Sex differences in the association between vitamin D and prediabetes in adults: A cross-sectional study

Background/Objectives: Vitamin D status has been shown to be associated with prediabetes risk. However, epidemiologic evidence on whether sex modulates the association between vitamin D and prediabetes is limited. The present study investigated sex-specific associations between vitamin D and prediabetes. Subjects/Methods: The Kuwait Wellbeing Study, a population-based cross-sectional study, enrolled nondiabetic adults. Prediabetes was defined as 5.7 ≤ HbA1c% ≤6.4; 25-hydroxyvitamin D (25(OH)D) was measured in venous blood and analyzed as a continuous, dichotomous (deficiency: <50 nmol/L vs. insufficiency/sufficiency ≥50 nmol/L), and categorical (tertiles) variable. Associations were evaluated by estimating adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), while stratifying by sex. Results: A total of 384 participants (214 males and 170 females) were included in the current analysis, with a median age of 40.5 (interquartile range: 33.0–48.0) years. The prevalence of prediabetes was 35.2%, and 63.0% of participants had vitamin D deficiency. Assessments of statistical interaction between sex and 25(OH)D status were statistically significant (P_{Sex × 25(OH)D Interaction} < 0.05). In the sex-stratified analysis, after adjustment for confounding factors, decreased 25(OH)D levels were associated with increased prevalence of prediabetes in males (aPR_{Deficiency vs. In-/Sufficiency}: 2.35, 95% CI: 1.36–4.07), but not in females (aPR_{Deficiency vs. In-/Sufficiency}: 1.03, 95% CI: 0.60–1.77). Moreover, the prevalence of prediabetes differed between males and females at 25(OH)D levels of ≤35 nmol/L, with a higher prevalence of prediabetes in males compared to females. Such a sex-specific difference was not observed at 25(OH)D levels of >35 nmol/L. Conclusions: Sex modified the association between vitamin D levels and prediabetes, with an inverse association observed among males, but not among females. Moreover, the observed sex-disparity in the prevalence of prediabetes was only pronounced at 25(OH)D levels of ≤35 nmol/L.