[Glucose toxicity--pros and cons. Useful adaptation and common cause of insulin resistance in diabetic patients].

Insulin resistance is directly proportional to the degree of glycaemic control in patients with insulin-dependent or non-insulin-dependent diabetes mellitus (IDDM and NIDDM) in whom hyperglycaemia induces insulin resistance within 24 hours. Glucose toxicity (i.e., glucose-induced insulin resistance) explains why apparently unrelated therapeutic measures to improve glycaemic control (e.g., weight reduction, and sulphonylurea, metformin or insulin administration) all also increase insulin sensitivity. The improvement is manifest when insulin-stimulated glucose uptake is measured at similar glucose and insulin concentrations in IDDM and NIDDM patients. In daily life, however, both IDDM and NIDDM patients utilise as much glucose in insulin-sensitive tissues as do non-diabetic individuals since, due to the mass action effect of glucose, glucose uptake increases in response to hyperglycaemia. Recent studies have shown that the hexosamine pathway may act as a cellular glucose monitor maintaining steady state glucose flux under both normo- and hyper-glycemic conditions. Thus, glucose toxicity may be seen as a mechanism protecting insulin-sensitive tissues from excessive glucose uptake and diabetic complications.