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Glucose-6-phosphate dehydrogenase activity and genetic variants in tunisian diabetic populations: A case-control
Yessine Amri1, Mariem Othmani2, Nada Hannachi2
1Biochemistry Laboratory (LR00SP03), Bechir Hamza Children's Hospital, Tunis, Tunisia.
Background:
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common X-linked enzymopathy, is highly prevalent in North Africa and impairs antioxidant defense by reducing NADPH production. Its relationship with diabetes mellitus (DM) remains unclear.
Aims:
To assess G6PD enzymatic activity, determine the prevalence of G6PD deficiency, and identify common G6PD gene variants in Tunisian patients with type 1 (T1D) and type 2 diabetes mellitus (T2D).
Methods:
This case-control study included 45 T1D and 46 T2D patients, each matched by age and sex to healthy non-diabetic controls (n = 45 and n = 46, respectively). Complete blood count, reticulocyte count, HbA1c, and G6PD activity were measured. Deficiency was defined as <4U/g Hb in males and <5.84U/g Hb in females. ARMS-PCR screened deficient patients for the African Gd A⁻(202A) and Mediterranean B⁻(563T) variants.
Results:
G6PD activity (mean ± SD) did not differ significantly between T1D patients and controls (9.29 ± 2.18 vs. 9.07 ± 1.77 U/g Hb; p = 0.8523). T2D patients had significantly lower activity (5.90 ± 1.40 vs. 7.23 ± 2.16 U/g Hb; p = 0.0024), with a deficiency prevalence of 18.33 % (95 % CI: 9.52-30.44) versus 9.43 % (95 % CI: 3.13-20.66) in controls (p = 0.032, McNemar's test). G6PD activity showed a significant inverse correlation with fasting blood glucose (beta = -0.0058, SE = 0.0016, p = 0.001) and HbA1c (beta = -0.289, SE = 0.062, p < 0.001) in the T2D group. This suggests that poorer glycemic control is associated with reduced enzymatic antioxidant capacity, particularly when HbA1c exceeds a threshold of 8.4 %. Of 11 deficient patients, four heterozygous T2D females (30.36 %) carried the African GdA⁻ variant; no Mediterranean B⁻ variants were found.
Conclusion:
T2D is associated with reduced G6PD activity and higher deficiency prevalence in Tunisia, especially in poorly controlled patients. The predominance of the African Gd A⁻ variant highlights the need for population-specific screening to prevent oxidative stress-related complications and guide personalized diabetes care.
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