Association of carbohydrate and fat intake with metabolic syndrome

Association of carbohydrate and fat intake with metabolic syndrome

Accepted Manuscript Association of carbohydrate and fat intake with metabolic syndrome Yu-Jin Kwon, Hye-Sun Lee, Ji-Won Lee PII: S0261-5614(17)30233-...

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Accepted Manuscript Association of carbohydrate and fat intake with metabolic syndrome Yu-Jin Kwon, Hye-Sun Lee, Ji-Won Lee PII:

S0261-5614(17)30233-9

DOI:

10.1016/j.clnu.2017.06.022

Reference:

YCLNU 3179

To appear in:

Clinical Nutrition

Received Date: 9 December 2016 Revised Date:

16 May 2017

Accepted Date: 23 June 2017

Please cite this article as: Kwon Y-J, Lee H-S, Lee J-W, Association of carbohydrate and fat intake with metabolic syndrome, Clinical Nutrition (2017), doi: 10.1016/j.clnu.2017.06.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Title page 1) Title: Association of carbohydrate and fat intake with metabolic syndrome 2) Author names and affiliations: Yu-Jin Kwona,b, Hye-Sun Leec, Ji-Won Leed Department of Family Medicine, Yong-In Severance Hospital, Yonsei University College of

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a

Medicine, Yong-In, Republic of Korea b

Biostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College

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c

Department of Medicine, Graduate School, Yonsei University, Seoul, Republic of Korea

of Medicine, Seoul, Republic of Korea

Department of Family Medicine, Gangnam Severance Hospital, Yonsei University College

of Medicine, Seoul, Republic of Korea

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d

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3) Corresponding author: Ji-Won Lee M.D., Ph.D.

4) Address for correspondence (): Ji-Won Lee M.D., Ph.D.

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Associate Professor, Department of Family Medicine Yonsei University College of Medicine, Gangnam Severance Hospital

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211 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea, 135-720 Tel: +82 2 2019 3480, Cell: +82 10 2949 5645, Fax: +82 3462 8209 E-mail: [email protected]

ACCEPTED MANUSCRIPT Summary Background and Aims: In Asia, dietary pattern has been changed with increased intake of refined carbohydrates, sugar, and saturated fat, while the prevalence of metabolic syndrome

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(MetS) is on the rise. However, it remains unclear whether a high-carbohydrate or a high-fat diet is more metabolically harmful, and the optimal amount of carbohydrates and fat has not been determined. The aim of our study was to examine the role of carbohydrate and fat intake in MetS in a Korean population.

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Methods: Data were obtained from a large, population-based, cross-sectional study (6737

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males and 8845 females). The subjects were divided into nine groups based on carbohydrate and fat proportion, and multiple logistic regression analysis was performed after adjusting for confounding variables.

Results: Regardless of fat intake, the risk of MetS significantly increased in males with higher carbohydrate proportions (of total energy intake). In females, the risk of MetS was

fat proportion.

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significantly elevated only in those with both the highest carbohydrate proportion and lowest

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Conclusion: A high carbohydrate proportion was associated with a higher prevalence of MetS in males, and a high carbohydrate proportion combined with a low fat proportion was

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associated with MetS in females. Our results indicate that reduction of excessive carbohydrate intake paired with an adequate fat intake, taking into consideration optimal types of fat, are useful for MetS prevention. Longitudinal studies are needed to clarify the optimal types and amounts of carbohydrate and fat proportions as well as the mechanism underlying these relationships.

Keywords: carbohydrate, diet, fat, Korean population, metabolic syndrome

ACCEPTED MANUSCRIPT 1. Introduction Metabolic syndrome (MetS) is a multifaceted risk factor related to cardiovascular disease (CVD) and all-cause mortality [1, 2]. The clinical characteristics of MetS vary depending on

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ethnicity, sex, lifestyle, and environmental variables [1, 3]. The Asian population has higher body fat and metabolic risks compared with Western populations, even though Asian populations are of normal weight [4]. The dietary pattern in Asia has recently changed, with

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an increased intake of refined carbohydrates (CHOs), sugar, and saturated fat. In addition, the prevalence of MetS is on the rise in Asia along with nutrition transition [5]. Although “bad

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fats” (saturated and trans fats) are criticized for contributing to cardiometabolic diseases, refined CHOs and added sugar are emerging as harmful risk factors for MetS, type 2 diabetes, and CVD. In contrast, whole grains, vegetables, fruits, and nuts, which are the main components of traditional Asian food, as well as olive oil, have protective effects against

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cardiometabolic diseases [6-8]. Several clinical trials and cohort studies consistently support the importance of CHO and fat quality [7, 9-11]. However, it remains unclear whether a highcarbohydrate or a high-fat diet is more metabolically harmful, and the optimal amount of

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CHO and fat was not verified in Asia. Therefore, the aim of our study was to examine the role

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of dietary CHO and fat as potential risk factors for MetS in a Korean population.

2. Methods

2.1. Study population

This study used data from the 2008-2011 Korean National Health and Nutrition Examination Survey (KNHANES) conducted by the Korea Centers for Disease Control and Prevention (KCDC). The KNHANES is a nationwide cross-sectional study that annually monitors the health and nutritional status of the Korean population. The sampling method of KNHANES is a stratified, multi-stage, probability sampling design based on geographic area, sex, and age

ACCEPTED MANUSCRIPT group. The sample weights are allocated to participants to represent the general Korean population [12, 13]. The 2008-2011 KNHANES evaluated body composition, as well as nutritional health epidemiology; this study was conducted for the project Good Eating,

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Exercise, Emotion, and Body Shape for Korean Population (GOOD3Es for KPOP). Informed consent was obtained from all participants and this survey was approved by the Institutional Review Board of KCDC. Adults between the ages of 20 and 64 years (n=21707)

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were included in the study. Of these subjects, 1705 were excluded for having one or more of the following diseases or conditions: cancer (n=381), hepatic disease (n=26), chronic kidney

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disease (n=46), thyroid disease (n=673), rheumatism (n=294), stroke (n=171), myocardial infarction (n=77), presence of pulmonary tuberculosis (n=15), and pregnancy (n=134). Finally, we excluded 4414 subjects with extreme energy intake (<500 kcal or >6000 kcal per day) and subjects who had missing data in at least one of the health questionnaires, blood

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samples, and/or anthropometric variables. Finally, a total of 15582 participants (6737 males and 8845 females) were analyzed (Fig. 1).

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2.2. Metabolic syndrome and covariates

MetS was assessed using the modified National Cholesterol Education Program-Adult

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Treatment Panel III (NCEP-ATP III) ethnicity-specific guidelines [1]. A subject with three or more of the following five features was defined as having MetS: 1) abdominal obesity (waist circumference ≥90 cm for males and ≥80 cm for females); 2) triglycerides ≥1.7 mmol/L; 3) high-density lipoprotein (HDL) cholesterol ≤1.03 mmol/L for males and ≤1.29 mmol/L for females; 4) systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥85 mmHg or current treatment for hypertension; 5) fasting plasma glucose ≥5.6 mmol/L or current treatment for diabetes. Body mass index (BMI) was calculated as weight (kg) divided by height (m) squared. According to the International Obesity Task Force of the World

ACCEPTED MANUSCRIPT Health Organization (IOTF-WHO) guidelines regarding overweight and obesity in the Asian population, individuals with BMI 23 to <25 kg/m2 are considered overweight and those with BMI ≥25 kg/m2 are considered obese [14]. Waist circumference (WC) was measured at the

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midpoint between the iliac crest and the costal margin. SBP and DBP were measured a total of three times, and the average of the last two values was recorded. Blood tests were performed after midnight fasting and were analyzed using a Hitachi 700-110 Chemistry

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Analyzer (Hitachi Co., Tokyo, Japan). Smoking and drinking statuses were obtained from a self-reporting questionnaire and were completed during the interview period. A current

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smoker was defined as one who currently smokes and has smoked more than 100 cigarettes during their lifetime. A high-risk alcohol drinker was defined as one who drinks at least seven (males) or five (females) drinks two or more times per week. The International Physical Activity Questionnaire (IPAQ) was used to assess the level of physical activity. “Regular

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exercise” was defined as vigorous-intensity exercise for ≥20 min for ≥3 days per week, or moderate-intensity exercise/walking ≥30 min for ≥5 days per week.

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2.3. Assessment of dietary intake

Dietary intake was surveyed with a face-to-face interview at the home of the participant. A

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24-h recall method was conducted to record foods and dishes with various measuring aids. The trained dietitians completed a thorough training course and conducted practice interviews under supervision before participating in an actual survey. Re-training was also conducted five to six times a year to enhance the technique and protocol. The detailed nutrition survey protocol is presented on the KNHANES website [15]. CHO was calculated as the total CHO count (g) minus indigestible fiber (g). The proportions of CHO and fat intake were calculated as follows: CHO intake calories/total calorie intake (%), and fat intake calories/total calorie intake (%). The proportion of carbohydrate (CHO) intake was categorized into three groups

ACCEPTED MANUSCRIPT by sex: T1 (≤61.0%), T2 (61.0-70.1%), and T3 (≥70.1%) for males and T1 (≤63.5%), T2 (63.5-72.8%), and T3 (≥72.8%) for females. The proportion of fat intake was also categorized into three groups: T1 (≤15.0%), T2 (15.0-22.4%), T3 (≥22.4%) for males and T1 (≤13.3%),

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T2 (13.3-20.8%), and T3 (≥20.8%) for females. In order to examine the joint impact of CHOs and fat on the prevalence of MetS, participants were divided into the following nine groups (for both males and females) according to their combined CHO and fat intake proportions: 1)

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CHO (T1) and fat (T1); 2) CHO (T1) and fat (T2); 3) CHO (T1) and fat (T3); 4) CHO (T2) and fat (T1); 5) CHO (T2) and fat (T2); 6) CHO (T2) and fat (T3); 7) CHO (T3) and fat (T1);

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8) CHO (T3) and fat (T2); and 9) CHO (T3) and fat (T3).

2.4. Statistical analysis

All analyses were performed using SPSS version 23.0 statistical software (SPSS version 23.0;

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IBM Corp., Armonk, NY, USA). All statistical tests were two-sided and statistical significance was set at a p-value of <0.05. In order to compare continuous variables between the two groups, we conducted weighted one-way analysis of variance (ANOVA). In addition,

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we applied analysis of covariance (ANCOVA) to compare the proportion of CHO, fat, and protein after adjusting for the composition of each macronutrient and total energy. We

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performed a weighted chi-square test for dichotomous variables. The odds ratios (ORs) and 95% confidence intervals (CIs) were determined using multiple logistic regression analysis after adjusting for age, BMI, smoking status, alcohol intake, regular exercise, total energy intake, protein intake, and anti-dyslipidemia medication. We presented adjusted ORs and 95% confidence band using the R statistical package (Institute for Statistics and Mathematics, Vienna, Austria, ver 3.2.5, www.R-project.org).

3. Results

ACCEPTED MANUSCRIPT Table 1 describes the characteristics of the study population. Of the males, 24.6% were overweight and 38.8% were obese, and of the females, 19.5% were overweight and 25.0% were obese. The prevalence of MetS was 38.0% in males and 31.8% in females.

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With regard to dietary intake, subjects with MetS consumed higher CHO proportions and lower fat proportions than those without MetS. Specifically, females without MetS exhibited higher proportions of protein intake, whereas there was no significant difference in the fat

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proportion of males after adjusting for total energy, CHOs, and protein (20.4 vs. 20.3%, p=0.276). Furthermore, the significant difference in the protein proportion in females

covariance (14.8 vs. 14.7%, p=0.439).

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disappeared after adjusting for total energy and CHO and fat intake through analysis of

The associations between CHO and fat proportion with MetS are presented in Table 2 and Figure 2. In males, the prevalence of MetS significantly increased as the proportion of CHOs

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increased (Fig. 2-A), but there was no significant difference in the decrease of MetS associated with a decrease in fat proportion (Fig. 2-C). In females, the prevalence of MetS significantly increased only in the highest tertile CHO group and decreased only in the

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highest tertile fat group (Fig. 2-B and 2-D).

Compared with the lowest CHO proportion group, the ORs (95% CIs) for MetS in the

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highest CHO proportion group were 1.346 (1.077-1.683) in males and 1.266 (1.027-1.560) in females after adjusting for age, BMI, smoking status, alcohol intake, regular exercise, total energy intake, protein intake, and anti-dyslipidemia medication. Compared with the lowest fat proportion group, the ORs (95% CIs) for MetS in the highest fat proportion group were 0.882 (0.732-1.062) for males and 0.793 (0.661-0.951) for females after controlling for the same confounders. Compared with the reference group (the lowest CHO proportion and the lowest fat proportion), the risk of MetS significantly increased with increasing CHO proportion in males, regardless of fat proportion, whereas the same association was seen only

ACCEPTED MANUSCRIPT in the highest CHO proportion and lowest fat proportion group in females (Table 2 and Fig. 2-E, F, G, H).

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4. Discussion In our study, the risk of MetS proportionally increased with a high percentage of CHO intake regardless of fat intake percentage in males; the risk of MetS is higher in females only when there is a high percentage of CHO intake and a low percentage of fat intake.

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High fat intake is regarded as an essential risk factor for obesity and cardiometabolic disease

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[16]. However, despite the many efforts to decrease fat consumption, the worldwide prevalence of obesity has nearly doubled between 1980 and 2008, with CVD remaining a leading cause of death globally [17]. Although the exact cause is unknown, total fat reduction inevitably results in increased intake of CHOs and decreased intake of healthy unsaturated fats [18], all of which may significantly contribute to an increase in CVD.

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The 2015 Dietary Guidelines Advisory Committee reported that there was insufficient evidence regarding the association between dietary cholesterol intake and serum cholesterol,

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stating that dietary cholesterol was not something to avoid, but instead advised an emphasis on a healthy diet pattern including whole grains, vegetables, fruits and nuts, and limitation of

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added sugar [19]. Numerous epidemiological studies and intervention trials indicate that the metabolic consequences of CHO and fat consumption depend on their quality and not necessarily on their quantity. In a recent meta-analysis study, trans fats, particularly industrially produced trans fats, are associated with all-cause mortality and that from coronary heart disease [20]. Refined CHOs, including syrups, biscuits, and cakes, are closely associated with MetS, type 2 diabetes, and CVDs [5, 21-23]. In addition, the traditional Mediterranean diet, which is characterized by high intake of olive oil, nuts, seeds, fruit, vegetables, whole grains, and a low intake of red meat, processed meats, and sweets, has been

ACCEPTED MANUSCRIPT highlighted as a useful dietary model to reduce type 2 diabetes and CVD [24, 25]. Perhaps there is a synergistic effect among the beneficial fats and CHOs that may affect cardiometabolic risks such as insulin resistance, blood lipid levels, oxidative stress, and

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inflammation [26]. Regarding the amount of food consumed, a large CHO proportion of total energy has a disadvantageous effect on weight loss, and recommendations to reduce refined grains and

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added sugar have been made [27, 28]. Cheung et al. [29] proposed that excessive fat intake is not a major contributor to insulin resistance and obesity in Asians, whereas a high CHO

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proportion of total energy intake is an important factor. However, controversy remains regarding whether a high-CHO or high-fat diet is more metabolically harmful with regard to appropriate diet composition. In addition, the optimal amount of CHO and fat in the diet was not verified in Asia.

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Though Asians have a relatively low BMI and consume a low-fat diet, the incidence of MetS and CVD is higher than that of the Western population [4]. Recently, MetS has rapidly increased in Asia, and several studies have demonstrated stronger associations between

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dietary CHO intake, high glycemic index (GI) or glycemic load (GL), low whole grain intake, and metabolic disease [30, 31]. Similarly, we found that the risk of MetS increased with

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increased CHO proportion regardless of fat proportion in males, and that the risk of MetS is higher in females with a high CHO proportion and a low fat proportion. These results indicate that excess CHO intake, not fat intake, is associated with MetS and CVD. Our study has several limitations. First, due to the cross-sectional study design, we could not confirm the causality of the relationship between diet composition and MetS. Second, diet composition was assessed by 24-h recall, so there could be day-to-day variation in these measures as well as under- or over-reporting. Lastly, the 2008-2011 KNHANES database only included data collected from a 24-h recall method and dietary pattern from a frequency

ACCEPTED MANUSCRIPT food questionnaire, but not the amount of each food consumed. Furthermore, we were not able to determine the exact amount by the type of CHOs and fat, or to collect information regarding GI, GL, and dietary patterns. However, previous Korean population studies,

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conducted with data from different time frames, have already demonstrated that the benefits of a healthy dietary pattern include whole grains, nuts, vegetables, fruits, and olive oil, as well as described the metabolic harmfulness of refined CHOs and saturated and trans fats

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[32-34]. In addition, the Ministry of Food and Drug Safety in Korea recently reported that the portion of sugar intake from processed foods and beverages comprised 44.4% of total sugar

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consumption, with the associated concern being that this consumption is increasing the prevalence of MetS [35]. In addition, we detected a combined effect of CHO and fat consumption (proportion of total energy) on MetS in the Korean population, leading us to suggest that restriction of excessive consumption of CHOs as well as consumption of an

incidence of MetS.

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5. Conclusions

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adequate amount of fat, despite not specifying the type of CHOs and fat, may decrease the

We found that the consumption of a higher CHO proportion of energy intake was associated

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with a higher prevalence of MetS in males, and a high CHO proportion with a low fat proportion in females had a higher OR of MetS after adjusting for the confounding variables. Our results indicate that reduction of excessive CHO intake and adequate intake of fat, considering the optimal type of fat, are useful for the prevention of MetS. Longitudinal studies are needed to clarify the optimal types and amounts of CHO and fat proportions and the mechanism underlying these relationships.

ACCEPTED MANUSCRIPT Author contributions: Kwon YJ and Lee JW: study concept and design, analysis, interpretation of analysis, and writing of the manuscript; Lee HS: analysis and interpretation

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of analysis.

Acknowledgements: This research was supported by the Bio and Medical Technology Development Program through the National Research Foundation of Korea funded by the

References

Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et

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[1]

M AN U

Conflict of interest: None

SC

Ministry of Science, ICT and Future Planning (NRF-2013M3A9B6046416).

al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circ

Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomileht

AC C

[2]

EP

ulation 2005;112(17):2735-52.

o J, et al. The metabolic syndrome and total and cardiovascular disease mortali ty in middle-aged men. Jama 2002;288(21):2709-16.

[3]

Okosun IS, Liao Y, Rotimi CN, Prewitt TE, Cooper RS. Abdominal adiposity and clustering of multiple metabolic syndrome in White, Black and Hispanic a mericans. Ann Epidemiol 2000;10(5):263-70.

[4]

Pan WH, Yeh WT, Weng LC. Epidemiology of metabolic syndrome in Asia. A sia Pac J Clin Nutr 2008;17 Suppl 1:37-42.

ACCEPTED MANUSCRIPT [5]

Hristova K, Pella D, Singh RB, Dimitrov BD, Chaves H, Juneja L, et al. Sofi a Declaration for prevention of cardiovascular diseases and type 2 diabetes mel litus: a scientific statement of the International College of Cardiology and Inter

[6]

RI PT

national College of Nutrition. World Heart Journal 2014;6(2):89. Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, et al . Effect of a mediterranean-style diet on endothelial dysfunction and markers of

SC

vascular inflammation in the metabolic syndrome: a randomized trial. Jama 20 04;292(12):1440-6.

Salas-Salvado J, Fernandez-Ballart J, Ros E, Martinez-Gonzalez MA, Fito M, E

M AN U

[7]

struch R, et al. Effect of a Mediterranean diet supplemented with nuts on meta bolic syndrome status: one-year results of the PREDIMED randomized trial. Ar ch Intern Med 2008;168(22):2449-58.

Salas-Salvadó J, Bulló M, Babio N, Martínez-González MÁ, Ibarrola-Jurado N,

TE D

[8]

Basora J, et al. Reduction in the incidence of type 2 diabetes with the Medit erranean diet. Diabetes care 2011;34(1):14-9. Menotti A, Kromhout D, Blackburn H, Fidanza F, Buzina R, Nissinen A. Food

EP

[9]

intake patterns and 25-year mortality from coronary heart disease: cross-cultura

AC C

l correlations in the Seven Countries Study. European journal of epidemiology 1999;15(6):507-15.

[10]

Singh RB, Dubnov G, Niaz MA, Ghosh S, Singh R, Rastogi SS, et al. Effect

of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomised single-blind trial. The Lancet 2002;360(9344):1455-61.

[11]

Kris-Etherton P, Eckel RH, Howard BV, Jeor SS, Bazzarre TL. Lyon diet heart study. Circulation 2001;103(13):1823-5.

ACCEPTED MANUSCRIPT [12]

Kweon S, Kim Y, Jang M-j, Kim Y, Kim K, Choi S, et al. Data resource pro file: the Korea national health and nutrition examination survey (KNHANES). I nternational journal of epidemiology 2014;43(1):69-77. Kim Y. The Korea National Health and Nutrition Examination Survey (KNHA

RI PT

[13]

NES): current status and challenges. Epidemiology and health 2014;36. [14]

Organization WH. The Asia-Pacific perspective: redefining obesity and its treat

[15]

SC

ment: Sydney: Health Communications Australia, 2000. Korean Centers for Disease Control and Prevention.

[16]

M AN U

.cdc.go.kr/knhanes/eng.)

(Accessed, at www.knahes

Feillet-Coudray C, Fouret G, Casas F, Coudray C. Impact of high dietary lipid intake and related metabolic disorders on the abundance and acyl composition of the unique mitochondrial phospholipid, cardiolipin. J Bioenerg Biomembr 2

[17]

TE D

014;46(5):447-57.

Organization WH. Global status report on noncommunicable diseases 2014: Wo rld Health Organization, 2014.

Mozaffarian D, Ludwig DS. The 2015 US Dietary Guidelines: Lifting the Ban

EP

[18]

on Total Dietary Fat. Jama 2015;313(24):2421-2. USDA/DHHS. Scientific Report of the 2015 Dietary Guidelines Advisory Com

AC C

[19]

mittee. In: Departments of Heatlh and Human Service and Agriculture, editor.: Departments of Heatlh and Human Service and Agriculture,, 2015.

[20]

de Souza RJ, Mente A, Maroleanu A, Cozma AI, Ha V, Kishibe T, et al. Inta ke of saturated and trans unsaturated fatty acids and risk of all cause mortality , cardiovascular disease, and type 2 diabetes: systematic review and meta-analy sis of observational studies. Bmj 2015;351:h3978.

ACCEPTED MANUSCRIPT [21]

Chauhan AK, Singh RB, Ozimek L, Singh M, Basu TK. View Point: Saturated Fatty Acid and Sugar; How Much Is Too Much for Health? A Scientific Stat ement of the International College of Nutrition. World Heart Journal 2016;8(1):

[22]

RI PT

71. Shastun S, Chauhan AK, Singh RB, Singh M, Singh RP, Itharat A, et al. Can functional food security decrease the epidemic of obesity and metabolic syndr

[23]

SC

ome? A viewpoint. World Heart Journal 2016;8(3):273.

Sacco RL, Roth GA, Reddy KS, Arnett DK, Bonita R, Gaziano TA, et al. Th

M AN U

e Heart of 25 by 25: Achieving the Goal of Reducing Global and Regional Pr emature Deaths From Cardiovascular Diseases and Stroke. Circulation 2016;133 (23):e674-e90. [24]

Mente A, de Koning L, Shannon HS, Anand SS. A systematic review of the e

TE D

vidence supporting a causal link between dietary factors and coronary heart dis ease. Arch Intern Med 2009;169(7):659-69. [25]

Amor AJ, Serra-Mir M, Martinez-Gonzalez MA, Corella D, Salas-Salvado J, Fi

EP

to M, et al. Prediction of Cardiovascular Disease by the Framingham-REGICO R Equation in the High-Risk PREDIMED Cohort: Impact of the Mediterranean

[26]

AC C

Diet Across Different Risk Strata. J Am Heart Assoc 2017;6(3). Jacobs DR, Jr., Gross MD, Tapsell LC. Food synergy: an operational concept f

or understanding nutrition. Am J Clin Nutr 2009;89(5):1543s-8s.

[27]

Song S, Lee JE, Song WO, Paik HY, Song Y. Carbohydrate intake and refined

-grain consumption are associated with metabolic syndrome in the Korean adult population. J Acad Nutr Diet 2014;114(1):54-62. [28]

USDA/DHHS. Scientific Report of the 2015 Dietary Guidelines Advisory Com mittee. In: Agriculture DoHaHSa, editor.: Departments of Heatlh and Human S

ACCEPTED MANUSCRIPT ervice and Agriculture,, 2015:8-13. [29]

Cheung BM. The cardiovascular continuum in Asia--a new paradigm for the m etabolic syndrome. J Cardiovasc Pharmacol 2005;46(2):125-9. McKeown NM, Meigs JB, Liu S, Saltzman E, Wilson PW, Jacques PF. Carboh

RI PT

[30]

ydrate nutrition, insulin resistance, and the prevalence of the metabolic syndrom e in the Framingham Offspring Cohort. Diabetes Care 2004;27(2):538-46.

Finley CE, Barlow CE, Halton TL, Haskell WL. Glycemic index, glycemic loa

SC

[31]

d, and prevalence of the metabolic syndrome in the cooper center longitudinal

[32]

M AN U

study. J Am Diet Assoc 2010;110(12):1820-9.

Kang Y, Kim J. Gender difference on the association between dietary patterns and metabolic syndrome in Korean population. European journal of nutrition 20 16;55(7):2321-30.

Song S, Paik H-Y, Song Y. High intake of whole grains and beans pattern is i

TE D

[33]

nversely associated with insulin resistance in healthy Korean adult population. Diabetes research and clinical practice 2012;98(3):e28-e31. Song S, Lee JE, Song WO, Paik H-Y, Song Y. Carbohydrate intake and refine

EP

[34]

d-grain consumption are associated with metabolic syndrome in the Korean adu

AC C

lt population. Journal of the Academy of Nutrition and Dietetics 2014;114(1):54 -62.

[35]

Ministry of Food and Drug Safety. ww.mfds.go.kr.)

(Accessed November, 1, 2016, at http://w

ACCEPTED MANUSCRIPT Figure captions Figure1. Study population: Data from the 2008-2011 KNHANES

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Figure 2. Adjusted odds ratios (OR) and confidence band for metabolic syndrome (M etS) according to carbohydrate and fat intake.

The proportion of carbohydrate (CHO) intake was categorized into three groups by se

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x: T1 (≤61.0%), T2 (61.0-70.1%), and T3 (≥70.1%) for males and T1 (≤63.5%), T2 (

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63.5-72.8%), and T3 (≥72.8%) for females. The proportion of fat intake was also cate gorized into three groups: T1 (≤15.0%), T2 (15.0-22.4%), T3 (≥22.4%) for males and T1 (≤13.3%), T2 (13.3-20.8%), and T3 (≥20.8%) for females. Solid lines and gray zones represent the OR (95% confidence band) for MetS accordi

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ng to CHOs, fat, and the combination of CHOs and fat. The dotted line represents th e reference line and the arrow indicates the significant point (A, C, E and B, D, F). The bar represents the OR for relative magnitude comparisons to MetS according to t

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he combination of CHOs and fat (G and H). Data are adjusted for age, body mass in dex (BMI), current smoking status, alcohol intake, regular exercise, total energy intake

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(Kcal), protein intake (g), and anti-dyslipidemia medication. *p<0.05, calculated by multiple logistic regression analysis

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Table 1. Clinical and nutritional characteristics of the study population according to the presence of metabolic syndrome: Data from the 2008-2011 KNHANES Metabolic syndrome*

2780 (38.0) 43.9 ± 0.3 26.1 ± 0.1 14.4 (0.9) 21.9 (1.1) 62.6 (1.3) 90.2 ± 0.2 122.7 ± 0.3 83.0 ± 0.2 6.0 ±0.0 2.7 ± 0.0 1.0 ± 0.0 50.1 (1.1) 50.8 (1.1) 45.3 (1.1) 16.2 (0.8) 30.4 (0.9) 4.2 (0.4) 2207.5 ± 19.0 64.7 ± 0.3 19.4 ± 0.2 15.9 ±0.1

<0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.538 <0.001 <0.001 <0.001 0.016 <0.001 <0.001 0.858

63.6 ± 0.1 20.4 ± 0.1 15.9 ± 0.0

63.9 ± 0.1 20.3 ± 0.1 15.8 ± 0.0

0.033 a 0.276 b 0.382 c

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<0.001 <0.001 <0.001

Women No Yes 5800 (68.2) 3045 (31.8) 37.8 ± 0.2 45.9 ± 0.3 21.6 ±0.0 25.7 ±0.1 72.4 (0.7) 19.8 (0.9) 17.4 (0.6) 22.8 (0.9) 10.2 (0.5) 72.5 (1.1) 72.7 ± 0.1 85.2 ± 0.2 108.0 ± 0.2 118.7 ± 0.4 71.4 ± 0.2 77.3 ± 0.2 4.9 ± 0.0 5.7 ± 0.0 0.9 ± 0.0 1.7 ± 0.0 1.4 ± 0.0 1.1 ± 0.0 51.4 (0.8) 49.8 (1.1) 6.2 (0.4) 6.2 (0.6) 20.6 (0.7) 16.6 (0.8) 0.5 (0.1) 12.0 (0.7) 7.4 (0.4) 27.7 (1.0) 1.0 (0.1) 5.8 (0.5) 1709.7 ± 10.5 1637.3 ± 14.0 65.4 ± 0.2 68.8 ± 0.3 19.7 ±0.1 16.8 ± 0.2 14.9 ± 0.1 14.4 ± 0.1

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p-value

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Unweighted number Age (years) Body mass index (kg/m2) (%) Normal Overweight (%) Obesity (%) Waist circumference (cm) Systolic blood pressure Diastolic blood pressure Fasting glucose (mmol/L) Triglyceride (mmol/L) HDL-cholesterol (mmol/L) Regular exercise (%) Current smoking (%) Alcohol intake (%) Type 2 diabetes (%) Hypertension (%) Anti-dyslipidemia medication (%) Total calorie intake (kcal) Carbohydrate (% of energy) Fat (% of energy) Protein (% of energy) Adjusted Carbohydrate (% of energy) Fat (% of energy) Protein (% of energy)

No 3957 (62.0) 37.9 ± 0.3 23.1 ± 0.0 50.6 (1.1) 25.6 (0.9) 23.8 (0.9) 80.5 ± 0.2 116.8 ± 0.3 78.4 ± 0.2 5.1 ± 0.0 1.2 ± 0.0 1.3 ± 0.0 58.3 (0.9) 45.5 (0.9) 44.3 (1.0) 2.4 (0.3) 9.0 ( 0.4) 0.9 (0.1) 2266.2 ± 16.6 63.2 ± 0.2 21.0 ± 0.2 15.9 ± 0.1

Men Yes

66.3 ± 0.1 18.9 ± 0.1 14.8 ± 0.0

66.9 ± 0.1 18.4 ± 0.1 14.7 ± 0.0

P-value† <0.001 <0.001 <0.001

<0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.226 0.992 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001a <0.001b 0.439 c

ACCEPTED MANUSCRIPT

* A person who had any three or more of the following five criteria was defined as having MetS: 1) abdominal obesity (waist circumference ≥90 cm for men and ≥80 cm for women); 2) triglycerides ≥1.7 mmol/L; 3) HDL cholesterol ≤1.03 mmol/L for men and ≤1.29 mmol/L for women; 4) systolic blood pressure ≥130 mmHg or diastolic

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blood pressure ≥85 mmHg or currently receiving treatment for hypertension; 5) fasting plasma glucose ≥5.6 mmol/L or currently receiving treatment for diabetes. Smoker was defined as those who currently smoked or have smoked more than 100 cigarettes during their lifetime.

High-risk alcohol drinker was defined as drinking at least seven glasses for men and five glasses for women more than two or more times a week.

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Regular exercise was defined as vigorous-intensity exercise for ≥20 min for ≥3 days a week, or moderate-intensity exercise / walking for ≥30 min for ≥5 days a week.

Data were described as mean (standard error, SE) and percentage (SE). †

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Overweight was defined with body mass index (BMI); 23 to <25 kg/m2 and obesity was defined with BMI >25 kg/m2.

p-values are determined by weighted chi-square tests of categorical variables and by weighted ANOVA of continuous variables.

a p-values were calculated by weighted ANCOVA adjusted for total energy calorie (kcal), fat (g) and protein (g) b p-values were calculated by weighted ANCOVA adjusted for total energy calorie (kcal), carbohydrate (g) and protein (g)

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c p-values were calculated by weighted ANCOVA adjusted for total energy calorie (kcal), carbohydrate (g) and fat (g)

ACCEPTED MANUSCRIPT

between metabolic syndrome and carbohydrate intake (%) and fat intake (%) in Korean adults: Data from the 2008-2011 Men

Women

Fat T1 T2 T3 Carbohydrate &Fat (n=men/ women) CHO, T1& Fat T1 (n=44/29) CHO, T1& Fat T2 (n=330/423) CHO, T1& Fat T3 (n=1760/2569) CHO, T2& Fat T1 (n=288/361) CHO, T2& Fat T2 (n=1440/2144) CHO, T2& Fat T3 (n=382/457) CHO, T3& Fat T1 (n=1727/2475) CHO, T3& Fat T2 (n=346/417) CHO, T3& Fat T3 (n=0/0)

1 (ref) 0.883 (0.760-1.026) 0.690 (0.594-0.800)

<0.001

0.105 <0.001

1 (ref) 0.973 (0.818-1.158) 0.882 (0.732-1.062)

1 (ref)

1 (ref) 1.446 (0.699-2.991) 1.149 (0.571-2.312) 1.547 (0.743-3.220) 1.492 (0.744-2.992) 1.150 (0.548-2.415) 1.711 (0.863-3.392) 1.418 (0.685-2.932) -

1 (ref) 1.288 (1.069-1.551) 1.346 (1.077-1.683)

0.320 0.697 0.243 0.259 0.711

0.124

0.346

0.008 0.009

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T3

0.012

p-value

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T2

1 (ref) 1.201 (1.041-1.386) 1.392 (1.203-1.612)

OR (95% CI)

1.741 (0.737-4.113) 2.123 (0.900-5.007) 2.357 (0.979-5.676) 2.691 (1.110-6.523) 2.871 (1.114-7.399) 2.827 (1.153-6.927) 2.925 (1.122-7.626) -

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Carbohydrate T1

p-value

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OR (95% CI)

Unadjusted OR OR (95% CI)

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Adjusted OR*

Unadjusted OR

0.758

0.185

0.206 0.085 0.056 0.029 0.029 0.023 0.028

1 (ref) 1.295 (1.124-1.491) 2.105 (1.839-2.409)

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Table 2. Association

1 (ref) 0.631 (0.556-0.717) 0.444 (0.390-0.506)

Adjusted OR* p-value

<0.001 <0.001

<0.001 <0.001

-

1 (ref) 1.026 (0.850-1.238) 1.266 (1.027-1.560)

0.876 (0.749-1.024) 0.793 (0.661-0.951)

p-value

0.791 0.027

0.095 0.013

1 (ref)

1 (ref) 1.418 (0.634-3.173) 1.110 (0.507-2.430) 1.941 (0.851-4.423) 1.549 (0.706-3.397) 0.968 (0.424-2.210) 2.565 (1.184-5.554) 1.683 (0.751-3.772)

OR (95% CI)

0.395 0.794 0.115 0.274 0.938 0.017 0.206

1.784 (0.876-3.634) 1.689 (0.858-3.323) 1.791 (0.835-3.838) 1.799 (0.906-3.575) 1.363 (0.643-2.889) 2.156 (1.072-4.336) 1.959 (0.923-4.161) -

0.110 0.129 0.134 0.093 0.419 0.031 0.080

ACCEPTED MANUSCRIPT

*Adjusted for age, BMI, current smoking, alcohol intake, regular exercise, total energy intake (Kcal), protein intake(g), anti-dyslipidemia medication The proportion of carbohydrate (CHO) intake was categorized into 3 groups by sex: T1 (≤61.0%), T2 (61.0-70.1%), and T3 (≥70.1%) for men and T1(≤63.5%), T2 (63.5-

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72.8%), and T3(≥72.8%) for women. The proportion of fat intake was also categorized into 3groups: T1 (≤15.0%), T2(15.0-22.4%), T3 (≥22.4%) for men and T1(≤

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13.3%), T2(13.3-20.8%), and T3(≥20.8%) for women.

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ACCEPTED MANUSCRIPT

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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT Highlights We examined the role of carbohydrate and fat in metabolic syndrome.

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This study was cross-sectionally designed based on the 2008-2011 KNHANES.

Participants were categorized to nine groups based on carbohydrate and fat proportion. A higher carbohydrate proportion is associated with a higher prevalence of MetS in men.

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A high carbohydrate proportion with a low fat proportion is associated with MetS in

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women.