Hyperglycaemia per se does not affect erythrocyte glucose-6-phosphate dehydrogenase activity in ketosis-prone diabetes.
OBJECTIVE
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 HbA1c levels.


METHODS
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 40 min during intravenous glucose ramping that allowed maintaining hyperglycaemia for more than 3h. In the second substudy, erythrocyte G6PD activity and HbA1c levels were evaluated in 108 consecutive African patients with either type 2 diabetes or KPD, and a potential correlation sought between the two variables.


RESULTS
The maximum plasma glucose level after 200 min of glucose perfusion was 20.9±3.7 mmol/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 HbA1c levels (r=-0.085, P=0.38).


CONCLUSIONS
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.
Department of Diabetes and Endocrinology, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, University Paris-Diderot Paris-7, 75010 Paris, France; Clinical Investigation Centre, Inserm-CIC9504, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, University Paris-Diderot Paris-7, 75010 Paris, France; Department of Internal Medicine and Paediatrics, Faculty of Health Sciences, University of Buea, Buea, Cameroon.
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Choukem
Department of Diabetes and Endocrinology, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, University Paris-Diderot Paris-7, 75010 Paris, France; Clinical Investigation Centre, Inserm-CIC9504, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, University Paris-Diderot Paris-7, 75010 Paris, France; Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
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Sobngwi
Biochemistry Laboratory, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, Faculty of Pharmacy, 75010 Paris, France.
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JP
Garnier
Biochemistry Laboratory, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, Faculty of Pharmacy, 75010 Paris, France.
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Letellier
Division of Endocrinology and Metabolism, Tulane University Health Sciences Center, School of Medicine, New Orleans, LA 70112, USA.
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Mauvais-Jarvis
Clinical Investigation Centre, Inserm-CIC9504, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, University Paris-Diderot Paris-7, 75010 Paris, France.
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Calvo
Department of Diabetes and Endocrinology, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, University Paris-Diderot Paris-7, 75010 Paris, France; Clinical Investigation Centre, Inserm-CIC9504, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris, University Paris-Diderot Paris-7, 75010 Paris, France; Inserm UMRS 1138, Cordeliers Research Centre, University Pierre-et-Marie-Curie Paris-6, 75006 Paris, France. Electronic address: jean-francois.gautier@lrb.aphp.fr.
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Gautier
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D016883:Diabetic Ketoacidosis / Q000097:blood / Q000150:complications / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000097:blood / Q000378:metabolism*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood* / Q000150:complications; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D005954:Glucosephosphate Dehydrogenase
Africans; G6PD; Hyperglycaemia; Ketosis-prone diabetes; Oxidative stress