Factors determining insulin resistance in chronic hemodialysis patients

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 provide 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), quantitative 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 multifactorial. The predominant pathophysiological mechanism of 'uremic insulin resistance' is a post-receptor defect in the skeletal muscle; however, other glucose metabolism abnormalities are also present. Some of the proposed 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 importance 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 population. There are only few interventional studies targeted at improving insulin resistance in CHD patients. Insulin sensitizers 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.