Association between Total Sugar Intake and Metabolic Syndrome in Middle-Aged Korean Men and Women

There is increasing evidence emerging that suggests high sugar intake may adversely increase the incidence of chronic diseases. However, there are only a few related studies in Korea. Based on the current Dietary Reference Intakes for Koreans, this study examined whether total sugar intake above 20% of the total energy was a risk factor for metabolic syndrome in middle-aged Korean adults. This cross-sectional study involved 7005 adults (3751 men and 3254 women) aged 40–69 years, who participated in the Korean Genome and Epidemiology Study (KoGES), a large community-based cohort study. Daily total sugar intake was estimated using a validated food frequency questionnaire. About 9% and 16% of the men and women, respectively, derived >20% of energy intake from total sugar. The males in this category had a significantly higher odds of obesity defined as having a BMI ≥ 25 (OR = 1.491, 95% CI = 1.162–1.914), low HDL-cholesterol (OR = 1.313, 95% CI = 1.038–1.660), and metabolic syndrome (OR = 1.332, 95% CI = 1.038–1.709) than those who received a lower proportion of energy intake from total sugar. These results suggest that high (>20%) energy intake from total sugar may be associated with an increased risk of metabolic syndrome in middle-aged Korean men.


Introduction
Unhealthy eating patterns and a growing prevalence of chronic diseases, including diabetes and obesity, are a global concern. Healthy food choice is closely linked with the quality of life and healthy life expectancy, as well as the burden of healthcare expenditure. Consequently, among researchers, the public, and policymakers alike, there is a strong desire to identify the risk factors of diet-related chronic diseases [1]. In accord with this pursuit, there is a growing interest in the role of dietary patterns in the etiology of chronic diseases. While there have been many studies on fat intake associated with chronic diseases, sugar consumption has become a major concern in relation to the development of cardiovascular and metabolic diseases.
Biochemically, sugars consist of monosaccharides (glucose, fructose, galactose) and disaccharides (sucrose, maltose, lactose), excluding oligosaccharides [2]. Sugars occur naturally in some food, such as fruits and vegetables [3], in co-existence with other micronutrients and, therefore, have nutritional value [4]. By contrast, added sugars, which include refined sugars, honey, syrups, and other caloric sweeteners added to food or meals during processing or at home [2], provide no nutritional benefits [4]. Sugar-sweetened beverages (SSB) include sodas, sweetened juices, energy drinks, teas, and coffee that have been sweetened with added sugar [2,5].
communities were selected, one from Ansung, representing a rural community, and the other from Ansan, representing an urban community. Detailed information on the study procedure was described in a previous report [20].
Among 10,030 participants, those diagnosed with myocardial infarction, stroke, coronary artery disease, congestive heart failure, and history of cancer were excluded (n = 436). The following participants were also excluded due to an incomplete food frequency questionnaire (FFQ) (n = 691), unreliable energy intake of ≤500 kcal or >5000 kcal (n = 76), missing data regarding metabolic syndrome-related indicators (n = 243), and missing covariates, such as menopausal status (n = 1,579). Finally, a total of 7005 subjects (3751 men and 3254 women) were included for this cross-sectional analysis.

General Characteristics
Individual questionnaires, including lifestyle and disease history questions, were filled out by all participants. Residential location was divided as Ansan and Ansung. Three levels of education (elementary school, middle school/high school, and college/graduate school), alcohol consumption (non-drinker, ex-drinker, current drinker), and smoking behavior (non-smoker, ex-smoker, current smoker) were formed. Physical activity was defined as none or more than 30 min/day. Menopausal status was defined as "yes" or "no", depending on whether menstruation had occurred for 12 months or more.

Measurement of Anthropometry and Metabolic Parameters
Anthropometry and metabolic parameters were measured by trained medical staff, with subjects wearing light clothes. Body mass index (BMI) was calculated as weight (kg) divided by the square of the height (m 2 ). Blood pressure measurement was conducted at least twice under comfortable conditions. Blood samples obtained from the participants who fasted for 8 h were analyzed for biochemical markers, such as HDL-cholesterol, triglycerides, fasting blood glucose, insulin, C-reactive protein, and glycosylated hemoglobin. The homeostatic model assessment of insulin resistance ([fasting insulin × fasting glucose]/405) [21], LDL-cholesterol (total cholesterol-HDL-cholesterol-[triglycerides]/5]) [21], and atherogenic index ([total cholesterol-HDL-cholesterol]/HDL-cholesterol) [22] were calculated as indicated.

Definitions of Metabolic Syndrome
Metabolic syndrome was diagnosed using two approaches: The Adult Treatment Panel III of the National Cholesterol Education Program's (NCEP ATP III) standard diagnostic criteria [23], and the Korean Society for the Study of Obesity guidelines on waist circumference (WC) for defining abdominal obesity [24]. Metabolic syndrome was defined as having three or more of the following:

Dietary Assessment
Dietary intake was assessed using a validated 103-item FFQ. All study procedures were conducted by trained interviewers. Participants were asked to report the usual frequency and portion size of each food consumed during the past year. The answer for frequency had nine options for each food: "never/almost," "once/month," "2-3 times/month," "1-2 times/week," "3-4 times/week," "5-6 times/week," "once/day," "2 times/day," and "≥3 times/day." The answer for portion size had three options for each food: "small (1/2 serving/day)," "standard (1 serving/day)," and "large (≥2 servings/day)." The portion size of each food was determined based on the KoGES FFQ guideline. For analysis, food consumption was converted to weekly frequencies and then multiplied by the reported portion sizes.
Dietary nutrient intake data were compared using the estimated energy requirement and the estimated average requirement of the 2015 KDRI [10].

Estimation of Total Sugar Intake
Daily total sugar intake was estimated from the total sugar database constructed by the Korea Food and Drug Administration (KFDA) [25] for the foods included in the FFQ recipe. The percentage of energy from sugar intake was calculated as daily total sugar intake × 4 kcal/energy intake × 100.

Statistical Analysis
Data were expressed as mean ± standard deviation for continuous variables and number (n, %) for categorical variables. To identify the significance of the difference in means and distribution of general characteristics and dietary intakes between the two groups (≤20% TEI from total sugar vs. >20% TEI from total sugar), the Student's t-test (for continuous variables: Age, BMI) and the chi-square test and Fisher's exact test (categorical variables: residential location, educational level, alcohol consumption, smoking behavior, physical activity, menopausal status) were used.
Differences in metabolic parameters between the two groups were evaluated using the general linear model (GLM) test after adjusting for potential confounders. The potential confounders included the following variables: Age, energy intake, residential location, educational level, alcohol consumption, smoking behavior, physical activity, and menopausal status.
Multiple logistic regression analysis was performed to estimate the odds ratios (OR) and 95% confidence intervals (CI) for cardiometabolic biomarkers and metabolic syndrome, depending on TEI from total sugar (≤20% vs. >20%). Potential confounders were included in the GLM and multiple logistic regression analysis as covariates. All statistical analyses were performed using SAS software version 9.4. Statistical significance was considered when p < 0.05.

General Characteristics of the Subjects According to the Percentage of Energy from Total Sugar Intake
The general characteristics of the two groups (≤20% TEI from total sugar vs. >20% TEI from total sugar) are displayed in Table 1. Mean total sugar intakes and mean percentage TEI from total sugar of men and women were 66.5 ± 40.6 and 68.0 ± 45.7 g/day and 12.8 ± 5.4% and 14.4 ± 6.7%/day, respectively (data not shown). About 9% of the men and 16% of the women derived >20% TEI from total sugar. The males in this category had a lower proportion of current drinkers, a higher proportion of current smokers, and were significantly older than the males who received ≤20% TEI from total sugar. Regarding residential location, the proportions of men and women who had >20% TEI from total sugar were significantly higher in Ansung than Ansan (p < 0.0001). In women, there was no difference in general characteristics between the two groups (≤20% TEI from total sugar vs. >20% TEI from total sugar), except for residential location.

Daily Nutrient Intake According to the Percentage of Energy from Total Sugar Intake
In men and women, daily intakes of all macronutrients, including energy, were significantly higher in the group with >20% TEI from total sugar than the group with ≤20% TEI from total sugar ( Table 2). Vitamin and mineral intakes showed the same trend (data not shown). When comparing the two groups as contribution percentage in the energy intake (i.e., not the absolute intake of macronutrients), the percentage of energy intake from carbohydrate in men, and the percentage of energy intake from fat and carbohydrate in women were significantly higher in the group with >20% TEI from total sugar.

Metabolic Parameters According to the Percentage of Energy from Total Sugar Intake
Men who received >20% TEI from total sugar had higher WC (p = 0.0481) and lower HDL-cholesterol (p = 0.0067) than those who derived ≤20% TEI from total sugar (Table 3). This trend was also evident in women (p = 0.0455).

Association between the Percentage of Energy from Total Sugar Intake and Cardiometabolic Biomarkers Risk
Men with >20% TEI from total sugar had a higher odds of obesity (defined as BMI ≥ 25 kg/m 2 ) (OR = 1.491, 95% CI = 1.162-1.914) after adjusting for covariates (Table 4) in comparison to the men with ≤20% TEI from total sugar Except for obesity, there was no difference in the odds of other cardiometabolic biomarker risk factors between the two groups of men. There was no difference in the odds of all cardiometabolic biomarker risk factors between the two groups of women.  Table 5 shows that men who derived >20% TEI from total sugar had a higher odds of low HDL-cholesterol (OR = 1.313, 95% CI = 1.038-1.660) and metabolic syndrome (OR = 1.332, 95% CI = 1.038-1.709) when compared with those who received ≤20% TEI from total sugar There was no difference in odds of metabolic syndrome between the two groups of women.

Discussion
This study found that deriving >20% TEI from total sugar was associated with higher odds of obesity, low HDL-cholesterol, and metabolic syndrome among Korean men aged 40-69 years, but not among women in the same age range.
The study of the relationship between sugar intake and chronic diseases has been mainly focused on SSB, with insufficient analysis of total sugar intake. In addition, investigations into the association between total sugar intake and chronic diseases, including metabolic syndrome, in adults who are not Korean adolescents are even rarer. Recently, the KFDA reported the results of a study examining the relationship between the total sugar intake (calculated using two-day 24-h recall data) and chronic diseases (using the KoGES data). It found that the risk of obesity, diabetes, and hypertension was not affected by whether total sugar intake was above or below 20% TEI. However, the risk of overweight was higher in men who derived >20% TEI from total sugar compared with those who received <20% TEI from total sugar [26].
The proportion of processed foods (56.8%) contributing to total sugar intake of Koreans was higher than that from food in which sugars occur naturally, and the top five processed food sources of total sugar intake were granulated sugar, carbonated beverages, coffee, bread, and fruit and vegetable drinks [11]. In other words, among processed foods, SSB were found to be the main source of sugar intake. It has been reported that SSB negatively affect health because they generally do not give a feeling of fullness and only increase energy density without providing other nutrients. Shin et al. [27] argued that high consumption of SSB was closely linked to a higher prevalence of obesity and metabolic syndrome in the Korean population. Analysis by Kwak et al. [28] demonstrated that among 5575 middle-aged participants in the KoGES, those in the highest SSB consumption group had a 21% greater risk of hypertension than those in the lowest SSB consumption group, and this association was most relevant for the participants with obesity. This relationship between SSB and chronic diseases has also been reported in Asian [29,30] and Western [31,32] populations.
There are several possible mechanisms explaining the link between SSB intake and chronic disease. First, the energy consumed in the form of SSB is rapidly absorbed, resulting in a positive energy balance, which, in turn, leads to increased weight since more energy is consumed in the next meal [33]. Second, apart from the weight gain effect, SSB intake increases the dietary glycemic load and fructose intake, which increases insulin resistance, beta-cell function, inflammation, hypertension, accumulation of visceral fat, and, eventually, increases the risk of metabolic syndrome, type 2 diabetes, and cardiovascular disease [34]. Moreover, artificial sweeteners have also been reported to enhance the risk of glucose intolerance. Continued consumption of artificial sweeteners can alter the composition and function of the gut microbiota, which may lead to the induction of metabolic abnormalities, such as glucose intolerance [35].
Interestingly, our study found a positive association between total sugar intake and metabolic syndrome in men, but not in women, even though the proportion of the highest consumption group in men was lower than that in women. It is unclear why only men showed a positive association between total sugar intake and metabolic disease. Different outcomes in the association of total sugar or SSB with metabolic disease between sexes can be found in the literature. In a cross-sectional study, SSB intake was significantly associated with obesity in men, but metabolic syndrome and obesity in women [27]. In other work, a positive association between total sugar intake and overweight was exclusively observed in men [26]. When examining the data of 5797 middle-aged Korean men and women, Kang and Kim [36] revealed that frequent soft drink consumption (>4 servings/week) was associated with an increased risk of developing metabolic syndrome and its components only in women. Elsewhere, women, but not men, who consumed ≥1 SSB/day had an increased incidence of type 2 diabetes [30]. These sex-dependent results might be explained by dietary intake and lifestyle differences between men and women that could alter hormone levels and metabolic profile, which could affect obesity or metabolic disease.
In the present study, in men, but not women, there was a significant association between high sugar intake and unhealthy lifestyle (such as smoking). High sugar consumption (particularly as SSB) is a known marker of an unhealthy lifestyle. Long-term high intake of soft drinks (≥3 times per week) has been significantly associated with a lower level of physical activity and a greater degree of smoking than long-term, low intake of soft drinks (<3 times per week) [37]. Another study found that high soft drink intake (≥ twice a day) was associated with more smoking than low soft drink intake (< once a day) [32].
Low estrogen concentration causes low HDL-cholesterol and leads to resistance to insulin-mediated glucose [38,39] because estrogen protects HDL-cholesterol by suppressing hepatic lipase and is tightly associated with lipoprotein profiles [40,41]. Since these processes contribute to obesity and type 2 diabetes, they increase the risk of exposure to metabolic syndrome and cardiovascular disease risk factors [33,42]. Therefore, women maintaining an HDL-cholesterol level at 10 mg/dL higher than men by estrogen have a relatively lower risk of metabolic syndrome and cardiovascular disease [43]. As a result, differences by sex can be interpreted according to evidence that estrogen's effect on lipid metabolism and lifestyle may contribute to the association between sugar intake and metabolic syndrome.
In our study, participants who exceeded 20% TEI from total sugar had higher nutrient intake than those with ≤20% TEI from total sugar. These results may be caused by differences in the major sources of sugar, highlighting the importance of measuring sugar intake, considering the main dietary source of sugar. Physiological metabolic pathways are affected by the form of sugars. Unlike simple sugars that are absorbed in the upper half of the gastrointestinal tract, complex carbohydrates are absorbed after decomposition by microbes in the large intestine [44]. During this process, short-chain fatty acids are produced, stimulating enteroendocrine pathways, thereby increasing the levels of satiety hormones [44]. In comparing solid intake with liquid intake, the masticatory movement of eating solid food triggers satiety hormones, which can reduce total energy intake [45]. Furthermore, pancreatic exocrine and endocrine mechanisms that act to release insulin function better, and this can enhance the regulation of glucose tolerance [45]. For these reasons, even with isoenergetic sugar intake, the outcomes on health appear different depending on the original form of the food.
This study had several limitations. First, because our data are based on a cross-sectional study, it is difficult to explain the causal relationship between sugar intake and metabolic syndrome. Therefore, a further prospective cohort study is needed. Second, it is difficult to generalize the results to the entire Korean population because we only selected participants in Ansan and Ansung. Therefore, the results should be interpreted carefully. Although the study had some limitations, we analyzed the data after controlling for potential confounders to reduce the impact of these limitations. To the best of our knowledge, this is the first study to examine the associations of total sugar intake with obesity and metabolic syndrome (including its discrete components) at the same time, among middle-aged Korean adults. In particular, it is important to examine total sugar intake as a contribution to energy rather than total sugar intake in relation to obesity or metabolic syndrome.
Unlike the ongoing research activities in the West, research on sugar intake and chronic diseases in Korea is at the beginning stage. Korea and the West have different diets, and so it is reasonable to propose that there will be differences in their vulnerability to chronic diseases in relation to their diet. This study examined the relevance of total sugar intake as a risk factor of metabolic syndrome in middle-aged Korean adults. It sets a precedent for further research in this population that will confirm or not the suggestive evidence provided in this investigation that found total sugar intake is significantly associated with metabolic syndrome in middle-aged Korean men (40-69 years) but not women. Furthermore, the results of this study can be used as a scientific basis for setting the target level in order to gradually reduce not only the sugar intake of Koreans but populations worldwide. The data may also be used to suggest the appropriate policy for reducing the sugar intake of middle-aged adults.

Conclusions
In conclusion, this study found that total sugar intake was significantly associated with metabolic syndrome in middle-aged Korean men (40-69 years). Total sugar intake exceeding >20% of the TEI was associated with higher risks of low HDL-cholesterol, obesity (defined as BMI ≥25 kg/m 2 ), and metabolic syndrome in men. While total sugar intake is important in terms of its contribution to the ratio of energy intake, other added-sugar/free-sugar intake levels and food sources are important and their causal relationship with metabolic syndrome should be identified using this comprehensive sugar intake evaluation.