Glucose Toxicity

Abstract

Chronic hyperglycemia is not only a marker of the diabetes state but also a factor that itself worsens the diabetic state by impairing glucose‐induced insulin secretion and insulin sensitivity. In patients with type 1 diabetes, maintenance of excellent glycemic control early in the course of the disease prolongs remission by preserving insulin secretion and normalizing insulin sensitivity. In these patients, chronic hyperglycemia can be regarded as a major cause for peripheral insulin resistance. Consequently, if excellent glycemic control is achieved, insulin sensitivity is normal. In patients with type 2 diabetes, glucose toxicity concept is likely to explain at least part of the beneficial effects of exogenous insulin therapy and weight loss on endogenous insulin secretion and insulin sensitivity.

Effect of increasing duration of diabetes mellitus type 2 on glycated hemoglobin and insulin sensitivity

“…To be healthy our body needs to produce the right amount of insulin and respond to the insulin appropriately. A confounding factor is that hyperglycemia and hyperinsulinemia in themselves can impair insulin secretion and insulin sensitivity (16,17,18). The body becomes more resistant to insulin with increasing duration of diabetes, so that insulin level is high or normal in the body but the available insulin is insufficient (19).…”

Thioredoxins, Glutaredoxins, and Peroxiredoxins—Molecular Mechanisms and Health Significance: from Cofactors to Antioxidants to Redox Signaling

“…Consequently, both conditions prohibit the regulation and cellular uptake of glucose and lead to hyperglycemia. Long-term, chronic hyperglycemia or ''glucose toxicity'' can affect various tissues, manifesting, for instance, in increased susceptibility to infections, micro-vascular complications as in retinopathy and neuropathy, atherosclerosis, and cardiovascular and neurological damage (375,850). Generation of ROS potentially via the reduction of sugars (366), the hexosamine pathway (367), and/or the mitochondrial respiratory chain (671) seems to be correlated to chronic hyperglycemia and the establishment of diabetes (78, 375) and diabetic complications (388).…”

Low Insulin-like Growth Factor-II Levels Predict Weight Gain in Normal Weight Subjects with Type 2 Diabetes

“…In study III we report from a group of patients with T2D that exhibited signs of secondary failure. The rationale for study III was the observations that chronic hyperglycemia attenuates insulin secretion and increases insulin resistance, (Rossetti, Giaccari et al 1990;Yki-Jarvinen 1992), and reports of improved betacell function and insulin sensitivity after "beta-cell rest" (Kosaka, Kuzuya et al 1980;Garvey, Olefsky et al 1985;Glaser, Leibovich et al 1988). Secondary failure has implications for choice of treatment and the risk for late complications second to deteriorated glucose control.…”

“…Secondary failure may, in part, be secondary to the diabetic state per se. Chronic hyperglycaemia thus attenuates insulin secretion and lowers sensitivity to insulin (Rossetti, Giaccari et al 1990;Leahy, Bonner-Weir et al 1992;Yki-Jarvinen 1992;Robertson, Olson et al 1994)." Glucotoxicity" is term frequently encoun-tered in the literature.…”