The high prevalence of type 2 diabetes has emerged as a critical public health issue worldwide (1). The global prevalence of type 2 diabetes mellitus (T2DM) in adults has surged from approximately 150 million in 2000 to 450 million in 2019, and projections suggest it will rise to around 700 million by 2045 (2). In 2017, the total economic burden of diagnosed diabetes in the United States was $327 billion, with patient care accounting for 24% of all healthcare costs (3). This underscores the urgency of diabetes prevention and treatment.

Oxidative stress is intricately involved in the onset and progression of type 2 diabetes, significantly contributing to this process. Insulin resistance and impaired beta-cell function are often present in the prodromal stages of diabetes. Elevated oxidative stress can exacerbate insulin resistance and impair insulin secretion. Furthermore, oxidative stress increases the incidence of diabetic complications. Elevated levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are associated with lipid peroxidation, non-enzymatic glycation of proteins, and glucose oxidation, all of which promote diabetes and its complications (4, 5).

Evidence is mounting that certain dietary antioxidants, such as vitamins C and E, and carotenoids, may reduce the risk of developing type 2 diabetes (6–8). However, the relationship between the intake of vitamin A, zinc, and diabetes remains contentious (9, 10). One study reported no significant correlation between total or supplemental zinc intake and type 2 diabetes mellitus (T2DM) (11). Conversely, another study indicated that sufficient vitamin A intake might help prevent diabetes, particularly in men (12). The association between selenium levels and diabetes risk is also inconclusive (13).

Diets typically contain various antioxidants that may have synergistic or additive effects (14). The Composite Dietary Antioxidant Index (CDAI) reflects an individual’s overall antioxidant capacity, with higher scores indicating greater capacity (15). Previous studies have reported that a high CDAI is associated with a reduced prevalence of chronic diseases like chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD) (16, 17). However, epidemiological evidence linking CDAI and diabetes is limited, with only one prior study examining this relationship (18).

This study aims to investigate the association between different dietary antioxidant levels and DM among adult participants in the National Health and Nutrition Examination Survey (NHANES) database. It further explores the potential association between CDAI and DM, contributing to the existing body of knowledge in this field.

To our knowledge, this is the first cross-sectional study examining the relationship between dietary antioxidant intake, CDAI, and diabetes mellitus (DM). We analyzed data from four NHANES cycles (2011–2018) and found that increased intake of vitamin C was associated with a reduced risk of DM. Notably, the negative correlation between CDAI and DM was significant only in the female population, suggesting that a diet high in vitamin C and other antioxidants may be crucial in preventing diabetes, especially among adult women.

There is substantial evidence indicating that oxidative stress plays a critical role in the pathogenesis of diabetes. Excessive production of free radicals and diminished antioxidant defenses lead to increased lipid peroxidation and the development of insulin resistance (25). In pre-diabetes and type 2 diabetes, insulin resistance emerges as a pivotal influencing factor (26).

While several studies have examined the relationship between single dietary antioxidants and type 2 diabetes, such as vitamin C, which may inhibit or ameliorate oxidative stress and insulin resistance, thereby protecting against the development of diabetes mellitus (DM) (6), our findings indicate that increased vitamin C intake correlates with a decreased risk of DM. Additionally, early NHS cohort studies have shown that higher dietary zinc intake is associated with a reduced risk of developing type 2 diabetes mellitus (T2DM) in subsequent years (27). Our findings suggest a similar potential; however, more comprehensive studies are required to elucidate this correlation. However, our study diverges from previous conclusions regarding vitamin A intake.

Vitamin C is a water-soluble antioxidant found in biological fluids (28). Numerous human in vivo studies have examined the effects of vitamin C supplementation on markers of lipid, protein, and DNA oxidation, both in the presence and absence of oxidative stress. Although the findings from these studies are generally mixed, evidence suggests that vitamin C supplementation reduces markers of lipid peroxidation (e.g., malondialdehyde and F2-isoprostanes), DNA oxidation (e.g., 8-oxoguanine), and protein oxidation (e.g., nitrotyrosine and protein carbonyls) in biological samples such as plasma, serum, and urine (29–32).Vitamin C also appears to play a crucial role in protecting cells from oxidative damage by accumulating in mitochondria (28). Zinc is essential for insulin crystallization and signaling (33), specifically promoting the activation of the PI3K/Akt pathway, which is vital for glucose metabolism (34). Additionally, zinc acts as a cofactor in antioxidant defense and carbohydrate metabolism (35, 36).

Given the complexity of diet, it is more appropriate to examine the combined effects of antioxidants. Therefore, we introduced the CDAI indicator. Previous studies have shown that high CDAI levels are associated with a reduced risk of diseases such as COPD, hyperlipidemia, and colorectal cancer (17, 37, 38). Additionally, one study found a negative correlation between CDAI and inflammatory cytokines, including IL-1b and TNF-a (39). Another study reported similar associations between CDAI and inflammatory markers like leukocytes and C-reactive protein (17). Oxidative stress can elevate inflammatory factors (40, 41), and inflammation is a known risk factor for DM development (42, 43). Therefore, we hypothesize that dietary antioxidants may mitigate the inflammatory response induced by oxidative stress by modulating leukocytes, C-reactive protein, and other inflammatory markers, thus reducing the risk of DM. This potential mechanism requires further exploration.

Only one previous study has examined the relationship between CDAI and diabetes, showing a negative correlation (18). However, this is not entirely consistent with our findings, which demonstrated a strong correlation only in adult women. The discrepancy may be attributed to differences in CDAI calculation methods. The previous study used a pooled score incorporating six dietary antioxidants (vitamins A, C, and E, manganese, selenium, and zinc) (15, 18). As the current dietary module of the NHANES database lacks information on dietary manganese, our study employed modified versions of vitamin A, vitamin C, vitamin E, carotenoids, selenium, and zinc to calculate the Composite Dietary Antioxidant Index (CDAI) (21). Dietary manganese deficiency can lead to increased ROS production and oxidative stress (44), and manganese is vital for normal insulin synthesis and secretion (45). This discrepancy may partly explain the differences in study outcomes.

Due to elevated estrogen levels in women, research has shown that estrogen binds to estrogen receptors and activates the MAP kinase-NF-κB pathway, which subsequently upregulates the expression of antioxidant enzymes (46, 47). Estrogen functions as an antioxidant by enhancing the expression of antioxidant and longevity-related genes. Additionally, estrogens are implicated in inflammation; they interact with their receptors to modulate various inflammatory factors, including cytokines and inducible nitric oxide synthase (48). These factors may further account for why our findings were significant only in the female population. Therefore, additional studies are necessary to further explore the relationship between the Composite Dietary Antioxidant Index (CDAI) and diabetes mellitus (DM).

This study has limitations. First, it was conducted on U.S. adults, excluding populations from other regions where dietary habits may differ. Second, CDAI data were derived from two 24-h dietary recall interviews, subject to recall bias. Lastly, as a cross-sectional study, it cannot establish causality between dietary antioxidant intake, CDAI, and DM, only associations.

In conclusion, this cross-sectional study suggests that a diet rich in vitamin C may serve as a significant preventive measure against diabetes mellitus (DM) in adults. In the female population, the Composite Dietary Antioxidant Index (CDAI) was strongly associated with the risk of developing DM. Although zinc intake showed a trend toward a lower risk of diabetes, further epidemiological evidence, particularly from prospective studies, is required to confirm these relationships and to develop more accurate and effective preventive and therapeutic strategies for DM.