Objective To determine whether individual fruits are differentially associated with risk of type 2 diabetes.
Design Prospective longitudinal cohort study.
Setting Health professionals in the United States.
Participants 66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies.
Main outcome measure Incident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires.
Results During 3 464 641 person years of follow-up, 12 198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.96 to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts).
Conclusion Our findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.
In three prospective cohorts of US men and women, we found that the associations with risk of type 2 diabetes differed significantly among individual fruits: greater consumption of blueberries, grapes, apples, bananas, and grapefruit were significantly associated with a reduced risk of type 2 diabetes. Most of these associations were quite consistent among three cohorts. Additionally, differences in the glycemic index/glycemic load values of fruits did not account for the association of specific fruits with risk of type 2 diabetes. Moreover, greater fruit juice consumption was associated with an increased risk, and substitution of whole fruits for fruit juice was associated with a lower risk, except for strawberries and cantaloupe.
Results in relation to other studies
In eight previous prospective studies, the association between total fruit consumption and risk of type 2 diabetes was examined,2 3 4 5 6 7 8 9 and the results were mixed. Similar to previous analyses in the Nurses’ Health Study3 and the Finnish Mobile Clinic Health Examination Survey study,2 the current findings supported an inverse association between total fruit consumption and risk of type 2 diabetes, but not in other studies.4 5 6 7 8 9 In contrast to total fruit consumption, evidence on consumption of individual fruits or fruit groups with risk of type 2 diabetes is limited and incomplete. In four prospective studies, consumption of citrus fruit was not associated with a lower risk of type 2 diabetes.5 6 7 8 Apple consumption was inversely associated with risk in the Women’s Health Study29 and in the Finnish study,30 but not in the Iowa Women’s Health Study.31 In addition, greater consumption of berries was associated with a lower risk in the Finnish study,2 but not in the Iowa Women’s Health Study.31 In our previous analyses that focused on anthocyanin rich fruits, intakes of blueberries, strawberries, and apples were associated with a lower risk of type 2 diabetes.32 Consistently, in a clinical trial, increased consumption of berries improved glycemic control among people with diabetes.33 Our current investigation extended the evidence in this regard and found novel, inverse associations for grapes, bananas, and grapefruit.
The different associations of individual fruits with diabetes risk may be due to the heterogeneous composition of these foods. Firstly, blueberries, apples, and red or black grapes contain high levels of anthocyanins.12 In mice with diabetes, bilberry extract rich in anthocyanins can activate adenosine monophosphate-activated protein kinase, enhance glucose uptake and utilization in white adipose tissue and skeletal muscle, and reduce glucose production in the liver.34 Our previous analyses also showed that levels of anthocyanin intake were inversely associated with risk of type 2 diabetes.32 In the current study, further adjustment for anthocyanins did not substantially change the associations for individual fruits, suggesting that the inverse associations of individual fruits are likely due to other constituents of these foods. Both red and white grapes contain high levels of resveratrol in skin.35 In mice, a high fat diet with 0.04% resveratrol increased insulin sensitivity at 24 months compared with the same diet without resveratrol.36 However, randomized controlled trials examining the effects of supplementation of resveratrol on glucose metabolism have generated inconsistent results.37 38 39 Prunes, peaches, plums, apricots, and apples contain chlorogenic acid,40 41 42 43 which may potentially mediate the beneficial effects of coffee consumption on diabetes risk.44 In rats, chlorogenic acid reduces glucose dependent insulinotropic peptide secretion by slowing glucose absorption in the intestine.45Moreover, chlorogenic acid increases muscle glucose uptake in mice with diabetes.46Finally, grapefruits contain high amounts of naringin.12 In rats, naringin inhibits dipeptidyl peptidase 4 similarly to sitagliptin, a dipeptidyl peptidase 4 inhibitor used for the treatment of diabetes.47 Inhibition of dipeptidyl peptidase 4 increases glucagon-like peptide 1, which subsequently leads to improved glucose tolerance.48 In contrast to these specific fruits mentioned above, cantaloupe was associated with an increased risk of type 2 diabetes in the current analysis. Melons have lower levels of phytochemicals than the aforementioned fruits.12 None the less, little evidence exists regarding the effects of melons on glucose metabolism. Although other fruits may also be beneficial for glucose metabolism, significant associations between other specific fruits and risk of type 2 diabetes were not found in the current and previous investigations.5 6 7 8
The glycemic index/glycemic load values of fruits did not seem to be the factor that determined their association with type 2 diabetes in the current study, although in a clinical trial, increased consumption of low glycemic index fruits improved glycemic control among people with diabetes.33 In recent meta-analyses, a higher dietary glycemic index/glycemic load was associated with a greater risk of type 2 diabetes.4950 In the Nurses’ Health Study and Health Professionals Follow-up Study, the associations between dietary glycemic index and risk of type 2 diabetes were positive, although the associations for dietary glycemic load were not significant.51 52 53 None the less, the contribution of total fruit consumption to dietary glycemic load was rather small (about 10%) in these populations. Of individual fruits, the top three contributors to dietary glycemic load were bananas (3-4%), apples (2%), and grapes (1%). In contrast, the relatively high glycemic load values of fruit juices13 along with reduced levels of beneficial nutrients through juicing processes11 12 (for example, the glycemic load values per serving are 6.2 for raw oranges and 13.4 for orange juice, and fibre levels per serving are 3.1 g and 0.5 g, respectively) may explain the positive associations between fruit juice consumption and risk of type 2 diabetes. Moreover, the difference in the viscosity of foods is also an important factor affecting postprandial blood glucose dynamics. Fluids pass through the stomach to the intestine more rapidly than solids even if nutritional content is similar.54 For example, fruit juices lead to more rapid and larger changes in serum levels of glucose and insulin than whole fruits.55 56 Although these mechanisms may potentially explain the diverse associations for individual fruits, further research is apparently needed to confirm our findings on specific fruits in relation to type 2 diabetes and to further elucidate underlying mechanisms.
Strengths and limitations of this study
The present study has several limitations. Firstly, measurement errors were inevitable in the estimates of fruit consumption, especially for individual fruits with lower consumption levels.17 18 Adjustment for energy intake and use of cumulatively averaged intake levels can reduce the magnitude of measurement errors to some extent.26 Generally, random errors in exposure assessments attenuate true associations toward the null. Secondly, the possibility of false positive findings may exist because we examined the associations of multiple fruits in the current investigation without adjusting for multiple comparisons based on a priori hypotheses. Meanwhile, most associations were consistent across three cohorts, and the associations for blueberries, grapes, and apples remained statistically significant even after applying the Bonferroni correction, a conservative method correcting for multiple comparisons. Thirdly, in our food frequency questionnaires, intakes of some individual fruits (apples and pears; peaches, plums, and apricots) were combined because these fruits have similar nutrient profiles. Therefore we could not determine whether the associations for these combined fruits can be ascribed to a specific individual fruit. Fourthly, we cannot exclude the possibility of recall bias in the assessments of diet based on the food frequency questionnaires. However, the prospective study design and exclusion of participants with chronic diseases at baseline should minimize such bias. Fifthly, although in the multivariable analysis we considered a multitude of lifestyle and dietary factors, including other individual fruits, residual or unmeasured confounding may still exist. Finally, our study populations primarily consist of health professionals with European ancestry. Thus our findings may not be generalized to other populations.
Our findings suggest that there is significant heterogeneity in the associations between individual fruits and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, was significantly associated with a lower risk of type 2 diabetes, whereas greater fruit juice consumption was associated with a higher risk. The differences in the associations between individual fruits were not accounted for by variation in the glycemic index/glycemic load values of individual fruits. Overall, these results support recommendations on increasing consumption of a variety of whole fruits, especially blueberries, grapes, and apples, as a measure for diabetes prevention.
What is already known on this topic
- Total fruit consumption is not consistently associated with a lower risk of type 2 diabetes
- The possible heterogeneity among individual fruits regarding the associations with risk of type 2 diabetes has not been examined
- The associations with risk of type 2 diabetes are different among individual fruits
- Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas increased consumption of fruit juices has the opposite association
- In addition, the associations of individual fruits are not determined by their glycemic index or glycemic load values
What this study adds