Associations of serum vitamin C concentrations with risk of all-cause and cause-specific mortality among individuals with and without type 2 diabetes

Abstract

Purpose: Compared with people without diabetes, people with type 2 diabetes (T2D) are at higher risk of both subnormal vitamin C status and increased oxidative stress. We aimed to investigate the associations of serum vitamin C concentrations with all-cause and cause-specific mortality among adults with and without T2D.

Methods: The current analysis included 20,045 adults (2691 people with T2D and 17,354 without T2D) from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2003-2006. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline analyses were used to examine the dose-response relationship.

Results: After a median follow-up of 17.3 years, 5211 deaths were documented. Individuals with T2D had a lower level of serum vitamin C concentrations compared with those without T2D (the median value: 40.1 vs. 44.9 μmol/L). Furthermore, the dose-response relationship between serum vitamin C and mortality showed different patterns between participants with and without T2D. In individuals without T2D, there was a nonlinear association of serum vitamin C concentrations with all-cause, cancer, and CVD mortality, with the lowest risk around a serum vitamin C concentration of 48.0 μmol/L (all P_overall < 0.05, P_nonlinearity < 0.05). In contrast, among those with T2D in the similar concentration range, higher serum vitamin C levels (ranged from 0.46 to 116.26 μmol/L) were linearly associated with lower all-cause and cancer mortality (both P_overall < 0.05, P_nonlinearity > 0.05). Significant additive interaction was observed between diabetes status and serum vitamin C levels with regard to all-cause and cancer mortality (P < 0.001). In addition, C-reactive protein, gamma-glutamyl transpeptidase, and HbA1c explained 14.08, 8.96, and 5.60% of the association between serum vitamin C and all-cause mortality among individuals with T2D, respectively.

Conclusions: Higher serum vitamin C concentrations were significantly associated with lower risk of mortality in participants with T2D in a linear dose-response manner, while a nonlinear association was observed in participants without T2D, with an apparent threshold around 48.0 μmol/L. These findings suggest that the optimal vitamin C requirement may differ in individuals with and without T2D.

Keywords: Epidemiology; Mortality; Type 2 diabetes; Vitamin C.