This Article Full Text Full Text (PDF) All Versions of this Article: 90/8/4446    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sobngwi, E. Articles by Mauvais-Jarvis, F. Search for Related Content PubMed PubMed Citation Articles by Sobngwi, E. Articles by Mauvais-Jarvis, F. Related Collections Diabetes and Insulin Metabolism

High Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency without Gene Mutation Suggests a Novel Genetic Mechanism Predisposing to Ketosis-Prone Diabetes

Departments of Endocrinology and Diabetes (E.S., J.-F.G., P.V., F.M.-J.) and Biochemistry (J.-M.V.), St. Louis Hospital, University of Paris VII School of Medicine, and Institut National de la Santé et de la Recherche Médicale, Unité 465 (E.S., J.-F.G., P.V., F.M.-J.), 75010 Paris, France; Diabetes Center and Department of Medicine, University of California San Francisco (S.Z., C.V., F.M.-J.), San Francisco, California 94143; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine (F.M.-J.), and Department of Molecular and Human Genetics (S.M.L.), Baylor College of Medicine, Houston, Texas 77030; Department of Internal Medicine B, Lariboisiere Hospital (J.-P.K.), 75010 Paris, France; and Department of Diabetes and Metabolic Diseases, Sud Francilien Hospital (J.-P.R.), 91100 Corbeil-Essonnes, France

Address all correspondence and requests for reprints to: Dr. Franck Mauvais-Jarvis, Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, BCMA 700B, Houston, Texas 77030. E-mail: fmjarvis{at}bcm.edu.

Abstract

Context: Ketosis-prone diabetes (KPD) is mostly observed in males of West African descent and is characterized by phasic or permanent insulin dependence without apparent autoimmune process.

Objective: KPD subjects display a propensity to hyperglycemia-induced acute insulin deficiency, suggesting that they exhibit a propensity to oxidative stress in ß-cells. The enzyme glucose-6-phosphate dehydrogenase (G6PD) is a defense mechanism against oxidative stress, and G6PD deficiency, an X-linked genetic disorder with male predominance, is frequent in West Africans. We hypothesized that mutations in the G6PD gene could predispose to KPD.

Design: We studied G6PD erythrocyte enzyme activity and the insulin secretory reserve (glucagon-stimulated C peptide) in a cohort of hospitalized West Africans with KPD (n = 59) or type 2 diabetes (T2DM; n = 59) and in normoglycemic controls (n = 55). We also studied the G6PD gene in an extended population of KPD patients (n = 100), T2DM patients (n = 59), and controls (n = 85).

Results: The prevalence of G6PD deficiency was higher in KPD than in T2DM and controls (42.3%; 16.9%; 16.4%; P = 0.01). In KPD, but not in T2DM, insulin deficiency was proportional to the decreased G6PD activity (r = 0.33; P = 0.04). We found no increase in the prevalence of G6PD gene mutations in KPD compared with T2DM and controls. Rather, we found a 20.3% prevalence of G6PD deficiency in KPD without gene mutation.

Conclusions: This study suggests that 1) G6PD deficiency alone is not causative of KPD; and 2) alterations in genes controlling both insulin secretion and G6PD-mediated antioxidant defenses may contribute to the predisposition to KPD in West Africans.

This article has been cited by other articles:

				A. Balasubramanyam, R. Nalini, C. S. Hampe, and M. Maldonado Syndromes of Ketosis-Prone Diabetes Mellitus Endocr. Rev., May 1, 2008; 29(3): 292 - 302. [Abstract] [Full Text] [PDF]

				A. E. Kitabchi, G. E. Umpierrez, M. B. Murphy, and R. A. Kreisberg Hyperglycemic Crises in Adult Patients With Diabetes: A consensus statement from the American Diabetes Association Diabetes Care, December 1, 2006; 29(12): 2739 - 2748. [Full Text] [PDF]

				C. Sze, D. Gould, G. Hitman, and T. A Chowdhury Relapsing and remitting insulin requiring diabetes: type 1 or type 2? J R Soc Med, August 1, 2006; 99(8): 415 - 416. [Full Text] [PDF]