This study is the first attempt to assess the relationship between the inflammatory potential of diet (as estimated by the DII score) and FBS, lipid profile, and inflammatory biomarkers in Iranian postmenopausal women. A diet rich in energy, total fat, and SFA (pro-inflammatory dietary factors) and poor in anti-inflammatory dietary factors (β-Carotene, vitamin C, and fiber) can lead to greater DII score which in turn can lead to increased levels of inflammation in individuals as determined by increased serum levels of IL-6 and higher levels of TG and TG/HDL-C ratio. No significant association was observed between DII score and serum levels of FBS, TC, LDL-C, HDL-C, hs-CRP, IL-1β, and TNF-α.
Pro-inflammatory diet (i.e., the greater DII score) was associated with higher serum levels of TG. This finding is in line with the study of Neufcourt et al. conducted on 4347 French adults [42]. In addition, an observational study carried out on Iranian adults demonstrated similar findings [37]. Likewise, another research conducted on American adults revealed a direct association between pro-inflammatory diet and the serum levels of TG [39]. These results may be due to an increase in levels of inflammatory biomarkers that stimulate TG production in liver [61-63]. Despite the observed association between the DII score and TG in the mentioned studies, Ren et al failed to find any association between the DII score and serum levels of TG in a national Chinese study conducted on 1,712 participants aged 18-75 years [64]. Similarly, the studies of Naja [65] and Sokol et al. [66] conducted on Lebanese and Polish adults, respectively, did not reveal this association. The absence of the relationship may be due to the smaller number of dietary factors used for the DII score calculation. Moreover, we showed a positive association between the DII score and TG/HDL-C ratio. Higher TG/HDL-C ratio is associated with coronary artery diseases [67]. In line with the current study, the findings of Mazidi study indicated a significant association between the DII score and TG/HDL-C ratio in adults [39].
Our findings were not consistent with our expectation of higher serum levels of TC and LDL-C and lower levels of HDL-C with higher DII scores. Previous studies conducted in Lebanon [65] and China [64] are consistent with our result of HDL-C. An observational study conducted with the aim of determination of association between dietary patterns and serum lipids on Latin America showed a significant inverse association between prudent diet and serum levels of TC and LDL-C [68]. Likewise, another cross-sectional study carried out on Singaporean subjects aged 21 to 94 years showed a significant association between alternative healthy eating index-2010, alternate Mediterranean diet score, and dietary approaches to stop hypertension diet score and selected serum lipids of TC, HDL-C, and LDL-C [69]. Difference in ethnic group and sample size of the studies may explain the different findings from these studies.
TNF-α can cause insulin resistance via several biochemical mechanisms such as increases in circulating free fatty acids [70-72], reduction of glucose transporter (GLUT)-4 transporter in muscle cells [70] and autophosphorylation of insulin receptors [70]. An observational study conducted on adults aged 18 years and older, showed a significant positive association between the increased pro-inflammatory diet and higher serum levels of fasting blood glucose (FBG), which is not in agreement with our results [39], which might be due to the relatively small sample size of the present study. Moreover, in an observational study, Vahid et al. found that individuals in the highest tertile of DII score had higher levels of fasting plasma glucose (FPG) than those in the first tertile [37]. On the contrary, findings of another cross-sectional study showed no significant association between the categorical or continues DII score and FBG [64]. In addition, two studies performed in Lebanon [65] and Poland [66] showed no association between the increased DII score and hyperglycemia. The reported differences between studies may be due to the number of dietary factors applied for the calculation of DII score and differences in sample size as noted.
The synthesis of 17 beta-estradiol (E2) in ovaries was decreased in menopause [73]. The levels of TNF-α, IL-6 and IL-1 (pro-inflammatory biomarkers) were increased in postmenopausal women following limitation of ovarian function [74]. In addition, the deposition of visceral fat increases in menopause releases the inflammatory cytokines [75]. Various studies demonstrated the higher levels of IL-2, IL-4 and IL-6 in postmenopausal women as compared with premenopausal women [76, 77].
In this study, participants in the highest tertile of DII score had higher serum levels of IL-6 compared to those in the first tertile of DII score. However, we observed no association for hs-CRP. In line with the present study, a cross-sectional study conducted on Belgian adults revealed a significant association between the DII scores and serum levels of IL-6, but not hs-CRP levels [78]. Similarly, Vahid et al. in a case-control study conducted on Iranian women demonstrated a direct association between the DII score and IL-6 levels [36]. In a large observational study carried out with the aim of determining the relationship between the DII score and serum levels of hs-CRP in China, there was a significant association between DII scores and hs-CRP levels, but only in subjects with MetS [64]. Moreover, in a case-control study of gastric cancer in Iran, Vahid et al. showed the positive association between the DII score and hs-CRP [35]. This discrepancy in the findings of the various studies may be due to the observed differences in lifestyles, dietary habits, and races in study participants as well as limitations of sample size with concomitant limitation in statistical power.
The results of the current study on the association between the DII score and serum levels of TNF-α showed no significant relationship in this regard. This lack of association may be due to the relatively small sample size of the current study. The finding is consistent with previous study conducted on the police-officers in Buffalo, New York [40]. On the other hand, two studies conducted on European adolescents [79] and American postmenopausal women [33] showed a positive association between pro-inflammatory diet (as measured by DII score) and serum levels of TNF-α. The discrepancy between the studies may be due to their different sample sizes.
No statistically significant association was addressed between the DII score and serum levels of IL-1β. By contrast, in an observational study Shivappa et al. showed a significant association between the increased DII score and higher serum levels of IL-1β [79]. Vahid et al. in a case-control study conducted on subjects with and without gastric cancer found a positive association between the DII score and serum levels of IL-1β [35]. The discrepancy between results of our study and these studies may be due to difference in participants of the studies.
To the best of our knowledge, this study was the first attempt that investigated the association between the DII score and FBS, lipid profile and inflammatory biomarkers among Iranian postmenopausal women. Using validated dietary and PA assessment tools, the estimation of dietary potential of diet using an updated and validated index, examining the association between the DII score and inflammatory biomarkers applying potential confounders such as the sociodemographic factors and use of anti-inflammatory medications, measuring biochemistry factors of FBS, lipid profile, and inflammatory biomarkers according to standardized procedures are the other strengths of the current study.
The cross-sectional nature of this study is the most important limitation of the current study; therefore, we are unable to elucidate the findings on causality. The population of our study included Iranian postmenopausal women. Thus, we cannot generalize the observed findings to all Iranian people or postmenopausal women in other countries. The FFQ was applied for individual dietary assessment in the current study. So, misclassification and recall bias are prevalent problems existing in most epidemiological studies. Another limitation is the use of an FFQ, known to be subject to a variety of errors, including both random and systematic [80, 81]. Non-availability of 11 dietary factors which may lead to not find any association between the DII score and some biomarkers. However, despite of absence of some dietary factors for the DII score calculation, we could demonstrate some expected associations between the DII score and lipid profile and inflammatory biomarkers.