Insulin resistance syndrome (IRS), also termed syndrome X, is a distinctive 
constellation of risk factors for the development of type 2 diabetes mellitus 
and cardiovascular disease. The syndrome's hallmarks are glucose intolerance, 
hyperinsulinemia, a characteristic dyslipidemia (high triglycerides; low 
high-density lipoprotein cholesterol, and small, dense low-density lipoprotein 
cholesterol), obesity, upper-body fat distribution, hypertension, and increased 
prothrombotic and antifibrinolytic factors. Insulin resistance, caused by a 
complex of genetic and environmental influences, is now recognized not just as a 
mechanism contributing to hyperglycemia in type 2 diabetes, but also as an early 
metabolic abnormality that precedes the development of overt diabetes. The 
clinical definition of insulin resistance is the impaired ability of insulin 
(either endogenous or exogenous) to lower blood glucose. In some 
insulin-resistant individuals, insulin secretion will begin to deteriorate under 
chronic stress (glucose toxicity) and overt diabetes will result. If not, 
individuals will remain hyperinsulinemic, with perhaps some degree of glucose 
intolerance, together with other hallmarks of the IRS. The statistical 
correlation between hypertension and impaired glucose tolerance is clear, 
although the mechanism is not yet fully understood. Epidemiologic evidence of 
insulin resistance as an independent risk factor for atherosclerosis and 
coronary heart disease (CHD) completed the evolving concept of IRS as the common 
soil for the development of both diabetes and CHD. No single laboratory test 
exists for diagnosis of IRS. Rather, IRS remains a clinically evident syndrome 
that can be suspected on the basis of physical and laboratory findings. This 
identifies individual patients whom the clinician should screen for associated 
comorbid conditions, aggressively control cardiovascular risk factors, and 
tailor drug therapy for optimal benefit. This article provides practical 
guidelines to achieve these goals and specific strategies to ameliorate 
cardiovascular and metabolic risk in the IRS.