Black women exhibit lower vitamin D levels and higher cardiometabolic risk than white women. The vitamin D-PTH endocrine system influences cardiometabolic factors through the vitamin D receptor, affecting insulin/glucose metabolism, the renin-angiotensin-aldosterone system (RAAS), and other processes. While clinical trials on vitamin D supplementation for diabetes prevention have yielded inconclusive results, observational studies suggest links between vitamin D deficiency and diabetes-related comorbidities. This study aimed to explore the joint associations of 25(OH)D and PTH with diabetes and comorbidities (obesity, hypertension, CKD) in a multiethnic cohort of postmenopausal women.

Existing literature highlights disparities in vitamin D status and cardiometabolic health between Black and White Americans. Studies show lower 25(OH)D levels in Black individuals, potentially due to reduced vitamin D synthesis. Black individuals also experience greater cardiometabolic risk. The vitamin D and PTH system is involved in regulating multiple cardiometabolic risk factors, including insulin/glucose metabolism, the RAAS, endothelial function, and immune response. Observational studies consistently demonstrate associations between vitamin D deficiency and diabetes-related disorders like obesity, hypertension, and CKD. However, research on the synergistic effects of vitamin D and PTH on cardiometabolic outcomes is limited.

This cross-sectional and prospective study analyzed data from 1850 Black and 3000 White postmenopausal women from the Women's Health Initiative-Observational Study (WHI-OS), excluding those with cardiovascular disease or dialysis. Weighted Cox proportional hazards analyses and weighted logistic regression models assessed the joint associations of 25(OH)D and PTH with incident diabetes and the prevalence of obesity, hypertension, and CKD. Baseline characteristics were compared using Kruskal-Wallis or χ² tests. Age-adjusted Spearman correlation coefficients analyzed associations between vitamin D biomarkers and cardiometabolic biomarkers. Inverse-probability weighted Cox proportional hazards models examined prospective associations with incident diabetes. Weighted logistic regression models assessed cross-sectional associations with comorbidities. The study controlled for age, race, clinical center, BMI, education, season of blood draw, smoking, alcohol consumption, physical activity, family history of diabetes, and postmenopausal hormone therapy use. Sensitivity analyses adjusted for eGFR, history of high cholesterol, and statin use.

The study identified 453 incident diabetes cases and 3322 prevalent cases of obesity, hypertension, or CKD. Cross-sectionally, lower 25(OH)D and higher PTH were independently associated with higher hypertension prevalence in White women. In non-diabetic women, vitamin D deficiency and PTH excess were associated with a higher prevalence of CKD, hypertension, or obesity (OR = 4.23; 95% CI: 2.90–6.18) compared to diabetic women (OR = 1.89; 95% CI: 0.96–3.71). Prospectively, lower 25(OH)D was associated with lower diabetes incidence (HR = 0.73; 95% CI: 0.62–0.86) in White women. Vitamin D deficiency increased diabetes risk in White women, regardless of PTH levels. Weighted distributions of 25(OH)D and PTH differed significantly between White and Black women stratified by diabetes status and comorbidities. Lower 25(OH)D or higher PTH was associated with greater obesity and composite endpoint prevalence across racial groups, with hypertension significance only in White women. The combination of vitamin D deficiency and PTH excess was associated with higher comorbidity prevalence in non-diabetic women only.

The findings support previous research showing links between vitamin D deficiency and diabetes risk, particularly in White women. The study's novel contribution lies in examining the combined effect of vitamin D and PTH. The stronger associations of vitamin D deficiency and PTH excess with comorbidities in non-diabetic women suggest a potential modifying role of diabetes. The racial differences observed highlight the complexity of vitamin D-PTH interplay and its impact on cardiometabolic health. Possible mechanisms include the RAAS, lipogenesis, insulin secretion, inflammation, and endothelial function, influenced by race-specific differences in vitamin D/PTH response.

This study demonstrates a joint association between vitamin D deficiency and PTH excess with diabetes risk in White postmenopausal women. Both deficiency and excess were associated with cardiometabolic comorbidities regardless of diabetes status, but the combined effect was more pronounced in non-diabetic women. Future research should confirm these findings and explore race-specific thresholds for vitamin D and PTH, guiding the design of effective vitamin D supplementation strategies.

The cross-sectional design limits causal inference. Single biomarker measurements might lead to underestimation of effects. Residual confounding from sun exposure, dietary intake, and other factors remains a possibility. The findings might not be generalizable to men or other populations.