Kuo-Chuan Hung, Ting-Sian Yu, Yi-Chen Lai, Wei-Cheng Liu, I-Wen Chen
In this propensity-matched retrospective cohort study, preexisting hypothyroidism was associated with modest but statistically significant increases in delayed osseous and hardware-related complications after operative ankle fracture surgery (P < .05 for both outcomes at 6 months and 1 year). These findings should be interpreted as associative and warrant prospective validation.
BACKGROUND: Zinc deficiency is common in patients with type 2 diabetes mellitus (T2DM) and is associated with an increased susceptibility to infection. However, because sepsis reflects a dysregulated host response to infection, whether low zinc status is more strongly associated with sepsis than with nonsepsis infections in patients with T2DM remains unclear.
METHODS: This retrospective cohort study used the TriNetX Global Collaborative Network to identify adult patients with T2DM and documented zinc measurements between 2010 and 2024. Patients were classified into low zinc status (<0.70 μg/mL) and normal zinc status (0.70-1.20 μg/mL) groups. The primary outcome was incident overall sepsis at five-year follow-up, comprising severe and other types of sepsis. Secondary outcomes included severe sepsis, bacteremia, all-cause mortality, and non-sepsis infections, defined as a composite of pneumonia, urinary tract infection, cellulitis, and abdominal infections. An exposure-gradient analysis was performed to compare severe zinc deficiency (<0.50 μg/mL) with normal zinc status.
RESULTS: After matching, 9,856 pairs were analyzed using propensity score matching. Low zinc status was associated with a higher risk of overall sepsis (HR, 1.37; 95% CI, 1.23-1.54), severe sepsis (HR, 1.30; 95% CI, 1.10-1.55), bacteremia (HR, 1.23; 95% CI, 1.02-1.48), and all-cause mortality (HR, 1.56; 95% CI, 1.41-1.73). The association with non-sepsis infections was smaller (HR, 1.08; 95% CI, 1.03-1.13). The association between low zinc status and overall sepsis remained consistent across sensitivity and subgroup analyses (HR range, 1.31-1.44). In the exposure-gradient analysis, severe zinc deficiency showed a stronger association with overall sepsis than with non-sepsis infection (HR, 1.98 vs. 1.21).
CONCLUSION: Low zinc status was associated with a higher long-term risk of incident sepsis in patients with T2DM, and the magnitude of association appeared to be greater for sepsis than for non-sepsis infections. These findings are hypothesis-generating and suggest that low zinc status may serve as a marker of sepsis vulnerability in patients with T2DM.