Article Summary Diagnosis of insulin resistance and associated syndromes: the spectrum from the metabolic syndrome to type 2 diabetes mellitus. Simonson GD, Kendall DM. Coronary Artery Disease. 2005;16:465-472. Objective: to review the current definition and diagnosis of insulin resistance (IR), IR syndrome (IRS), and metabolic syndrome (MS); to measure IR, and to examine the potential clinical markers that may have application for everyday practice with the goal of delaying or preventing type 2 diabetes and limiting cardiovascular disease (CVD) risk. Background: AIR has been implicated as a central underlying pathophysiologic feature of a constellation of metabolic abnormalities (eg, glucose intolerance, dyslipidemia, hypertension, hyperuricemia, endothelial dysfunction, and a prothrombotic, proinflammatory vascular environment). This constellation of metabolic abnormalities has been grouped into syndromes associated with IR (ie, IRS, MS). Together, they are a common physiologic abnormality whose cause is not well understood. They have been defined as the lowest range of insulin action as measured by a variety of techniques, but from a clinical perspective could be defined as a level of resistance above which there is a substantial risk for developing overt type 2 diabetes or CVD. Methods: IR is measured by a variety of techniques, including, hyperinsulinemic-euglycemic clamp technique, frequently sampled IV glucose tolerance test, mathematical models for estimating IR using fasting insulin and glucose levels, fasting and stimulated insulin levels, and measures of obesity, body mass and adiposity, among others. The various methods are described in this review article and the advantages and disadvantages of the most commonly used approaches are outlined in the article. While there is little agreement as to the best means for doing so, a practical clinically relevant means to determine IR is suggested. Recommendation: Recent data support the recommendation that simple morphologic measures (ie, the presence of a BMI ≥ 29kg/m2 in both non-Hispanic and Hispanic whites and African Americans can serve as a reliable, easily measured and appropriate determinant of IR in the general population. Several studies have demonstrated BMI as appropriately predictive of IR, and the observation that elevated BMI is strongly associated with both CVD risk, the presence of CVD risk factors, and the future development of diabetes. Fasting glucose and fasting insulin values do not appear to provide superior diagnostic sensitivity. Additional clinical data (elevated triglycerides, low-HDL cholesterol, hypertension, and glucose intolerance) also provide additional support for the diagnosis of IR. Conclusion: The authors express concern over the ambiguity of the current definitions of MS and suggest that underlying pathophysiology is not currently well understood. IR is an increasingly common disorder and is associated with substantial risk for CVD and diabetes, although its role remains unclear. Several therapies (eg, thiazolidinedione class) allow clinicians to target IR directly and may reduce the risk of MI, stroke, and death in those high-risk individuals with diabetes.