Organic food consumption linked to future risk of type 2 diabetes in a large health study

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The prevalence of type 2 diabetes (T2D) has significantly increased over recent decades, concomitantly to the obesity epidemic, making diabetes the fourth leading cause of global disability [1] and contributing largely to the global disability burden [2]. Currently in European countries, about 60 million people are living with diabetes and, in 2010 [3]. Diabetes is a multifactorial disease and scientific literature has underlined, beyond genetic and psychosocial factors, the crucial role of adiposity and several lifestyles-related factors, including physical activity, smoking, alcohol consumption and dietary patterns, in diabetes etiology [1].

According to a recent meta-analysis, there is a high level of evidence that processed meat, red meat and sweetened beverage consumption increases the risk of T2D, while whole grain consumption decreases the risk [4]. Other potential dietary factors involved in T2D etiology, although graded lower certainty, include fruit, vegetables, fish, nuts and dairy products (especially yoghurt) [4].

Among the emergent risk factors, exposure to environmental contaminants including pesticides is of major concern. Occupational exposure to pesticides has been associated with metabolic disorders [5–7]. In general population, exposure to pesticide residues is often multi-sources but diet is the most important route in the general population [8]. In particular, organochlorine compounds, highly persistent but now banned from agriculture in Europe, have been systematically associated with an increased risk of T2D [9]. Although scientific evidence for other types of pesticides is still limited, some epidemiological or experimental studies in animals support the biological plausibility that exposure to several classes of pesticides can affect the risk of obesity or diabetes [5, 10, 11]. Indeed, some specific molecules (pyrethroids, organophosphates, and organochlorides), are potential endocrine disruptors, responsible for possible metabolic disorders [12, 13]. For instance, a recent review reported a role of currently used organophosphorus, carbamate and pyrethroid pesticides in the incidence of diabetes [14]. In France, the organic agriculture is based on the European organic principles prohibiting use of synthetic fertilizers and pesticides and promoting the diversification of crops and livestock [15]. In terms of nutritional content, organic plant-based foods exhibit higher concentrations in some antioxidants such as carotenoids while organic animal-based foods exhibit higher concentrations in n-3 fatty acids [16]. Besides, a recent European Food Safety Authority report indicated that 44% of conventional crop-based food contained at least one quantifiable pesticide residue, vs 6.5% in organic-labeled foods (OF) [17]. In turn, OF consumption has been related to lower urinary pesticide exposure in a broad range of settings and different populations [16]. This is in line with our previous findings showing that high consumers of OF in subsample of the NutriNet-Santé cohort exhibited lower exposure to pesticide residues except for spinosad authorized in organic farming [18, 19]. Moreover, a recent cross-sectional study conducted in the United States found that participants in the National Health and Nutrition Examination Survey reporting purchasing OF had a 20% lower prevalence of diabetes c [20]ompared to those who did not purchase OF after adjustment for known diabetes-related risk factors .

In that context, the objective of the present study conducted in a large prospective cohort was 1) to investigate the prospective association between OF consumption and the risk of T2D, and 2) to estimate the mediation effect by the potential healthiness of a plant-based diet. Indeed, we hypothesize that OF consumers, as less exposed to pesticides residues from diet, may exhibit a lower risk of developing T2D. In addition, as we previously documented an association between OF preferences and a diet rich in plant-based food [18], we hypothesize that the association, if any, would be more pronounced among high plant-based food consumers, due to their higher intake of pesticide-contaminated foods.

The mean follow-up was 4.06 (SD = 1.03) years and the mean age at baseline was 52.95 (SD = 14.2) years old. During follow-up (134,990 person-years), 293 incident T2D cases were identified.

In the present study conducted in a large sample from the French adult population, an inverse association between OF consumption and T2D risk was observed. This association persisted after accounting for potential confounding effects of various factors, including lifestyles, dietary patterns and adiposity. Of note, the inverse relationship was observed more specifically among women and high consumers of plant-based foods.

Epidemiological evidence dealing with potential links between OF consumption and metabolic-related outcomes are scarce [20, 31, 32]. Two performed in the NutriNet-Santé study have shown that a high level of OF consumption is associated with a significantly lower probability of overweight and obesity in both men and women [31] as well as a reduced risk of metabolic syndrome [32]. An inverse association between BMI and OF consumption has been previously observed in this cohort thus adjustment for BMI has been performed in the models.

To the best of our knowledge, the present study is the first prospective cohort study to examine the association between OF consumption and T2D risk. Consistent with our findings, a recent cross-sectional study, found that frequent OF purchase, as a proxy of higher consumption of OF was inversely associated with diabetes prevalence among adults in the United States [20].

As healthy diets have been positively correlated with OF consumption in our cohort and other studies [18, 33, 34], it can be assumed that our findings can be, at least partially, explained by healthier diet of high consumers of OF. However, adjustment for dietary factors (specific and holistic) only marginally attenuated the association. Similarly, the mediation analysis carried out to quantify the direct and indirect effects of OF consumption on the risk of T2D suggested a specific role of OF consumption beyond the healthiness of the diet of high OF consumers.

With regard to type of organic foods, organic plant-food consumption was specifically associated with a reduced T2D risk in our study while no clear-cut association was observed with organic animal-food consumption. We observed a lower point estimate in Q5 than in Q4. It cannot be ruled that this association is an artefact resulting from an underlying association rather than a true association or due to imprecise estimation or reverse causation. Further studies investigating specific associations on detailed food groups may help to better understand this finding.

Furthermore, in the stratified analyses leading to a lower statistical power, a lower risk of T2D was only detected in participants exhibiting high level of adherence to food-based dietary guidelines (correlated to plant-based food consumption).

It is also noteworthy that we did not observe an inverse association among men.

In fact, a higher risk was observed among men who were OF consumers, although not statistically significant, while a strong link was detected among women. In the NHANES analysis [20], inverse association between OF and diabetes was similar among men and women (OR < 1) but did not reach statistical significance due possibly to limited statistical power.

The sex specific association may be biased by the lack of statistical power among men (N = 120 cases only). However, a sexual dimorphic response to pesticide exposure has been already reported in population-based [35] and in animal experiment [36–38] studies. Moreover, the sexual dimorphism in response to pesticide exposure may be related to different detoxifying capacities between males and females, or difference in regulation of the microbiota [39]. Further research is needed to clarify the sex-specific association of OF consumption with T2D risk.

The underlying mechanisms of the observed relationships can be seen in light of the differences in bioactive component contents between organic and conventional foods. First, some literature reviews have documented higher concentrations of some antioxidant compounds in organic plant-food [16]. As to carotenoids, this has also been established in a subsample of the NutriNet-Santé study comparing plasma concentrations of matched low and high OF consumers with similar characteristics including sociodemographic data, lifestyles and profiles of dietary consumption [40]. These antioxidants may play a marginal role in the etiology of T2D by reducing oxidative stress that disrupts glucose absorption by cells and can improve insulin sensitivity [41, 42].

Second, fatty acids profiles are potentially different in organic and conventional animal foods [16]. Organic meat and milk exhibit higher contents in n-3 fatty acids which may play a role against insulin-resistance. Differential fatty acids profiles have also been observed in low vs high OF consumers [40]. However, in the present study, a higher organic animal-based food consumption was not associated with lower T2D risk (in the whole sample) whereas this was observed in the American study [20]. This may be due to differences in food composition, levels of food consumption or differences in nutritional profiles between the two populations studied.

The third hypothesis relies on the fact that organic plant foods contain much less synthetic pesticide residues than their conventional counterparts [17] due to specifications and regulations prohibiting the use of these molecules during production, storage and processing. This is translated into different human exposures as checked by experimental and observational epidemiological studies [19, 43–47], documenting lower urinary concentration in some pesticide residues in relation to OF consumption. Scientific studies acknowledge that most pesticide moieties act as endocrine disruptors [48]. Harmful effects of organochlorine pesticides, which are now widely prohibited, on the development of T2D have been well documented [9]. Although less often studied, currently used pesticides such as organophosphorus, pyrethroids and neonicotinoids may also display properties involved in the etiology of T2D [5]. Experimental studies have reported an effect of low doses of these molecules on various mechanisms involved in the dysregulation of glucose hemostasis and insulin resistance including inflammatory pathways, disturbance of oxidative homeostasis, mitochondrial dysfunction, endocrine disruption and epigenetic alterations [11, 13, 49]. In our study, a stronger negative association between OF consumption and risk of T2D was observed in individuals with higher intakes of plant-based foods (i.e. who complied better with dietary recommendations). Indeed, the subgroup of individuals with the highest consumption of plant foods were those who benefited most from consuming OF in terms of T2D risk. Thus, the noticeably reduced pesticides residue exposure provided by organic plant foods is consistent with mechanistic data and support this hypothesis.

These findings are of public health relevance. Indeed, if our results are confirmed by research in other settings and populations and coupled with specific experimental studies, organic food consumption promotion may serve in T2D prevention strategies, as part of a dimension of a healthy diet.

Some limitations of our study should be noted. First, as the design is observational, causal inference is limited and residual confounding cannot be entirely ruled out. However, a wide range of sensitivity analyses were conducted to test the robustness of our findings. Second, generalizability to other populations is limited due to the characteristic of this population composed of volunteers, as illustrated by the low incidence of T2D which may have lowered the statistical power. Indeed, the participants included in this cohort were more often women, younger, with higher formal education, healthier dietary patterns and higher consumption of OF [22, 50, 51] compared to the general French population. However, the latter allows estimating the role of OF consumption at higher levels than those generally observed population. Third, the ascertainment of T2D cases was based on several sources but non-identification of some cases of diabetes cannot be totally excluded. Next, this study is based on self-reported data, in particular dietary consumption, which are prone to measurement errors and desirability bias. However, our previous work showed that organic and non-organic consumers exhibited differences in concentrations of some urinary pesticide residues which provides some evidence for the reliability of our nutritional data [19]. Finally, the follow-up of 4 years was relatively short, so that there may be reverse causality (i.e., people with subclinical diabetes chose to eat more organic foods instead of non-organic foods).

The strengths of our study include large sample size with various dietary patterns, in particular high OF consumers allowing assessment of the potential role of high proportion of OF in the diet with sufficient statistical power. In addition, for the first time, the OF consumption was assessed quantitatively for a high number of food items allowing an accurate estimation of the overall proportion of OF in the diet. Finally, the prospective design improved causal inference.

In conclusion, this prospective study supports an inverse association between OF consumption, in particular organic plant-based foods, and the risk of T2D, in adults, especially women. Randomized trials would be helpful to fully demonstrate causal inference but such long-term interventional studies raise concerns about logistical feasibility. Overall, further investigations in observational studies in other settings and carefully designed randomized controlled trials are required to replicate these findings for confirmation purpose and to elucidate underlying mechanisms.

The authors warmly thank all the volunteers of the NutriNet-Santé cohort.

We also thank Cédric Agaesse (dietitian); Thi Hong Van Duong, Younes Esseddik (IT manager), Régis Gatibelza, Djamal Lamri, Jagatjit Mohinder and Aladi Timera (computer scientists); Julien Allegre, Nathalie Arnault, Laurent Bourhis and Fabien Szabo de Edelenyi, PhD (supervisor) (data-manager/statisticians) for their technical contribution to the NutriNet- Santé study.

The authors’ contributions were as follows – EKG, JB: designed the research; SH, PG, MT, JB, DL: conducted the research; EKG: performed statistical analysis and drafted the manuscript. PR, LP, BA, LKF, NDP, BS, WB, MT, PG, SH, DL and JB contributed to the data interpretation and revised each draft for important intellectual content. All authors read and approved the final manuscript. EKG had full access to all the data in the study, EKG takes responsibility for the integrity of the data and the accuracy of the data analysis, she is the guarantor. The corresponding author (EKG) attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. The authors read and approved the final manuscript.

The BioNutriNet project was supported by the French National Research Agency (Agence Nationale de la Recherche) in the context of the 2013 Programme de Recherche Systèmes Alimentaires Durables (ANR-13-ALID-0001). The NutriNet-Santé cohort study is funded by the following public institutions: Ministère de la Santé, Santé Publique France, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA), Conservatoire National des Arts et Métiers (CNAM) and Sorbonne Paris Nord University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The datasets generated and/or analyzed during the current study are not publicly available due protection under the protection of health data regulation set by the French National Commission for Information Technology and Liberties (Commission Nationale de l’Informatique et des Libertés, CNIL). The data are available upon reasonable request to the study’s operational manager, Nathalie Pecollo (dev@null), for review by the steering committee of the NutriNet-Santé study.

The NutriNet-Santé study is conducted according to the Declaration of Helsinki guidelines and was approved by the Institutional Review Board of the French Institute for Health and Medical Research (IRB Inserm n°0000388FWA00005831) and the “Commission Nationale de l’Informatique et des Libertés” (CNIL n°908450/n°909216). The study protocol is recorded at Clinicaltrials.gov↗ under the number: NCT03335644↗. All subjects provided informed consent.

Not applicable.

The authors declare that they have no competing interests.