Glycemic index, glycemic load, and cancer risk: a meta-analysis

BACKGROUND: Factors linked to glucose metabolism play an important role in the development of cancers, and both glycemic index (GI) and glycemic load (GL) have been investigated as potential etiologic factors. OBJECTIVE: A meta-analysis was performed to explore the association between GI and GL and cancer risk from published studies. DESIGN: A comprehensive, systematic bibliographic search of the medical literature was conducted to identify relevant studies. Case-control and cohort studies published before October 2007 that reported cancer risk estimates for GI and GL were included. Pooled relative risks (RRs) were estimated for breast, colorectal, endometrial, and pancreatic cancer. RESULTS: Thirty-nine studies were included in the meta-analysis. The interquantile ranges of GL were significantly wider in case-control studies, most of which were conducted in European countries, than in cohort studies. Cohort studies that presented lower ranges of GL also reported lower risk estimates. Overall, both GL and GI were significantly associated with a greater risk of colorectal (summary RR = 1.26; 95% CI: 1.11, 1.44 and RR = 1.18; 95% CI: 1.05, 1.34, respectively) and endometrial (RR = 1.36; 95% CI: 1.14, 1.62 and RR = 1.22; 95% CI: 1.01, 1.49) cancer than of breast and pancreatic cancer. There was, however, a significant between-study heterogeneity for colorectal cancer (P < 0.0001). The association between GL and breast cancer disappeared when publication bias was taken into account. No association was found for pancreatic cancer. CONCLUSION: This comprehensive meta-analysis of GI and GL and cancer risk suggested an overall direct association with colorectal and endometrial cancer.     

Glycemic impact, glycemic glucose equivalents, glycemic index, and glycemic load: definitions, distinctions, and implications

Glycemic impact, defined as "the weight of glucose that would induce a glycemic response equivalent to that induced by a given amount of food" (American Association of Cereal Chemists Glycemic Carbohydrate Definition Committee, 2007), expresses relative glycemic potential in grams of glycemic glucose equivalents (GGEs) per specified amount of food. Therefore, GGE behaves as a food component, and (relative) glycemic impact (RGI) is the GGE intake responsible for a glycemic response. RGI differs from glycemic index (GI) because it refers to food and depends on food intake, whereas GI refers to carbohydrate and is a unitless index value unresponsive to food intake. Glycemic load (GL) is the theoretical cumulative exposure to glycemia over a period of time and is derived from GI as GI x carbohydrate intake. Contracted to a single intake of food, GL approximates RGI but cannot be accurately expressed in terms of glucose equivalents, because GI is measured by using equal carbohydrate intakes with usually unequal responses. RGI, on the other hand, is based on relative food and reference quantities required to give equal glycemic responses and so is accurately expressed as GGE. The properties of GGE allow it to be used as a virtual food component in food labeling and in food-composition databases linked to nutrition management systems to represent the glycemic impact of foods alongside nutrient intakes. GGE can also indicate carbohydrate quality when used to compare foods in equal carbohydrate food groupings.     

Glycemic index,glycemic load,and risk of type 2 diabetes

The possibility that high, long-term intake of carbohydrates that are rapidly absorbed as glucose may increase the risk of type 2 diabetes has been a long-standing controversy. Two main mechanisms have been hypothesized, one mediated by increases in insulin resistance and the other by pancreatic exhaustion as a result of the increased demand for insulin. During the past decade, several lines of evidence have collectively provided strong support for a relation between such diets and diabetes incidence. In animals and in short-term human studies, a high intake of carbohydrates with a high glycemic index (a relative measure of the incremental glucose response per gram of carbohydrate) produced greater insulin resistance than did the intake of low-glycemic-index carbohydrates. In large prospective epidemiologic studies, both the glycemic index and the glycemic load (the glycemic index multiplied by the amount of carbohydrate) of the overall diet have been associated with a greater risk of type 2 diabetes in both men and women. Conversely, a higher intake of cereal fiber has been consistently associated with lower diabetes risk. In diabetic patients, evidence from medium-term studies suggests that replacing high-glycemic-index carbohydrates with a low-glycemic-index forms will improve glycemic control and, among persons treated with insulin, will reduce hypoglycemic episodes. These dietary changes, which can be made by replacing products made with white flour and potatoes with whole-grain, minimally refined cereal products, have also been associated with a lower risk of cardiovascular disease and can be an appropriate component of recommendations for an overall healthy diet.     

Glycemic index and glycemic load in relation to body mass index and waist to hip ratio

Purpose  

High-glycemic index (GI) diet has been associated with obesity, but epidemiological data are inconsistent. We therefore investigated the relation between GI and glycemic load (GL) with body mass index (BMI) and waist to hip ratio (WHR), as a measure of body fat distribution.     

Glycemic index, glycemic load, and chronic disease risk--a meta-analysis of observational studies

BACKGROUND: Inconsistent findings from observational studies have prolonged the controversy over the effects of dietary glycemic index (GI) and glycemic load (GL) on the risk of certain chronic diseases. OBJECTIVE: The objective was to evaluate the association between GI, GL, and chronic disease risk with the use of meta-analysis techniques. DESIGN: A systematic review of published reports identified a total of 37 prospective cohort studies of GI and GL and chronic disease risk. Studies were stratified further according to the validity of the tools used to assess dietary intake. Rate ratios (RRs) were estimated in a Cox proportional hazards model and combined by using a random-effects model. RESULTS: From 4 to 20 y of follow-up across studies, a total of 40 129 incident cases were identified. For the comparison between the highest and lowest quantiles of GI and GL, significant positive associations were found in fully adjusted models of validated studies for type 2 diabetes (GI RR = 1.40, 95% CI: 1.23, 1.59; GL RR = 1.27, 95% CI: 1.12, 1.45), coronary heart disease (GI RR = 1.25, 95% CI: 1.00, 1.56), gallbladder disease (GI RR = 1.26, 95% CI: 1.13, 1.40; GL RR = 1.41, 95% CI: 1.25, 1.60), breast cancer (GI RR = 1.08, 95% CI: 1.02, 1.16), and all diseases combined (GI RR = 1.14, 95% CI: 1.09, 1.19; GL RR = 1.09, 95% CI: 1.04, 1.15). CONCLUSIONS: Low-GI and/or low-GL diets are independently associated with a reduced risk of certain chronic diseases. In diabetes and heart disease, the protection is comparable with that seen for whole grain and high fiber intakes. The findings support the hypothesis that higher postprandial glycemia is a universal mechanism for disease progression.     

Glycemic index and glycemic load are not associated with brain lesions in the elderly

Objective  The goal of this study was to determine if brain lesion volume was correlated with dietary glycemic index and glycemic load in elderly individuals. Design and Setting  This cross-sectional study was performed at an academic medical center as part of a clinical study of late-life depression. Participants  Subjects (n=137) were age 60 or over, and were participating as non-depressed comparison subjects. Measurements  Food intake was assessed using the Block 1998 food frequency questionnaire. Glycemic index and glycemic load measures were derived from reported food intake. Brain lesion volumes were calculated from magnetic resonance imaging (MRI). Results  No significant associations were found between glycemic index or glycemic load, and brain lesion volume. Conclusion  Dietary glycemic measures may be unrelated to brain lesions or may be related to brain lesions only in individuals with impaired glycemic control or other vascular risk factors. Further studies are needed to confirm this finding and to determine if glycemic control moderates this association. (work was completed as part of the Master of Science in Clinical Research program)     

Glycemic index, glycemic load, and incidence of endometrial cancer: the Iowa women's health study

Although specific foods or nutrients have not been linked consistently with risk of endometrial cancer, obesity and diabetes are associated with increased risk. These conditions may be influenced by the glycemic index or load of the usual diet. We therefore examined the association of glycemic index and load measured at baseline using a food frequency questionnaire in a cohort of 23335 postmenopausal women. Over 15 yr of follow-up, we identified 415 incident endometrial cancers. The average glycemic index was not associated with endometrial cancer occurrence. After adjustment for other risk factors, the average glycemic load was positively but weakly associated, with a relative risk of 1.24 (95% CI = 0.90-1.72) for the highest versus lowest quintile of glycemic load (P for trend = 0.08). This relative risk was 1.46 (95% CI = 1.02-2.08; P for trend = 0.02) among nondiabetic women, but the trend was in the opposite direction among diabetic women. Our study indicates that a higher dietary glycemic load may be a risk factor for endometrial cancer incidence in nondiabetic women.     

Glycemic load, glycemic index, and pancreatic cancer risk in the Netherlands Cohort Study

BACKGROUND: Recent studies of pancreatic cancer suggest a role for hyperinsulinemia in carcinogenesis. Because insulin is secreted in response to elevated blood glucose concentrations, dietary factors that increase these concentrations may be important in pancreatic carcinogenesis. OBJECTIVE: The objective was to examine prospectively the relation between pancreatic cancer risk and dietary glycemic load (GL), overall glycemic index (GI), and intake of total carbohydrates and mono- and disaccharides. DESIGN: The Netherlands Cohort Study consisted of 120,852 men and women who completed a baseline questionnaire in 1986. After 13.3 y of follow-up, 408 pancreatic cancer cases were detected, 66% of which were microscopically confirmed. A validated 150-item food-frequency questionnaire, completed at baseline, was used to calculate carbohydrate and mono- and disaccharide intakes and the GL and GI of the diet. RESULTS: Dietary GL, GI, or intake of carbohydrates and mono- and disaccharides were not associated with pancreatic cancer risk in this cohort. Also, the associations were not modified by sex. Our results did not change after the analysis was restricted to microscopically confirmed pancreatic cancer cases or after individuals who reported a history of diabetes at baseline were excluded from the analyses. CONCLUSIONS: Overall, our findings do not support the hypothesis that GL, GI, or intake of carbohydrates and mono- and disaccharides are positively associated with pancreatic cancer risk. This is in agreement with previous prospective studies that investigated the relation between GL and GI and pancreatic cancer risk.     

International table of glycemic index and glycemic load values: 2002

Reliable tables of glycemic index (GI) compiled from the scientific literature are instrumental in improving the quality of research examining the relation between GI, glycemic load, and health. The GI has proven to be a more useful nutritional concept than is the chemical classification of carbohydrate (as simple or complex, as sugars or starches, or as available or unavailable), permitting new insights into the relation between the physiologic effects of carbohydrate-rich foods and health. Several prospective observational studies have shown that the chronic consumption of a diet with a high glycemic load (GI x dietary carbohydrate content) is independently associated with an increased risk of developing type 2 diabetes, cardiovascular disease, and certain cancers. This revised table contains almost 3 times the number of foods listed in the original table (first published in this Journal in 1995) and contains nearly 1300 data entries derived from published and unpublished verified sources, representing > 750 different types of foods tested with the use of standard methods. The revised table also lists the glycemic load associated with the consumption of specified serving sizes of different foods.     

Glycemic, insulinemic index, glycemic load of soy beverage with low and high content of carbohydrates

Consumption of soy has increased in Western countries due to the benefits on health and the attitude of the people to consume natural products as alternative to the use of pharmacological therapies. However, there is no evidence whether the consumption of 25 g of soy protein as recommended by the Food and Drug Administration has some effect on glucose absorption and consequently on insulin secretion. The aim of the present study was to determine glycemic index (GI), insulinemic index (InIn), and glycemic load (GL) of several soy beverages containing low or high concentration of carbohydrates, and compare them with other foods such as peanuts, whole milk, soluble fiber and a mixed meal on GI and InIn. The results showed that soy beverages had low or moderate GI, depending of the presence of other compounds like carbohydrates and fiber. Consumption of soy beverages with low concentration of carbohydrates produced the lowest insulin secretion. Therefore, these products can be recommended in obese and diabetic patients. Finally soy beverages should contain low maltodextrins concentration and be added of soluble fiber.     

Effect of glycemic index and glycemic load on energy intake in children

ObjectiveSeveral studies assessed the effect of glycemic index (GI) and glycemic load (GL) on energy intake in children but findings are not consistent in this regard. The aim of this study is to summarize and assess the evidence for the effect of GI and GL on energy intake by conducting a meta-analysis on published randomized clinical trials.MethodOur search process was conducted in PUBMED, Web of Science, and Google Scholar databases. The following keywords were searched in any part of published articles: “glycemic index” OR “glycaemic index” OR “glycemic load” OR “glycaemic load” OR “energy intake” AND “child” OR “children” OR “adolescent” OR “youth.”ResultsWe gathered 5099 articles. Non-clinical trial studies that did not intervene by GI or GL or those not assessing energy intake as a dependent variable and those that were conducted on patients over age 18 y were excluded. Each included study was evaluated three times and the exclusion criteria was checked. Eventually, six studies from 1999 to 2012 met the criteria (213 participants ages 4–17.5 y). There is heterogeneity in the study’s participants in the present paper. Children with type 2 diabetes, obesity, or normal-weight children were recruited in different studies. Overall effect of consuming low GI (LGI) and low GL (LGL) meals on energy intake was not significant. Subgroup analysis showed that LGI (not LGL) meals decreased subsequent energy intake, whereas heterogeneity was significant in the LGI group of studies. Although a slight asymmetry was shown by Begg’s funnel plot, the Egger’s asymmetry was not significant. We did not find any evidence of publication bias for studies assessing the effect of low GI or GL meals on energy intake.ConclusionConsuming LGI diet (not LGL) has favorable effect on reducing energy intake and obesity, subsequently.     

Association between dietary glycemic index and glycemic load with depression: a systematic review

Background

A combination of genetic and environmental factors is involved in depression etiology. During the last years, the prevalence of depression has increased in both developed and developing countries. Several studies indicated an association between dietary glycemic index (GI) and glycemic load (GL) with risk of depression. This systematic review was undertaken to summarize the effect of these diet indicators in depression pathogenesis.

Methods

A comprehensive search strategy was performed in the Pubmed, Embase, Cochrane Library and Scopus databases from 1966 to March 2017. Finally, six studies (three prospective cohort studies and three cross-sectional) were ultimately selected for inclusion in the systematic review.

Results

75298 adults and elderly entered the reviewed studies. All of the included studies had high methodological quality. The present study indicated that the intake of foods with higher GI is associated with disease risk. However, the relationship was found to be inverse for GL, though the association was rather weak.

Conclusions

Overall, the findings indicated that a diet with lower dietary glycemic index may be effective to reduce the risk or risk of depression.

     

Glycemic index and glycemic load in relation to food and nutrient intake and metabolic risk factors in a Dutch population

BACKGROUND: Previous studies on the glycemic index (GI) and glycemic load (GL) reported inconsistent findings on their association with metabolic risk factors. This may partly have been due to differences in underlying dietary patterns. OBJECTIVE: We aimed to examine the association of GI and GL with food and nutrient intake and with metabolic risk factors including blood glucose, insulin, lipids, and high-sensitivity C-reactive protein (CRP). DESIGN: The study entailed cross-sectional analyses of data from 2 joint observational studies, the CoDAM Study and the Hoorn Study. RESULTS: In total, 974 subjects aged 42-87 y were included in the study. The mean (+/-SD) GI was 57 +/- 4 and the mean GL was 130 +/- 39. Dairy products, potatoes and other tubers, cereal products, and fruit were the main predictive food groups for GI. GL was closely correlated with intake of total carbohydrates (r(s) = 0.97), which explained >95% of the variation in GL. After adjustment for potential confounders, GI was significantly inversely associated with HDL cholesterol and positively associated with fasting insulin, the homeostasis model assessment index of insulin resistance, the ratio of total to HDL cholesterol, and CRP. No association was observed between GL and any of the metabolic risk factors, except for a borderline significant positive association with CRP. CONCLUSIONS: In this population, a low-GI diet, which is high in dairy and fruit but low in potatoes and cereals, is associated with improved insulin sensitivity and lipid metabolism and reduced chronic inflammation. GL is highly correlated with carbohydrate intake and is not clearly associated with the investigated metabolic risk factors.     

Relations of glycemic index and glycemic load with plasma oxidative stress markers

BACKGROUND: Recent data suggest that acute hyperglycemia may increase in vivo free radical production. This increased production has been implicated in many disease processes. OBJECTIVE: The objective was to investigate whether a diet with a high glycemic index (GI) or glycemic load (GL) is associated with greater oxidative stress as measured by 2 lipid peroxidation markers, malondialdehyde (MDA) and F2-isoprostanes (IsoPs). DESIGN: Plasma MDA and IsoP concentrations were measured in 292 healthy adults, and dietary GI and GL were assessed by using a validated food-frequency questionnaire. Cross-sectional associations between GI, GL, and the 2 markers were examined by using multiple regression techniques with adjustment for potential confounding variables. RESULTS: Dietary GI was positively associated with both plasma MDA and IsoPs. The mean multivariate-adjusted MDA concentrations increased from 0.55 to 0.73 micromol/L as GI increased from the lowest to the highest quartile (P for trend = 0.02); the corresponding IsoP concentrations increased from 0.034 to 0.040 ng/mL (P for trend = 0.03). GL was positively associated with both MDA and IsoPs, but the linear relation was significant only for MDA. In addition, a marginally significant interaction between overall GI and body mass index (BMI; in kg/m2) for plasma MDA was observed (P = 0.09). The positive association between overall GI and MDA was stronger in those with a BMI < 26.5 than for those with a BMI > or = 26.5. CONCLUSIONS: Chronic consumption of high-GI foods may lead to chronically high oxidative stress. A low-GI diet, not a low-carbohydrate diet, appears to be beneficial in reducing oxidative stress.     

Glycemic index, glycemic load, and dietary fiber intake and incidence of type 2 diabetes in younger and middle-aged women

BACKGROUND: Increasing evidence suggests an important role of carbohydrate quality in the development of type 2 diabetes. OBJECTIVE: Our objective was to prospectively examine the association between glycemic index, glycemic load, and dietary fiber and the risk of type 2 diabetes in a large cohort of young women. DESIGN: In 1991, 91249 women completed a semiquantitative food-frequency questionnaire that assessed dietary intake. The women were followed for 8 y for the development of incident type 2 diabetes, and dietary information was updated in 1995. RESULTS: We identified 741 incident cases of confirmed type 2 diabetes during 8 y (716 300 person-years) of follow-up. After adjustment for age, body mass index, family history of diabetes, and other potential confounders, glycemic index was significantly associated with an increased risk of diabetes (multivariate relative risks for quintiles 1-5, respectively: 1, 1.15, 1.07, 1.27, and 1.59; 95% CI: 1.21, 2.10; P for trend = 0.001). Conversely, cereal fiber intake was associated with a decreased risk of diabetes (multivariate relative risks for quintiles 1-5, respectively: 1, 0.85, 0.87, 0.82, and 0.64; 95% CI: 0.48, 0.86; P for trend = 0.004). Glycemic load was not significantly associated with risk in the overall cohort (multivariate relative risks for quintiles 1-5, respectively: 1, 1.31, 1.20, 1.14, and 1.33; 95% CI: 0.92, 1.91; P for trend = 0.21). CONCLUSIONS: A diet high in rapidly absorbed carbohydrates and low in cereal fiber is associated with an increased risk of type 2 diabetes.     

Association between dietary glycemic index, glycemic load, and high-sensitivity C-reactive protein

OBJECTIVE: This study examined the relation between quality of dietary carbohydrate intake, as measured by glycemic index (GI) and glycemic load (GL), and serum high-sensitivity C-reactive protein (hs-CRP) levels. METHODS: During a 1-y observational study, data were collected at baseline and at each quarter thereafter. GI and GL were calculated from multiple 24-h dietary recalls (24HRs), 3 randomly selected 24HRs at every quarter, with up to 15 24HRs per participant. The hs-CRP was measured in blood samples collected at baseline and each of the four quarterly measurement points. Multivariable linear mixed models were used to examine the cross-sectional and longitudinal associations of GI, GL, and hs-CRP. RESULTS: Among 582 adult men and women with at least two measurements of diet and hs-CRP, average daily GI score (white bread = 100) was 85 and average GL was 198, and average hs-CRP was 1.84 mg/L. Overall, there was no association between GI or GL and hs-CRP. Subgroup analyses revealed an inverse association between GL and hs-CRP among obese individuals (body mass index > or =30 kg/m(2)). CONCLUSION: Quality of dietary carbohydrates does not appear to be associated with serum hs-CRP levels. Among obese individuals, higher dietary GL appears to be related to lower hs-CRP levels. Due to the limited number of studies on this topic and their conflicting results, further investigation is warranted.     

Glycemic index, glycemic load and endometrial cancer risk: results from the Australian National Endometrial Cancer study and an updated systematic review and meta-analysis

Purpose

The relationship between habitual consumption of foods with a high glycemic index (GI) and/or a diet with a high glycemic load (GL) and risk of endometrial cancer is uncertain, and relatively few studies have investigated these associations. The objectives of this study were to examine the association between GI/GL and risk of endometrial cancer using data from an Australian population-based case–control study and systematically review all the available evidence to quantify the magnitude of the association using meta-analysis.

Methods

The case–control study included 1,290 women aged 18–79 years with newly diagnosed, histologically confirmed endometrial cancer and 1,436 population controls. Controls were selected to match the expected Australian state of residence and age distribution (in 5-year bands) of cases. For the systematic review, relevant studies were identified by searching PubMed and Embase databases through to July 2011. Random-effects models were used to calculate the summary risk estimates, overall and dose–response.

Results

In our case–control study, we observed a modest positive association between high dietary GI (OR 1.43, 95 % CI 1.11–1.83) and risk of endometrial cancer, but no association with high dietary GL (OR 1.15, 95 % CI 0.90–1.48). For the meta-analysis, we collated information from six cohort and two case–control studies, involving a total of 5,569 cases. The pooled OR for the highest versus the lowest intake category of GI was 1.15 (0.95–1.40); however, there was significant heterogeneity (p 0.004) by study design (RR 1.00 [95 % CI 0.87–1.14] for cohort studies and 1.56 [95 % CI 1.21–2.02] for case–control studies). There was no association in the dose–response meta-analysis of GI (RR per 5 unit/day increment of GI 1.00, 95 % CI 0.97–1.03). GL was positively associated with endometrial cancer. The pooled RR for the highest versus the lowest GL intake was 1.21 (95 % CI 1.09–1.33) and 1.06 (95 % CI 1.01–1.11) per 50 unit/day increment of GL in the dose–response meta-analysis.

Conclusion

The pooled results from observational studies, including our case–control results, provide evidence of a modest positive association between high GL, but not GI, and endometrial cancer risk.     

Compiling glycemic index and glycemic load values for addition to a food composition database

The glycemic index (GI) provides an indication of a food's carbohydrate quality by measuring the blood glucose response to consuming the food. The glycemic load (GL) is calculated as the GI times the available carbohydrate in a fixed amount of the food. GI and GL are currently of interest for the study of associations of diet and chronic disease including diabetes, cardiovascular disease, cancer and obesity. An international table of GI values is available and provides a compilation of currently available data. The purpose of this project was to use these data, as well as other available references, to expand the Cancer Research Center of Hawaii Food Composition Table (FCT) to include GI and GL values. All of the individual foods in the FCT (n=1592) were assigned GI values as a direct match (n=181), imputation (n=948), calculated value (n=208), or assigned a zero value (n=255). GL per 100 g was then calculated using the assigned GI and available carbohydrate per 100 g of food. The addition of GI and GL values to the FCT will allow researchers to estimate the effect of dietary carbohydrate quality on various health outcomes.