Consumption of citrus and cruciferous vegetables with incident type 2 diabetes mellitus based on a meta-analysis of prospective study

doi:10.1016/j.pcd.2015.12.004

Primary Care Diabetes

Volume 10, Issue 4, August 2016, Pages 272-280

https://doi.org/10.1016/j.pcd.2015.12.004 Get rights and content

Highlights

•
A meta-analysis of seven prospective studies was performed.
•
Evaluate the association of citrus and cruciferous vegetables and type 2 diabetes.
•
Intake of citrus fruits was not associated with risk of type 2 diabetes.
•
Cruciferous vegetables intake was inversely associated with type 2 diabetes risk.

Abstract

Background

Observational studies and meta-analyses suggested that increased total fruits and vegetables consumption have a protective role in incidence of type 2 diabetes mellitus (T2DM). However, we still don’t know whether the subtypes, such as citrus fruits and cruciferous vegetables (CV), have a preventive role.

Methods

We systematically searched the MEDLINE and EMBASE databases up to December 31, 2014. Summary relative risks (SRRs) and 95% confidence intervals (CIs) were calculated using random-effects models.

Results

Seven distinct prospective cohort studies (five articles) were identified for this study. A total of 16,544 incident cases of type 2 diabetes were ascertained among 306,723 participants with follow-up periods ranging from 4.6 to 24 years. Based on four prospective cohort studies, we found that overall, consumption of CV had a protective role in the T2DM incidence (highest vs. lowest analysis: SRR = 0.84, 95% CI: 0.73 to 0.96), with evidence of significant heterogeneity (P = 0.09, I² = 54.4%). This association was independent of the main risk factors for cardiovascular disease: smoking, alcohol use, BMI, and physical activity etc. Consumption of citrus fruits did not have a protective role in the T2DM development (highest vs. lowest analysis: SRR = 1.02, 95% CI: 0.96 to 1.08), with no evidence of significant heterogeneity (P = 0.49, I² = 0).

Conclusions

Higher consumption of CV, but not citrus fruits, is associated with a significantly decreased risk of type 2 diabetes. Further large prospective studies are needed to elucidate both relationships.

Introduction

Over the past two decades, the prevalence of type 2 diabetes mellitus (T2DM) has been elevated markedly worldwide [1]. Studies have shown that increased exercise, quit smoking, weight lost among obese individuals, adoption of a diet rich in fiber may reduce the incidence of T2DM [2], [3].

Dietary factors are potential risk factors, but the relationship between fruit and vegetable intake and incidence of T2DM is not fully understood. Although a meta-analysis published in 2010, which included six prospective cohort studies, reported that greater intake of fruits was not associated with risk of T2DM [Summary relative risk (SRR) = 0.93, 95% confidence interval (CI): 0.83 to 1.01] [4], the updated two meta-analyses, which included 10 prospective cohort studies, found a protective role for fruit intake [5], [6]. Furthermore, a significantly inverse association between citrus fruits consumption and risk of T2DM was observed among one cohort of Chinese women with intermediate levels of citrus consumption (10.0–25.2 g/day) as compared to low citrus consumption, but no significant association was found for a high intake (median, 44.4 g/day) [7]. Others, studies from USA and Europe found a non-significant association between citrus consumption and risk of T2DM [8], [9], [10]. Likewise, mixed results were reported for the association between CV consumption and T2DM [7], [8], [9], [10]. Like other fruits, both citrus fruits and CV contain many nutrients, such as carotenoids, polyphenols, flavonoids, limonoids, folic acid, and dietary fiber, which are believed to delay the digestion and absorption of carbohydrates and suppress postprandial glycemia, oxidative stress, and low-grade inflammation [10]. Importantly, CVs are unique in that they are rich sources of glucosinolates [11], [12], the precursors of isothiocyanates and indole-3-carbinol [13], [14]. Researches have observed a protective role of isothiocyanate in the development of DM via improved glucose tolerance and insulin signaling [15]. In addition, researches [16], [17] have indicated that extract of citrus fruits has hypoglycemic effects in the diabetic experimental models.

In this meta-analysis, we focused on only prospective cohort studies due to the following: (1) no systematic reviews and meta-analyses have looked at the effects of intake of citrus fruits and CV on the overall risk of T2DM. (2) Both case-control and cross-sectional designs are subjected to the selection and recall bias, and the prospective evidences on these associations have been reported with inconsistent results [7], [8], [9], [10], [18]. (3) Only several clinical trials investigate the effects of intakes of citrus [19] and CV [20], [21] on the development of complications in patients with T2DM, but not the development of T2DM. Therefore, to better characterize this issue, we conducted a meta-analysis of prospective cohort studies to evaluate such relationships following the meta-analysis of observational studies in epidemiology (MOOSE) [22].

Section snippets

Search strategy

For this meta-analysis, searches were performed electronically through the MEDLINE and EMBASE database for prospective cohort studies examining the association between citrus fruits and CV intake and risk of T2DM. We supplemented this search by hand-searching the reference lists of the retrieved articles. The search strategy used the following terms of Medical Subject Headings or keywords: (1) fruit OR citrus OR grapefruit OR orange OR tangerine OR lemon OR lime OR cruciferous vegetables OR

Search results

The search strategy generated 1439 citations (Fig. 1). We assessed titles and abstracts and 23 were considered of potential value and the full text was retrieved for detailed evaluation. Eighteen of these 23 articles were subsequently excluded from the meta-analysis for various reasons. No additional articles were included from reference review. So, a total of 5 publications with 7 prospective cohort studies were used in this meta-analysis [7], [8], [9], [10], [18]. Of these, the Nurses’ Health

Discussion

In this meta-analysis of prospective cohort studies, we investigated the association between citrus and CV consumption and T2DM incidence. We found that consumption of CV had a protective role in the T2DM incidence. This association was independent of the main risk factors for cardiovascular disease: smoking, alcohol use, BMI, and physical activity etc. Consumption of citrus fruits did not have a protective role in the T2DM development.

Several laboratory studies might explain an inverse

Conflict of interest

There are no conflicts of interest to declare.

References (48)

J.E. Shaw et al.
Global estimates of the prevalence of diabetes for 2010 and 2030
Diabetes Res. Clin. Pract.
(2010)
Y. Wu et al.
Fruit and vegetable consumption and risk of type 2 diabetes mellitus: a dose-response meta-analysis of prospective cohort studies
Nutr. Metab. Cardiovasc. Dis.
(2015)
R. Villegas et al.
Vegetable but not fruit consumption reduces the risk of type 2 diabetes in Chinese women
J. Nutr.
(2008)
J. Mursu et al.
Intake of fruit, berries, and vegetables and risk of type 2 diabetes in Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study
Am. J. Clin. Nutr.
(2014)
D.T. Verhoeven et al.
A review of mechanisms underlying anticarcinogenicity by brassica vegetables
Chem. Biol. Interact.
(1997)
P. Gupta et al.
Phenethyl isothiocyanate: a comprehensive review of anti-cancer mechanisms
Biochim. Biophys. Acta
(2014)
N. Uddin et al.
In vitro alpha-amylase inhibitory activity and in vivo hypoglycemic effect of methanol extract of Citrus macroptera Montr. fruit
Asian Pac. J. Trop. Biomed.
(2014)
S. Buscemi et al.
Effects of red orange juice intake on endothelial function and inflammatory markers in adult subjects with increased cardiovascular risk
Am. J. Clin. Nutr.
(2012)
Z. Bahadoran et al.
Broccoli sprouts powder could improve serum triglyceride and oxidized LDL/LDL-cholesterol ratio in type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial
Diabetes Res. Clin. Pract.
(2012)
R. DerSimonian et al.
Meta-analysis in clinical trials
Controlled Clin. Trials
(1986)

Y.J. Liu et al.

Dietary flavonoids intake and risk of type 2 diabetes: a meta-analysis of prospective cohort studies

Clin. Nutr.

(2014)

X. Wang et al.

Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects

Mol. Cell Endocrinol.

(2013)

E.Q. Ye et al.

Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain

J. Nutr.

(2012)

D. Feskanich et al.

Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire

J. Am. Diet. Assoc.

(1993)

F.B. Hu et al.

Reproducibility and validity of dietary patterns assessed with a food-frequency questionnaire

Am. J. Clin. Nutr.

(1999)

S.M. George et al.

Fruit and vegetable intake and risk of cancer: a prospective cohort study

Am. J. Clin. Nutr.

(2009)

F.J. van Duijnhoven et al.

Fruit, vegetables, and colorectal cancer risk: the European prospective investigation into cancer and nutrition

Am. J. Clin. Nutr.

(2009)

X.W. Zhu et al.

Meta-analysis of atherogenic index of plasma and other lipid parameters in relation to risk of type 2 diabetes mellitus

Prim. Care Diabetes.

(2015)

J. Tuomilehto et al.

Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance

N. Engl. J. Med.

(2001)

W.C. Knowler et al.

Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin

N. Engl. J. Med.

(2002)

P. Carter et al.

Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis

BMJ

(2010)

M. Li et al.

Fruit and vegetable intake and risk of type 2 diabetes mellitus: meta-analysis of prospective cohort studies

BMJ Open

(2014)

S. Liu et al.

A prospective study of fruit and vegetable intake and the risk of type 2 diabetes in women

Diabetes Care

(2004)

A.J. Cooper et al.

Fruit and vegetable intake and type 2 diabetes: EPIC-InterAct prospective study and meta-analysis

Eur. J. Clin. Nutr.

(2012)

Cited by (36)

Dietary Recommendations for Ethiopians on the Basis of Priority Diet-Related Diseases and Causes of Death in Ethiopia: An Umbrella Review
2023, Advances in Nutrition
Food-based dietary guidelines (FBDG) need to be evidence-based. As part of the development of Ethiopian FBDG, we conducted an umbrella review to develop dietary recommendations. Protein-energy malnutrition (PEM), deficiencies of vitamin A, zinc, calcium, or folate, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM) were selected as a priority. Systematic reviews were eligible if they investigated the impact of foods, food groups, diet, or dietary patterns on priority diseases. After a search, 1513 articles were identified in PubMed, Scopus, and Google Scholar published from January 2014 to December 2021. The results showed that 19 out of 164 systematic reviews reported the impact of diet on PEM or micronutrient deficiencies. Daily 30–90 g whole-grain consumption reduces risk of CVD and T2DM. Pulses improve protein status, and consuming 50–150 g/d is associated with a reduced incidence of CVD and T2DM. Nuts are a good source of minerals, and consuming 15–35 g/d improves antioxidant status and is inversely associated with CVD risk. A daily intake of 200–300 mL of milk and dairy foods is a good source of calcium and contributes to bone mineral density. Limiting processed meat intake to <50 g/d reduces CVD risk. Fruits and vegetables are good sources of vitamins A and C. CVD and T2DM risks are reduced by consuming 200–300 g of vegetables plus fruits daily. Daily sugar consumption should be below 10% of total energy to lower risk of obesity, CVD, and T2DM. Plant-based fat has favorable nutrient profiles and modest saturated fat content. The association of saturated fatty acids with CVD and T2DM is inconclusive, but intake should be limited because of the low-density lipoprotein cholesterol-raising effect. Plant-based diets lower risk of CVD and T2DM but reduce micronutrient bioavailability. The review concludes with 9 key dietary recommendations proposed to be implemented in the Ethiopian FBDG. This review was registered at PROSPERO (CRD42019125490).
Aryl Hydrocarbon Receptor Activation Coordinates Mouse Small Intestinal Epithelial Cell Programming
2023, Laboratory Investigation
In the face of mechanical, chemical, microbial, and immunologic pressure, intestinal homeostasis is maintained through balanced cellular turnover, proliferation, differentiation, and self-renewal. Here, we present evidence supporting the role of the aryl hydrocarbon receptor (AHR) in the adaptive reprogramming of small intestinal gene expression, leading to altered proliferation, lineage commitment, and remodeling of the cellular repertoire that comprises the intestinal epithelium to promote intestinal resilience. Ahr gene/protein expression and transcriptional activity exhibit marked proximal^HI to distal^LO and crypt^HI to villi^LO gradients. Genetic ablation of Ahr impairs commitment/differentiation of the secretory Paneth and goblet cell lineages and associated mucin production, restricts expression of secretory/enterocyte differentiation markers, and increases crypt-associated proliferation and villi-associated enterocyte luminal exfoliation. Ahr^-/- mice display a decrease in intestinal barrier function. Ahr^+/+ mice that maintain a diet devoid of AHR ligands intestinally phenocopy Ahr^-/- mice. In contrast, Ahr^+/+ mice exposed to AHR ligands reverse these phenotypes. Ligand-induced AHR transcriptional activity positively correlates with gene expression (Math1, Klf4, Tff3) associated with differentiation of the goblet cell secretory lineage. Math1 was identified as a direct target gene of AHR, a transcription factor critical to the development of goblet cells. These data suggest that dietary cues, relayed through the transcriptional activity of AHR, can reshape the cellular repertoire of the gastrointestinal tract.
American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan—2022 Update
2022, Endocrine Practice
Citation Excerpt :
There is a large body of data indicating that isocaloric substitution of specific macronutrients can improve insulin sensitivity assessed by clamp studies and CVD risk factors.836 These data would generally support macronutrient intake as follows: (1) limitations on fat intake, (2) emphasis on poly/mono-unsaturated fats over saturated fats, (3) no trans fats,835 (4) complex over simple carbohydrates, (5) whole grains over refined grains934, (6) fruits and vegetables,837 (7) dietary fiber,838 and (8) reduced consumption of processed food.839 Dietary enrichment of these macronutrients can enhance insulin sensitivity,836 aligning with the Mediterranean diet and other meal patterns that are epidemiologically associated with reduced prevalence of T2D,839 and predictably would be beneficial based on the role of insulin resistance in the pathophysiology of CMD.
The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers.
The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development.
This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes.
This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.
Effect of citrus fruit and juice consumption on risk of developing type 2 diabetes: Evidence on polyphenols from epidemiological and intervention studies
2021, Trends in Food Science and Technology
Citation Excerpt :
A study in postmenopausal women (Women's Health Initiative study) found no association between 100% citrus (orange and grapefruit) and other fruit juice intake and risk of type 2 diabetes, even at high levels of consumption (Auerbach et al., 2017). Similarly, no effect was reported in several other studies (Jia et al., 2016; Murphy, Barrett, Bresnahan, & Barraj, 2017; Palmer, 2008). In a cross-sectional study of females aged 18–76 years, higher intakes of both anthocyanins and flavones improved insulin resistance and lowered high-sensitivity C-reactive protein, while no association was found with flavanone, flavanol and flavan-3-ol intake (Jennings, Welch, Spector, Macgregor, & Cassidy, 2014).
Citrus fruits are commonly consumed worldwide in both fresh and processed forms, especially as juices. While fruit consumption is perceived as beneficial for long-term health, the effects of fruit juices are more controversial, linked to high intrinsic sugar content. On the other hand, citrus juices, like the fruits, are rich in many nutrients including vitamin C, and also contain various bioactive components such as (poly)phenols.
This review examines the effect of citrus fruits, juices and constituent (poly)phenols on the risk of type 2 diabetes through a critical evaluation of the literature, considering data from epidemiological and human intervention studies, both acutely and chronically.
Epidemiological studies show some protection from consuming citrus fruits against developing type 2 diabetes, but the outcomes for citrus juices are conflicting. The direct acute effect of citrus (poly)phenols on postprandial glycaemic response, a risk factor for type 2 diabetes, is relatively small. Improved fasting glucose, fasting insulin and insulin resistance were observed after longer periods of citrus juice consumption. High inter-individual variation in flavanone bioavailability is possibly one of the main factors affecting the physiological responses in humans, as well as changes in gut microbiota. To further understand the effect of citrus consumption on type 2 diabetes risk and to shed light on the interconnection between the gut microbiome, bioavailability and bioefficacy, future acute and chronic studies linking these factors with clinical outcomes are recommended.
Different Food Sources of Fructose-Containing Sugars and Fasting Blood Uric Acid Levels: A Systematic Review and Meta-Analysis of Controlled Feeding Trials
2021, Journal of Nutrition
Although fructose as a source of excess calories increases uric acid, the effect of the food matrix is unclear.
To assess the effects of fructose-containing sugars by food source at different levels of energy control on uric acid, we conducted a systematic review and meta-analysis of controlled trials.
MEDLINE, Embase, and the Cochrane Library were searched (through 11 January 2021) for trials ≥ 7 days. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets) designs. Independent reviewers (≥2) extracted data and assessed the risk of bias. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the certainty of evidence.
We included 47 trials (85 comparisons; N = 2763) assessing 9 food sources [sugar-sweetened beverages (SSBs), sweetened dairy, fruit drinks, 100% fruit juice, fruit, dried fruit, sweets and desserts, added nutritive sweetener, and mixed sources] across 4 energy control levels in predominantly healthy, mixed-weight adults. Total fructose-containing sugars increased uric acid levels in substitution trials (mean difference, 0.16 mg/dL; 95% CI: 0.06–0.27 mg/dL; P = 0.003), with no effect across the other energy control levels. There was evidence of an interaction by food source: SSBs and sweets and desserts increased uric acid levels in the substitution design, while SSBs increased and 100% fruit juice decreased uric acid levels in addition trials. The certainty of evidence was high for the increasing effect of SSBs in substitution and addition trials and the decreasing effect of 100% fruit juice in addition trials and was moderate to very low for all other comparisons.
Food source more than energy control appears to mediate the effects of fructose-containing sugars on uric acid. The available evidence provides reliable indications that SSBs increase and 100% fruit juice decreases uric acid levels. More high-quality trials of different food sources are needed. This trial was registered at clinicaltrials.gov as NCT02716870.
Polyphenol exposure and risk of type 2 diabetes: Dose-response meta-analyses and systematic review of prospective cohort studies
2018, American Journal of Clinical Nutrition
Type 2 diabetes is characterized by impaired glucose metabolism. Bioactive compounds in fruits and vegetables such as polyphenols have been suggested to influence glucose metabolism.
The aim of the current study was to systematically review the literature and conduct dose-response meta-analyses to summarize evidence of polyphenol exposure in association with incident type 2 diabetes.
Prospective epidemiologic studies published before January 2018 were searched through 2 databases. Log-transformed multivariable adjusted hazard and odds ratios were combined in a random-effects model. Meta-analyses comparing extreme quantiles of polyphenol exposure were further explored with the use of linear and nonlinear dose-response meta-analyses.
Eighteen studies investigated the association between polyphenols (51 different compounds in total) and type 2 diabetes. A comparison of extreme quantiles revealed inverse associations for intakes of polyphenols (HR: 0.56; 95% CI: 0.34, 0.93), flavonoids (HR: 0.88; 95% CI: 0.81, 0.96), flavonols (HR: 0.92; 95% CI: 0.85, 0.98), flavan-3-ols (HR: 0.89; 95% CI: 0.81, 0.99), catechins (HR: 0.86; 95% CI: 0.75, 0.97), anthocyanidins (HR: 0.86; 95% CI: 0.81, 0.91), isoflavones (HR: 0.92; 0.86, 0.97), daidzein (HR: 0.89; 95% CI: 0.83, 0.95), genistein (HR: 0.92; 95% CI: 0.86, 0.99), and stilbenes (HR: 0.44; 95% CI: 0.26, 0.72), and biomarkers of daidzein (HR: 0.81; 95% CI: 0.66, 0.99) and genistein (HR: 0.79; 95% CI: 0.62, 0.99). In the dose-response meta-analysis, nonlinear associations were observed for intakes of polyphenols, flavonoids, flavanones, anthocyanidins, anthocyanins, and biomarkers of genistein. A linear dose-response association was observed for phenolic acids.
This study adds to the evidence showing that diets rich in polyphenols, and particularly flavonoids, play a role in the prevention of type 2 diabetes. For most associations evidence for nonlinearity was found, suggesting a recommendable amount of intake associated with the lowest risk of type 2 diabetes. Therefore, future studies are warranted in which nonlinear associations are further explored.

View all citing articles on Scopus

^☆: Funds of Scientific and Technological Development from Medicine and Healthcare in Shandong Province (2013BJYB05).

View full text

Original researchConsumption of citrus and cruciferous vegetables with incident type 2 diabetes mellitus based on a meta-analysis of prospective study☆

Highlights

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Search strategy

Search results

Discussion

Conflict of interest

Diabetes Res. Clin. Pract.

Nutr. Metab. Cardiovasc. Dis.

J. Nutr.

Am. J. Clin. Nutr.

Chem. Biol. Interact.

Biochim. Biophys. Acta

Asian Pac. J. Trop. Biomed.

Am. J. Clin. Nutr.

Diabetes Res. Clin. Pract.

Controlled Clin. Trials

Clin. Nutr.

Mol. Cell Endocrinol.

J. Nutr.

J. Am. Diet. Assoc.

Am. J. Clin. Nutr.

Am. J. Clin. Nutr.

Am. J. Clin. Nutr.

Prim. Care Diabetes.

Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance

N. Engl. J. Med.

Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin

N. Engl. J. Med.

Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis

BMJ

Fruit and vegetable intake and risk of type 2 diabetes mellitus: meta-analysis of prospective cohort studies

BMJ Open

A prospective study of fruit and vegetable intake and the risk of type 2 diabetes in women

Diabetes Care

Fruit and vegetable intake and type 2 diabetes: EPIC-InterAct prospective study and meta-analysis

Eur. J. Clin. Nutr.

Original research
Consumption of citrus and cruciferous vegetables with incident type 2 diabetes mellitus based on a meta-analysis of prospective study☆