Diabetes has become a significant public health concern worldwide, with the incidence of diabetes continuing to rise globally (1–4). As of 2019, the number of people living with diabetes globally is estimated at 463 million, and is projected to increase to 578 million by 2030 and 700 million by 2045 (5). Recognized as the fifth highest cause of mortality globally (6), diabetes may lead to various chronic complications including cancer (7), depression (8), diabetic retinopathy (9), diabetic neuropathy (10) and cardiovascular diseases (11). These diseases greatly reduce the enjoyment of quality of an individual’s life with diabetes and even increase the risk of death, greatly contributing to the medical and economic stress on society (12). Prediabetes refers to the transitional phase before the onset of diabetes, which is an intermediate hyperglycemic state between normoglycemia and diabetes, featuring impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) (13, 14). The number of prediabetic adults has been increasing in recent years and is projected to grow to 418 million by 2025 (15). A study by the American Diabetes Association (ADA) shows that nearly 70% of prediabetes eventually develops into diabetes. Some studies have demonstrated that the pathogenesis of diabetes and prediabetes is multifactorial (13, 16–18), involving genetic predisposition, lifestyle choice and environmental factors, among which diet habits stands out as a key modifiable risk factor (19, 20).

In more recent times, there has been increasing emphasis on the contribution of nutritional fatty acids in development and progression of diabetes mellitus (21, 22). Decanoic Acid is one of medium chain fatty acids (MCFAs) containing 10 carbon atoms, which natural sources are limited, typically found in milk fat, coconut oil and palm kernel oil (23, 24). Multiple studies suggest that decanoic acid may control the incidence of coronary artery disease and epilepsy (25–27). In comparison to long-chain fatty acids (LCFAs), decanoic acid has unique metabolic characteristics that may affect blood glucose homeostasis and insulin sensitivity (28). The biological mechanisms of the metabolic effects of decanoic acid are well known, but there are no relevant studies based large-scale population examining the association between dietary decanoic acid (DDA) intake and diabetes or prediabetes (29).

In this research, we sourced data on DDA, as well as individuals with diabetes and prediabetes, from the database named National Health and Nutrition Examination Survey (NHANES) 2005 to 2016. The objective was to investigate the potential link between DDA intake and the risk of developing prediabetes or diabetes among adult Americans.

Our study confirmed the negative correlation between DDA and diabetes for the first time based on large-scale population surveys.

As we all know, the development of diabetes is usually a gradual process, which generally goes through three stages: from normal blood sugar level to prediabetes, and finally to diabetes (14). As revealed by the multiple regression analysis and the RCS curve, the findings from this study demonstrate a significant negative relationship between DDA intake and the risk of diabetes among both prediabetic and normal individuals. However, no significant correlation was detected between DDA intake and the risk of prediabetes in the normal population. These inconsistent correlations implied that DDA potentially exerts a protective influence against the advancement of prediabetes rather than the onset of prediabetes. The results suggest that the role of DDA in lowering the prevalence of diabetes is primarily through its effect on slowing the transition from a prediabetic state to diabetes, rather than from a normal level to prediabetes. Compared with the DDA intake ≤0.18 g/day, DDA intake >0.58 g/day is related to reduced risk of progression to diabetes in prediabetic patients. Nevertheless, given prediabetic pivotal position in the progression to diabetes, the overall impact of DDA extends to reducing the risk of diabetes among normal individuals as well. This is because the preventive effect of DDA on the transition from prediabetes to diabetes indirectly lowers the overall prevalence of diabetes in the general population.

Prediabetes is the earlier stage before diabetes and eventually it contributed to the development of diabetes without effective treatment and control. About 5–10% of prediabetes patients become diabetes patients every year (30). Some studies show that 37% of prediabetes patients may develop diabetes within 4 years without timely treatment (31). Therefore, it is urgent to treat diabetes and prediabetes. Encouragingly, some studies have shown that the condition in the prediabetes stage is reversible, which provides a potential way for fighting against diabetes. Lifestyle intervention, pharmacological intervention and bariatric surgery are all important measures to prevent developing from prediabetes stage into diabetes (13, 32, 33). Lifestyle interventions stand out as the more rational and safer approach when juxtaposed with other two methods (32). Extensive longitudinal research has substantiated that adopting lifestyle modifications can notably extend the timeline before the transition from a prediabetic state to diabetes, with benefits observed over a decade (31). Regular and nutritious diet is also an important segment of lifestyle intervention. A plethora of research indicates that adhering to a diet rich in nutritious elements, particularly those with a low glycemic index like cereal fiber, whole grains, and bran, can lead to a decrease in diabetes risk by 18–40% (34). Additionally, the intakes of sugary drink has been shown to have a substantial impact on diabetes. Specifically, the risk of diabetes development escalates by 26% for individuals who regularly consume over one cup of sugar-sweetened drinks per day, in contrast to those who partake in less than one cup monthly (35, 36). These all highlights the significance of dietary habits in mitigating the risk of diabetes.

For over a decade, the role of MCFAs as a dietary component of ketogenic diet in regulating glucose and lipid metabolism has gradually become known (28). Ketogenic diet is a high-fat, moderate protein, and low carbohydrate diet that simulates the metabolic pattern of the body in a state of hunger by promoting the metabolism of fat in the body to produce ketone bodies (KBs) (37). The ingested medium chain triglycerides (MCT) are broken down into glycerol and MCFAs in the stomach and duodenum. Relying on the hydrophilicity and short carbon chain of MCFAs, they are allowed for a direct transportation via the portal vein to the liver and enter directly the mitochondria no need for the carnitine system (23). This enables a swift β-oxidation process to rapidly produce energy and MCFAs are converted into KBs, which may save consumption of muscle glycogen and liver glycogen, and reduce insulin demand (38). Under low-carbon or sugar free conditions, KBs produced by decanoic acid metabolism can serve as an energy source for the brain and other tissues, especially when glucose supply is limited (39).

The results in our study showed that an increased intake of DDA is linked to a reduced incidence of diabetes among the studied population. However, the underlying mechanism this correlation remains to be fully elucidated. It is likely that because decanoic acid plays a crucial role in alleviating insulin resistance (IR) and inflammatory response, which are key factors in the onset and progress of diabetes (18, 40). IR is the common pathway of prediabetes and diabetes, usually occurring in the years before diabetes or even prediabetes, and existing in the whole process from prediabetes to late diabetes (14, 18). An animal study based on male mice found that decanoic acid intake can effectively prevent obesity and promote glucagon-like peptide-1 (GLP-1) secretion through the MCFA receptor GPR84 to enhance glucose tolerance and improve insulin resistance (41). Abe et al. (42) found that decanoic acid enhances fatty acid oxidation capacity in mice without suppressing glycolysis in skeletal muscle. This effect is achieved by activating the peroxisome proliferator-activated receptor-δ (PPAR-δ), which in turn upregulates the expression of uncoupling protein 3 (UCP3) in skeletal muscle. Notably, this process does not interfere with the insulin-mediated phosphorylation of Akt, thus maintaining insulin signaling integrity.

Inflammation is a critical factor in the development of both diabetes and prediabetes (18, 43). The findings of a prospective study lasting 177 months in Rotterdam shown, after adjusting for multiple confounding factors, interleukin 13 (IL-13), extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE) and C-reactive protein (CRP) are still associated with prediabetes. In addition, certain inflammatory biomarkers, including adiponectin, CRP, and interleukin 6 (IL-6), have been correlated with the transition from a prediabetic state to diabetes (44). IL-6 and TNF-α, both pro-inflammatory cytokines involved in inflammation and immune responses, have some effects on regulating metabolism. IL-6 has been shown to increase IR and induce fasting hyperglycemia by stimulating glucagon release (45). TNF-α may increase IR through the promotion of phosphorylation of insulin receptor substrate-1 (IRS-1) (46). A study conducted both in vitro and in vivo using a acne murine model have demonstrated that capric acid (C10), the decanoic acid counterpart, exerts anti-inflammatory properties. This effect is achieved by curbing the phosphorylation of mitogen-activated protein kinase (MAPK) and the activation of nuclear factor kappa-B (NF-κB), thereby reducing the secretion of IL-6, IL-8 and TNF-α (47). In an animal experiment, it was observed that the supplementation of decanoic acid in the diet for miniature pigs led to a decrease in the levels of TNF-α and IL-6, attributed to the suppression of inflammatory gene expression (48). Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a transcription factor that has anti-inflammatory properties and regulates mitochondrial function. The genetic variation and change of its gene expression may lead to mitochondrial dysfunction, which plays a role in the pathogenesis of IR (49, 50). As a direct ligand of PPAR-γ, decanoic acid can bind and partially activate PPAR-γ, stimulating mitochondrial biogenesis and increasing mitochondrial complex I activity to enhance mitochondrial function and improve glucose sensitivity (50–52). Although higher DDA intake can reduce the prevalence of diabetes and not prediabetes, we still recommend that they all need to increase the intake of decanoic acid, whether in people with normal blood glucose level or prediabetes. Because most prediabetes patients do not know their current status, these people can also slow down the progress to diabetes by supplementing appropriate decanoic acid.

As we discussed, decanoic acid, as one of MCFAs, has shown a positive effect in reducing the risk of diabetes. Other fatty acids also play different roles in the management of diabetes. The impact of fatty acids on metabolism varies with the length and saturation of the carbon chain. LCFAs have longer carbon chains compared to MCFAs. LCFAs such as palmitic acid may trigger insulin resistance in pancreatic beta cells by activating c-Jun N-terminal kinase expression (53). Excessive intake of LCFAs can cause lipid accumulation in the body, leading to lipotoxicity and insulin resistance (54). Long chain unsaturated fatty acids may promote the secretion of GLP-1 by activating the expression of G protein coupled receptors 120 (GPR120), thereby increasing circulating insulin (55).

The results of stratified analysis showed that among people with education level of college or above, DDA was still negatively correlated with the prevalence of diabetes in prediabetes patients, and there was interaction. Education level is an unchangeable social risk factor (56). A survey of educational differences among people with diabetes from 232 Latin American cities showed that there was a negative dose–response relationship between educational level and diabetes prevalence (57). In addition, genetic evidence suggests that higher levels of genetic decision education are associated with lower risk of type 2 diabetes (58). Individuals with higher levels of education are usually able to effectively access and understand the latest health research information, and tend to adopt healthy lifestyles, such as regular exercise and a healthy diet, which helps maintain a healthy weight and insulin sensitivity. They may have a deeper understanding of healthy diet and dietary fatty acids, including knowledge of different types of fatty acids in their diet. They may be more inclined to choose a diet containing healthy fats, which may indirectly affect the intake and metabolism of decanoic acid and reduce the risk of diabetes.

This study has some obvious advantages. Firstly, this study used data from NHANES 2005–2016, covering 6 cycles for a total of 12 years. This is a nationally representative large-scale sample database that ensures the accuracy of research results. Secondly, we established multiple models and adjusted for various potential confounding factors in order to reduce interference from other factors. In addition, we studied the relationship between DDA and people with different blood glucose status to ensure the reliability of the study. However, there are also some limitations that cannot be ignored. In the study, the diagnosis of patients with diabetes and prediabetes partly depends on the patient’s self-report, and dietary data was obtained through two 24-h dietary recalls, which may introduce memory bias to affect accuracy. This study adopts a cross-sectional design. We found that there is a negative correlation between DDA and the increased risk of diabetes, but it is difficult to determine the chronological order or causal relationship between them. Although the study has adjusted for multiple potential confounding factors, there may still be other unknown confounding factors that may affect the accurate assessment of true correlations. This study is based on American adults, and the conclusions drawn may not be applicable to populations in other countries.

Our study found that higher DDA intake was associated with lower prevalence of diabetes among prediabetic patients, suggesting that DDA is a protective factor for diabetes. In the population with high education level, this relationship still holds and there is interaction.