To our knowledge, this is the first case–control study designed to assess the relationship between a dietary phytochemical index and the risk of diabetic nephropathy in Iranian women. In the current study, lower levels of FBS were observed in higher adherence of median of PI in the case group. Similar to our study, Aghdam et al., in a cross-sectional study, observed that participants with a higher PI had lower FBG . Also, a longitudinal study reported a significant negative association between FBS level and PI at baseline, but not after 3-years of follow-up . Numerous studies have reported a significant relationship between intake of various phytochemicals and better FBS levels in healthy participants  and patients with type 2 diabetes mellitus (T2DM) [21, 22]. However, some studies have suggested no significant association between FBS and PI in healthy subjects was evident .
Our results showed that, compared to the control group, case group participants had a lower daily intake of vegetables, fruits, grains, legumes, and olives. In addition, higher intakes of mentioned food groups in the higher adherence of median of dietary PI in controls may have an effective influence in the decreasing risk of DN in control group. No significant relationship was found between PI and lipid profile; however, in contrast to our study, Aghdam et al.  reported that a higher intake of phytochemical-rich food may be related to lower LDL and higher HDL levels. Golzarand et al.  found that the levels of TC, TG, and HDL were, in the highest quartile of PI, significantly reduced in healthy men, but not in women, after 3 years of follow-up . The difference in characteristics of participants, study design, study sample size, food patterns, and eating habits of people in different countries are likely contributors to the inconsistent results in the literature. Also, the findings of our study suggest that phytochemicals could have a protective effect on DN, as we observed a negative relationship between dietary PI and the risk of DN. In line with our results, in 2020, a systematic review and meta-analysis comparing different dietary patterns, which had several common components including olive oil, whole grains, fruits, nuts, vegetables, and legumes, reported that these components might reduce diabetes and its complications . The relationship and potential effects of dietary phytochemicals on the prohibition of T2DM and hyperinsulinemia have been corroborated in recent studies ; however, prior to our study, the relationship between PI and diabetic nephropathy has not previously been determined.
In general, several mechanisms might be involved in the relationship between PI and DN. Phytochemicals have been shown to confer ameliorative effects on diabetes and its complications . It has also been reported that the properties of phytochemicals can ameliorate renal injury and pathologic metabolic alteration via the control of numerous signaling pathways. Additionally, plants are a major source of antioxidants and facilitate nephron conservation through a decrease in oxidative pressure, which consequently helps to control diabetes and its complications . Mono and polyunsaturated fatty acids, and other bioactive compounds containing fiber, tocopherols, phenolic compounds, and phytosterols, have been reported to be beneficial in alleviating inflammation and oxidative stress and in reducing insulin resistance and secretion, which are pathogenic factors in diabetes  and diabetic microvascular complications . Phytochemicals can impact carbohydrate metabolism and improve FBS  through inhibition of carbohydrate digestion and intestinal glucose absorption, stimulation of insulin secretion from pancreatic β-cells, stimulation of hepatic glycolysis and glycogenesis, antioxidant properties, effect on intracellular signaling pathway, and gene expression . The use of phytochemicals has also been related to reduced mortality and chronic disease risk [33, 34]. However, reduction in dietary fiber (as a rich source of phytochemicals) may influence glycemic control, insulin sensitivity, and augment inflammation . Thus, foods rich in phytochemicals may provide advantages in the inhibition of chronic disease.
Numerous strengths of the current study are worthy of consideration. To our knowledge, this is the first study to have assessed the association between PI and the risk of diabetic nephropathy in a case–control design. In addition, we considered non-calorie phytochemical-rich foods such as tea and spices. However, our study also has some limitations. The case–control nature of the study precludes cause and effect conclusions. Moreover, small errors in the dietary assessment may be present, mostly due to mis-recalling the data and misclassification errors by using FFQ. Another limitation is the lack of control for education in the analysis that might affect our findings. Moreover, our study only included women, thus, results are not generalizable to men.