No glucotoxicity after 53 hours of 6.0 mmol/l hyperglycaemia in normal man

In vitro and in vivo studies have suggested that metabolic deterioration can be induced by hyperglycaemia per se. The effect of 53 h of 2.2 mg glucose · kg ideal body weight−1· min−1 was examined in four normal male subjects. This produced overnight hyperglycaemia of 6.0 mmol/l on the two nights of the study compared with 4.7 mmol/l on the control night (p<0.05). In response there was a sustained, two-fold increase in basal plasma insulin (p<0.005) and C-peptide (p<0.05) levels. After two days of hyperglycaemia an increased Beta-cell response was demonstrated in response to an additional glucose infusion stimulus (estimated Beta-cell function median of 84% on the control day to 100% after two days glucose infusion). Plasma insulin and C-peptide responses to a 10.0 mmol/l hyperglycaemic clamp increased over the two days of the study (insulin from median 48 mU/l to 73 mU/l and C-peptide from median 2.0 pmol/ml to 2.6 pmol/ml). Glucose tolerance to the additional glucose infusion stimulus improved, suggesting that the increased insulin response during hyperglycaemia was enhancing peripheral glucose uptake. The calculated peripheral insulin sensitivity was unchanged during the hyperglycaemic clamp. Thus, in response to the two days of basal hyperglycaemia, both the basal and stimulated Beta-cell responses were enhanced and there was no evidence for ‘glucose toxicity’ to the Beta-cells.