Abstract
Background
Although whole grain consumption has been associated with a lower risk of cardiovascular diseases (CVD) and mortality in the general population, the association of whole grain with mortality in diabetic patients remain to be determined. This study investigated whole grain and its components cereal fiber, bran and germ in relation to all-cause and CVD-specific mortality in patients with type 2 diabetes.
Methods and Results
We followed 7,822 US women with type 2 diabetes in the Nurses’ Health Study (NHS). Dietary intakes and potential confounders were assessed with regularly administered questionnaires. We documented 852 all-cause deaths and 295 CVD-deaths during up to 26 years of follow-up. After adjustment for age, the highest versus the lowest fifth of intakes of whole grain, cereal fiber, bran, and germ were associated with 16–31% lower all-cause mortality. After further adjustment for lifestyle and dietary risk factors, only the association for bran intake remained significant (P for trend = 0.01). The multivariate relative risks (RRs) across the fifths of bran intake were 1.0 (reference), 0.94 (0.75–1.18), 0.80 (0.64–1.01), 0.82 (0.65–1.04), and 0.72 (0.56–0.92). Similarly, bran intake was inversely associated with CVD-specific mortality (P for trend = 0.04). The RRs across the fifths of bran intake were 1.0 (reference), 0.95 (0.66–1.38), 0.80 (0.55–1.16), 0.76 (0.51–1.14), and 0.65 (0.43–0.99). Similar results were observed for added bran alone.
Conclusions
Whole grain and bran intakes were associated with reduced all-cause and CVD-specific mortality in women with diabetes. These findings suggest a potential benefit of whole grain intake in reducing mortality and cardiovascular risk in diabetic patients.
Keywords: Cardiovascular diseases, mortality, diabetes mellitus, whole grain, bran
Several epidemiologic studies have suggested that whole grain intake may reduce the risk of type 2 diabetes1, cardiovascular disease (CVD)2 and mortality 3,4. Whole-grain foods contain fiber, vitamins, minerals, phenolic compounds, phytoestrogens, and other un-measured constituents5, which may have favorable effects on health by lowering serum lipids6 and blood pressure7, improving glucose and insulin metabolism8, endothelial function, and alleviating oxidative stress9 and inflammation10.
Patients with type 2 diabetes have 2–3 fold higher risk of cardiovascular disease (CVD) and premature mortality than the general population11. A randomized crossover trial indicated that high-fiber diet can improve glycemic control, lower hyperinsulinemia, and improve blood lipid concentrations in diabetic patients12. In addition, results from our previous study among diabetic participants suggested that high intakes of whole grain and components such as cereal fiber and bran might protect against systemic inflammation and endothelial dysfunction 13. We therefore hypothesized that whole grain consumption might lower mortality especially cardiovascular mortality in diabetic patients.
To test this hypothesis, we prospectively examined the association between long-term intakes of whole grain, the grain subcomponents cereal fiber, bran, and germ, and the risks of all-cause and CVD-specific mortality among diabetic women from the Nurses’ Health Study (NHS).
Methods
Study population
The NHS cohort began in 1976 with the recruitment of 121,700 female registered nurses (aged 30–55 years old) residing in 11 large US states. The medical history, lifestyle information and disease diagnosis were updated every 2 years by using a validated questionnaire14. The current study included 7,822 women with type 2 diabetes diagnosed between 1976 and 2006. Women with diabetes diagnosed before the age of 30 years, or with a history of CVD (including stroke, myocardial infarction [MI], angina, and/or coronary revascularization) or cancer reported on the 1980 questionnaire (when diet was first assessed) or before, were excluded. The present study was approved by the institutional review board at Brigham and Women’s Hospital and returning the questionnaires was supposed to imply informed consent.
Confirmation of diabetes mellitus
Incident cases of type 2 diabetes were defined as self-reported diabetes confirmed by a validated supplementary questionnaire regarding symptoms, diagnostics tests, and hypoglycemic therapy. We used National Diabetes Data Group criteria 15 to diagnose diabetes before the release of the American Diabetes Association (ADA) criteria in 1997. The ADA diagnostic criteria was adopted to diagnose of diabetes cases during the 1998 and 2006 cycles16. Our validation study revealed that 98% of the self-reported type 2 diabetes cases were confirmed by medical records review 17. The diagnostic criteria that we used have been reported in detail elsewhere 18.
Death ascertainment
The end points in this study included all-cause and CVD-specific mortality. The ascertainment of death has been documented in previous study19. Briefly, deaths were reported by next of kin or the postal system or identified through the National Death Index. We previously estimated that follow-up for deaths was more than 98% complete20. We obtained death certificate copies and medical records, and determined causes of death according to the International Classification of Diseases, Ninth Revision.
Assessment of whole grain, cereal fiber, bran, and germ consumption
Semi-quantitative food-frequency questionnaires were sent to the NHS participants in 1980, 1984, 1986, 1990, 1994, 1998 and 2002. On each questionnaire, participants were asked to report how often on average they had consumed of foods and beverages with a specified used unit or portion size during the previous year. Whole grain were defined and calculated as previously described21. Briefly, the portions were converted to grams per serving, and intake of whole grains was calculated by multiplying the consumption frequency of each unit of food by the whole grain content in grams. Intake of whole grain (in grams per day) was estimated based on the dry weight of whole grain ingredients of all grain foods (including rice, pasta, bread, and breakfast cereals). Whole grain intake from the breakfast cereals was calculated from more than 250 brand name cereals according to the information from product labels or provided by breakfast cereal manufacturers. Total intake of bran and germ (in grams per day) in this study included added and naturally occurring forms from whole grain and was calculated in a similar manner. We used the residual method to energy-adjust the intakes of whole-grain and fiber22.
Statistical analysis
We calculated cumulative averages of food and nutrient intakes from the repeated questionnaires. Non-dietary covariates were updated at each biennial follow-up cycle. Person-time was calculated for each participant from the return of the questionnaire on which type 2 diabetes was first diagnosed to the occurrence of death or the end of the study period (1 June 2006). Cox proportional hazards regression was used to examine the associations between the dietary factors and all-cause and CVD-specific mortality. Multivariable models were first adjusted for age, smoking status, BMI, alcohol intake, physical activity, parental history of MI, menopausal status and use of hormone therapy, and duration of diabetes. We further adjusted for cumulative averages of dietary factors including total energy, intakes of polyunsaturated fat, saturated fat, trans fat, magnesium, and folate. The median value of each category of dietary factors consumption was used as a continuous variable to test for linear trends. To represent the long-term intake of dietary factors and to reduce measurement error, we conducted analyses using updating dietary data by taking the average of all available dietary questionnaires23. To minimize residual confounding, we performed additional analyses of the association of these specific dietary factors with all-cause mortality stratified by BMI, smoking, alcohol intake and physical activity. The SAS statistical package was used for all analyses (SAS, Version 9.0 for UNIX; SAS Institute, Cary, NC). All P values are two sided.
Results
Baseline characteristics
Compared with the lowest fifth of whole grain intake, women in the higher fifth had a lower BMI and were less likely to smoke, but more likely to be engaged in physical activity, to use postmenopausal hormones, and to have hypercholesterolemia and hypertension. Women with higher intakes of whole grain also had higher intakes of folate, multivitamin supplements, and vitamin E supplements, and lower intakes of alcohol, saturated fat, polyunsaturated fat, and trans fat (Table 1). The baseline characteristics across the fifths of cereal fiber, germ, and bran were similar to those for whole grains (data not shown). Correlations with whole grain intake were 0.69 for cereal fiber, 0.78 for bran, and 0.61 for germ.
Table 1.
Baseline characteristics according to quintiles of whole grain intake among women with type 2 diabetes (n = 7,822)*
| Variables | Whole-grain intake (g/day) | |||||
|---|---|---|---|---|---|---|
| Q1 | Q2 | Q3 | Q4 | Q5 | P trend | |
| Age (years) | 46 | 47 | 46 | 47 | 49 | |
| Risk factors | ||||||
| BMI (kg/m2) | 30.3 | 30.2 | 30.2 | 29.8 | 28.5 | < 0.01 |
| Current smokers (%) | 21.3 | 16.9 | 11.6 | 9.0 | 10.6 | < 0.01 |
| History of hypertension (%) | 41.5 | 41.9 | 49.1 | 50.0 | 46.0 | < 0.01 |
| History of hypercholesterolemia (%) | 34.2 | 31.7 | 42.9 | 45.3 | 45.1 | < 0.01 |
| Parental history of MI (%) | 22.6 | 21.2 | 23.6 | 21.4 | 24.1 | 0.23 |
| Postmenopausal hormone use (%) | 14.1 | 14.4 | 22.9 | 22.5 | 24.7 | < 0.01 |
| Aspirin use (%) | 14.9 | 15.5 | 15.4 | 18.2 | 18.4 | 0.015 |
| Physical activity (h/week) | 1.95 | 2.17 | 2.39 | 2.50 | 2.74 | < 0.01 |
| Alcohol(g/day) | 5.5 | 3.8 | 3.5 | 3.1 | 2.8 | < 0.01 |
| Dietary daily intake | ||||||
| Saturated fat (% energy) | 14.3 | 14.2 | 13.7 | 13.2 | 12.4 | < 0.01 |
| Polyunsaturated fat (% energy) | 5.8 | 5.7 | 5.8 | 5.7 | 5.5 | < 0.01 |
| Trans fat (% energy) | 2.1 | 2.1 | 2.0 | 1.9 | 1.8 | < 0.01 |
| Folate (ug/day) | 341.3 | 364.0 | 386.6 | 408.8 | 440.8 | < 0.01 |
| Glycemic load | 100.0 | 100.8 | 101.9 | 103.3 | 99.2 | 0.61 |
| Supplements | ||||||
| Multivitamins (%) | 34.1 | 35.2 | 39.5 | 46.0 | 50.0 | < 0.01 |
| Vitamin E (%) | 19.5 | 19.3 | 25.9 | 32.1 | 35.5 | < 0.01 |
Values are means, unless otherwise indicated. MI, myocardial infarction.
Intakes of whole grain, cereal fiber, bran, and germ in relation to all-cause mortality
During up to 26 years of follow up (70,102 person-years), we confirmed 852 deaths (295 deaths from CVD, including 195 deaths from coronary heart disease [CHD] and 100 from stroke). In an age-adjusted analysis, we observed an inverse association between whole grain intake and all-cause mortality (P for trend = 0.004; Table 2). Compared with the lowest fifth of whole grain intake, the relative risk (RR) for all-cause mortality was 0.80 (95% CI: 0.64–1.00) in the highest fifth. Further adjustment for lifestyle and dietary covariates attenuated the association to borderline significance. The multivariable RRs across the fifths of whole grain intakes were 1.0 (reference), 1.24 (0.99–1.54), 0.82 (0.65–1.04), 0.89 (0.70–1.13), and 0.89 (0.69–1.14). Per 20-g/d increment in whole grain intake corresponded to 13% reduction (95% CI: 2–23%) in all-cause mortality after adjustment for age.
Table 2.
Relative risk (95% confidence interval) of all-cause mortality in women with diabetes according to the cumulative average intakes of whole grain, cereal fiber, bran, and germ (g/day) (1980–2006)*
| Variables | RR (95% CI) according to intakes | P trend | ||||
|---|---|---|---|---|---|---|
| Q1 | Q2 | Q3 | Q4 | Q5 | ||
| Whole-grain intake | 4.8 (< 7.8) | 10.5 (7.8–12.1) | 14.4(12.2–17.4) | 20.6 (17.5–25.4) | 32.6 (25.5–146.0) | |
| Number of cases | 154 | 191 | 154 | 175 | 178 | |
| Person-years | 13994 | 14163 | 13947 | 13945 | 14053 | |
| Age- adjusted | 1.00 | 1.18(0.95–1.45) | 0.81(0.65–1.02) | 0.83(0.67–1.04) | 0.80(0.64–1.00) | 0.004 |
| Multivariate model 1† | 1.00 | 1.24(1.00–1.54) | 0.84(0.67–1.06) | 0.91(0.73–1.14) | 0.89(0.71–1.11) | 0.06 |
| Multivariate model 2‡ | 1.00 | 1.24(0.99–1.54) | 0.82(0.65–1.04) | 0.89(0.70–1.13) | 0.89(0.69–1.14) | 0.11 |
| Cereal fiber intake | 1.9 (< 2.57) | 2.99 (2.57–3.40) | 3.80(3.41–4.22) | 4.70 (4.23–5.30) | 6.29 (5.31–22.50) | |
| Number of cases | 147 | 176 | 177 | 176 | 176 | |
| Person-years | 13956 | 13949 | 14079 | 14084 | 14035 | |
| Age- adjusted | 1.00 | 0.94(0.75–1.18) | 0.86(0.68–1.07) | 0.77(0.61–0.97) | 0.69(0.54–0.87) | 0.0003 |
| Multivariate model 1† | 1.00 | 1.03(0.82–1.29) | 0.99(0.78–1.25) | 0.88(0.70–1.12) | 0.81(0.64–1.03) | 0.02 |
| Multivariate model 2‡ | 1.00 | 1.08(0.85–1.36) | 1.06(0.83–1.35) | 0.95(0.74–1.23) | 0.86(0.66–1.12) | 0.10 |
| Bran intake | 0.8 (< 1.40) | 1.88 (1.40–2.50) | 3.22(2.51–4.04) | 5.16 (4.05–6.85) | 9.73 (6.86–68.4) | |
| Number of cases | 164 | 160 | 177 | 174 | 177 | |
| Person-years | 14116 | 14045 | 14209 | 13687 | 14044 | |
| Age- adjusted | 1.00 | 0.90(0.72–1.12) | 0.81(0.65–1.00) | 0.75(0.60–0.94) | 0.69(0.55–0.86) | 0.001 |
| Multivariate model 1† | 1.00 | 0.95(0.76–1.18) | 0.85(0.68–1.05) | 0.86(0.68–1.07) | 0.75(0.60–0.95) | 0.01 |
| Multivariate model 2‡ | 1.00 | 0.94(0.75–1.18) | 0.80(0.64–1.01) | 0.82(0.65–1.04) | 0.72(0.56–0.92) | 0.01 |
| Germ intake | 0.2 (< 0.33) | 0.46 (0.33–0.51) | 0.61(0.52–0.74) | 0.9 (0.75–1.10) | 1.51 (1.11–18.3) | |
| Number of cases | 166 | 178 | 175 | 160 | 173 | |
| Person-years | 14218 | 14014 | 13914 | 13969 | 13987 | |
| Age- adjusted | 1.00 | 1.10(0.89–1.35) | 0.90(0.72–1.11) | 0.80(0.64–0.99) | 0.84(0.68–1.05) | 0.03 |
| Multivariate model 1† | 1.00 | 1.13(0.91–1.40) | 0.92(0.74–1.14) | 0.89(0.71–1.12) | 0.95(0.76–1.18) | 0.35 |
| Multivariate model 2‡ | 1.00 | 1.12(0.91–1.40) | 0.89(0.72–1.11) | 0.89(0.71–1.13) | 0.99(0.78–1.26) | 0.69 |
For the intake level at each quintile, values were expressed as median (range).
Adjusted for age (5-year categories), smoking status (never, past and current 1–14, 15–24 or ≥ 25 cigarettes/day), BMI (<23.0, 23.0–24.9, 25.0–27.9, 28.0–29.9 or ≥ 30.0 kg/m2), alcohol intake (0, 0.1–4.9, 5–14 or ≥ 15 g/day), physical activity (<1, 1–1.9, 2–3.9, 4–6.9 or ≥ 7 h/week), parental history of MI, menopausal status and use of hormone therapy, and duration of diabetes (<5, 5–10, 11–15 or ≥ 15 years).
Adjusted for covariates in model 1 plus total energy, intakes of polyunsaturated, saturated and trans fat, magnesium, and folate (all in quintiles). RR, relative risk; CI, confidence interval.
We then examined the associations between the components of whole grain (cereal fiber, bran, and germ) and all-cause mortality. All three components were significantly, inversely associated with risk, after adjustment for age. The association between bran intake and all-cause mortality remained significant after adjustment for lifestyle factors and other covariates (RR: 0.75, 95% CI: 0.60–0.95 for the highest versus the lowest fifth; P for trend = 0.01). Further adjustment for dietary factors did not materially change the association. The RRs across the fifths of bran intakes were 1.0 (reference), 0.94 (0.75–1.18), 0.80 (0.64–1.01), 0.82 (0.65–1.04), and 0.72 (0.56–0.92; P for trend = 0.01). Per 1-g/d increment in bran intake corresponded to a 2% (95% CI: 1–4%) reduction in all-cause mortality after adjustment for age. Significant associations were found for cereal fiber after adjustment for lifestyle and other covariates. The RRs across the fifths of cereal fiber intakes were 1.0 (reference), 1.03 (0.82–1.29), 0.99 (0.78–1.25), 0.88 (0.70–1.12), and 0.81 (0.64–1.03) (P for trend = 0.02). Further adjustment for dietary factors weakened the association (P for trend = 0.10). Per 1-g/d increment in cereal fiber intake corresponded to 8% (95% CI: 4–11%) reduction in all-cause mortality after adjustment for age. The association between germ intake and total-mortality was not significant in the multivariate models. The RRs across the fifths of germ intakes were 1.0 (reference), 1.12 (0.91–1.40), 0.89 (0.72–1.11), 0.89 (0.71–1.13), and 0.99 (0.78–1.26) (P for trend = 0.69; Table 2). We found similar inverse associations between these dietary factors with all-cause mortality stratified by BMI (< 30 vs. ≥ 30 kg/m2), smoking (never vs. past and current smoking), alcohol intake (nondrinkers vs. drinkers) and physical activity (used median as the cut point; <11.8 vs. ≥ 11.8 MET h/week) (data not shown).
Intakes of whole grain, cereal fiber, bran, and germ and CVD-specific mortality
We further examined the associations between intakes of whole grain and subcomponents with CVD-specific mortality. In age-adjusted models, intakes of whole grain, cereal fiber, and bran were inversely associated with CVD-specific mortality. Further adjustment for lifestyle and dietary variables attenuated the associations for whole grain (The multivariable RRs and 95% CI across the fifths of whole grain intakes were 1.0 [reference], 1.06 [0.74–1.52], 0.66 [0.44–0.97], 0.77 [0.52–1.14], and 0.70 [0.46–1.06; P for trend = 0.07]) and cereal fiber (The multivariable RRs and 95% CI across the fifths of cereal fiber intakes were 1.0 [reference], 1.20 [0.81–1.76], 1.12 [0.75–1.69], 1.09 [0.71–1.67], and 0.89 [0.57–1.41; P for trend = 0.41]). However, the association between bran intake and CVD-specific mortality remained significant in the fully-adjusted model. The highest fifth of bran intake were associated with 35% lower risk of CVD-specific mortality as compared with the lowest fifth (RR: 0.65, 95% CI: 0.43–0.99; P for trend = 0.04) (Table 3). Germ intake was not substantially associated with CVD-specific mortality. The RRs across the fifths of germ intakes were 1.0 (reference), 0.96 (0.68–1.37), 0.71 (0.49–1.02), 0.61 (0.41–0.91), and 0.85 (0.58–1.25) in the fully-adjusted model (P for trend = 0.37).
Table 3.
Relative risk (95% confidence interval) of CVD-specific mortality in women with diabetes according to the cumulative average intakes of whole grain, cereal fiber, bran, and germ (1980–2006)
| Variables | RR (95% CI) according to intakes |
P trend | ||||
|---|---|---|---|---|---|---|
| Q1 | Q2 | Q3 | Q4 | Q5 | ||
| Whole-grain intake | ||||||
| Number of cases | 62 | 65 | 52 | 59 | 57 | |
| Age- adjusted | 1.00 | 1.03(0.73–1.46) | 0.70(0.48–1.02) | 0.78(0.55–1.13) | 0.71(0.49–1.03) | 0.04 |
| Multivariate model 1* | 1.00 | 1.10(0.78–1.57) | 0.73(0.50–1.07) | 0.88(0.61–1.27) | 0.81(0.56–1.19) | 0.21 |
| Multivariate model 2† | 1.00 | 1.06(0.74–1.52) | 0.66(0.44–0.97) | 0.77(0.52–1.14) | 0.70(0.46–1.06) | 0.07 |
| Cereal fiber intake | ||||||
| Number of cases | 53 | 65 | 61 | 62 | 54 | |
| Age- adjusted | 1.00 | 0.99(0.68–1.43) | 0.88(0.60–1.29) | 0.84(0.57–1.24) | 0.69(0.46–1.02) | 0.03 |
| Multivariate model 1* | 1.00 | 1.08(0.74–1.57) | 1.04(0.70–1.54) | 1.00(0.68–1.49) | 0.85(0.56–1.29) | 0.31 |
| Multivariate model 2† | 1.00 | 1.20(0.81–1.76) | 1.12(0.75–1.69) | 1.09(0.71–1.67) | 0.89(0.57–1.41) | 0.41 |
| Bran intake | ||||||
| Number of cases | 61 | 57 | 65 | 55 | 57 | |
| Age- adjusted | 1.00 | 0.90(0.62–1.29) | 0.83(0.58–1.19) | 0.73(0.50–1.06) | 0.69(0.47–1.00) | 0.04 |
| Multivariate model 1* | 1.00 | 0.98(0.68–1.42) | 0.88(0.62–1.27) | 0.86(0.58–1.25) | 0.78(0.53–1.15) | 0.18 |
| Multivariate model 2† | 1.00 | 0.95(0.66–1.38) | 0.80(0.55–1.16) | 0.76(0.51–1.14) | 0.65(0.43–0.99) | 0.04 |
| Germ intake | ||||||
| Number of cases | 69 | 62 | 59 | 44 | 61 | |
| Age- adjusted | 1.00 | 0.96(0.68–1.35) | 0.76(0.54–1.08) | 0.59(0.41–0.87) | 0.80(0.56–1.13) | 0.13 |
| Multivariate model 1* | 1.00 | 0.98(0.69–1.39) | 0.77(0.54–1.11) | 0.66(0.45–0.97) | 0.91(0.64–1.31) | 0.50 |
| Multivariate model 2† | 1.00 | 0.96(0.68–1.37) | 0.71(0.49–1.02) | 0.61(0.41–0.91) | 0.85(0.58–1.25) | 0.37 |
Adjustment for covariates as described in the footnotes to Table 2. RR, relative risk; CI, confidence interval.
In order to assess whether added bran has similar benefits as total bran, we further examined the association of added bran intakes with all-cause and CVD-specific mortality. A large proportion (26,705 person-years) of the study population did not eat products with added bran. We defined these participants with “no intake” as the reference group, and created four additional categories for those who did consume added bran. Compared with non-consumers of added bran, the inverse association for added bran and all-cause mortality was similar with that observed for total bran intake after adjusting for age. Further adjustment for lifestyle and dietary factors did not attenuate the inverse association when the subjects with the highest intake of added bran was compared with nonuser (RR: 0.45, 95% CI: 0.36–0.57; P for trend < 0.001). Similar results were observed for CVD-specific mortality (RR: 0.36, 95% CI: 0.24–0.54; P for trend < 0.001; data not shown). We did not find associations of added germ intake and all-cause or CVD-specific mortality.
Discussion
In this prospective study of 7,822 women with type 2 diabetes, we observed that intakes of whole grain, cereal fiber and bran were inversely associated with all-cause and CVD-specific mortality during 26-y follow-up. The association for bran intake was independent of other lifestyle and dietary factors. We did not find an association of germ intake with all-cause or CVD-specific mortality.
Several mechanisms have been suggested to be underlying the protective effects of whole grain and it’s components on health, including reduction in serum lipids6 and blood pressure7, improvement of glucose and insulin metabolism8 and endothelial function, and alleviation of oxidative stress9 and inflammation10. Whole grain is composed of three parts: bran, germ, and endosperm. The bran and germ contain many nutrients and phytochemicals and have various potential beneficial health effects 24. In line with our observation in participants without diabetes in the NHS cohort, bran intake was more strongly associated with reduced CHD risk than germ intake25. Bran is the major source of cereal fiber and contains important bioactive constituents26. Jacobs et al. found that fiber from whole grain products, but not fiber from refined grain products was inversely associated with mortality, suggesting that the botanically linked fiber and phytochemicals in bran may confer additional health benefits beyond the effect of fiber alone3. Although germ also contains micronutrients and phytochemicals, our previous study in men only found inverse associations of whole grain and bran, but not germ, with CHD27, consistent with our results.
Our findings are also consistent with findings from clinic trials that whole grain and bran consumption may improve the metabolic profiles in diabetic patients. In a randomized controlled trial conducted in hyperinsulinemic adults, consumptions of whole grains for six weeks improved insulin sensitivity when compared with refined grains28. Another clinical trial found that consumption of whole grain and legume powder can reduce fasting glucose levels in diabetic patient with coronary artery disease when compared with those consumption of refined rice29. Results of intervention studies of wheat bran are inconsistent. Two studies found there were beneficial effects on glucose tolerance in individuals with or without glucose intolerance30,31, another study including 23 diabetic patients who completed two 3-month phases diet intervention did not find favorable effects of wheat bran on glycemic control32. Nevertheless, oat bran can improve glycemic and insulinemic responses and beneficially influence plasma lipid levels in diabetic patients 33. In the present study, although we did not analyze different sources of bran, both total and added bran intakes were inversely associated with all-cause or CVD-specific mortality in diabetic patients. However, additional investigations relating difference sources of bran to beneficial effects on diabetic patients are warranted in future studies.
Several cohort studies found that the whole grain components magnesium and folate were inversely associated with risk of all-cause mortality and CVD-specific mortality34,35. However, in our study, magnesium and folate did not fully explain the inverse associations between whole grain and subcomponents and mortality, suggesting other components of whole grain may play important roles.
Our study had several strengths. First, we analyzed data collected in a prospective cohort study. This minimizes recall bias and reverse causation. Second, we used cumulative average intakes of multiple repeated measurements of dietary intakes from updated dietary questionnaires reflecting the long-term dietary intakes, and therefore reduced the measurement error23. There are several potential limitations that also need to be considered. Higher intake of whole grain is part of a cluster of healthier dietary and lifestyle habits (eg, less smoking, more physical activity, and lower BMI). Although we adjusted for the lifestyle and dietary factors known to be associated with CVD and mortality, the potential of uncontrolled and unmeasured confounders might still remain. The observed associations may be confounded by the correlation between whole grain intakes and other greater health conscious behaviors and better glycemic control through unknown means. In addition, although we used cumulative average intakes of multiple repeated measurements reflecting the long-term diet, the measurement error of dietary intake assessment is unavoidable. Despite a relatively large sample size, our study was still underpowered to detect modest associations. For the all-cause mortality, we had 80% power to detect the association with RR ≤ 0.72 (or RR ≥ 1.38; α = 0.05); for CVD-specific mortality, we could detect RR ≤ 0.59 (or RR ≥ 1.69) with 80% power and α = 0.05. Thus, the nonsignificant associations with whole grains and cereal fiber may be due to limited power of our study. Finally, because the present study was conducted in white women, the associations need to be examined in men and other ethnic groups.
In summary, we found that intakes of whole grain especially its subcomponent bran were inversely associated with all-cause and CVD-specific mortality among women with type 2 diabetes. Our findings suggest that low whole grain intake may be considered an important modifiable risk factor for decreasing mortality and cardiovascular risk in diabetic patients.
CLINICAL PERSPECTIVE
Although whole grain consumption has been associated with a lower risk of cardiovascular disease incidence and mortality in the general population, little is known about the effect of whole grain and its components on cardiovascular risk and mortality in diabetic patients. In this prospective study, we followed 7,822 US women with type 2 diabetes for up to 26 years to investigate intakes of whole grain and its components cereal fiber, bran and germ in relation to all-cause and CVD-specific mortality. Our results indicated that intakes of whole grain especially its subcomponent bran were inversely associated with all-cause and CVD-specific mortality among women with type 2 diabetes. Low whole grain intake may be considered an important modifiable risk factor for decreasing mortality and cardiovascular risk in persons with diabetes.
Acknowledgments
We thank all the participants of the Nurses’ Health Study for their continued cooperation and thank Al Wing for computer programming assistance.
Funding Sources
This study was supported by the National Institutes of Health RO1 HL71981, DK58845, and HL60712, American Heart Association Scientist Development Award and the Boston Obesity Nutrition Research Center (DK46200 to LQ).
Footnotes
Disclosures
None.
References
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