[Clinical importance and pathogenic mechanisms of insulin resistance in chronic renal insufficiency (part I): insulin resistance in patients with chronic renal insufficiency].
BACKGROUND
This paper presents new investigations of abnormal insulin action in patients with chronic renal failure. Reduced tissue sensitivity to insulin action and the effects of the impairments on carbohydrate, protein and lipid metabolism have important pathophysiological implications in the genesis of the uremic syndrome. We analyzed confounding factors of reduced insulin sensitivity and potential sites of insulin resistance.
Insulin resistance is associated with a number of metabolic and vascular abnormalities known as "syndrome X" or metabolic syndrome. Other features include obesity, particularly truncal distribution, glucose intolerance and non-insulin-dependent diabetes mellitus (NIDDM), hypertension, a specific dyslipidemia with raised triglyceride concentrations and a high low-density lipoprotein: high-density lipoprotein ratio, and hyperuricemia. These features, are all associated with accelerated atherogenesis and cardiovascular disease, the main cause of premature mortality. Some genetic (mutations affecting postreceptor signalling pathways) and environmental factors that could contribute to insulin resistance are discussed.
The most prominent metabolic disturbance in uremic patients is insulin resistance due to a post-receptor defect. Insulin secretion is also impared, because the pancreatic beta-cell response to hyperglycemia is blunted. Insulin clearance by renal and extrarenal mechanisms is reduced.
Increase in hepatic glucose production or impaired hepatic glucose uptake were overestimated. Impaired glucose uptake by peripheral tissues, primarily muscle and adipose tissue, has been extensively studied, and there is abundant evidence in patients with chronic renal failure. Decrease in renal glucose production would lead to a decrease in glucose appearance in circulation and decrease of insulin sensitivity.


CONCLUSIONS
Cellular basis for insulin resistance in uremic patients is, however, unknown. It is now recognized that insulin-stimulated glucose transport in skeletal muscles and in other peripheral tissues is reduced. Although the majority of uremic patients are insulin resistant and about half of them are glucose intolerant, they are rarely diabetics. But, there are clinical implications of abnormal insulin metabolism in uremia. Cardiovascular complications are the most important consequences and significant cause of mortality in these patients.
Rasić-Milutinović
Z
Z
Odeljenje za endokrinologiju, Klinicko-bolnicki centar Zemun/Beograd.
Perunicić-Peković
G
G
D006801:Humans; D007333:Insulin Resistance; D007676:Kidney Failure, Chronic / Q000378:metabolism*