Previously, we described patients with ketosis-prone type 2 diabetes (KPD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but no mutation of the G6PD gene. Our present study used two complementary approaches to test whether hyperglycaemia might inhibit G6PD activity: (1) effect of acute hyperglycaemia induced by glucose ramping; and (2) effect of chronic hyperglycaemia using correlation between G6PD activity and HbA_1c levels.

In the first substudy, 16 KPD patients were compared with 11 healthy, non-diabetic control subjects of the same geographical background. Erythrocyte G6PD activity and plasma glucose were assessed at baseline and every 40min during intravenous glucose ramping that allowed maintaining hyperglycaemia for more than 3h. In the second substudy, erythrocyte G6PD activity and HbA_1c levels were evaluated in 108 consecutive African patients with either type 2 diabetes or KPD, and a potential correlation sought between the two variables.

The maximum plasma glucose level after 200min of glucose perfusion was 20.9±3.7mmol/L for patients and 10.7±2.3mmol/L for controls. There was no difference between baseline and repeated G6PD activity levels during acute hyperglycaemia in either KPD patients (P=0.94) or controls (P=0.57), nor was there any significant correlation between residual erythrocyte G6PD activity and HbA_1c levels (r=−0.085, P=0.38).

Neither acute nor chronic hyperglycaemia affects erythrocyte G6PD activity. Thus, hyperglycaemia alone does not explain cases of G6PD deficiency in the absence of gene mutation as described earlier.