# The U-shaped association of fasting plasma glucose to HbA1c ratio with mortality in diabetic and prediabetic populations: the mediating role of systemic immune-inflammation index

## TL;DR

This study found that the ratio of fasting glucose to HbA1c has a U-shaped link to mortality in people with diabetes or prediabetes, with immune-inflammation playing a key role.

## Contribution

The study reveals a U-shaped association of the FPG/HbA1c ratio with mortality and identifies the mediating role of the systemic immune-inflammation index.

## Key findings

- A U-shaped relationship was observed between the FPG/HbA1c ratio and both CVD and all-cause mortality.
- The systemic immune-inflammation index mediated 19.02% of the association with CVD mortality and 8.86% with all-cause mortality.
- Threshold points for the FPG/HbA1c ratio were identified at 1.080 for CVD and 1.013 for all-cause mortality.

## Abstract

This study aimed to assess the association between fasting plasma glucose to glycated hemoglobin (FPG/HbA1c) ratio and mortality and to explore the mediating role of immunity and inflammation in diabetic and prediabetic populations.

Our analysis included 10,267 participants with prediabetes or diabetes from the NHANES (1999-2018). The association between the FPG/HbA1c ratio and all-cause and cardiovascular(CVD) mortality was assessed using multivariate Cox proportional hazards models, restricted cubic splines(RCS), two-piecewise Cox proportional hazards models and sensitivity analysis. Mediation analysis was conducted to evaluate the systemic immune-inflammation index (SII) as a potential mediator.

Over a median follow-up of 103 months, there were 535 CVD deaths and 1918 all-cause deaths. After multivariate adjustment, a U-shaped relationship was observed between the FPG/HbA1c ratio and both CVD and all-cause mortality, with threshold points at 1.080 and 1.013, respectively. Below the thresholds, the FPG/HbA1c ratio was negatively associated with CVD mortality (HR:0.200, 95% CI: 0.072, 0.559) and all-cause mortality(HR: 0.242, 95% CI: 0.118, 0.494). Above the thresholds, the ratio was positively associated with CVD mortality (HR=3.691, 95% CI: 2.011, 6.772) and all-cause mortality (HR=3.025, 95% CI: 2.279, 4.016). Mediation analysis revealed that SII mediated 19.02% of the association with CVD mortality and 8.86% with all-cause mortality (P < 0.05).

In the prospective cohort, the FPG/HbA1c ratio demonstrated a U-shaped association with mortality in diabetic and prediabetic adults, with SII playing a significant mediating role. These findings suggest that interventions targeting immunity and inflammation may improve clinical outcomes in these populations.