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The Association of the Consumption Time for Different Food with the Cardiovascular Disease and All-Cause Mortality Among Diabetes Patients

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Abstract

Background: This study aims to investigate whether food consumed time and distribution at three-meals is associated with long-term survival among the people with diabetes. Methods: This study included 4,699 diabetes patients participating in the National Health and Nutrition Examination Survey from 2003 to 2014. Food consumed across a day including the forenoon, afternoon, evening, were divided into quantiles based on their distribution. Cox proportional hazards regression models were used to analyze the survival relationship between food intakes time and distribution (with a constant quality and quantity) and mortality. Results: After adjustment for multiple covariates, in the forenoon, compared to the participants with diabetes in the lowest consumption quantile of potato and starchy-vegetable, participants with diabetes in the highest consumption quantile had lower mortality risk of CVD(HRpotato=0.52, 95%CI: 0.38-0.87; HRstarchy-vegetable= 0.51, 95%CI: 0.29-0.90). In the evening, the highest quantile of dark-vegetable intake is related to lower mortality risk of CVD(HR=0.64, 95%CI: 0.45-0.92) and all-cause(HR=0.81, 95%CI: 0.66-0.99), whereas participants in the highest quantile of intakes of refined grain and processed meat are more likely to die due to CVD(HRrefined-grain=1.54, 95%CI:1.10-2.15; HRprocessed-meat=1.83, 95%CI:1.20-2.77) and all-cause(HRrefined-grain=1.29, 95%CI:1.01-1.65; HRprocessed-meat=1.37, 95%CI:1.06-1.75). Iso-calorically switching 0.1 serving refined grain or processed meat consumed in the evening to the forenoon, and 0.1 serving dark vegetable consumed in the afternoon to the evening reduced the risk of CVD mortality. Conclusions: Higher intake of potato, starchy-vegetable in forenoon, dark-vegetable in the evening, and lower intake of refined-grain and processed-meat in the evening was associated with better long-term survival in people with diabetes.
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The Association of the Consumption Time for
Different Food with the Cardiovascular Disease and
All-Cause Mortality Among Diabetes Patients
Wenbo Jiang
Harbin Medical University School of Public Health
Qingrao Song
Harbin Medical University School of Public Health
Jia Zhang
Harbin Medical University School of Public Health
Yunyan Chen
Harbin Medical University School of Public Health
Changhao Sun
Harbin Medical University School of Public Health
Ying Li
Harbin Medical University School of Public Health
Tianshu Han
Harbin Medical University School of Public Health
Wei Wei ( weiweibubble1994@163.com )
Harbin Medical University
Original investigation
Keywords: Diabetes, Distribution of food consumption, CVD mortality, All-cause mortality.
Posted Date: September 27th, 2021
DOI: https://doi.org/10.21203/rs.3.rs-876102/v1
License: This work is licensed under a Creative Commons Attribution 4.0 International License. 
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Abstract
Background:
This study aims to investigate whether food consumed time and distribution at three-meals is associated
with long-term survival among the people with diabetes.
Methods:
This study included 4,699 diabetes patients participating in the National Health and Nutrition
Examination Survey from 2003 to 2014. Food consumed across a day including the forenoon, afternoon,
evening, were divided into quantiles based on their distribution. Cox proportional hazards regression
models were used to analyze the survival relationship between food intakes time and distribution (with a
constant quality and quantity) and mortality.
Results:
After adjustment for multiple covariates, in the forenoon, compared to the participants with diabetes in
the lowest consumption quantile of potato and starchy-vegetable, participants with diabetes in the
highest consumption quantile had lower mortality risk of CVD(HRpotato=0.52, 95%CI: 0.38-0.87; HRstarchy-
vegetable= 0.51, 95%CI: 0.29-0.90). In the evening, the highest quantile of dark-vegetable intake is related to
lower mortality risk of CVD(HR=0.64, 95%CI: 0.45-0.92) and all-cause(HR=0.81, 95%CI: 0.66-0.99),
whereas participants in the highest quantile of intakes of rened grain and processed meat are more
likely to die due to CVD(HRrened-grain=1.54, 95%CI:1.10-2.15; HRprocessed-meat=1.83, 95%CI:1.20-2.77) and
all-cause(HRrened-grain=1.29, 95%CI:1.01-1.65; HRprocessed-meat=1.37, 95%CI:1.06-1.75). Iso-calorically
switching 0.1 serving rened grain or processed meat consumed in the evening to the forenoon, and 0.1
serving dark vegetable consumed in the afternoon to the evening reduced the risk of CVD mortality.
Conclusions:
Higher intake of potato, starchy-vegetable in forenoon, dark-vegetable in the evening, and lower intake of
rened-grain and processed-meat in the evening was associated with better long-term survival in people
with diabetes.
Background
Diet is an accepted modiable behavior that could be helpful for the prevention and therapy of diabetes
[1]. Previous studies frequently focused on the health impact of the quantity and quality of different
foods or nutrients on the management of diabetes. However, in recent years, overwhelming animal
studies have demonstrated that the ingestion time is another major factor for the well-being of organisms
because of the circadian effects [2–5]. Meanwhile, accumulating human studies also found that
breakfast skipping, high frequency of eating in a day, higher energy intake at dinner, and late-night eating
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are associated with higher inammation levels, poorer cardio-metabolic health and greater incidence of
obesity and type 2 diabetes [6–11]. Additionally, our recent study also found that the consumption model
of higher energy at breakfast with lower energy at dinner was associated with a better long-term survival
among people with diabetes [12].
Although the above evidence has suggested that the time of ingestion plays an important role in the
prevention and treatment of diabetes, few studies have examined the association of consumption time of
different food (especially distribution of food consumption across a day under a constant quality and
quantity) with the nature course of diabetes. Therefore, based on current evidence, we hypothesis that
different food might have different optimal consumption time for people with diabetes, and it may aid in
helping the people with diabetes to select appropriate food at optimal time, thereby improving the
nutritional management by understanding the association between consumption time of different food
and long-term survival. Based on the data from the National Health and Nutrition Examination Survey
(NHANES), this study aims to examine the association of different food groups consumed at different
time and consumed distribution with cardiovascular disease (CVD) and all-cause mortality in people with
diabetes.
Methods
Study population
As a stratied and multistage study, NHANES is designed by National Center for Health Statistics (NCHS).
A nationally representative sample of the non-institutionalized civilian population of the U.S. was
investigated to assess the health and nutritional status. The detailed introduction about NHANES has
been described elsewhere[13]. This study recruited people aged over 18 years with diabetes who
participated in the NHANES during 2003-2014. Diabetes was dened by the following any criteria: 1) self-
reported information, 2) fasting plasma glucose level (FPG) > 7.0 mmol/l, 3) hemoglobin A1c level (HA1c)
> 6.5%. After excluding participants with diabetes who had 1) missing or unknown information on any
dietary nutrient intake, 2) missing information of mortality. Finally, 4699 participants with diabetes (2413
men and 2286 women) were included. Research Ethics Review Board of National Center for Health
Statistics approved NHANES, and all participants with diabetes had already provided written informed
consent before initial exam. The NHANESdata could be accessed
throughhttps://wwwn.cdc.gov/nchs/nhane.
Dietary assessment
Information about food intakes for two non-consecutive days were collected through 24-hour dietary
recall interviews. In the rst one, the dietary investigation was conducted in-person, and in the other one,
the dietary investigation was conducted 3–10 days afterwards by calling. According to the United States
Department of Agricultures Food and Nutrient Database for Dietary Studies, the individual energy and
nutrient intake was estimated. In line with the MyPyramid Equivalents Database 2.0 for USDA Survey
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Foods (MPED 2.0), dietary food consumption of participants with diabetes in the NHANES was also
integrated into 18 denable MyPyramid major food groups.
Main exposure
Align with the consumption time, we split the major food groups intake into different period, such as the
forenoon (breakfast plus snack between breakfast and lunch), the afternoon (lunch plus snack between
lunch and dinner), the evening (dinner plus snack after dinner).
Main outcome
In this research, the status of CVD and all-cause mortality was the major outcome variable. The mortality
status was determined by the National Death Index (NDI) until 31 December 2015. The NDI is a highly
reliable resource, which has been widely used for death identication. As an international disease
classication method, the ICD-10 is used for the determination of disease-specic death. The ICD-10
codes I00–I09, I11, I13, I20–I51, or I60–I69 was dened as CVD mortality. In total, this study documented
913 deaths, including 314 deaths due to CVD death.
Assessment of covariates
Non-dietary covariates were sex (male/female), age (years), BMI (kg/m2), drink (yes/no), smoke (yes/no),
regular exercise (yes/no), education ( less than 9th grade, between 9th and 11th grade, graduate from high
school, GED or equivalent, Arts degree of some college or Associate, college graduate or above),
race/ethnicity (non-Hispanic white/non-Hispanic black/Mexican American/other), household income per
year (<$20,000, $20,000–$45,000, $45,000–$75,000, or >$100,000), family history of diabetes (yes/no),
diagnosis record of hypertension or dyslipidemia (yes/no), drug use for controlling blood pressure,
cholesterol and glucose. And the dietary covariates included total intakes of energy (kcal/day),
carbohydrate (g/d), dietary fat (g/day), protein (g/day), major food groups and Alternate Healthy Eating
Index (AHEI), which is an indicator of dietary quality.
Statistical analysis
All analyses were performed according to the guidelines analytic of NHANES. Continuous variables about
demographic characteristics, anthropometric measurements, and dietary nutrient and food intakes, were
showed as mean (SD) or median (P25, P75); whereas, categorical variables were showed as number
(percentage). General linear models adjusting for age and x2 tests were used to compare baseline
characteristics by mortality status. All statistical analyses were conducted by R 4.0.2, and two-sided
P
<
0.05 was considered to be statistically signicant.
Cox proportional hazards models
Food groups consumed in forenoon, afternoon, and evening were transformed into categorical variables
based on their distribution, respectively. Cox proportional hazards (CPH) models were performed to
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estimate the hazards ratio(HR) and 95% condence interval (CI) for the association of food consumed in
the forenoon, afternoon and evening with CVD and all-cause mortality. Follow-up years of participants
with diabetes between interview date and death or census date (31 December 2015) was dened as
Survival time. A series of covariates was also controlled, which were including age, sex, ethnics,
education, income, smoking, drinking, regular exercise habits, BMI, total intake of daily energy, fat,
carbohydrate, protein, family history of diabetes, hypertension and dyslipidemia, and medication.
Moreover, when analyzing one food group consumed in one time period across a day, we also controlled
the total intake of this food group in the whole day.
Predicted isocaloric models
Based on the CPH model developed in previous steps, we also built several isocaloric models to evaluate
relative risk of deaths with altered distribution of food consumption time, which was conducted via one
food group consumed at one time period theoretically replacing with the equivalent food group
consumed at another time period[12]. A key rationale of the substitution analysis is that, in the isocaloric
setting, the total intake of energy, macronutrients and the food group are held constant.
Sensitivity analysis
We performed three kinds of sensitivity analyses. In the rst analysis, we excluded the diabetes patients,
whose survival time less than two years or follow-up duration less than two years to examine the impact
of severe illness or accident on the results. In the second analysis, the indicator of overall dietary quality
and breakfast skipping were additionally adjusted in the CPH model to evaluate whether these
confounders would inuence the results.
Results
Baseline characteristics
In terms of CVD mortality status, the baseline characteristics of demographic information,
anthropometric results, nutrition intakes, are showed in Table 1. Compared to diabetes patients who not
died and died of non-CVD, patients with CVD mortality were more likely to be men, non-Hispanic white,
had higher age, prevalence of hypertension, and had lower BMI, education level, family annual income,
diet quality, energy and macronutrient intake (
P
<0.05).
Mortality
Among the18 major food groups,the intake distribution of potato, starchy vegetable, dark vegetable,
rened grain and processed meat at different time periods across a day were observed to be related to the
mortality risk of CVD and all-cause. As shown in Figure 1, compared to the participants with diabetes in
the lowest quantile of intakes of rened grain, potato and starchy vegetable in the forenoon, participants
with diabetes in the highest quantile had lower mortality risk of CVD (HRrened grain = 0.68, 95%CI: 0.49-
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0.92; HRpotato = 0.52, 95%CI: 0.32-0.87; HRstarchy vegetable = 0.51, 95%CI: 0.29-0.90), all-cause (HRrened grain
= 0.72, 95%CI: 0.57-0.91). In the evening, the higher intake of rened grain or processed meat was
associated with a higher probability of deaths due to CVD and all-cause. The HR indicated participants
with diabetes who were in the highest quantile were more likely to die due to CVD (HRrened grain =1.54,
95%CI: 1.10-2.15; HRprocessed meat =1.83, 95%CI: 1.20-2.77) and all-cause (HRrened grain =1.29, 95%CI: 1.01-
1.65; HRprocessed meat =1.37, 95%CI: 1.06-1.75). Moreover, compared to the participants with diabetes in
the lowest quantile of dark vegetable intake in the evening, participants with diabetes in the highest
quantile had lower mortality risk of CVD (HRdark vegetable = 0.64, 95%CI: 0.45-0.92), all-cause (HRdark
vegetable= 0.81, 95%CI: 0.66-0.99). Additionally, no signicant association between the intakes of other
food groups at different time periods within a day and mortality risk was observed, which were presented
in Supplementary Table A to C.
Isocaloric substitution analysis
Because the intakes of rened grain, potato, starchy vegetable in the forenoon, and the intakes of dark
vegetable, rened grain and processed meat in the evening were associated with CVD mortality. To
examine the association of changed distribution of diet food intake with CVD death risk, the isocaloric
substitution analyses were therefore performed to examine whether switching these food groups
consumed at different time points would modify the mortality risk. Figure 1 showed that the HR of CVD
mortality decreased by 2% (HRrened grain=0.98, 95%CI: 0.97-0.99) when 0.1 serving rened grain
consumed in the evening was iso-calorically switched to the rened grain consumed in the forenoon.
Similarly, the HR of CVD mortality decreased by 1% (HRprocessed meat=0.99, 95%CI: 0.98-0.99) when 0.1
serving processed meat consumed in the evening was iso-calorically replaced by the same serving
consumption in the forenoon. Meanwhile, the HR of CVD mortality decreased by 9% (HRdark vegetable=0.91,
95%CI: 0.85-0.97) when 0.1 serving dark vegetable consumed in the evening was used to iso-calorically
replace the same serving consumption in the afternoon.
Sensitivity Analysis
In the rst sensitivity analysis, after the exclusion of participants with diabetes who died within two years
of follow-up or had follow-up duration of less than two years, the negative association of higher intake of
potato in the forenoon and higher intake of dark vegetable in the evening with lower CVD and all-cause
mortality was still signicant, and the positive association of higher intake of rened-grain, processed
meat with greater CVD and all-cause mortality was also signicant (Supplementary Table D). These
results indicated the above association was not affected by the severe illness. Moreover, results of
second sensitivity analysis supported that after additionally adjusting for the confounders of dietary
quality and breakfast skipping in the CPH models, most of the relationships between food groups and
CVD and all-cause mortality (except rened grain in forenoon ) were robust signicant, which suggested
that the overall dietary quality and breakfast skipping hardly inuence the results (Supplementary Table E
and F).
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In these three sensitivity analysis, the HR of CVD mortality was decreased (Supplementary Figure1-3)
when changing distribution of consumption time for rened grain (from evening to forenoon), processed
meat(from evening to forenoon and afternoon), and dark vegetables(from evening to afternoon). These
results supported the distribution of consumption time for diet food groups could impact the CVD
mortality risk.
Discussion
Our study demonstrated that diabetes patients with more potato and starchy-vegetable consumption in
the forenoon and dark-vegetable in the evening had lower mortality risk of CVD and all-cause; however,
diabetes patients with more rened grain and processed meat consumption in the evening had a greater
mortality risk of CVD and all-cause. Further, under a constant quality and quantity, iso-calorically
switching 0.1 serving intake of rened grain or processed meat consumption from the evening to the
forenoon, and 0.1 serving intake of dark vegetable from the afternoon to the evening could signicantly
reduce the risk of CVD-mortality.
We rstly examined the association between different food groups consumed at different time and the
long-term survival among people with diabetes. Therefore, the most nding of our study was that food
groups including potato, starchy-vegetable, dark vegetable, rened grain and processed, had optimal
consumption time for decreasing the risk of CVD mortality among people with diabetes, which were
independent of the nutritional confounders. It has been documented that the carbohydrate metabolism
including the hepatic and peripheral insulin sensitivity, and the secretion of insulin have biological
rhythm, which are in high levels in the forenoon, and gradually decrease from day to night [14]. The
potato and starchy-vegetable contain high amount of carbohydrate [15], therefore, the uctuation of
glucose after higher intakes of them in the forenoon are likely more accordance with the biological
rhythm of insulin sensitivity, probably aiding in the glucose control, which is a possible reason for
explaining their benecial effect in the forenoon among people with diabetes. Moreover, the recent study
demonstrated that people with diabetes had disrupt expression of clock gene, REV-ERB-α and REV-ERB-β
in the peripheral tissue [16], and evidence have found that higher energy intake during the active period
could reverse the disrupted clock gene expression [10, 17–19]. Another human study found that the three-
meal diet with a carbohydrate-rich breakfast would up-regulate clock gene expression, leading to weight
loss and maintain a good glycemic level allow in diabetes patients [11]. All above research further
support the benecial effect of high intakes of potato, starchy-vegetable in the forenoon on the long-term
survival among people with diabetes.
Moreover, although the benecial effect of dark vegetable consumption on the glucose control among
people with diabetes has been abundantly demonstrated in previous studies [20–22], it is still largely
unknown whether there is an optimal intake time of dark vegetable for diabetes. This study suggested
that its optimal ingestion time might be in the evening. Iso-calorically substitution model result displayed
that 0.1 serving dark vegetable intake switched from the afternoon to the evening could signicantly
reduce the risk of CVD mortality under a constant daily dark vegetable intake. Our recent study has
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demonstrated that vegetable dietary pattern in evening was related to low mortality risk of CVD and all-
cause in general population, further supporting the results of this study [23]. In diabetes patients, the
progression of microvascular disorder interferes with the normal nocturnal blood pressure decline in the
evening, and induce a persistently increased pulse pressure, which further contributes to their raised
cardiovascular risk [24–25]. Thus, the vegetable consumed distribution with a high intake at night might
improve the increased blood pressure in evening for diabetes patients. And the low energy intake is
another possible mechanism for such benecial effect. Abundant studies have illustrated that the low
energy intake in evening had improving effects on cardiometabolic health and long-term survival. The
low-energy food was a lower inammatory index food, consumed in evening is likely to reduce the stream
pro-inammation cytokines (peak at nigh) of organism [26–27], so as to prevent cardiovascular disease.
In addition, it has been reported that gut microbes have their internal circadian pattern [28–29]. The
relative abundance of bacteria producing short-chain fatty acids is frequently highest at night, and then
tend to decrease in daytime [30]. Hence, intaking more dark vegetable in the evening is align with amount
rhythm of that kind bacteria, which stimulate them to generate much more short-chain fatty acids, and
accordingly promotes nutritional metabolic processing [31–32].
Further, we also observed that participants with diabetes who consumed the rened grain and processed
meat in the evening were more likely to die due to CVD and all-cause. Generally, higher intakes of them in
the evening are usually related to higher energy intake. In contrast to the benecial effect of rened grain
consumed in the forenoon, higher intake of them in the evening is likely contradictory to the biological
rhythm of insulin sensitivity and secretion, probably resulting in the poorer glucose control among people
with diabetes. Processed meat contains relative high amount of saturated fatty acids and protein [33–
34]. The previous study has indicated that higher intake of saturated fatty acids and animal protein at
dinner is associated with CVD and all-cause mortality, which may support the harmful effects of
processed meat consumed in the evening on the long-term survival among people with diabetes [12].
Additionally, higher intake of processed meat is frequently related to higher inammation levels [35].
Therefore, higher intake of processed meat in the evening may further increase the inammation level at
night. A previous animal research reported that the later intake of saturated, the worse pro-inammation
cytokines circadian patterns, which aggravates the chronic low inammation state [36].
The ndings in our study have important implications. In recent years, due to the people with diabetes are
under a disrupted biological rhythm of glucose metabolism, accumulating evidence has indicated that
food intake time is as important as quantity and quality for maintaining health. Therefore, the nutritional
therapy with considering the consumption time will be a major component of diabetes treatment. Based
on the results in this study, we believed that people with diabetes might largely decrease their mortality
risk of CVD by choosing consumption time for the specic food. This information provides an
opportunity for individualized nutritional therapy plans for patients with diabetes. Certain limitations also
presence in our study. First, self-reported 24-h dietary recall was used instrument to collect diet
information. Although it is a common method in observational studies, the measurement error still exits
due to the day-to-day variations in food intake. Second, some unmeasured confounding factors is hard to
control. Third, this study was not able to distinguish different types of diabetes. Future studies are needed
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to examine this association in terms of type 1 and type 2 diabetes in order to provide more
comprehensive evidence.
Conclusions
In this study, we suggested that diabetes should intake more potato and starchy-vegetable in the
forenoon and dark-vegetable in the evening, as well as less rened-grain and processed-meat in the
evening, which was associated with better long-term survival.
Abbreviations
NHANES
National Health and Nutrition Examination Survey; HR:hazards ratio; CI:condence interval;
CVD:cardiovascular disease; NCHS:National Center for Health Statistics ; FPG:fasting plasma glucose
level; HA1c:hemoglobin A1c level; MPED:MyPyramid Equivalents Database; NDI:National Death Index;
CPH:Cox proportional hazards.
Declarations
Acknowledgments
The authors thank the contributions from participants and staff of the National Health and Nutrition
Examination Survey 2003–2014.
Authors’ Contributions
YL andTS.H designed this study. WW and WB.J carried out the statistical analysis. QR.S, JZ and YY.C
repeated the analysis. WW wrote and reported the manuscript. WB.J and CH.S revised this manuscript. All
authors critically assessed and reviewed the paper and approved the version to be published. TS.H is the
guarantor of this work.
Funding
Research was supported by funds fromtheNationalNaturalScienceFoundationofChina(82073534 to
Changhao Sun, 82030100toYing Li).
Availability of data and materials
The data in this study are available from websitehttps://wwwn.cdc.gov/nchs/nhane.
Ethics approval and consent to participate
Not applicable.
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Consent for publication
Not applicable.
Competing interests
There is no competing interests with this manuscript.
Author detail
1National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin
Medical University, 157 Baojian Road, Harbin, P. R. China 150081
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Tables
Table-1 Baseline characteristics in terms of CVD mortality status
Page 13/18
CVD mortality
(n=314) Non-CVD
mortality
(n=4385)
P value
Ageyears 70.20 (10.59) 60.49(13.862) 0.000
Female,% 132(42.04) 2154(49.12) 0.015
Non-Hispanic white,% 159(50.64) 1634(37.26) 0.000
Current smoking,% 55(17.52) 844(19.25) 0.462
Current drinking,% 173(55.10) 2613(59.59) 0.268
College graduate or above,% 24(7.64) 621(14.16) 0.000
$100,000 annual household income,% 6(1.91) 299(6.82) 0.000
BMI,kg/m229.00 (8.72) 31.99 (8.08) 0.001
Regular exercise,% 55(17.52) 705(16.08) 0.696
Total energykcal/day 1573.4 (591.70) 1816.8 (773.52) 0.001
Total protein,g/d 67.10 (28.08) 75.67 (34.38) 0.008
Total carbohydrate,g/d 189.68 (74.08) 217.09 (96.07) 0.004
Total fat,g/d 59.82 (28.15) 70.84 (37.26) 0.001
Family history of diabetes,% 0(0.00) 130(2.96) 0.002
Ever controlled diabetes,% 269(85.67) 3737(85.22) 0.829
Prevalent hypertension,% 250(79.62) 3162(72.11) 0.004
Ever controlled hypertension,% 215(68.47) 2578(58.79) 0.001
Prevalent dyslipidemia,% 173(55.10) 2421(55.22) 0.968
Ever controlled dyslipidemia,% 166(52.87) 2171(49.51) 0.389
Whole grain (Ounce equivalents) 0.52 (0.00-1.21) 0.49(0.00-1.24) 0.934
Rened grain (Ounce equivalents) 3.96(2.61-5.68) 4.66(3.05-6.65) 0.000
Red and orange vegetable (Cup
equivalents) 0.14(0.00-0.42) 0.26(0.070.56) 0.000
Potato (Cup equivalents) 0.18(0.00-0.56) 0.20(0.00-0.54) 0.342
Starchy vegetable (Cup equivalents) 0.11(0.00-0.57) 0.28(0.00-0.70) 0.000
Tomato (Cup equivalents) 0.12(0.00-0.34) 0.17(0.03-0.39) 0.001
Fruit (Cup equivalents) 0.01(0.00-0.36) 0.00(0.00-0.24) 0.001
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Milk (Cup equivalents) 0.57(0.12-1.13) 0.47(0.13-1.03) 0.207
Cheese (Cup equivalents) 0.11(0.00-0.46) 0.27(0.00-0.73) 0.000
Red meat (Ounce equivalents) 1.08(0.00-2.40) 1.02(0.00-2.36) 0.689
Poultry (Ounce equivalents) 0.14(0.00-1.60) 0.78(0.00-2.15) 0.000
Eggs (Ounce equivalents) 0.21(0.02-0.90) 0.29(0.03-0.95) 0.077
Soy (Ounce equivalents) 0.00(0.00-0.00) 0.00(0.00-0.00) 0.027
Processed meat (Ounce equivalents) 4.31(2.61-6.82) 4.89(2.96-7.52) 0.017
Yogurt (Yes/No), % 25(7.06%) 455(10.38%) 0.172
Dark vegetable (Yes/No), % 87(27.7%) 1471(33.5%) 0.034
Seafood (Yes/No), % 91(29.0%) 1358(31.0%) 0.461
Legumes (Yes/No), % 85(27.1%) 1432(32.7%) 0.041
Continuous variables are presented as mean (SD) or median (P25, P75), and Categorical variables are
presented as Number (percentage).
Table 2-adjusted HRs for the rened grain, dark vegetable, potato, starchy vegetable and processed meat
consumed in the forenoon and evening and CVD-mortality and all-cause mortality
Page 15/18
CVD mortality All-cause mortality
Case/N HR (95%CI) Case/N HR (95%CI)
In the forenoon    
Rened grain (Quartiles)
Q1 79/990 1 206/990 1
Q2 90/1263 0.70 (0.47-1.05) 268/1263 0.78 (0.65-0.94)
Q3 94/1351 0.71 (0.52-0.98) 287/1351 0.81 (0.67-0.98)
Q4 51/1095 0.68 (0.49-0.92) 152/1095 0.72 (0.57-0.91)
P for trend 0.079 0.012
P interaction with sex  0.545  0.381
Dark vegetable (Yes/No)
No 309/4562 1 895/4562 1
Yes 5/137 0.68 (0.27-1.69) 18/137 0.95 (0.59-1.54)
P for trend 0.407 0.840
P interaction with sex  0.841  0.553
Potato (Yes/No)
No 297/4186 1 836/4186 1
Yes 17/513 0.52 (0.32-0.87) 77/513 0.88 (0.69-1.13)
P for trend 0.013 0.326
P interaction with sex  0.171  0.384
Starchy vegetable
No 301/4174 1 852/4174 1
Yes 13/525 0.51 (0.29-0.90) 61/525 0.83 (0.63-1.10)
P for trend 0.020 0.193
P interaction with sex  0.525  0.552
Processed Meat (Tertiles)
T1 212/2818 1 610/2818 1
T2 42/616 0.89 (0.63-1.26) 110/616 0.82 (0.66-1.01)
T3 60/1265 0.77 (0.56-1.05) 193/1265 0.88 (0.74-1.06)
Page 16/18
P for trend 0.089 0.093
P interaction with sex  0.433  0.844
In the evening    
Rened grain (Quartiles)
Q1 73/1031 1 211/1031 1
Q2 89/1334 1.09 (0.79-1.50) 270/1334 1.08 (0.90-1.30)
Q3 51/1049 1.40 (0.90-2.16) 171/1049 1.19 (0.98-1.46)
Q4 101/1285 1.54 (1.10-2.15) 261/1285 1.29 (1.01-1.65)
P for trend 0.023 0.029
P interaction with sex  0.997  0.493
Dark vegetable (Yes/No)
No 263/3653 1 746/3653 1
Yes 51/1046 0.64 (0.45-0.92) 167/1046 0.81 (0.66-0.99)
P for trend 0.015 0.046
P interaction with sex  0.252  0.281
Potato (Tertiles)
T1 176/2664 1 502/2664 1
T2 49/750 0.86 (0.63-1.20) 161/750 0.97 (0.81-1.17)
T3 89/1285 0.88 (0.63-1.24) 250/1285 0.86 (0.70-1.04)
P for trend 0.401 0.148
P interaction with sex  0.661  0.957
Starchy vegetable(Tertiles)
T1 176/2380 1 491/2380 1
T2 54/980 0.78 (0.57-1.06) 187/980 0.94 (0.79-1.12)
T3 84/1339 0.96 (0.67-1.36) 235/1339 0.88 (0.71-1.08)
P for trend 0.503 0.195
P interaction with sex  0.183  0.093
Processed meat (Quartiles)
Page 17/18
Q1 67/1049 1 209/1049 1
Q2 83/1258 1.14 (0.82-1.58) 262/1258 1.11 (0.92-1.34)
Q3 81/1278 1.21 (0.85-1.73) 232/1278 1.07 (0.87-1.31)
Q4 83/1114 1.83 (1.20-2.77) 210/1114 1.37 (1.06-1.75)
P for trend 0.009 0.043
P interaction with sex  0.583  0.996
Data are HRs and (95%CI), and confounders included age, sex, ethnics, education, income, smoking,
drinking, regular exercise habits, BMI, total intake of daily energy, fat, carbohydrate, protein, family history
of diabetes, hypertension and dyslipidemia, and medication, total intake of specic food group in a day.
Case/N, mortality number/total number.
Figures
Figure 1
Page 18/18
Adjusted HR for CVD mortality: isocaloric substitution of rened grain, potato, starchy vegetable or
processed meat consumed in the evening to the forenoon, and isocaloric substitution of dark vegetable
consumed in the forenoon or afternoon to the evening. Adjustments included age, sex, ethnics, education,
income, smoking, drinking, regular exercise habits, BMI, total intake of daily energy, fat, carbohydrate,
protein, family history of diabetes, hypertension and dyslipidemia, and medication, total intake of specic
food group in a day. Case/N, mortality number/total number.
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Objective: This study aims to evaluate the association of energy and macronutrient intake at dinner versus breakfast with disease-specific and all-cause mortality in people with diabetes. Research design and methods: A total of 4,699 people with diabetes who enrolled in the National Health and Nutrition Examination Survey from 2003 to 2014 were recruited for this study. Energy and macronutrient intake was measured by a 24-h dietary recall. The differences (Δ) in energy and macronutrient intake between dinner and breakfast (Δ = dinner - breakfast) were categorized into quintiles. Death information was obtained from the National Death Index until 2015. Cox proportional hazards regression models were developed to evaluate the survival relationship between Δ and diabetes, cardiovascular disease (CVD), and all-cause mortality. Results: Among the 4,699 participants, 913 deaths, including 269 deaths due to diabetes and 314 deaths due to CVD, were documented. After adjustment for potential confounders, compared with participants in the lowest quintile of Δ in terms of total energy and protein, participants in the highest quintile were more likely to die due to diabetes (hazard ratio [HR]Δenergy 1.92, 99% CI 1.08-3.42; HRΔprotein 1.92, 99% CI 1.06-3.49) and CVD (HRΔenergy 1.69, 99% CI 1.02-2.80; HRΔprotein 1.96, 99% CI 1.14-3.39). The highest quintile of Δtotal fat was related to CVD mortality (HR 1.67, 99% CI 1.01-2.76). Isocalorically replacing 5% of total energy at dinner with breakfast was associated with 4% and 5% lower risk of diabetes (HR 0.96, 95% CI 0.94-0.98) and CVD (HR 0.95, 95% CI 0.93-0.97) mortality, respectively. Conclusions: Higher intake of energy, total fat, and protein from dinner than breakfast was associated with greater diabetes, CVD, and all-cause mortality in people with diabetes.
Article
Importance Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. Objective To evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and Participants Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). Exposures Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and Measures Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). Results Among 11 135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P < .001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and Relevance In this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.