Joint effect of hyperuricemia and severe vitamin D deficiency on all-cause and cardiovascular mortality among individuals with diabetes

This study aims to investigate the individual and joint associations of hyperuricemia (HUA) and severe Vitamin D deficiency (SVDD) on the all-cause and cardiovascular disease (CVD) mortality among patients with diabetes mellitus (DM) by analyzing data from the National Health and Nutrition Examination Survey (NHANES). Data of DM patients aged ≥20 years from the NHANES 2001-2018 were included in this study. Survey-weighted multivariable cox proportional hazards regression models, Kaplan-meier curve and restricted cubic spline analysis were employed to evaluate the individual and joint associations of HUA and SVDD with the all-cause and CVD mortality of DM patients. Sensitivity analyses, propensity score matching, and stratified analyses were performed to test the stability of our findings. Mediation analysis based on SIRI and HbA1c was also conducted. A total of 7,869 (Weighted N=27512325) patients with DM aged 20 and older were involved. The weighted mean (standard deviation (SD)) level of SUA and 25-hydroxyvitamin D (25(OH)D) were 5.74 (1.58) mg/dL and 62.51 (27.80) nmol/L, respectively. The mean follow-up time was 6.83±4.63 years, and 1,967 deaths were documented. The all-cause and CVD mortality rates per 1,000 person-year among DM patients were 28.30 and 9.49, respectively. After adjusting for confounding factors, patients with HUA and SVDD exhibited the higher risk of all-cause [HR: 1.28 (1.09-1.50) for HUA and 1.44 (1.07-1.94) for SVDD] and CVD [HR: 11.54 (1.01-2.36) for HUA and 1.98 (1.19-3.28) for SVDD] mortality. Kaplan-Meier curves demonstrated a statistically significant difference in survival probability over different HUA and SVDD categories among DM patients. The joint analysis revealed that HUA and SVDD have a joint effect on all-cause mortality (HR: 1.90 [1.23-2.93]) and CVD mortality (HR: 2.60 [1.45-4.65]) among patients with DM. Sensitivity analysis, propensity score matching and stratified analyses confirmed the stability of the research results. Mediation analyses further revealed that 11.4% of the SUA-mortality association was mediated through SIRI, and 1.96% of the 25(OH)D-mortality association through glycated hemoglobinA1c (HbA1c). HUA and SVDD comorbidity is significantly associated with elevated risk of all-cause and CVD mortality in DM patients. These findings indicate that concurrent management of HUA and SVDD may improve prognosis of DM patients.