[Clinical significance and pathogenic mechanisms of insulin resistance in chronic renal insufficiency (part II): pathogenic factors of insulin resistance in chronic renal insufficiency].

Introduction: Factors implicated in the pathogenesis of insulin resistance in chronic renal failure are: uremic toxins, exercise tolerance, metabolic acidosis, secondary hyperparathyroidism, vitamin D deficiency. Many of them may contribute, but are not the main cause of insulin resistance in uremia. The aim of this review is to debate about each, separately.

Uremic Toxins: Hippurate and pseudouridine are specific for uremia and inhibit glucose utilization at concentrations found in sera of uremic subjects. Partially purified toxins from uremic sera, after hemodialysis therapy, ameliorate beta-cell response to hyperglycemia and increase tissue sensitivity to insulin.

Exercise Intolerance: Exercise intolerance is common among hemodialysis patients, and also it can be the cause of insulin resistance. Moderate endurance training program improved both the exercise tolerance and insulin sensitivity in patients on hemodialysis.

Metabolic Acidosis: Metabolic acidosis is frequent in uremia, but not in hemodialysis patients. Treatment of metabolic acidosis increases insulin sensitivity and insulin secretion, but significant degree of insulin resistance still exists in uremic patients.

Secondary Hyperparathyroidism: After surgical correction of hyperparathyroidism, in hemodialysis patients, glucose tolerance and insulin secretion increase without significant changes in insulin sensitivity. Defect in insulin release attributable to reduced ATP content in the pancreatic islets induced partially by high intracellular calcium, secondary to augmented PTH-induced calcium entry into cells.

Vitamin D Deficiency: Acute and chronic intravenous 1,25-Dihydroxycholecalciferol therapy corrects insulin resistance in dialysis patients, in absence of PTH suppression. These results are consistent with the hypothesis that 1,25(OH)2 D3 deficiency is a primary factor of insulin resistance.

Erythropoietin Therapy: Corrects insulin resistance beside anaemia.

Conclusion: Now we know more about pathogenesis of insulin resistance in uremic patients, and we must begin with early treatment of every pathogenic factor. Insulin sensitivity improved after hemodialysis, although it was still lower than control values.