Vincent Rigalleau1, Henri Gin. 1. Université de Bordeaux 2-Victor Segalen, Bordeaux, France. vincent.rigalleau@wanadoo.fr
Abstract
PURPOSE OF REVIEW: Most uraemic patients are insulin resistant. This review focuses on the occurrence, mechanisms and consequences of this insulin resistance. Hypoglycaemia is also possible in a minority of uraemic patients; its causes are discussed at the end of the review. RECENT FINDINGS: Insulin resistance is detectable when the glomerular filtration rate is below 50 ml/min per 1.73 m in non-diabetic uraemic individuals. Uraemia can alter insulin sensitivity even in diabetic patients; familial insulin resistance may favour the occurrence of diabetic nephropathy. Although reduced glucose non-oxidative disposal is the most evident defect of carbohydrate metabolism, abnormal glucose oxidation, endogenous glucose production and insulin secretion are also contributors. The accumulation of nitrogenous compounds is the most important mechanism of a specific state of insulin resistance in uraemia. Their identification is progressing, particularly in the field of carbamoylated amino acids. The consequences of chronic renal failure such as anaemia, metabolic acidosis and secondary hyperparathyroidism also indirectly play a role. SUMMARY: The treatment of uraemia by renal replacement therapies or low-protein diets improves insulin sensitivity. However, patients still have a high cardiovascular risk. The identification of the accumulating molecular species that specifically alter insulin sensitivity is therefore of great interest. The favourable effect of non-specific insulin sensitizers such as glitazone may also help to reduce this risk.
PURPOSE OF REVIEW: Most uraemic patients are insulin resistant. This review focuses on the occurrence, mechanisms and consequences of this insulin resistance. Hypoglycaemia is also possible in a minority of uraemic patients; its causes are discussed at the end of the review. RECENT FINDINGS:Insulin resistance is detectable when the glomerular filtration rate is below 50 ml/min per 1.73 m in non-diabetic uraemic individuals. Uraemia can alter insulin sensitivity even in diabeticpatients; familial insulin resistance may favour the occurrence of diabetic nephropathy. Although reduced glucose non-oxidative disposal is the most evident defect of carbohydrate metabolism, abnormal glucose oxidation, endogenous glucose production and insulin secretion are also contributors. The accumulation of nitrogenous compounds is the most important mechanism of a specific state of insulin resistance in uraemia. Their identification is progressing, particularly in the field of carbamoylated amino acids. The consequences of chronic renal failure such as anaemia, metabolic acidosis and secondary hyperparathyroidism also indirectly play a role. SUMMARY: The treatment of uraemia by renal replacement therapies or low-protein diets improves insulin sensitivity. However, patients still have a high cardiovascular risk. The identification of the accumulating molecular species that specifically alter insulin sensitivity is therefore of great interest. The favourable effect of non-specific insulin sensitizers such as glitazone may also help to reduce this risk.