The current study provided evidence that the highest score of dietary GL was significantly associated with an increased risk of CVD, independent of potential confounding factors including age, sex, BMI, physical activity, smoking, diabetes, hypertension, and daily energy intake in Tehranian adults. However, there was no significant association between dietary GI, II, and IL score and the risk of CVD in adults.
In the last decade, meta-analyses and review reports summarized the association of GI and GI with risk of cardiovascular events [10, 11, 29]; our findings are comparable with results of these previously published studies conducted on adult population which reported high dietary GL and GI were associated with increased risk of CVD events, specifically for women. Three reviews have suggested that gender may significantly modified the association of dietary GL and GI with risk of CVD outcomes [10, 11, 29]. Xiang-yu et al revealed that high dietary GL and GI are related with a 23% and 13% increased risk of CVD events, respectively. This estimated risk of GL and GI for men were lower than women. This dose–response meta-analysis has been found an increased risk of CVD events by 18% per 50 unit increment of GL of diet [10]. Also, based on findings of two previously published reviews, diet with high GL and GI significantly increased CVD events risk in women but not in men [11, 29]. The Knopp et al study reports that increase in triacylglycerol and the decrease in high-density lipoprotein cholesterol concentration in response to a high glycemic diet are greater in women than in men, which can caused differences in results between men and women [30].
Iranians consume more than 55% of energy from carbohydrate, which is higher than the amounts consumed in most western countries [31]. Our population have high carbohydrate intakes with plant sources such as refined grain, rice, and potato [32, 33]. Therefore, in our study, white rice and bread especially white bread were the major contributors of dietary GL and GI; these food items have high carbohydrates content and low amount of fiber which can play a possible role in development of cardio-metabolic risk factors. However, higher adherence to low GL diet which is characterised by high consumption of whole-grain bread, fruits, vegetables, and legumes with high fibre content, if combined with lower consumption of white bread and rice could be have protective role in decreasing CVD risk [34, 35].
Although insulin response almost induced by carbohydrates, other nutrients such as dietary protein and fats can affect insulin secretion. Protein rich foods or some fats can induce the insulin response; also dietary protein augments the insulin response after consuming the carbohydrate foods [8]. Recently, pprevious reports declared that dietary II and IL can be more applicable to assess the effect of insulin exposure in development of non-communicable chronic diseases than other factors such as GI, GL, or total carbohydrate intake; because, II is directly based on the insulin response and this index could directly quantifies the insulin secretion in response to the carbohydrate and protein rich foods [36]. Despite the lack of longitudinal study on the association of dietary II and IL with CVD, several studies with reported controversial findings on association of dietary II or IL with cardiovascular risk factors, including hyperglycemia, insulin resistance, obesity, high level of CRP, and dyslipidemia [12–15]. The Nimptsch et al study have shown that dietary II was directly associated with low HDL-C and high triglycerides levels in obese individuals; however, there are no association between dietary II and IL and LDL-C, CRP, and biomarkers of glycemic control [15]. In a cohort study in the framework of TLGS, dietary II and IL has been mentioned as independent dietary risk factors for risk of insulin resistance [13]. Also, a cross- sectional study has reported that the high II of diet was associated with higher odds of obesity among women, but not in men [12]. Furthermore, Mozaffari et al has indicated adherence to a diet with a high IL was positively related with serum FBS and hs-CRP levels. However, no association was reported between high dietary IL and BMI or lipid profiles [14].
This is the first study that assessed the association of dietary II and IL with the incidence of CVD events and showed that there is no significant association between these insulin indices scores with risk of CVD. Our failure to find significant association of dietary II and IL with risk of CVD may be due to some reasons. First, due to lack of dietary insulin data, some food items of FFQ such as some fruits or vegetables were not included in the final dietary II and IL scoring, which could be effective on this association. Second, in the current study, individuals in highest quartile of dietary IL have higher intakes of fiber and lower intakes of fat compared to those in the lowest one; in addition to the influencing on calculated dietary IL score, these nutritional factors can also be have modifying effect on the association between insulin indices and development of CVD, independently in the form of a healthy diet. Third, the insulin index values of food items were derived from a reports which was conducted on young lean students whose insulin responses can be relatively different from our adult and elderly participants [8]. Fourth, the incidence rate of CVD events in participants in the fourth quartile of the IL was significantly higher than those in lowest quartile (Q4: 59.0 per 10000 person-years vs. Q1: 41.1 per 10000 person-years). This significant difference in incidence rate of CVD was also observed in participants based on quartiles of GL (Q4: 69.9 per 10000 person-years vs. Q1: 49.8 per 10000 person-years). However, the low power of study due to low sample size and limited number of CVD cases in each quartile of IL has been led to provide non-significant finding in our study.
A subgroup analysis in this prospective cohort study on 243 individuals with dysglycemia revealed that dietary pattern with high GL and IL can be related strongly with increased risk of CVD in high risk participants. Previously reported that, the most of individuals with dysglycemia have both hyperinsulinemia and insulin resistance and they are prone to CVD outcomes such as coronary heart disease and stroke. Therefore, a dietary pattern with high GL and IL is likely to be associated with an increased risk of insulin resistance, atherogenesis, and subsequently an increased risk of CVD [37].
Some reports suggest supporting mechanisms and pathways which can explain a beneficial association between these indices with risk of CVD incident. The beneficial effect of low GL or GI diets on reducing cardio-metabolic risk factors, including total cholesterol, LDL-C, TGs, BMI, plasminogen activator inhibitor-1 concentrations have been reported previously [38, 39]. Also, high dietary GI was associated with higher plasma levels of TNF-a, IL-6, and CRP [39, 40]. Furthermore, after consuming high-GI foods with the same amount of carbohydrate, blood glucose concentration increases and stimulates insulin release. The chronically increased insulin demand may eventually leads to the destruction of pancreatic β cell, and, as a consequence, impaired glucose tolerance. Also, high-GI diets can directly increase insulin resistance through their effect on glycemia and free fatty acids [41]. Some reports suggested the potential mechanisms through which dietary II and IL might influence CVD risk factors. High II of diet may increase risk of obesity by stimulating more insulin secretion, which can reduce fat oxidation and increase carbohydrate oxidation, causing increase fat storage [42]. Also, high dietary IL and II can be linked to β-cell dysfunction and increasing insulin resistance with influencing on insulin secretion [13].
The current study is subject to some limitations; the Iranian food composition table was incomplete and the USDA nutrient databank was mostly used for dietary analyses. Also, despite adjusting of a wide variety of variables in our analysis, the confounding effect of some unknown or unmeasured residual confounding may have occurred. Despite these limitations, to date, this is the first study that assessed the association of dietary II and IL with the incidence of CVD conducted in the Middle East and North Africa (MENA) region. Prospective setting, the long duration of follow-up, and the use of a valid and reliable food-frequency and physical activity questionnaire were other strengths of current study.
In conclusion, the findings of current population-based cohort study provide evidence that a dietary pattern with a higher GL were associated with increased risk of CVD; however, there was no association between dietary GI, II, and IL and the risk for CVD. Further observational studies with long-term follow up are required to address the role of diet with high II and IL in the development of CVD outcomes and its potential mechanisms.