title: High prevalence of glucose-6-phosphate dehydrogenase deficiency without gene mutation suggests a novel genetic mechanism predisposing to ketosis-prone diabetes.
abstract: BACKGROUND
  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 beta-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.
  
  
  METHODS
  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.
authors.affiliation: Department of Endocrinology and Diabetes, St. Louis Hospital, University of Paris VII School of Medicine, France.
authors.forename: Eugene
authors.initials: E
authors.lastname: Sobngwi
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gautier
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Kevorkian
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Villette
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Riveline
authors.forename: Sumei
authors.initials: S
authors.lastname: Zhang
authors.forename: Patrick
authors.initials: P
authors.lastname: Vexiau
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
authors.forename: Christian
authors.initials: C
authors.lastname: Vaisse
authors.forename: Franck
authors.initials: F
authors.lastname: Mauvais-Jarvis
mesh_terms: D000354:Africa, Western / Q000208:ethnology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics; D016883:Diabetic Ketoacidosis / Q000453:epidemiology* / Q000235:genetics*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007515:Islets of Langerhans / Q000503:physiopathology; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012720:Severity of Illness Index
chemical_list: D005954:Glucosephosphate Dehydrogenase