Sex-specific differences in overnight nitrate levels in persons with obstructive sleep apnea and type 2 diabetes

Sex-specific differences in OSA-associated symptoms and polysomnographic findings are well recognized. However, sex differences in intermediate pathways potentially linking OSA and cardiometabolic outcomes are limited. OSA is known to be associated with decreased nitric oxide (NO)-related vasodilation and endothelial dysfunction. The current study sought to characterize the independent association between OSA severity and overnight NO metabolites (i.e. markers of oxidative stress) and determine if there were differences by sex in persons with type 2 diabetes mellitus (T2DM).

Adults with T2DM and undiagnosed OSA were recruited from the community. Demographic information, an overnight polysomnogram, and pre- and post-sleep plasma samples were collected. The association between OSA and nitrite and nitrate levels were examined using multivariable linear regression. Analyses were done for the entire sample and stratified by sex.

The sample included 83 participants with 52 % men. Stratified, fully adjusted models showed that compared to women with mild OSA, women with moderate or severe OSA did not exhibit the expected decline in overnight nitrate levels: 4.84 microM (-12.3, 2.7: p = 0.09) and 5.82 microM (-4.7, 16.3: p < 0.01) for moderate and severe OSA, respectively. Overnight nitrate levels decreased in males regardless of OSA severity, without significant differences across severity categories. An interaction between OSA severity and sex was seen for post-sleep nitrates in women with severe OSA.

The association between OSA and overnight nitrates varies by sex and OSA severity. Women with severe OSA did not have a decline in overnight nitrate levels whereas men did, suggesting they have higher overnight oxidative stress.