Abstract Insulin resistance (IR) is common in chronic hemodialysis (CHD) patients and is associated with excess mortality. The gold standard for assessment of insulin sensitivity is hyperinsulinemic euglycemic clamp studies which pro- vide the precision and accuracy necessary, especially for mechanistic studies. However, clamp studies are labor- intensive and complicated for more practical use. Accordingly, additional indices such as homeostatic model assessment of insulin resistance (HOMA), quanti- tative insulin sensitivity check index, and adipokine- based measurements represent appropriate alternatives for large epidemiological and interventional studies. The etiology of IR in the CHD population is complex and mul- tifactorial. The predominant pathophysiological mecha- nism of ‘uremic insulin resistance’ is a post-receptor defect in the skeletal muscle; however, other glucose metabo- lism abnormalities are also present. Some of the pro- posed determinants of IR in CHD patients include chronic inflammation, excess visceral fat, adipokine deregulation and accumulation, metabolic acidosis, oxidative stress, vitamin D deficiency, anemia, decreased physical activity, and accumulation of uremic toxins. The relative impor- tance of each of these abnormalities is not well-defined, although excess visceral fat and inflammation seem to be the most important correlates of IR in this patient popula- tion. There are only few interventional studies targeted at improving insulin resistance in CHD patients. Insulin sen- sitizers such as metformin and PPAR-γ agonists are either contraindicated or sparingly used due to their potential side effects, even in CHD patients with overt diabetes mellitus. More novel approaches to improving IR in this patient population might lead to potential strategies for preventing excess mortality. Copyright © 2011 S. Karger AG, Basel The death rate in chronic hemodialysis patients (CHD) is unacceptably high, with adjusted all- cause mortality between 6.4 and 7.8 times higher for CHD patients compared to the US general population [1]. Insulin resistance (IR) is highly prevalent in CHD patients [2, 3]. It is an estab- lished risk factor for the development of car- diovascular disease and all-cause mortality in the general population [4, 5] and in the CHD population [6, 7]. Strategies aimed at preventing or improving IR might therefore represent novel interventions for improving poor clinical out- comes in CHD patients. Assessment of Glucose Metabolism and Insulin Sensitivity Given its strong correlation with poor clinical outcomes, appropriate measurement of insu- lin sensitivity is critically important in CHD patients. These measurements are not only Lipid Disorders and Metabolism Ronco C, Rosner MH (eds): Hemodialysis: New Methods and Future Technology. Contrib Nephrol. Basel, Karger, 2011, vol 171, pp 127–134 Factors Determining Insulin Resistance in Chronic Hemodialysis Patients Adriana M. Hung a,b  T. Alp Ikizler a,b a Veterans Administration Tennessee Valley Healthcare System, and b Vanderbilt University Medical Center, Nashville, Tenn., USA