restricted. T hiazolidinediones enhance insulin action and seem to be very promising ; however, they are not yet available for prescription and will first have to show that they are safe drugs. Other substrates which improve insulin action are a hemodialysate and thioctic acid, which were shown to improve insulin sensitivity in type II diabetes. The pathophysiolo gy of the metabolic syndrome emphasizes the benefits of a healthy life style, which is the best and also the most effective pre-/interventio n.