Key result
G6PD deficiency in men with high glucose is linked to an ~81% steeper increase in PWV.
Why the study?
An association between G6PD deficiency and arterial stiffness had been cross-sectionally reported in diabetic subjects in Sardinia, but longitudinal sex differences, the impact of hyperglycemia, and underlying mechanisms were unknown.
Does glucose-6-phosphate dehydrogenase deficiency accelerate the trajectory of arterial stiffness in individuals with high glucose?
Cohort (n=4,000)
Does glucose-6-phosphate dehydrogenase deficiency accelerate the trajectory of arterial stiffness in individuals with high glucose?
Absolute Event Rate: 12.5% vs 6.9%
G6PD deficiency is associated with an accelerated increase in arterial stiffness in men with high glucose, but not in women, highlighting a sex-specific interaction between glucose metabolism and vascular aging.
Hypothesis-generating for sex-specific G6PDdef effects on arterial stiffness progression in hyperglycemia; prospective studies needed before clinical adoption.
BACKGROUND: An association between glucose-6-phosphate dehydrogenase deficiency (G6PDdef) and arterial stiffness has cross sectionally been reported in diabetic, but not in nondiabetic, subjects in Sardinia. The aims of the present longitudinal study were to evaluate: (1) sex differences in the influence of G6PDdef on trajectory of arterial stiffness; (2) the impact of hyperglycemia on trajectory of arterial stiffness; and (3) mechanistic pathways underlying this influence. METHODS: In the Sardinia Study, repeated measurements of pulse-wave velocity were analyzed to characterize trajectories of arterial stiffness in >4000 men and women, aged 20 to 100 years, during a 9.4-year follow-up. RESULTS: In men with high glucose, G6PDdef was associated with a steeper longitudinal increase in pulse-wave velocity (yearly change: 12.5 versus 6.9 cm/s in those without G6PDdef). In contrast, in women with high glucose, the longitudinal change is not influenced by the presence or absence of G6PDdef (yearly change: 4.5 cm/s in both groups). With high glucose, men with G6PDdef showed similar trends in fat deposition, but no substantial increase in triglycerides, over time compared with those without G6PDdef. Conversely, women with G6PDdef showed a greater gluteofemoral fat deposition over time, with no increase in visceral fat deposition, and a similar trajectory in triglycerides compared with those without G6PDdef. CONCLUSIONS: Lower G6PD activity is associated with an accelerated increase in arterial stiffness in men, but not in women. This effect is accompanied by sex-specific changes in metabolic factors. Future studies will characterize the link between metabolic reprogramming and changes in arterial stiffness.
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Scuteri et al. (2026) conducted a cohort in Arterial stiffness (n=4,000). G6PD deficiency vs. No G6PD deficiency was evaluated on Trajectory of arterial stiffness (pulse-wave velocity). In men with high glucose, G6PD deficiency was associated with a steeper longitudinal increase in pulse-wave velocity (12.5 vs 6.9 cm/s per year), whereas no such effect was observed in women.
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