Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Silverchair Information Systems full text link Silverchair Information Systems Free PMC article
Full text links

Actions

Share

.2005 Aug;90(8):4446-51.
doi: 10.1210/jc.2004-2545. Epub 2005 May 24.

High prevalence of glucose-6-phosphate dehydrogenase deficiency without gene mutation suggests a novel genetic mechanism predisposing to ketosis-prone diabetes

Affiliations

High prevalence of glucose-6-phosphate dehydrogenase deficiency without gene mutation suggests a novel genetic mechanism predisposing to ketosis-prone diabetes

Eugene Sobngwi et al. J Clin Endocrinol Metab.2005 Aug.

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 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.

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.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Prevalence of G6PD deficiency in KPD. A, REA in controls, T2DM, and KPD subjects. Results are expressed as the mean ± SE (percentage). *, By ANOVA: F = 7.80;P = 0.001. B, Prevalence of erythrocyte G6PD deficiency in controls, T2DM, and KPD subjects (percentage of the population). *,P = 0.005, KPDvs. T2DM;P = 0.006, KPDvs. controls. Relation between G6PD deficiency and insulin secretion in KPD. C,β-Cell insulin secretory reserve was assessed in a cohort of normoglycemic controls (n = 7), KPD patients (n = 34), and T2DM patients (n = 36) by measuring basal C peptide (0 min) and C peptide response after an iv glucagon injection (8 min). Data represent the mean ± SE. *,P < 0.01. D, Correlation between residual erythrocyte G6PD activity (percentage) and glucagon-stimulated incremental C peptide (nanograms per milliliter) in 34 patients with KPD. Spearman rank-order correlation coefficient: rs = −0.33;P = 0.04.
FIG. 2.
FIG. 2.
Proposed mechanism for the predisposition to KPD.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mauvais-Jarvis F, Sobngwi E, Porcher R, Riveline JP, Kevorkian JP, Vaisse C, Guillausseau PJ, Charpentier G, Vexiau P, Gautier JF 2004. Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of β-cell dysfunction and insulin resistance. Diabetes 53:645–653 - PubMed
    1. Mauvais-Jarvis F, Smith SB, Le May C, Leal SM, Gautier JF, Molokhia M, Riveline JP, Rajan AS, Kevorkian JP, Zhang S, Vexiau P, German MS, Vaisse C 2004. PAX4 gene variations predispose to ketosis-prone diabetes. Hum Mol Genet 13:3151–3159 - PMC - PubMed
    1. Umpierrez GE, Casals MM, Gebhart SP, Mixon PS, Clark WS, Phillips LS 1995. Diabetic ketoacidosis in obese African-Americans. Diabetes 44:790–795 - PubMed
    1. Poitout V, Robertson RP 2002. Minireview: secondary β-cell failure in type 2 diabetes: a convergence of glucotoxicity and lipotoxicity. Endocrinology 143: 339–342 - PubMed
    1. Prentki M, Joly E, El-Assaad W, Roduit R 2002. Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: role in β-cell adaptation and failure in the etiology of diabetes. Diabetes 51(Suppl 3):S405–S413 - PubMed

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full text links
Silverchair Information Systems full text link Silverchair Information Systems Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp