Dietary glycemic index, glycemic load, insulin index, insulin load and risk of diabetes-related cancers: A systematic review of cohort studies

Summary

Background & aims

It is believed that diets high in glycemic index (GI), glycemic load (GL), Insulin index (II), and Insulin load (IL) are associated with the increased risks of certain cancers through increasing serum glucose or insulin levels.

Methods

We conducted this systematic review of cohort studies to evaluate the possible relation between GI, GL, II, and IL with diabetes-related cancers, including colorectal, bladder, breast, endometrium, liver, pancreas, and prostate cancers. Two separate investigators conducted a literature search through PubMed/Medline, Scopus, and Web of Science databases up to February 2020, plus reference lists of relevant articles.

Results

Fifty-three cohort studies with a total of 100 098 cancer cases were included in this systematic review. Fifteen out of eighteen studies among breast cancer cases reported no significant association between GI/GL and cancer risk. These numbers were 4 out of 13 for colorectal cancer, 7 out of 9 for endometrial cancer, 2 out of 3 for liver cancer, 8 out of 10 for pancreatic cancer, and 3 out of 3 for prostate cancer. Only one cohort investigated this association in terms of bladder cancer and reported a significant association. Also, five studies reported this relation in terms of II/IL, and only one cohort among endometrial cancer patients observed a significant positive association between the risk of cancer and IL.

Conclusion

We concluded a weak association between dietary GI/GL and no association between II/IL with diabetes-related cancer risk. More cohort studies are required to be performed regarding II/IL and the risk of cancer.

Introduction

Diabetes and cancer are among the most prevalent diseases worldwide, with cancer being the second and diabetes being the twelfth leading cause of death [1,2]. Based on a large body of epidemiological evidence, diabetic patients are at a greater risk of heterogeneous cancer types including liver, pancreas, colorectal, breast, endometrial, and bladder cancers [3]. However, diabetes may act as a protective factor for prostate cancer [4]. The underlying mechanism for this association is not yet well-understood, but it appears that hyperinsulinemia and insulin resistance, hyperglycemia, and chronic inflammation existing in diabetes provide the opportunity for the cancer cells to proliferate [5,6]. It is also notable that these two diseases share many of the same risk factors, including age, sex, obesity, physical activity, diet, alcohol, and smoking [7].

Food intake has been strongly linked with chronic diseases such as diabetes and cancer, not only regarding the volume of food but also the composition and quality of diet [8,9]. The Glycemic Index (GI) reflects how the carbohydrate content of each food affects blood glucose levels. Glycemic load (GL) reflects the effect of total dietary carbohydrate on postprandial glucose [9]. However, since carbohydrates were not the only stimulus for insulin secretion, dietary insulin index (II) and insulin load (IL) were introduced [10]. II represents the postprandial insulin response to a food consisting of carbohydrates, protein, and fat, compared to an isoenergetic portion of a reference food (glucose or white bread). IL is calculated by multiplying the DII of each food by its energy content and the consumption frequency [11]. In other words, GI and II show the quantity, and GL and IL represent the quality of the diet.

High dietary GI, GL, II, and IL are equal to increased serum insulin and insulin-like growth factor 1 (IGF-1) [12]. Insulin can stimulate cell proliferation and inhibit cell apoptosis [13]. IGF-1 can also exert mitogenic effects and inhibit apoptosis through multiple cell pathways and regulate gene expression [14]. Insulin and IGF-1 can also stimulate the secretion of leptin from adipose tissue, and since leptin is involved in cell growth and proliferation, insulin can indirectly promote cancer cell growth and proliferation [15].

Evidence from systematic reviews and meta-analysis showed that there exists an association between high GI and GL and risk of endometrial, breast, and prostate cancer [[16], [17], [18]], while no association was found between GI and GL and colorectal cancer risk [19]. To the best of our knowledge, no systematic review has investigated the association of II and IL with the risk of cancer. Therefore, we aimed to assess whether dietary GI, GL, II, and IL could affect the risk of diabetes-related cancers. The most similar study to the present research is the meta-analysis by Choi et al. [1]; nevertheless, since II and IL had not been assessed and more than 8 years has passed from the publication of the mentioned study, we decided to perform this study as a more comprehensive update to that of Choi et al.