Glucose-6-Phosphate Dehydrogenase Modifies the Impact of Glucose on Arterial Aging in A Sex-Specific Manner

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.